A study to compare bioavailability of AZD5055 film-coated tablet with AZD5055 oral suspension and to assess the effect of food and an acid reducing agent on pharmacokinetics (PK) of AZD5055 in healthy subjects.

Study identifier:D8960C00002

ClinicalTrials.gov identifier:NCT05630677

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

An Open-Label, Five-Period Study in Healthy Subjects to Investigate the Relative Bioavailability of AZD5055 Film-Coated Tablet versus AZD5055 Oral Suspension Formulation, the Absolute Oral Bioavailability of AZD5055 and to Evaluate the Effect of Food and an Acid Reducing Agent on the Pharmacokinetics of AZD5055.

Medical condition

Healthy Volunteers

Phase

Phase 1

Healthy volunteers

Yes

Study drug

AZD5055 solution for infusion, AZD5055 oral suspension, AZD5055 film-coated tablet, Rabeprazole, Delayed-release tablet

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 55 Years

Date

Study Start Date: 04 Nov 2022

Primary Completion Date: 09 Feb 2023

Study Completion Date: 09 Feb 2023

Study design

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

Verification:

Verified 01 May 2025 by AstraZeneca

Collaborators

PAREXEL

Inclusion and exclusion criteria

Inclusion Criteria

1. Healthy male and female (of non-childbearing potential) subjects aged 18 to 55 years.
2. Female subjects must have a negative pregnancy test.
3. Male subjects must adhere to the contraception methods as per Protocol.
4. Have a BMI between 18 and 30 kg/m2 inclusive.

Exclusion Criteria

1. History of any clinically significant disease or disorder which may either put the subject at risk because of participation in the study or influence the results or the subject’s ability to participate in the study.
2. Ongoing acute Gastrointestinal (GI), hepatic, or renal disease, a history of chronic GI, hepatic, or renal disease, pancreatic disease, diabetes mellitus, or any condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
3. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of study drug.
4. Ongoing acquired or inherited immunodeficiency disorders, including but not limited to Human Immunodeficiency Virus (HIV) or common variable immunodeficiency, or the subject is taking immune replacement therapy.
5. Individuals with chronic infections or who are at increased risk of infection.
6. History of cancer within the last 10 years (20 years for breast cancer). Any history of lymphoma is not allowed.
7. History of osteoporosis, osteomalacia, Paget's disease of the bone, thyrotoxicosis, rheumatoid arthritis, Cushing's disease, or a pathological fracture.
8. History of a traumatic fracture within 6 months of the Screening Visit.
9. Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis.
10. Abnormal vital signs. Any clinically important abnormalities in rhythm, conduction, or morphology of the resting ECG and any clinically important abnormalities in the 12-lead ECG.
11. Untreated tuberculosis (TB) or a positive result for the Interferon gamma release assay (IGRA) (ie, QuantiFERON TB Gold).
12. Any positive result at Screening for serum hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C antibody, and HIV antibody.
13. History of severe COVID-19 infection requiring hospitalization within the last 12 months prior to Screening, or clinical history compatible with Long COVID-19 (symptoms beyond 12 weeks of acute infection).
14. Confirmed COVID-19 infection during at admission.
15. Has received live or live attenuated vaccine in the 30 days prior to dosing, the first dose of COVID- vaccine within 30 days prior to randomization, or a COVID-19 vaccine second or booster vaccination within 10 days of Screening.
16. Known or suspected history of drug abuse.
17. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity.
18. Current smokers or use of any tobacco in any other form.
19. Known or suspected history of alcohol or drug abuse or excessive intake of alcohol.
20. Use of drugs with enzyme-inducing properties such as St John’s Wort.

This will be an Open-Label, Five-Period Study in healthy subjects. The study will comprise of a Screening Period of maximum 28 days. The treatment groups are as follows: · Treatment A: AZD5055 solution for infusion as 20-minute infusion and an overnight fasted state after the 20-minute infusion. · Treatment B: AZD5055 oral suspension and an overnight fasted state after the oral suspension. · Treatment C: AZD5055 film-coated tablet and an overnight fasted state after the film-coated tablet.. · Treatment D: AZD5055 film-coated tablet, fed state (after a high-fat, high-calorie standard breakfast). · Treatment E: Twice daily oral doses of 20 mg rabeprazole for 3 days prior a single dose of AZD5055 film-coated tablet under fasted conditions, and then rabeprazole will be continued for 2 days. · Treatment F: Twice daily oral doses of 20 mg rabeprazole continuing from Treatment E prior to a single dose of AZD5055 film-coated tablet under fed conditions (low-fat standard breakfast) and then rabeprazole will be continued for 2 days. Five (5) periods during which subjects will participate from Day -1 of Period 1 to 72 hours after the AZD5055 dose in Period 5. · Period 1: On Day 1, the subjects will receive either Treatment A or Treatment B. · Period 2: On Day 4, the subjects will receive Treatment C. · Period 3: On Day 8, the subjects will receiveTreatment D. · Period 4: On Day 10, three days prior to Day 1, rabeprazole will be administered twice daily. On Day 13, subject will receive Treatment E. · Period 5: On Day 17, the subjects will receive Treatment F. Rabeprazole will continue twice daily, the last dose is on the evening of Study Day 18. A Follow-up Visit, or telephone call, approximately 6 days after the last AZD5055 dose in Period 5. There will be a minimum washout of 3 days between the AZD5055 dose administration in Period 1 and Period 2 and a minimum washout of 4 days between AZD5055 doses administrations for subsequent study periods. Each subject will participate in the study for approximately 8 weeks.

Location

Research Site

Brooklyn, MD, United States, 21225

Arms	Assigned Interventions
Experimental: Treatment A Subjects will receive AZD5055 solution as a 20-minute infusion in overnight fasted state on Day 1 in Period 1.	Drug: AZD5055 solution for infusion Subjects will receive a single dose intravenous infusion of AZD5055 as 20-minute infusion on Day 1 of the respective period in overnight fasted state.
Experimental: Treatment B Subjects will receive oral suspension of AZD5055 in an overnight fasted state on Day 1 in Period 1.	Drug: AZD5055 oral suspension Subjects will receive single dose of AZD5055 oral suspension on Day 1 of the respective period in overnight fasted state.
Experimental: Treatment C Subjects will receive AZD5055 film-coated tablet in overnight fasted state on Day 1 (Study Day 4) in Period 2.	Drug: AZD5055 film-coated tablet Subjects will receive single oral dose of AZD5055 film-coated tablets on Day 1 of the respective period in overnight fasted state.
Experimental: Treatment D Subjects will receive a standardized high-fat breakfast 30 minutes before film-coated tablet of AZD5055 administered as On Day 1 (Study Day 8) in Period 3.	Drug: AZD5055 film-coated tablet Subjects will receive single oral dose of AZD5055 film-coated tablets on Day 1 of the respective period in fed state (either a high fat meal or low-fat meal calorie standard breakfast)
Experimental: Treatment E Subjects will receive rabeprazole twice daily on Day 10. On Day 1 (Study Day 13), AZD5055 film-coated tablet will be administered, under fasted conditions, together with rabeprazole and rabeprazole dosing will continue twice daily in Period 4.	Drug: AZD5055 film-coated tablet Subjects will receive single oral dose of AZD5055 film-coated tablets on Day 1 of the respective period in overnight fasted state. Drug: Rabeprazole, Delayed-release tablet Subjects will receive oral doses of rabeprazole twice daily 3 days prior to AZD5055 single dose and 4 days after the AZD5055 single dose including the day that AZD5055 is dosed under fasted conditions [Study Day 10 to 18].
Experimental: Treatment F Subjects will receive a low-fat breakfast 30 minutes before AZD5055 film-coated tablet administered together with rabeprazole on Day 17. Rabeprazole will continue twice daily, the last dose is on the evening of Study Day 18 in Period 5.	Drug: AZD5055 film-coated tablet Subjects will receive single oral dose of AZD5055 film-coated tablets on Day 1 of the respective period in fed state (either a high fat meal or low-fat meal calorie standard breakfast) Drug: Rabeprazole, Delayed-release tablet Subjects will receive oral doses of rabeprazole twice daily prior to AZD5055 single dose under fed conditions (low-fat standard breakfast) and then continued for 2 days.

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was conducted between 04 November 2022 (first subject first visit) to 09 February 2023 (last subject last visit) in Baltimore (Parexel Early Phase Clinical Unit).

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The screening period was 28 days. Participants who met all the inclusion criteria were enrolled in the study. All the assessments were performed asper the schedule of the assessments.

Reporting Groups

	Description
Treatment sequence ACDEF	Participant received treatment of AZD5055 in 5 occasions. Participant received AZD5055 solution for infusion as a 20-minute infusion in overnight fasted state on Day 1 (Treatment A); then film-coated tablet in overnight fasted state on Day 4 (Treatment C); then receive a standardized high-fat breakfast before film-coated tablet of AZD5055 administered On Day 8 (Treatment D); then received rabeprazole twice daily on Day 10 and later AZD5055 film-coated tablet on Day 13 under fasted conditions, together with rabeprazole (Treatment E); then received a low-fat breakfast before AZD5055 film-coated tablet administered together with rabeprazole on Day 17 (Treatment F) separated by minimum washout of 3 days (treatment between A and C) and 4 days (treatment between D and E).
Treatment sequence BCDEF	Participant received treatment of AZD5055 in 5 occasions. Participant received oral suspension of AZD5055 in an overnight fasted state on Day 1 (Treatment B); then film-coated tablet in overnight fasted state on Day 4 (Treatment C); then receive a standardized high-fat breakfast before film-coated tablet of AZD5055 administered as On Day 8 (Treatment D); then received rabeprazole twice daily on Day 10 and later AZD5055 film-coated tablet on Day 13 under fasted conditions, together with rabeprazole (Treatment E); then received a low-fat breakfast before AZD5055 film-coated tablet administered together with rabeprazole on Day 17 (Treatment F) separated by minimum washout of 4 days (treatment between D and E).

Description

Treatment sequence ACDEF

Participant received treatment of AZD5055 in 5 occasions. Participant received AZD5055 solution for infusion as a 20-minute infusion in overnight fasted state on Day 1 (Treatment A); then film-coated tablet in overnight fasted state on Day 4 (Treatment C); then receive a standardized high-fat breakfast before film-coated tablet of AZD5055 administered On Day 8 (Treatment D); then received rabeprazole twice daily on Day 10 and later AZD5055 film-coated tablet on Day 13 under fasted conditions, together with rabeprazole (Treatment E); then received a low-fat breakfast before AZD5055 film-coated tablet administered together with rabeprazole on Day 17 (Treatment F) separated by minimum washout of 3 days (treatment between A and C) and 4 days (treatment between D and E).

Treatment sequence BCDEF

Participant received treatment of AZD5055 in 5 occasions. Participant received oral suspension of AZD5055 in an overnight fasted state on Day 1 (Treatment B); then film-coated tablet in overnight fasted state on Day 4 (Treatment C); then receive a standardized high-fat breakfast before film-coated tablet of AZD5055 administered as On Day 8 (Treatment D); then received rabeprazole twice daily on Day 10 and later AZD5055 film-coated tablet on Day 13 under fasted conditions, together with rabeprazole (Treatment E); then received a low-fat breakfast before AZD5055 film-coated tablet administered together with rabeprazole on Day 17 (Treatment F) separated by minimum washout of 4 days (treatment between D and E).

Participant Flow: Overall Study

	Treatment sequence ACDEF	Treatment sequence BCDEF
STARTED	8	13
COMPLETED	8	13
NOT COMPLETED	0	0

Baseline Characteristics

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

Randomized set consisted of all the participants were randomized in the study.

Reporting Groups

	Description
Treatment sequence ACDEF	Participant received treatment of AZD5055 in 5 occasions. Participant received AZD5055 solution for infusion as a 20-minute infusion in overnight fasted state on Day 1 (Treatment A); then film-coated tablet in overnight fasted state on Day 4 (Treatment C); then receive a standardized high-fat breakfast before film-coated tablet of AZD5055 administered On Day 8 (Treatment D); then received rabeprazole twice daily on Day 10 and later AZD5055 film-coated tablet on Day 13 under fasted conditions, together with rabeprazole (Treatment E); then received a low-fat breakfast before AZD5055 film-coated tablet administered together with rabeprazole on Day 17 (Treatment F) separated by minimum washout of 3 days (treatment between A and C) and 4 days (treatment between D and E).
Treatment sequence BCDEF	Participant received treatment of AZD5055 in 5 occasions. Participant received oral suspension of AZD5055 in an overnight fasted state on Day 1 (Treatment B); then film-coated tablet in overnight fasted state on Day 4 (Treatment C); then receive a standardized high-fat breakfast before film-coated tablet of AZD5055 administered as On Day 8 (Treatment D); then received rabeprazole twice daily on Day 10 and later AZD5055 film-coated tablet on Day 13 under fasted conditions, together with rabeprazole (Treatment E); then received a low-fat breakfast before AZD5055 film-coated tablet administered together with rabeprazole on Day 17 (Treatment F) separated by minimum washout of 4 days (treatment between D and E).

Description

Treatment sequence ACDEF

Treatment sequence BCDEF

Baseline Measures

	Treatment sequence ACDEF	Treatment sequence BCDEF	Total
Number of Participants [units: Participants]	8	13	21
Age Continuous [units: Years] Mean ± Standard Deviation	36.4 ± 9.7	38.5 ± 9.8	37.7 ± 9.6
Sex: Female, Male [units: Participants]
Female	0	2	2
Male	8	11	19
Race (NIH/OMB) [units: Participants]
American Indian or Alaska Native	0	0	0
Asian	0	1	1
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	4	6	10
White	4	4	8
More than one race	0	0	0
Unknown or Not Reported	0	2	2
Ethnicity (NIH/OMB) [units: Participants]
Hispanic or Latino	0	2	2
Not Hispanic or Latino	8	11	19
Unknown or Not Reported	0	0	0

Outcome Measures

1. Primary Outcome Measure: Maximum observed concentration (Cmax) [ Time Frame: Day 1 to 6; Day 8 to 10; Day 13 to 15; Day 17 to 19 ]

Measure Type	Primary
Measure Name	Maximum observed concentration (Cmax)
Measure Description	-The relative bioavailability of the film-coated tablet versus oral suspension formulation was evaluated. -The absolute bioavailability of oral suspension and film-coated tablet formulation. -The effect of the food on the pharmacokinetic (PK) on the Cmax of AZD5055 was evaluated. - The effect of acid reducing agent, rabeprazole on the Cmax of AZD5055 was evaluated. -The effect of acid reducing agent, rabeprazole on the Cmax of AZD5055 when administered with food, was evaluated.
Time Frame	Day 1 to 6; Day 8 to 10; Day 13 to 15; Day 17 to 19
Safety Issue?	No

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 participants in the safety analysis set for whom the primary PK parameters could be calculated for at least 2 treatment periods including the reference formulation, and who had no major protocol deviations thought to impact on the analysis of the PK data.

Reporting Groups

	Description
Treatment A	Treatment A: Participants received AZD5055 solution for infusion as a 20-minute infusion in overnight fasted state on Day 1.
Treatment B	Treatment B: Participants received AZD5055 oral suspension in overnight fasted state on Day 1.
Treatment C	Treatment C: Participants received AZD5055 film-coated tablet in overnight fasted state on Day 4.
Treatment D	Treatment D: Participants received a standardized high-fat breakfast before film-coated tablet of AZD5055 was administered on Day 8.
Treatment E	Treatment E: Participants received rabeprazole twice daily on Day 10 and later AZD5055 film-coated tablet on Day 13 under fasted conditions, together with rabeprazole.
Treatment F	Treatment F: Participants received a low-fat breakfast before AZD5055 film-coated tablet administered together with rabeprazole on Day 17.

Measured Values

	Treatment A	Treatment B	Treatment C	Treatment D	Treatment E	Treatment F
Number of Participants Analyzed [units:participants]	8	13	21	21	19	19
Maximum observed concentration (Cmax) [units: Nanomoles/Liter (nmol/L)] Geometric Mean (Geometric Coefficient of Variation)	174.6 (42.97%)	296.0 (26.59%)	173.0 (63.87%)	211.8 (27.28%)	117.6 (41.89%)	137.6 (32.98%)

Statistical Analysis 1 for Maximum observed concentration (Cmax)

Groups^[1]	Treatment A, Treatment C
Other^[5]	20.88
90% Confidence Interval	( 16.23 to 26.85 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Comparison of Relative bioavailability between the film-coated tablet (Treatment C) versus intravenous (IV) infusion (Treatment A).
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Maximum observed concentration (Cmax)

Groups^[1]	Treatment B, Treatment C
Other^[5]	64.92
90% Confidence Interval	( 52.72 to 79.95 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Comparison of absolute bioavailability between film-coated tablet (Treatment C) versus oral suspension (Treatment B).
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Maximum observed concentration (Cmax)

Groups^[1]	Treatment C, Treatment D
Method^[3]	ANOVA
Other^[5]	122.42
90% Confidence Interval	( 102.60 to 146.07 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Comparison of Food effect on AZD5055: Treatment D (fed) versus Treatment C (fasted).
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Results are assessed using an ANOVA model with fixed effect for treatment, period and sequence and random effect for participants within sequence.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 4 for Maximum observed concentration (Cmax)

Groups^[1]	Treatment C, Treatment E
Method^[3]	ANOVA
Other^[5]	68.35
90% Confidence Interval	( 56.97 to 82.00 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Comparison of effect on AZD5055 when co-administered with rabeprazole in fasted state versus alone in fasted state: Treatment E (fasted) versus Treatment C (fasted).
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Results are assessed using an ANOVA model with fixed effect for treatment, period and sequence and random effect for participants within sequence.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 5 for Maximum observed concentration (Cmax)

Groups^[1]	Treatment C, Treatment F
Method^[3]	ANOVA
Other^[5]	79.94
90% Confidence Interval	( 66.63 to 95.90 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Comparison of effect on AZD5055 co-administered with rabeprazole in fed state versus alone in fasted state: Treatment F (fed) versus Treatment C (fasted).
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Results are assessed using an ANOVA model with fixed effect for treatment, period and sequence and random effect for participants within sequence.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 6 for Maximum observed concentration (Cmax)

Groups^[1]	Treatment E, Treatment F
Method^[3]	ANOVA
Other^[5]	116.96
90% Confidence Interval	( 97.14 to 140.82 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Comparison of effect on AZD5055 when co-administered with rabeprazole in fed state versus fasted state: Treatment F (fed) versus Treatment E (fasted).
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Results are assessed using an ANOVA model with fixed effect for treatment, period and sequence and random effect for participants within sequence.
[5]	Other relevant estimation information:
	No text entered.

2. Primary Outcome Measure: Area under plasma concentration-time curve from zero to infinity (AUCinf) [ Time Frame: Day 1 to 6; Day 8 to 10; Day 13 to 15; Day 17 to 19 ]

Measure Type	Primary
Measure Name	Area under plasma concentration-time curve from zero to infinity (AUCinf)
Measure Description	-The relative bioavailability of the film-coated tablet versus oral suspension formulation was evaluated. -The absolute bioavailability of oral suspension and film-coated tablet formulation. -The effect of the food on the pharmacokinetic (PK) on the Cmax of AZD5055 was evaluated. - The effect of acid reducing agent, rabeprazole on the Cmax of AZD5055 was evaluated. -The effect of acid reducing agent, rabeprazole on the Cmax of AZD5055 when administered with food, was evaluated.
Time Frame	Day 1 to 6; Day 8 to 10; Day 13 to 15; Day 17 to 19
Safety Issue?	No

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 participants in the safety analysis set for whom the primary PK parameters could be calculated for at least 2 treatment periods including the reference formulation, and who had no major protocol deviations thought to impact on the analysis of the PK data.

Reporting Groups

	Description
Treatment A	Treatment A: Participant received AZD5055 solution for infusion as a 20-minute infusion in overnight fasted state on Day 1.
Treatment B	Treatment B: Participants received AZD5055 oral suspension in overnight fasted state on Day 1.
Treatment C	Treatment C: Participants received AZD5055 film-coated tablet in overnight fasted state on Day 4.
Treatment D	Treatment D: Participant received a standardized high-fat breakfast before film-coated tablet of AZD5055 was administered on Day 8.
Treatment E	Treatment E: Participants received rabeprazole twice daily on Day 10 and later AZD5055 film-coated tablet on Day 13 under fasted conditions, together with rabeprazole.
Treatment F	Treatment F: Participants received a low-fat breakfast before AZD5055 film-coated tablet administered together with rabeprazole on Day 17.

Measured Values

	Treatment A	Treatment B	Treatment C	Treatment D	Treatment E	Treatment F
Number of Participants Analyzed [units:participants]	8	13	21	21	19	19
Area under plasma concentration-time curve from zero to infinity (AUCinf) [units: hournanomole/Liter (hnmol/L)] Geometric Mean (Geometric Coefficient of Variation)	595.6 (13.92%)	1829 (25.21%)	1702 (35.61%)	2211 (20.54%)	1761 (20.48%)	1795 (22.58%)

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

Groups^[1]	Treatment A, Treatment C
Other^[5]	66.09
90% Confidence Interval	( 58.34 to 74.86 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Comparison of Relative bioavailability between the film-coated tablet (Treatment C) versus intravenous (IV) infusion (Treatment A).
[5]	Other relevant estimation information:
	No text entered.

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

Groups^[1]	Treatment B, Treatment C
Other^[5]	97.66
90% Confidence Interval	( 88.09 to 108.27 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Comparison of absolute bioavailability between film-coated tablet (Treatment C) versus oral suspension (Treatment B).
[5]	Other relevant estimation information:
	No text entered.

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

Groups^[1]	Treatment C, Treatment D
Method^[3]	ANOVA
Other^[5]	129.89
90% Confidence Interval	( 119.01 to 141.77 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Comparison of Food effect on AZD5055: Treatment D (fed) versus Treatment C (fasted)
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Results are assessed using an ANOVA model with fixed effect for treatment, period and sequence and random effect for participants within sequence.
[5]	Other relevant estimation information:
	No text entered.

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

Groups^[1]	Treatment C, Treatment E
Method^[3]	ANOVA
Other^[5]	103.88
90% Confidence Interval	( 94.90 to 113.71 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Comparison of effect on AZD5055 alone in fasted state versus when co-administered with rabeprazole in fasted state: Treatment E (fasted) versus Treatment C (fasted).
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Results are assessed using an ANOVA model with fixed effect for treatment, period and sequence and random effect for participants within sequence.
[5]	Other relevant estimation information:
	No text entered.

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

Groups^[1]	Treatment C, Treatment F
Method^[3]	ANOVA
Other^[5]	105.91
90% Confidence Interval	( 96.76 to 115.93 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Comparison of effect on AZD5055 o-administered with rabeprazole in fed state versus alone in fasted state: Treatment F (fed) versus Treatment C (fasted).
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Results are assessed using an ANOVA model with fixed effect for treatment, period and sequence and random effect for participants within sequence.
[5]	Other relevant estimation information:
	No text entered.

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

Groups^[1]	Treatment E, Treatment F
Method^[3]	ANOVA
Other^[5]	101.96
90% Confidence Interval	( 92.99 to 111.78 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Comparison of effect on AZD5055 when co-administered with rabeprazole in fed state versus fasted state: Treatment F (fed) versus Treatment E (fasted).
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Results are assessed using an ANOVA model with fixed effect for treatment, period and sequence and random effect for participants within sequence.
[5]	Other relevant estimation information:
	No text entered.

3. Primary Outcome Measure: Area under plasma concentration curve from time zero to time of last quantifiable concentration (AUClast) [ Time Frame: Day 1 to 6; Day 8 to 10; Day 13 to 15; Day 17 to 19 ]

Measure Type	Primary
Measure Name	Area under plasma concentration curve from time zero to time of last quantifiable concentration (AUClast)
Measure Description	-The relative bioavailability of the film-coated tablet versus oral suspension formulation was evaluated. -The absolute bioavailability of oral suspension and film-coated tablet formulation. -The effect of the food on the pharmacokinetic (PK) on the Cmax of AZD5055 was evaluated. - The effect of acid reducing agent, rabeprazole on the Cmax of AZD5055 was evaluated. -The effect of acid reducing agent, rabeprazole on the Cmax of AZD5055 when administered with food, was evaluated.
Time Frame	Day 1 to 6; Day 8 to 10; Day 13 to 15; Day 17 to 19
Safety Issue?	No

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 participants in the safety analysis set for whom the primary PK parameters could be calculated for at least 2 treatment periods including the reference formulation, and who had no major protocol deviations thought to impact on the analysis of the PK data.

Reporting Groups

	Description
Treatment A	Treatment A: Participant received AZD5055 solution for infusion as a 20-minute infusion in overnight fasted state on Day 1.
Treatment B	Treatment B: Participants received AZD5055 oral suspension in overnight fasted state on Day 1.
Treatment C	Treatment C: Participants received AZD5055 film-coated tablet in overnight fasted state on Day 4.
Treatment D	Treatment D: Participant received a standardized high-fat breakfast before film-coated tablet of AZD5055 was administered on Day 8.
Treatment E	Treatment E: Participants received rabeprazole twice daily on Day 10 and later AZD5055 film-coated tablet on Day 13 under fasted conditions, together with rabeprazole.
Treatment F	Treatment F: Participants received a low-fat breakfast before AZD5055 film-coated tablet administered together with rabeprazole on Day 17.

Measured Values

	Treatment A	Treatment B	Treatment C	Treatment D	Treatment E	Treatment F
Number of Participants Analyzed [units:participants]	8	13	21	21	19	19
Area under plasma concentration curve from time zero to time of last quantifiable concentration (AUClast) [units: h*nmol/L] Geometric Mean (Geometric Coefficient of Variation)	577.1 (14.47%)	1759 (25.71%)	1606 (36.85%)	2111 (20.29%)	1599 (21.61%)	1690 (21.73%)

Statistical Analysis 1 for Area under plasma concentration curve from time zero to time of last quantifiable concentration (AUClast)

Groups^[1]	Treatment A, Treatment C
Other^[5]	64.01
90% Confidence Interval	( 56.03 to 73.13 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Comparison of Relative bioavailability between the film-coated tablet (Treatment C) versus intravenous (IV) infusion (Treatment A).
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Area under plasma concentration curve from time zero to time of last quantifiable concentration (AUClast)

Groups^[1]	Treatment B, Treatment C
Other^[5]	96.07
90% Confidence Interval	( 86.05 to 107.26 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Comparison of absolute bioavailability between film-coated tablet (Treatment C) versus oral suspension (Treatment B).
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Area under plasma concentration curve from time zero to time of last quantifiable concentration (AUClast)

Groups^[1]	Treatment C, Treatment D
Method^[3]	ANOVA
Other^[5]	131.48
90% Confidence Interval	( 119.74 to 144.36 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Comparison of Food effect on AZD5055: Treatment D (fed) versus Treatment C (fasted).
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Results are assessed using an ANOVA model with fixed effect for treatment, period and sequence and random effect for participants within sequence.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 4 for Area under plasma concentration curve from time zero to time of last quantifiable concentration (AUClast)

Groups^[1]	Treatment C, Treatment E
Method^[3]	ANOVA
Other^[5]	99.93
90% Confidence Interval	( 90.74 to 110.06 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Comparison of effect on AZD5055 when co-administered with rabeprazole in fasted state versus alone in fasted state: Treatment E (fasted) versus Treatment C (fasted).
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Results are assessed using an ANOVA model with fixed effect for treatment, period and sequence and random effect for participants within sequence.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 5 for Area under plasma concentration curve from time zero to time of last quantifiable concentration (AUClast)

Groups^[1]	Treatment C, Treatment F
Method^[3]	ANOVA
Other^[5]	105.66
90% Confidence Interval	( 95.93 to 116.36 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Comparison of effect on AZD5055 o-administered with rabeprazole in fed state versus alone in fasted state: Treatment F (fed) versus Treatment C (fasted).
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Results are assessed using an ANOVA model with fixed effect for treatment, period and sequence and random effect for participants within sequence.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 6 for Area under plasma concentration curve from time zero to time of last quantifiable concentration (AUClast)

Groups^[1]	Treatment E, Treatment F
Method^[3]	ANOVA
Other^[5]	105.72
90% Confidence Interval	( 95.83 to 116.64 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Comparison of effect on AZD5055 when co-administered with rabeprazole in fed state versus fasted state: Treatment F (fed) versus Treatment E (fasted).
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Results are assessed using an ANOVA model with fixed effect for treatment, period and sequence and random effect for participants within sequence.
[5]	Other relevant estimation information:
	No text entered.

4. Secondary Outcome Measure: Number of participants with Adverse events (AE) and Serious Adverse events (SAE) [ Time Frame: Screening (Day-28 to Day -2) to Follow-up (Day 23 to 6 days post last dose) ]

Measure Type	Secondary
Measure Name	Number of participants with Adverse events (AE) and Serious Adverse events (SAE)
Measure Description	The AE as a variable of safety after administration of single oral and IV doses of AZ5055 in healthy participants were assessed.
Time Frame	Screening (Day-28 to Day -2) to Follow-up (Day 23 to 6 days post last dose)
Safety Issue?	Yes

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 safety analysis set consisted of all participants who received at least 1 dose of AZD5055 and, for whom any safety post-dose data are available and for whom any safety post-dose data were available.

Reporting Groups

	Description
Treatment A	Treatment A: Participant received AZD5055 solution for infusion as a 20-minute infusion in overnight fasted state on Day 1.
Treatment B	Treatment B: Participants received AZD5055 oral suspension in overnight fasted state on Day 1.
Treatment C	Treatment C: Participants received AZD5055 film-coated tablet in overnight fasted state on Day 4.
Treatment D	Treatment D: Participant received a standardized high-fat breakfast before film-coated tablet of AZD5055 was administered on Day 8.
Treatment E	Treatment E: Participants received rabeprazole twice daily on Day 10 and later AZD5055 film-coated tablet on Day 13 under fasted conditions, together with rabeprazole.
Treatment F	Treatment F: Participants received a low-fat breakfast before AZD5055 film-coated tablet administered together with rabeprazole on Day 17.

Measured Values

	Treatment A	Treatment B	Treatment C	Treatment D	Treatment E	Treatment F
Number of Participants Analyzed [units:participants]	8	13	21	21	19	19
Number of participants with Adverse events (AE) and Serious Adverse events (SAE) [units: Participants]
Any AE	2	0	1	5	3	4
Any Serious Adverse Event (SAE)	0	0	0	1	0	0
Any SAE with outcome of death	0	0	0	0	0	0
Any AE leading to discontinuation of investigational medicinal product	0	0	0	2	0	0
Any possibly related AE	2	0	0	2	2	1
Any possibly related SAE	0	0	0	1	0	0

No statistical analysis provided for Number of participants with Adverse events (AE) and Serious Adverse events (SAE)

Serious Adverse Events

Time Frame	Screening (Day-28 to Day -2) to Follow-up (Day 23 to 6 days post last dose)
Additional Description	No text entered.

Reporting Groups

	Description
Treatment A	Treatment A: Participants received AZD5055 solution for infusion as a 20-minute infusion in overnight fasted state on Day 1.
Treatment B	Treatment B: Participants received AZD5055 oral suspension in overnight fasted state on Day 1.
Treatment C	Treatment C: Participants received AZD5055 film-coated tablet in overnight fasted state on Day 4.
Treatment D	Treatment D: Participants received a standardized high-fat breakfast before film-coated tablet of AZD5055 was administered on Day 8.
Treatment E	Treatment E: Participants received rabeprazole twice daily on Day 10 and later AZD5055 film-coated tablet on Day 13 under fasted conditions, together with rabeprazole.
Treatment F	Treatment F: Participants received a low-fat breakfast before AZD5055 film-coated tablet administered together with rabeprazole on Day 17.

Serious Adverse Events

Treatment A

Treatment B

Treatment C

Treatment D

Treatment E

Treatment F

Total, serious adverse events

# participants affected / at risk

0/8 (0.00%)

0/13 (0.00%)

0/21 (0.00%)

1/21 (4.76%)

0/19 (0.00%)

Investigations

Transaminase increased¹

# participants affected / at risk

0/8 (0.00%)

0/13 (0.00%)

0/21 (0.00%)

1/21 (4.76%)

0/19 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA version 25.1

Other Adverse Events

Time Frame	Screening (Day-28 to Day -2) to Follow-up (Day 23 to 6 days post last dose)
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	0%

Reporting Groups

	Description
Treatment A	Treatment A: Participants received AZD5055 solution for infusion as a 20-minute infusion in overnight fasted state on Day 1.
Treatment B	Treatment B: Participants received AZD5055 oral suspension in overnight fasted state on Day 1.
Treatment C	Treatment C: Participants received AZD5055 film-coated tablet in overnight fasted state on Day 4.
Treatment D	Treatment D: Participants received a standardized high-fat breakfast before film-coated tablet of AZD5055 was administered on Day 8.
Treatment E	Treatment E: Participants received rabeprazole twice daily on Day 10 and later AZD5055 film-coated tablet on Day 13 under fasted conditions, together with rabeprazole.
Treatment F	Treatment F: Participants received a low-fat breakfast before AZD5055 film-coated tablet administered together with rabeprazole on Day 17.

Other Adverse Events

Treatment A

Treatment B

Treatment C

Treatment D

Treatment E

Treatment F

Total, other (not including serious) adverse events

# participants affected / at risk

2/8 (25.00%)

0/13 (0.00%)

1/21 (4.76%)

5/21 (23.81%)

3/19 (15.79%)

4/19 (21.05%)

Immune system disorders

Viral upper respiratory tract infection¹

# participants affected / at risk

0/8 (0.00%)

0/13 (0.00%)

0/21 (0.00%)

0/19 (0.00%)

1/19 (5.26%)

# events

Nervous system disorders

Headache¹

# participants affected / at risk

0/8 (0.00%)

0/13 (0.00%)

0/21 (0.00%)

1/21 (4.76%)

2/19 (10.53%)

# events

Nervous system disorders

Somnolence¹

# participants affected / at risk

1/8 (12.50%)

0/13 (0.00%)

0/21 (0.00%)

0/19 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Nasal congestion¹

# participants affected / at risk

0/8 (0.00%)

0/13 (0.00%)

0/21 (0.00%)

1/21 (4.76%)

0/19 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Upper-airway cough syndrome¹

# participants affected / at risk

0/8 (0.00%)

0/13 (0.00%)

0/21 (0.00%)

1/21 (4.76%)

0/19 (0.00%)

# events

Gastrointestinal disorders

Abdominal pain¹

# participants affected / at risk

0/8 (0.00%)

0/13 (0.00%)

0/21 (0.00%)

1/21 (4.76%)

0/19 (0.00%)

# events

Gastrointestinal disorders

Abdominal pain upper¹

# participants affected / at risk

1/8 (12.50%)

0/13 (0.00%)

0/21 (0.00%)

0/19 (0.00%)

# events

Skin and subcutaneous tissue disorders

Dermatitis contact¹

# participants affected / at risk

1/8 (12.50%)

0/13 (0.00%)

0/21 (0.00%)

0/19 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Musculoskeletal chest pain¹

# participants affected / at risk

0/8 (0.00%)

0/13 (0.00%)

0/21 (0.00%)

0/19 (0.00%)

1/19 (5.26%)

# events

General disorders

Fatigue¹

# participants affected / at risk

0/8 (0.00%)

0/13 (0.00%)

0/21 (0.00%)

1/19 (5.26%)

0/19 (0.00%)

# events

General disorders

Medical device site dermatitis¹

# participants affected / at risk

0/8 (0.00%)

0/13 (0.00%)

1/21 (4.76%)

0/19 (0.00%)

# events

General disorders

Non-cardiac chest pain¹

# participants affected / at risk

0/8 (0.00%)

0/13 (0.00%)

0/21 (0.00%)

1/21 (4.76%)

0/19 (0.00%)

# events

General disorders

Vessel puncture site bruise¹

# participants affected / at risk

0/8 (0.00%)

0/13 (0.00%)

0/21 (0.00%)

0/19 (0.00%)

1/19 (5.26%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA version 25.1

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: No unpublished information contained herein may be disclosed without prior written approval from AstraZeneca AB. Access to this document must berestricted 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:	Global Clinical Lead
Organization:	AstraZeneca Clinical Study Information Center
Phone	1-877-240-9479
E-mail:	[email protected]

Documents available

Download
D8960C00002_CSR Synopsis_Redacted.pdf
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Ronald Goldwater

Parexel Early Phase Clinical Unit Baltimore

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

D8960C00002_CSR Synopsis_Redacted.pdf

Trial Results Summaries