A study to assess the relative bioavailability of 3 different formulations under fasted and fed condition

Study identifier:D5495C00005

ClinicalTrials.gov identifier:NCT04024501

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Randomised, Single-dose, 5-period, 5-treatment, Crossover Study to Assess the Relative Bioavailability of 3 Different Extended-release Formulations of Verinurad in Healthy Subjects

Medical condition

Chronic Kidney Disease

Phase

Phase 1

Healthy volunteers

Yes

Study drug

Verinurad ER8 capsule formulation (fasted), Verinurad A-capsule formulation (fasted), Verinurad A-capsule formulation (fed), Verinurad B-capsule formulation (fasted), Verinurad B-capsule formulation (fed)

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 50 Years

Date

Study Start Date: 20 Jul 2019

Primary Completion Date: 18 Sept 2019

Study Completion Date: 18 Sept 2019

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Crossover Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Feb 2021 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

1. Provision of signed and dated, written informed consent prior to any study specific procedures.
2. Healthy male and female participants aged 18 to 50 years with suitable veins for cannulation or repeated venepuncture.
3. Have a body mass index (BMI) between 18 and 30 kg/m2 and weigh at least 50 kg and no more than 100 kg.
4. Females must have a negative pregnancy test at screening and on admission to the unit and must be:
(1) not pregnant or currently lactating or breastfeeding.
(2) of non-childbearing potential, confirmed at screening by fulfilling one of the following criteria:
(i) postmenopausal defined as amenorrhoea for at least 12 months or more following cessation of all exogenous hormonal treatments and FSH levels in the postmenopausal range (FSH levels > 40 IU/mL).
(ii) documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
(3) OR if of childbearing potential must be willing to use an acceptable method of contraception to avoid pregnancy for the entire study period.

Exclusion Criteria

1. History of gout or any clinically significant disease or disorder which, in the opinion of the Principal Investigator (PI), may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer’s ability to participate in the study.
2. Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the first administration of verinurad.
3. History or presence of gastrointestinal (GI), hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
4. Any clinically important abnormalities in clinical chemistry, haematology or urinalysis results as judged by the Investigator at screening and first admission, including: (1) Alanine aminotransferase (ALT) > 1.5 x upper limit of normal (ULN), (2) Aspartate aminotransferase (AST) > 1.5 x ULN, (3) Bilirubin (total) > 1.5 x ULN, (4) Gamma glutamyl transpeptidase (GGT) > 1.5 x ULN. (5) If any of these tests are out-of-range, the tests can be repeated once.
5. Any clinically significant abnormal findings in vital signs at the Screening Visit and/or admission to the Clinical Unit, including, but not limited to, any of the following:
(1) Heart rate (resting, supine) < 50 beats per minute (bpm) or > 85 bpm,
(2) Systolic BP < 90 mmHg or > 140 mmHg and/or diastolic BP < 50 mmHg or > 90 mmHg sustained for > 10 min while resting in a supine position.
6. Any clinically significant abnormalities on 12-lead Electrocardiogram (ECG) at the Screening Visit, including, but not limited to any of the following:
(1) ECG interval measured from the onset of the QRS complex to the end of the T wave (QT) interval corrected for heart rate using Fridericia’s formula (QTcF) > 450 ms or < 340 ms or family history of long QT syndrome,
(2) Any significant arrhythmia,
(3) Conduction abnormalities:
(4) Clinically significant PR (PQ) interval prolongation (> 240 ms); intermittent second or third degree atrioventricular (AV) block, or AV dissociation,
(5) Complete bundle branch block and/or QRS duration > 120 ms.
7. Any positive result at the Screening Visit for serum hepatitis B surface antigen or antiHBc antibody, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.
8. Suspicion or known Gilbert’s and/or Lesch-Nyhan syndrome.
9. Known or suspected history of alcohol or drug abuse or excessive intake of alcohol as judged by the PI. Excessive intake of alcohol defined as the regular consumption of more than 24 g of alcohol per day for men or 12 g of alcohol per day for women.
10. Has received another new chemical entity (defined as a compound which has not been approved for marketing in the US) within 30 days or at least 5 half-lives (whichever is longer) of the first administration of verinurad in this study.
11. Participants who have previously received verinurad.
12. Plasma donation within 1 month of screening or any blood donation/loss of more than 500 mL during the 3 months prior to the Screening Visit.
13. Participants who are pregnant, lactating or planning to become pregnant.
14. History of severe allergy/hypersensitivity or ongoing clinically relevant allergy/hypersensitivity, as judged by the PI or history of hypersensitivity to drugs with a similar chemical structure or class to verinurad.
15. Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the 3 months prior to screening.
16. Excessive intake of caffeine-containing drinks or food (e.g., coffee, tea, chocolate) as judged by the PI. Excessive intake of caffeine defined as regular consumption of more than 600 mg of caffeine per day (e.g., > 5 cups of coffee) or would likely be unable to refrain from the use of caffeine containing beverages during confinement at the investigational site.
17. Positive screen for drugs of abuse or cotinine (nicotine) at the Screening Visit or positive screen for alcohol, drugs of abuse and cotinine on each admission to the study centre.
18. Use of drugs with enzyme-inducing properties such as St John’s Wort within 3 weeks prior to the first administration of verinurad.
19. Use of any prescribed or non-prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to the first administration of verinurad or longer if the medication has a long half-life. The use of hormonal contraception therapy and hormonal replacement therapy for females are permitted.
20. Any AstraZeneca, PAREXEL or study site employee or their close relatives.
21. Participants who cannot communicate reliably with the PI and/or is not able to read, speak and understand the German language.
22. Judgment by the PI that the participant should not participate in the study if they have any ongoing or recent (i.e., during the screening period) minor medical complaints that may interfere with the interpretation of study data or are considered unlikely to comply with study procedures, restrictions, and requirements.
23. Vulnerable participants, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
24. Participants with any special dietary restrictions such as participants that are lactose intolerant or are vegetarians/vegans.

This study will be a randomised, open-label, single-dose, 5-period, 5-treatment, crossover study in healthy male and female participants, performed at a single study centre. This study is intended to assess the relative bioavailability between the ER8 capsule formulation (the formulation that is currently used for verinurad development) given under fasted conditions and 2 new capsule formulation of verinurad (A-capsule and B-capsule) given under fed or fasted conditions. All three capsules target an 8-hour release profile (extended-release). The highest dose (12 mg) currently tested in participants will be tested in this study. The study is designed to provide information to optimize the verinurad part of a fixed dose combination capsule to be used in future development. The study will comprise: a screening period of maximum 28 days; five treatment periods during which participants will be resident from the morning of the day before dosing with verinurad (Day -1) until at least 72 hours after dosing; discharged on the morning of Day 4 of each Treatment Period; and a follow-up Visit within 7 to 14 days after the last administration of verinurad. There will be a minimum washout period of 5 days between each dose administration. A total of 25 healthy male and female participants will be randomised into this study. Each participant will receive five single-dose treatments of 12 mg verinurad with 240 mL water, following an overnight fast of at least 10 hours. Participants will follow an overnight fast of at least 10 hours before the dosing procedures: for the fed dosing, a high-fat, high-calorie standard breakfast will be served 30 minutes before the planned administration of verinurad to be consumed in full at least 5 minutes before dosing; for the fasted dosing, no breakfast will be served. A meal can be given 4 hours after administration of verinurad for both dosing states. The duration of the study is expected to be approximately 9 weeks for each individual participant (including the 28-day screening period).

Location

Research Site

Berlin, Germany, 14050

Arms	Assigned Interventions
Experimental: Treatment 1 During this treatment period, healthy participants will receive 1 x 12 mg verinurad ER8 capsule formulation in fasted state.	Drug: Verinurad ER8 capsule formulation (fasted) Each participant will receive single-dose treatment of 12 mg verinurad ER8 capsule with 240 mL water, following an overnight fast of at least 10 hours.
Experimental: Treatment 2 During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fasted state.	Drug: Verinurad A-capsule formulation (fasted) Each participant will receive single-dose treatment of 12 mg verinurad A-capsule with 240 mL water, following an overnight fast of at least 10 hours.
Experimental: Treatment 3 During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fed state.	Drug: Verinurad A-capsule formulation (fed) Each participant will receive single dose treatment of 12 mg verinurad A-capsule with 240 mL water, following a high-fat, high-calorie breakfast (after the overnight fast).
Experimental: Treatment 4 During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fasted state.	Drug: Verinurad B-capsule formulation (fasted) Each participant will receive single-dose treatment of 12 mg verinurad B-capsule with 240 mL water, following an overnight fast of at least 10 hours.
Experimental: Treatment 5 During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fed state.	Drug: Verinurad B-capsule formulation (fed) Each participant will receive single dose treatment of 12 mg verinurad B-capsule with 240 mL water, following a high-fat, high-calorie breakfast (after the overnight fast).

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
All subjects signed and dated the informed consent form (ICF) before any study procedures were performed.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The study included a Screening Period of maximum 28 days.

Reporting Groups

	Description
Overall-All Subjects	All subjects were randomized into 5-period, 5-treatment, crossover study to receive a single oral dose of 12 mg verinurad: • Treatment 1: 1 x 12 mg verinurad ER8 capsule formulation, fasted. • Treatment 2: 2 x 6 mg verinurad A-capsule formulation, fasted. • Treatment 3: 2 x 6 mg verinurad A-capsule formulation, fed. • Treatment 4: 2 x 6 mg verinurad B-capsule formulation, fasted. • Treatment 5: 2 x 6 mg verinurad B-capsule formulation, fed.

Description

Overall-All Subjects

All subjects were randomized into 5-period, 5-treatment, crossover study to receive a single oral dose of 12 mg verinurad:

• Treatment 1: 1 x 12 mg verinurad ER8 capsule formulation, fasted.
• Treatment 2: 2 x 6 mg verinurad A-capsule formulation, fasted.
• Treatment 3: 2 x 6 mg verinurad A-capsule formulation, fed.
• Treatment 4: 2 x 6 mg verinurad B-capsule formulation, fasted.
• Treatment 5: 2 x 6 mg verinurad B-capsule formulation, fed.

Participant Flow: Overall Study

	Overall-All Subjects
STARTED	25
COMPLETED	25
NOT COMPLETED	0

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
Overall-All Subjects	All subjects were randomized into 5-period, 5-treatment, crossover study to receive a single oral dose of 12 mg verinurad: • Treatment 1: 1 x 12 mg verinurad ER8 capsule formulation, fasted. • Treatment 2: 2 x 6 mg verinurad A-capsule formulation, fasted. • Treatment 3: 2 x 6 mg verinurad A-capsule formulation, fed. • Treatment 4: 2 x 6 mg verinurad B-capsule formulation, fasted. • Treatment 5: 2 x 6 mg verinurad B-capsule formulation, fed.

Description

Overall-All Subjects

All subjects were randomized into 5-period, 5-treatment, crossover study to receive a single oral dose of 12 mg verinurad: • Treatment 1: 1 x 12 mg verinurad ER8 capsule formulation, fasted. • Treatment 2: 2 x 6 mg verinurad A-capsule formulation, fasted. • Treatment 3: 2 x 6 mg verinurad A-capsule formulation, fed. • Treatment 4: 2 x 6 mg verinurad B-capsule formulation, fasted. • Treatment 5: 2 x 6 mg verinurad B-capsule formulation, fed.

Baseline Measures

	Overall-All Subjects
Number of Participants [units: Participants]	25
Age Continuous [units: Years] Mean ± Standard Deviation	38.1 ± 9.4
Sex: Female, Male [units: ]
Female	11
Male	14
Race (NIH/OMB) [units: ]
American Indian or Alaska Native	0
Asian	0
Native Hawaiian or Other Pacific Islander	0
Black or African American	0
White	25
More than one race	0
Unknown or Not Reported	0
Ethnicity (NIH/OMB) [units: ]
Hispanic or Latino	0
Not Hispanic or Latino	25
Unknown or Not Reported	0

Outcome Measures

1. Primary Outcome Measure: Area under plasma concentration-time curve from zero to infinity (AUC) [ Time Frame: Day 1: Pre-dose and up to 72-hour Post-dose ]

Measure Type	Primary
Measure Name	Area under plasma concentration-time curve from zero to infinity (AUC)
Measure Description	To evaluate the relative bioavailability between the A-capsule and B-capsule formulations under both fed and fasted conditions with the ER8 capsule formulation under fasted conditions and with each other under the same food conditions.
Time Frame	Day 1: Pre-dose and up to 72-hour Post-dose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set for whom at least 1 of the primary PK parameters could be calculated, and who had no major protocol deviations thought to impact on the analysis of the PK data.

Reporting Groups

	Description
Treatment 1: 1 x 12 mg ER8 capsule Fasted	During this treatment period, healthy participants will receive 1 x 12 mg verinurad ER8 capsule formulation in fasted state.
Treatment 2: 2 x 6 mg A-capsule Fasted	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fasted state.
Treatment 3: 2 x 6 mg A-capsule Fed	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fed state.
Treatment 4: 2 x 6 mg B-capsule Fasted	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fasted state.
Treatment 5: 2 x 6 mg B-capsule Fed	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fed state.

Measured Values

	Treatment 1: 1 x 12 mg ER8 capsule Fasted	Treatment 2: 2 x 6 mg A-capsule Fasted	Treatment 3: 2 x 6 mg A-capsule Fed	Treatment 4: 2 x 6 mg B-capsule Fasted	Treatment 5: 2 x 6 mg B-capsule Fed
Number of Participants Analyzed [units:participants]	25	25	25	25	25
Area under plasma concentration-time curve from zero to infinity (AUC) [units: ng*h/mL] Geometric Mean (Geometric Coefficient of Variation)	171.3 (47.60%)	167.5 (33.72%)	87.14 (65.84%)	149.0 (39.78%)	150.2 (42.57%)

Statistical Analysis 1 for Area under plasma concentration-time curve from zero to infinity (AUC)

Groups^[1]	Treatment 1: 1 x 12 mg ER8 capsule Fasted, Treatment 2: 2 x 6 mg A-capsule Fasted
Method^[3]	Other [Mixed Model Analysis]
Other^[5]	106.20
90% Confidence Interval	( 91.73 to 122.96 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Pairwise comparison: Treatment 2/Treatment 1
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The number of subjects in this analysis: 22
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Area under plasma concentration-time curve from zero to infinity (AUC)

Groups^[1]	Treatment 1: 1 x 12 mg ER8 capsule Fasted, Treatment 3: 2 x 6 mg A-capsule Fed
Method^[3]	Other [Mixed Model Analysis]
Other^[5]	50.02
90% Confidence Interval	( 42.34 to 59.10 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Pairwise comparison: Treatment 3/Treatment 1
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The number of subjects in this analysis: 22
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Area under plasma concentration-time curve from zero to infinity (AUC)

Groups^[1]	Treatment 2: 2 x 6 mg A-capsule Fasted, Treatment 3: 2 x 6 mg A-capsule Fed
Method^[3]	Other [Mixed Model Analysis]
Other^[5]	47.10
90% Confidence Interval	( 39.85 to 55.68 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Pairwise comparison: Treatment 3/Treatment 2
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The number of subjects in this analysis: 15
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 4 for Area under plasma concentration-time curve from zero to infinity (AUC)

Groups^[1]	Treatment 3: 2 x 6 mg A-capsule Fed, Treatment 4: 2 x 6 mg B-capsule Fasted
Method^[3]	Other [Mixed Model Analysis]
Other^[5]	58.40
90% Confidence Interval	( 49.49 to 68.92 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Pairwise comparison: Treatment 3/Treatment 4
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The number of subjects in this analysis: 15
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 5 for Area under plasma concentration-time curve from zero to infinity (AUC)

Groups^[1]	Treatment 1: 1 x 12 mg ER8 capsule Fasted, Treatment 4: 2 x 6 mg B-capsule Fasted
Method^[3]	Other [Mixed Model Analysis]
Other^[5]	85.65
90% Confidence Interval	( 73.78 to 99.43 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Pairwise comparison: Treatment 4/Treatment 1
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The number of subjects in this analysis: 21
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 6 for Area under plasma concentration-time curve from zero to infinity (AUC)

Groups^[1]	Treatment 2: 2 x 6 mg A-capsule Fasted, Treatment 4: 2 x 6 mg B-capsule Fasted
Method^[3]	Other [Mixed Model Analysis]
Other^[5]	80.65
90% Confidence Interval	( 69.48 to 93.62 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Pairwise comparison: Treatment 4/Treatment 2
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The number of subjects in this analysis: 21
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 7 for Area under plasma concentration-time curve from zero to infinity (AUC)

Groups^[1]	Treatment 1: 1 x 12 mg ER8 capsule Fasted, Treatment 5: 2 x 6 mg B-capsule Fed
Method^[3]	Other [Mixed Model Analysis]
Other^[5]	89.88
90% Confidence Interval	( 77.61 to 104.09 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Pairwise comparison: Treatment 5/Treatment 1
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The number of subjects in this analysis: 21
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 8 for Area under plasma concentration-time curve from zero to infinity (AUC)

Groups^[1]	Treatment 2: 2 x 6 mg A-capsule Fasted, Treatment 5: 2 x 6 mg B-capsule Fed
Method^[3]	Other [Mixed Model Analysis]
Other^[5]	84.64
90% Confidence Interval	( 72.94 to 98.20 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Pairwise comparison: Treatment 5/Treatment 2
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The number of subjects in this analysis: 21
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 9 for Area under plasma concentration-time curve from zero to infinity (AUC)

Groups^[1]	Treatment 3: 2 x 6 mg A-capsule Fed, Treatment 5: 2 x 6 mg B-capsule Fed
Method^[3]	Other [Mixed Model Analysis]
Other^[5]	179.68
90% Confidence Interval	( 151.57 to 212.99 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Pairwise comparison: Treatment 5/Treatment 3
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The number of subjects in this analysis: 21
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 10 for Area under plasma concentration-time curve from zero to infinity (AUC)

Groups^[1]	Treatment 4: 2 x 6 mg B-capsule Fasted, Treatment 5: 2 x 6 mg B-capsule Fed
Method^[3]	Other [Mixed Model Analysis]
Other^[5]	104.94
90% Confidence Interval	( 90.18 to 122.11 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Pairwise comparison: Treatment 5/Treatment 4
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The number of subjects in this analysis: 21
[5]	Other relevant estimation information:
	No text entered.

2. Primary Outcome Measure: AUC from time 0 to the last quantifiable concentration (AUC0-t) for the analysis of PK parameter [ Time Frame: Day 1: Pre-dose and up to 72-hour Post-dose ]

Measure Type	Primary
Measure Name	AUC from time 0 to the last quantifiable concentration (AUC0-t) for the analysis of PK parameter
Measure Description	To evaluate the relative bioavailability between the A-capsule and B-capsule formulations under both fed and fasted conditions with the ER8 capsule formulation under fasted conditions and with each other under the same food conditions.
Time Frame	Day 1: Pre-dose and up to 72-hour Post-dose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set for whom at least 1 of the primary PK parameters could be calculated, and who had no major protocol deviations thought to impact on the analysis of the PK data.

Reporting Groups

	Description
Treatment 1: 1 x 12 mg ER8 capsule Fasted	During this treatment period, healthy participants will receive 1 x 12 mg verinurad ER8 capsule formulation in fasted state.
Treatment 2: 2 x 6 mg A-capsule Fasted	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fasted state.
Treatment 3: 2 x 6 mg A-capsule Fed	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fed state.
Treatment 4: 2 x 6 mg B-capsule Fasted	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fasted state.
Treatment 5: 2 x 6 mg B-capsule Fed	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fed state.

Measured Values

	Treatment 1: 1 x 12 mg ER8 capsule Fasted	Treatment 2: 2 x 6 mg A-capsule Fasted	Treatment 3: 2 x 6 mg A-capsule Fed	Treatment 4: 2 x 6 mg B-capsule Fasted	Treatment 5: 2 x 6 mg B-capsule Fed
Number of Participants Analyzed [units:participants]	25	25	25	25	25
AUC from time 0 to the last quantifiable concentration (AUC0-t) for the analysis of PK parameter [units: ng*h/mL] Geometric Mean (Geometric Coefficient of Variation)	166.8 (47.57%)	167.5 (35.96%)	67.04 (80.37%)	128.5 (49.29%)	139.6 (44.36%)

Statistical Analysis 1 for AUC from time 0 to the last quantifiable concentration (AUC0-t) for the analysis of PK parameter

Groups^[1]	Treatment 1: 1 x 12 mg ER8 capsule Fasted, Treatment 2: 2 x 6 mg A-capsule Fasted
Method^[3]	Other [Mixed Model Analysis]
Other^[5]	100.39
90% Confidence Interval	( 84.94 to 118.65 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Pairwise comparison: Treatment 2/Treatment 1
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The number of subjects in this analysis: 25
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for AUC from time 0 to the last quantifiable concentration (AUC0-t) for the analysis of PK parameter

Groups^[1]	Treatment 1: 1 x 12 mg ER8 capsule Fasted, Treatment 3: 2 x 6 mg A-capsule Fed
Method^[3]	Other [Mixed Model Analysis]
Other^[5]	41.26
90% Confidence Interval	( 34.74 to 49.00 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Pairwise comparison: Treatment 3/Treatment 1
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The number of subjects in this analysis: 23
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for AUC from time 0 to the last quantifiable concentration (AUC0-t) for the analysis of PK parameter

Groups^[1]	Treatment 2: 2 x 6 mg A-capsule Fasted, Treatment 3: 2 x 6 mg A-capsule Fed
Method^[3]	Other [Mixed Model Analysis]
Other^[5]	41.10
90% Confidence Interval	( 34.61 to 48.81 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Pairwise comparison: Treatment 3/Treatment 2
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The number of subjects in this analysis: 23
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 4 for AUC from time 0 to the last quantifiable concentration (AUC0-t) for the analysis of PK parameter

Groups^[1]	Treatment 3: 2 x 6 mg A-capsule Fed, Treatment 4: 2 x 6 mg B-capsule Fasted
Method^[3]	Other [Mixed Model Analysis]
Other^[5]	53.55
90% Confidence Interval	( 45.09 to 63.59 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Pairwise comparison: Treatment 3/Treatment 4
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The number of subjects in this analysis: 23
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 5 for AUC from time 0 to the last quantifiable concentration (AUC0-t) for the analysis of PK parameter

Groups^[1]	Treatment 1: 1 x 12 mg ER8 capsule Fasted, Treatment 4: 2 x 6 mg B-capsule Fasted
Method^[3]	Other [Mixed Model Analysis]
Other^[5]	77.05
90% Confidence Interval	( 65.19 to 91.06 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Pairwise comparison: Treatment 4/Treatment 1
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The number of subjects in this analysis: 25
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 6 for AUC from time 0 to the last quantifiable concentration (AUC0-t) for the analysis of PK parameter

Groups^[1]	Treatment 2: 2 x 6 mg A-capsule Fasted, Treatment 4: 2 x 6 mg B-capsule Fasted
Method^[3]	Other [Mixed Model Analysis]
Other^[5]	76.75
90% Confidence Interval	( 64.94 to 90.71 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Pairwise comparison: Treatment 4/Treatment 2
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The number of subjects in this analysis: 25
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 7 for AUC from time 0 to the last quantifiable concentration (AUC0-t) for the analysis of PK parameter

Groups^[1]	Treatment 1: 1 x 12 mg ER8 capsule Fasted, Treatment 5: 2 x 6 mg B-capsule Fed
Method^[3]	Other [Mixed Model Analysis]
Other^[5]	84.23
90% Confidence Interval	( 70.93 to 100.03 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Pairwise comparison: Treatment 5/Treatment 1
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The number of subjects in this analysis: 23
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 8 for AUC from time 0 to the last quantifiable concentration (AUC0-t) for the analysis of PK parameter

Groups^[1]	Treatment 2: 2 x 6 mg A-capsule Fasted, Treatment 5: 2 x 6 mg B-capsule Fed
Method^[3]	Other [Mixed Model Analysis]
Other^[5]	83.90
90% Confidence Interval	( 70.65 to 99.64 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Pairwise comparison: Treatment 5/Treatment 2
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The number of subjects in this analysis: 23
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 9 for AUC from time 0 to the last quantifiable concentration (AUC0-t) for the analysis of PK parameter

Groups^[1]	Treatment 3: 2 x 6 mg A-capsule Fed, Treatment 5: 2 x 6 mg B-capsule Fed
Method^[3]	Other [Mixed Model Analysis]
Other^[5]	204.16
90% Confidence Interval	( 171.22 to 243.42 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Pairwise comparison: Treatment 5/Treatment 3
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The number of subjects in this analysis: 23
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 10 for AUC from time 0 to the last quantifiable concentration (AUC0-t) for the analysis of PK parameter

Groups^[1]	Treatment 4: 2 x 6 mg B-capsule Fasted, Treatment 5: 2 x 6 mg B-capsule Fed
Method^[3]	Other [Mixed Model Analysis]
Other^[5]	109.32
90% Confidence Interval	( 92.06 to 129.83 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Pairwise comparison: Treatment 5/Treatment 4
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The number of subjects in this analysis: 23
[5]	Other relevant estimation information:
	No text entered.

3. Primary Outcome Measure: Maximum observed plasma concentration (Cmax) for the analysis of PK parameter [ Time Frame: Day 1: Pre-dose and up to 72-hour Post-dose ]

Measure Type	Primary
Measure Name	Maximum observed plasma concentration (Cmax) for the analysis of PK parameter
Measure Description	To evaluate the relative bioavailability between the A-capsule and B-capsule formulations under both fed and fasted conditions with the ER8 capsule formulation under fasted conditions and with each other under the same food conditions.
Time Frame	Day 1: Pre-dose and up to 72-hour Post-dose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set for whom at least 1 of the primary PK parameters could be calculated, and who had no major protocol deviations thought to impact on the analysis of the PK data.

Reporting Groups

	Description
Treatment 1: 1 x 12 mg ER8 capsule Fasted	During this treatment period, healthy participants will receive 1 x 12 mg verinurad ER8 capsule formulation in fasted state.
Treatment 2: 2 x 6 mg A-capsule Fasted	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fasted state.
Treatment 3: 2 x 6 mg A-capsule Fed	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fed state.
Treatment 4: 2 x 6 mg B-capsule Fasted	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fasted state.
Treatment 5: 2 x 6 mg B-capsule Fed	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fed state.

Measured Values

	Treatment 1: 1 x 12 mg ER8 capsule Fasted	Treatment 2: 2 x 6 mg A-capsule Fasted	Treatment 3: 2 x 6 mg A-capsule Fed	Treatment 4: 2 x 6 mg B-capsule Fasted	Treatment 5: 2 x 6 mg B-capsule Fed
Number of Participants Analyzed [units:participants]	25	25	25	25	25
Maximum observed plasma concentration (Cmax) for the analysis of PK parameter [units: ng/mL] Geometric Mean (Geometric Coefficient of Variation)	25.51 (53.66%)	31.88 (62.41%)	8.243 (81.12%)	23.39 (66.08%)	17.02 (54.00%)

Statistical Analysis 1 for Maximum observed plasma concentration (Cmax) for the analysis of PK parameter

Groups^[1]	Treatment 1: 1 x 12 mg ER8 capsule Fasted, Treatment 2: 2 x 6 mg A-capsule Fasted
Method^[3]	Other [Mixed Model Analysis]
Other^[5]	124.99
90% Confidence Interval	( 101.09 to 154.54 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Pairwise comparison: Treatment 2/Treatment 1
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The number of subjects in this analysis: 25
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Maximum observed plasma concentration (Cmax) for the analysis of PK parameter

Groups^[1]	Treatment 1: 1 x 12 mg ER8 capsule Fasted, Treatment 3: 2 x 6 mg A-capsule Fed
Method^[3]	Other [Mixed Model Analysis]
Other^[5]	33.77
90% Confidence Interval	( 27.15 to 42.01 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Pairwise comparison: Treatment 3/Treatment 1
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The number of subjects in this analysis: 23
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Maximum observed plasma concentration (Cmax) for the analysis of PK parameter

Groups^[1]	Treatment 2: 2 x 6 mg A-capsule Fasted, Treatment 3: 2 x 6 mg A-capsule Fed
Method^[3]	Other [Mixed Model Analysis]
Other^[5]	27.02
90% Confidence Interval	( 21.72 to 33.61 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Pairwise comparison: Treatment 3/Treatment 2
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The number of subjects in this analysis: 23
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 4 for Maximum observed plasma concentration (Cmax) for the analysis of PK parameter

Groups^[1]	Treatment 3: 2 x 6 mg A-capsule Fed, Treatment 4: 2 x 6 mg B-capsule Fasted
Method^[3]	Other [Mixed Model Analysis]
Other^[5]	36.84
90% Confidence Interval	( 29.61 to 45.82 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Pairwise comparison: Treatment 3/Treatment 4
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The number of subjects in this analysis: 23
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 5 for Maximum observed plasma concentration (Cmax) for the analysis of PK parameter

Groups^[1]	Treatment 1: 1 x 12 mg ER8 capsule Fasted, Treatment 4: 2 x 6 mg B-capsule Fasted
Method^[3]	Other [Mixed Model Analysis]
Other^[5]	91.69
90% Confidence Interval	( 74.15 to 113.36 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Pairwise comparison: Treatment 4/Treatment 1
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The number of subjects in this analysis: 25
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 6 for Maximum observed plasma concentration (Cmax) for the analysis of PK parameter

Groups^[1]	Treatment 2: 2 x 6 mg A-capsule Fasted, Treatment 4: 2 x 6 mg B-capsule Fasted
Method^[3]	Other [Mixed Model Analysis]
Other^[5]	73.36
90% Confidence Interval	( 59.33 to 90.70 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Pairwise comparison: Treatment 4/Treatment 2
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The number of subjects in this analysis: 25
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 7 for Maximum observed plasma concentration (Cmax) for the analysis of PK parameter

Groups^[1]	Treatment 1: 1 x 12 mg ER8 capsule Fasted, Treatment 5: 2 x 6 mg B-capsule Fed
Method^[3]	Other [Mixed Model Analysis]
Other^[5]	67.62
90% Confidence Interval	( 54.37 to 84.12 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Pairwise comparison: Treatment 5/Treatment 1
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The number of subjects in this analysis: 23
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 8 for Maximum observed plasma concentration (Cmax) for the analysis of PK parameter

Groups^[1]	Treatment 2: 2 x 6 mg A-capsule Fasted, Treatment 5: 2 x 6 mg B-capsule Fed
Method^[3]	Other [Mixed Model Analysis]
Other^[5]	54.11
90% Confidence Interval	( 43.50 to 67.30 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Pairwise comparison: Treatment 5/Treatment 2
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The number of subjects in this analysis: 23
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 9 for Maximum observed plasma concentration (Cmax) for the analysis of PK parameter

Groups^[1]	Treatment 3: 2 x 6 mg A-capsule Fed, Treatment 5: 2 x 6 mg B-capsule Fed
Method^[3]	Other [Mixed Model Analysis]
Other^[5]	200.23
90% Confidence Interval	( 160.15 to 250.32 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Pairwise comparison: Treatment 5/Treatment 3
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The number of subjects in this analysis: 23
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 10 for Maximum observed plasma concentration (Cmax) for the analysis of PK parameter

Groups^[1]	Treatment 4: 2 x 6 mg B-capsule Fasted, Treatment 5: 2 x 6 mg B-capsule Fed
Method^[3]	Other [Mixed Model Analysis]
Other^[5]	73.76
90% Confidence Interval	( 59.30 to 91.75 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Pairwise comparison: Treatment 5/Treatment 4
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The number of subjects in this analysis: 23
[5]	Other relevant estimation information:
	No text entered.

4. Secondary Outcome Measure: AUC from time 0 to 24 hours post dose (AUC0-24) for the analysis of PK parameter [ Time Frame: Pre-dose and up to 24-hours Post-dose ]

Measure Type	Secondary
Measure Name	AUC from time 0 to 24 hours post dose (AUC0-24) for the analysis of PK parameter
Measure Description	To examine the PK profiles of verinurad when administered as the 3 different capsule formulations under fasted conditions.
Time Frame	Pre-dose and up to 24-hours Post-dose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set for whom at least 1 of the primary PK parameters could be calculated, and who had no major protocol deviations thought to impact on the analysis of the PK data.

Reporting Groups

	Description
Treatment 1: 1 x 12 mg ER8 capsule Fasted	During this treatment period, healthy participants will receive 1 x 12 mg verinurad ER8 capsule formulation in fasted state.
Treatment 2: 2 x 6 mg A-capsule Fasted	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fasted state.
Treatment 3: 2 x 6 mg A-capsule Fed	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fed state.
Treatment 4: 2 x 6 mg B-capsule Fasted	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fasted state.
Treatment 5: 2 x 6 mg B-capsule Fed	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fed state.

Measured Values

	Treatment 1: 1 x 12 mg ER8 capsule Fasted	Treatment 2: 2 x 6 mg A-capsule Fasted	Treatment 3: 2 x 6 mg A-capsule Fed	Treatment 4: 2 x 6 mg B-capsule Fasted	Treatment 5: 2 x 6 mg B-capsule Fed
Number of Participants Analyzed [units:participants]	25	25	25	25	25
AUC from time 0 to 24 hours post dose (AUC0-24) for the analysis of PK parameter [units: ng*h/mL] Geometric Mean (Geometric Coefficient of Variation)	132.6 (48.40%)	138.5 (39.67%)	54.85 (80.02%)	102.9 (54.45%)	110.6 (47.83%)

No statistical analysis provided for AUC from time 0 to 24 hours post dose (AUC0-24) for the analysis of PK parameter

5. Secondary Outcome Measure: Time to reach maximum observed plasma concentration (tmax) for the analysis of PK parameter [ Time Frame: Day 1: Pre-dose and up to 72-hour Post-dose ]

Measure Type	Secondary
Measure Name	Time to reach maximum observed plasma concentration (tmax) for the analysis of PK parameter
Measure Description	To examine the PK profiles of verinurad when administered as the 3 different capsule formulations under fasted conditions.
Time Frame	Day 1: Pre-dose and up to 72-hour Post-dose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set for whom at least 1 of the primary PK parameters could be calculated, and who had no major protocol deviations thought to impact on the analysis of the PK data.

Reporting Groups

	Description
Treatment 1: 1 x 12 mg ER8 capsule Fasted	During this treatment period, healthy participants will receive 1 x 12 mg verinurad ER8 capsule formulation in fasted state.
Treatment 2: 2 x 6 mg A-capsule Fasted	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fasted state.
Treatment 3: 2 x 6 mg A-capsule Fed	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fed state.
Treatment 4: 2 x 6 mg B-capsule Fasted	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fasted state.
Treatment 5: 2 x 6 mg B-capsule Fed	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fed state.

Measured Values

	Treatment 1: 1 x 12 mg ER8 capsule Fasted	Treatment 2: 2 x 6 mg A-capsule Fasted	Treatment 3: 2 x 6 mg A-capsule Fed	Treatment 4: 2 x 6 mg B-capsule Fasted	Treatment 5: 2 x 6 mg B-capsule Fed
Number of Participants Analyzed [units:participants]	25	25	25	25	25
Time to reach maximum observed plasma concentration (tmax) for the analysis of PK parameter [units: Hour] Median (Full Range)	4.98 (3.00 to 8.00)	4.98 (2.98 to 6.02)	5.00 (3.00 to 10.00)	4.00 (2.00 to 6.00)	7.98 (4.00 to 12.00)

No statistical analysis provided for Time to reach maximum observed plasma concentration (tmax) for the analysis of PK parameter

6. Secondary Outcome Measure: Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½λz) for the analysis of PK parameter [ Time Frame: Day 1: Pre-dose and up to 72-hour Post-dose ]

Measure Type	Secondary
Measure Name	Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½λz) for the analysis of PK parameter
Measure Description	To examine the PK profiles of verinurad when administered as the 3 different capsule formulations under fasted conditions.
Time Frame	Day 1: Pre-dose and up to 72-hour Post-dose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set for whom at least 1 of the primary PK parameters could be calculated, and who had no major protocol deviations thought to impact on the analysis of the PK data.

Reporting Groups

	Description
Treatment 1: 1 x 12 mg ER8 capsule Fasted	During this treatment period, healthy participants will receive 1 x 12 mg verinurad ER8 capsule formulation in fasted state.
Treatment 2: 2 x 6 mg A-capsule Fasted	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fasted state.
Treatment 3: 2 x 6 mg A-capsule Fed	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fed state.
Treatment 4: 2 x 6 mg B-capsule Fasted	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fasted state.
Treatment 5: 2 x 6 mg B-capsule Fed	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fed state.

Measured Values

	Treatment 1: 1 x 12 mg ER8 capsule Fasted	Treatment 2: 2 x 6 mg A-capsule Fasted	Treatment 3: 2 x 6 mg A-capsule Fed	Treatment 4: 2 x 6 mg B-capsule Fasted	Treatment 5: 2 x 6 mg B-capsule Fed
Number of Participants Analyzed [units:participants]	25	25	25	25	25
Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½λz) for the analysis of PK parameter [units: Hour] Mean (Standard Deviation)	14.02 (4.732)	13.61 (5.748)	13.42 (5.549)	14.36 (5.477)	12.40 (5.038)

No statistical analysis provided for Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½λz) for the analysis of PK parameter

7. Secondary Outcome Measure: Apparent total body clearance of drug from plasma after extravascular administration (CL/F) for the analysis of PK parameter [ Time Frame: Day 1: Pre-dose and up to 72-hour Post-dose ]

Measure Type	Secondary
Measure Name	Apparent total body clearance of drug from plasma after extravascular administration (CL/F) for the analysis of PK parameter
Measure Description	To examine the PK profiles of verinurad when administered as the 3 different capsule formulations under fasted conditions.
Time Frame	Day 1: Pre-dose and up to 72-hour Post-dose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set for whom at least 1 of the primary PK parameters could be calculated, and who had no major protocol deviations thought to impact on the analysis of the PK data.

Reporting Groups

	Description
Treatment 1: 1 x 12 mg ER8 capsule Fasted	During this treatment period, healthy participants will receive 1 x 12 mg verinurad ER8 capsule formulation in fasted state.
Treatment 2: 2 x 6 mg A-capsule Fasted	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fasted state.
Treatment 3: 2 x 6 mg A-capsule Fed	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fed state.
Treatment 4: 2 x 6 mg B-capsule Fasted	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fasted state.
Treatment 5: 2 x 6 mg B-capsule Fed	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fed state.

Measured Values

	Treatment 1: 1 x 12 mg ER8 capsule Fasted	Treatment 2: 2 x 6 mg A-capsule Fasted	Treatment 3: 2 x 6 mg A-capsule Fed	Treatment 4: 2 x 6 mg B-capsule Fasted	Treatment 5: 2 x 6 mg B-capsule Fed
Number of Participants Analyzed [units:participants]	25	25	25	25	25
Apparent total body clearance of drug from plasma after extravascular administration (CL/F) for the analysis of PK parameter [units: Litre/hour] Mean (Standard Deviation)	77.86 (42.15)	75.43 (25.71)	160.5 (86.96)	86.26 (32.22)	87.10 (41.78)

No statistical analysis provided for Apparent total body clearance of drug from plasma after extravascular administration (CL/F) for the analysis of PK parameter

8. Secondary Outcome Measure: Mean residence time of the unchanged drug in the systemic circulation from zero to infinity (MRT) for the analysis of PK parameter [ Time Frame: Day 1: Pre-dose and up to 72-hour Post-dose ]

Measure Type	Secondary
Measure Name	Mean residence time of the unchanged drug in the systemic circulation from zero to infinity (MRT) for the analysis of PK parameter
Measure Description	To examine the PK profiles of verinurad when administered as the 3 different capsule formulations under fasted conditions.
Time Frame	Day 1: Pre-dose and up to 72-hour Post-dose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set for whom at least 1 of the primary PK parameters could be calculated, and who had no major protocol deviations thought to impact on the analysis of the PK data.

Reporting Groups

	Description
Treatment 1: 1 x 12 mg ER8 capsule Fasted	During this treatment period, healthy participants will receive 1 x 12 mg verinurad ER8 capsule formulation in fasted state.
Treatment 2: 2 x 6 mg A-capsule Fasted	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fasted state.
Treatment 3: 2 x 6 mg A-capsule Fed	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fed state.
Treatment 4: 2 x 6 mg B-capsule Fasted	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fasted state.
Treatment 5: 2 x 6 mg B-capsule Fed	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fed state.

Measured Values

	Treatment 1: 1 x 12 mg ER8 capsule Fasted	Treatment 2: 2 x 6 mg A-capsule Fasted	Treatment 3: 2 x 6 mg A-capsule Fed	Treatment 4: 2 x 6 mg B-capsule Fasted	Treatment 5: 2 x 6 mg B-capsule Fed
Number of Participants Analyzed [units:participants]	25	25	25	25	25
Mean residence time of the unchanged drug in the systemic circulation from zero to infinity (MRT) for the analysis of PK parameter [units: Hour] Mean (Standard Deviation)	16.98 (4.006)	15.52 (5.843)	17.43 (4.974)	16.61 (6.049)	18.28 (4.841)

No statistical analysis provided for Mean residence time of the unchanged drug in the systemic circulation from zero to infinity (MRT) for the analysis of PK parameter

9. Secondary Outcome Measure: Time of last quantifiable plasma concentration (tlast) for the analysis of PK parameter [ Time Frame: Day 1: Pre-dose and up to 72-hour Post-dose ]

Measure Type	Secondary
Measure Name	Time of last quantifiable plasma concentration (tlast) for the analysis of PK parameter
Measure Description	To examine the PK profiles of verinurad when administered as the 3 different capsule formulations under fasted conditions.
Time Frame	Day 1: Pre-dose and up to 72-hour Post-dose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set for whom at least 1 of the primary PK parameters could be calculated, and who had no major protocol deviations thought to impact on the analysis of the PK data.

Reporting Groups

	Description
Treatment 1: 1 x 12 mg ER8 capsule Fasted	During this treatment period, healthy participants will receive 1 x 12 mg verinurad ER8 capsule formulation in fasted state.
Treatment 2: 2 x 6 mg A-capsule Fasted	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fasted state.
Treatment 3: 2 x 6 mg A-capsule Fed	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fed state.
Treatment 4: 2 x 6 mg B-capsule Fasted	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fasted state.
Treatment 5: 2 x 6 mg B-capsule Fed	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fed state.

Measured Values

	Treatment 1: 1 x 12 mg ER8 capsule Fasted	Treatment 2: 2 x 6 mg A-capsule Fasted	Treatment 3: 2 x 6 mg A-capsule Fed	Treatment 4: 2 x 6 mg B-capsule Fasted	Treatment 5: 2 x 6 mg B-capsule Fed
Number of Participants Analyzed [units:participants]	25	25	25	25	25
Time of last quantifiable plasma concentration (tlast) for the analysis of PK parameter [units: Hour] Median (Full Range)	71.65 (47.67 to 72.93)	48.47 (36.00 to 72.05)	47.97 (35.97 to 72.07)	48.03 (35.57 to 73.08)	48.03 (47.77 to 72.07)

No statistical analysis provided for Time of last quantifiable plasma concentration (tlast) for the analysis of PK parameter

10. Secondary Outcome Measure: Volume of distribution at steady state (intravenous dosing) (Vss/F) for the analysis of PK parameter [ Time Frame: Day 1: Pre-dose and up to 72-hour Post-dose ]

Measure Type	Secondary
Measure Name	Volume of distribution at steady state (intravenous dosing) (Vss/F) for the analysis of PK parameter
Measure Description	To examine the PK profiles of verinurad when administered as the 3 different capsule formulations under fasted conditions.
Time Frame	Day 1: Pre-dose and up to 72-hour Post-dose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set for whom at least 1 of the primary PK parameters could be calculated, and who had no major protocol deviations thought to impact on the analysis of the PK data.

Reporting Groups

	Description
Treatment 1: 1 x 12 mg ER8 capsule Fasted	During this treatment period, healthy participants will receive 1 x 12 mg verinurad ER8 capsule formulation in fasted state.
Treatment 2: 2 x 6 mg A-capsule Fasted	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fasted state.
Treatment 3: 2 x 6 mg A-capsule Fed	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fed state.
Treatment 4: 2 x 6 mg B-capsule Fasted	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fasted state.
Treatment 5: 2 x 6 mg B-capsule Fed	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fed state.

Measured Values

	Treatment 1: 1 x 12 mg ER8 capsule Fasted	Treatment 2: 2 x 6 mg A-capsule Fasted	Treatment 3: 2 x 6 mg A-capsule Fed	Treatment 4: 2 x 6 mg B-capsule Fasted	Treatment 5: 2 x 6 mg B-capsule Fed
Number of Participants Analyzed [units:participants]	25	25	25	25	25
Volume of distribution at steady state (intravenous dosing) (Vss/F) for the analysis of PK parameter [units: Litre] Mean (Standard Deviation)	1275 (612.8)	1190 (586.4)	2756 (1577)	1472 (855.9)	1645 (1157)

No statistical analysis provided for Volume of distribution at steady state (intravenous dosing) (Vss/F) for the analysis of PK parameter

11. Secondary Outcome Measure: Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) for the analysis of PK parameter [ Time Frame: Day 1: Pre-dose and up to 72-hour Post-dose ]

Measure Type	Secondary
Measure Name	Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) for the analysis of PK parameter
Measure Description	To examine the PK profiles of verinurad when administered as the 3 different capsule formulations under fasted conditions.
Time Frame	Day 1: Pre-dose and up to 72-hour Post-dose
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set for whom at least 1 of the primary PK parameters could be calculated, and who had no major protocol deviations thought to impact on the analysis of the PK data.

Reporting Groups

	Description
Treatment 1: 1 x 12 mg ER8 capsule Fasted	During this treatment period, healthy participants will receive 1 x 12 mg verinurad ER8 capsule formulation in fasted state.
Treatment 2: 2 x 6 mg A-capsule Fasted	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fasted state.
Treatment 3: 2 x 6 mg A-capsule Fed	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fed state.
Treatment 4: 2 x 6 mg B-capsule Fasted	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fasted state.
Treatment 5: 2 x 6 mg B-capsule Fed	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fed state.

Measured Values

	Treatment 1: 1 x 12 mg ER8 capsule Fasted	Treatment 2: 2 x 6 mg A-capsule Fasted	Treatment 3: 2 x 6 mg A-capsule Fed	Treatment 4: 2 x 6 mg B-capsule Fasted	Treatment 5: 2 x 6 mg B-capsule Fed
Number of Participants Analyzed [units:participants]	25	25	25	25	25
Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) for the analysis of PK parameter [units: Litre] Mean (Standard Deviation)	1529 (953.1)	1490 (779.9)	3120 (2066)	1810 (1120)	1719 (1608)

No statistical analysis provided for Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) for the analysis of PK parameter

12. Secondary Outcome Measure: Number of participants with adverse events (AEs) [ Time Frame: From screening (Day -28 to Day -2) till follow-up visit (7 to 14 days post-final dose) ]

Measure Type	Secondary
Measure Name	Number of participants with adverse events (AEs)
Measure Description	To assess AEs as variable of safety and tolerability of single doses of verinurad in healthy participants.
Time Frame	From screening (Day -28 to Day -2) till follow-up visit (7 to 14 days post-final dose)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All subjects who received at least 1 dose of verinurad (any formulation) were included in the safety analysis for the study.

Reporting Groups

	Description
Treatment 1: 1 x 12 mg ER8 capsule Fasted	During this treatment period, healthy participants will receive 1 x 12 mg verinurad ER8 capsule formulation in fasted state.
Treatment 2: 2 x 6 mg A-capsule Fasted	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fasted state.
Treatment 3: 2 x 6 mg A-capsule Fed	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fed state.
Treatment 4: 2 x 6 mg B-capsule Fasted	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fasted state.
Treatment 5: 2 x 6 mg B-capsule Fed	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fed state.

Measured Values

	Treatment 1: 1 x 12 mg ER8 capsule Fasted	Treatment 2: 2 x 6 mg A-capsule Fasted	Treatment 3: 2 x 6 mg A-capsule Fed	Treatment 4: 2 x 6 mg B-capsule Fasted	Treatment 5: 2 x 6 mg B-capsule Fed
Number of Participants Analyzed [units:participants]	25	25	25	25	25
Number of participants with adverse events (AEs) [units: ]
Any treatment emergent adverse event (TEAE)	5	6	2	4	3
Related TEAEs	2	0	1	3	0
Any serious TEAE (including death)	0	0	0	0	0
Any TEAE leading to discontinuation of IMP	0	0	0	0	0
Any TEAE leading to withdrawal from study	0	0	0	0	0

No statistical analysis provided for Number of participants with adverse events (AEs)

Serious Adverse Events

Time Frame	From screening (Day -28 to Day -2) till follow-up visit (7 to 14 days post-final dose)
Additional Description	No text entered.

Reporting Groups

	Description
Treatment 1: 1 x 12 mg ER8 capsule Fasted	During this treatment period, healthy participants will receive 1 x 12 mg verinurad ER8 capsule formulation in fasted state.
Treatment 2: 2 x 6 mg A-capsule Fasted	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fasted state.
Treatment 3: 2 x 6 mg A-capsule Fed	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fed state.
Treatment 4: 2 x 6 mg B-capsule Fasted	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fasted state.
Treatment 5: 2 x 6 mg B-capsule Fed	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fed state.

Serious Adverse Events

	Treatment 1: 1 x 12 mg ER8 capsule Fasted	Treatment 2: 2 x 6 mg A-capsule Fasted	Treatment 3: 2 x 6 mg A-capsule Fed	Treatment 4: 2 x 6 mg B-capsule Fasted	Treatment 5: 2 x 6 mg B-capsule Fed
Total, serious adverse events
# participants affected / at risk	0/25 (0.00%)	0/25 (0.00%)	0/25 (0.00%)	0/25 (0.00%)	0/25 (0.00%)

Other Adverse Events

Time Frame	From screening (Day -28 to Day -2) till follow-up visit (7 to 14 days post-final dose)
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	1%

Reporting Groups

	Description
Treatment 1: 1 x 12 mg ER8 capsule Fasted	During this treatment period, healthy participants will receive 1 x 12 mg verinurad ER8 capsule formulation in fasted state.
Treatment 2: 2 x 6 mg A-capsule Fasted	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fasted state.
Treatment 3: 2 x 6 mg A-capsule Fed	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fed state.
Treatment 4: 2 x 6 mg B-capsule Fasted	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fasted state.
Treatment 5: 2 x 6 mg B-capsule Fed	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fed state.

Other Adverse Events

Treatment 1: 1 x 12 mg ER8 capsule Fasted

Treatment 2: 2 x 6 mg A-capsule Fasted

Treatment 3: 2 x 6 mg A-capsule Fed

Treatment 4: 2 x 6 mg B-capsule Fasted

Treatment 5: 2 x 6 mg B-capsule Fed

Total, other (not including serious) adverse events

# participants affected / at risk

5/25 (20.00%)

6/25 (24.00%)

2/25 (8.00%)

4/25 (16.00%)

3/25 (12.00%)

Gastrointestinal disorders

Abdominal discomfort¹

# participants affected / at risk

0/25 (0.00%)

1/25 (4.00%)

# events

Gastrointestinal disorders

Abdominal pain¹

# participants affected / at risk

0/25 (0.00%)

1/25 (4.00%)

0/25 (0.00%)

# events

Gastrointestinal disorders

Diarrhoea¹

# participants affected / at risk

0/25 (0.00%)

1/25 (4.00%)

0/25 (0.00%)

# events

General disorders

Catheter site pain¹

# participants affected / at risk

1/25 (4.00%)

0/25 (0.00%)

# events

General disorders

Catheter site related reaction¹

# participants affected / at risk

0/25 (0.00%)

1/25 (4.00%)

0/25 (0.00%)

1/25 (4.00%)

0/25 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Back pain¹

# participants affected / at risk

2/25 (8.00%)

1/25 (4.00%)

0/25 (0.00%)

# events

Infections and infestations

Oral herpes¹

# participants affected / at risk

0/25 (0.00%)

1/25 (4.00%)

0/25 (0.00%)

1/25 (4.00%)

0/25 (0.00%)

# events

Nervous system disorders

Headache¹

# participants affected / at risk

1/25 (4.00%)

# events

Reproductive system and breast disorders

Dysmenorrhoea¹

# participants affected / at risk

1/25 (4.00%)

0/25 (0.00%)

1/25 (4.00%)

0/25 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Throat irritation¹

# participants affected / at risk

0/25 (0.00%)

1/25 (4.00%)

0/25 (0.00%)

1/25 (4.00%)

# events

Skin and subcutaneous tissue disorders

Rash¹

# participants affected / at risk

0/25 (0.00%)

1/25 (4.00%)

0/25 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 22.0

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: This confidential document is the property of AstraZeneca AB. No unpublished information contained herein may be disclosed without prior written approval from AstraZeneca AB. Access to this document must be restricted to relevant parties.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	AstraZeneca information Centre
Organization:	AstraZeneca
Phone	1-877-240-9479
E-mail:	[email protected]

Documents available

redacted CSP and SAP
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

redacted CSP and SAP

Trial Results Summaries