Single + multiple ascending dose and food effect study of AZD7986 in healthy volunteers, PK, PD and safety study

Study identifier:D6190C00001

ClinicalTrials.gov identifier:NCT02303574

EudraCT identifier:2014-004043-13

CTIS identifier:N/A

Study Complete

Official Title

A PHASE I, RANDOMISED, SINGLE-BLIND, PLACEBO-CONTROLLED, 2-PART STUDY TO ASSESS THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS AND FOOD EFFECT OF SINGLE AND MULTIPLE ORAL DOSES OF AZD7986 IN HEALTHY VOLUNTEERS.

Medical condition

Safety, pharmacokinetics, pharmacodynamics, food effect

Phase

Phase 1

Healthy volunteers

Yes

Study drug

AZD7986, oral solution, 1 to 50 mg/mL, Placebo, oral solution

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 50 Years

Date

Study Start Date: 03 Dec 2014

Primary Completion Date: 03 Aug 2016

Study Completion Date: 03 Aug 2016

Study design

Allocation: Randomized
Endpoint Classification: Safety
Intervention Model: Parallel Assignment
Masking: Single Blind
Primary Purpose: Basic Science

Verification:

Verified 01 Nov 2018 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 or female subjects aged 18 to 50 years (inclusive) at screening with suitable veins for cannulation or repeated venepuncture.
3. Females must be of non-child-bearing potential, confirmed at screening by fulfilling one of the following criteria:
• Post-menopausal defined as amenorrhoea for at least 12 months or more following cessation of all exogenous hormonal treatments and follicle stimulating hormone (FSH) and luteinising hormone (LH) levels in the post menopausal range.
• Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
4. Male subjects must be non fertile, i.e., surgically sterilised with documentation of azoospermia or must practice an effective contraceptive method to prevent pregnancies. Effective contraceptive methods are:
• Sexual abstinence from before the first administration of the IMP until 3 months after final administration of the IMP, only if this is in line with the preferred and usual lifestyle of the subject.
• Use of a condom plus spermicide agent in addition to having their partner use another acceptable method (oral or injectable hormonal contraceptives, contraceptive patch, intrauterine devices, vaginal hormonal rings, vaginal diaphragm or cervical caps) from before the first administration of the IMP until 3 months after final administration of the IMP.
• Subject’s sexual partner is of non childbearing potential, i.e., post menopausal or surgically sterilised (e.g., tubal ligation, hysterectomy in medical history).
5. Have a body mass index (BMI) between 18.0 and 30.0 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive at screening.

Exclusion Criteria

- History of any clinically significant disease or disorder which, in the opinion of the Investigator, 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.
- History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
- Subject has increased risk of infection:
• History and/or presence of tuberculosis (TB); positive result for interferon gamma release assay (IGRA) (i.e., QuantiFERON TB-Gold), subjects who have resided in regions where tuberculosis and mycosis are endemic during 90 days before screening, or who intend to visit such a region during the duration of the study i.e. deserts areas, Eastern Europe, Central and South America, Africa except Egypt, Russia, Asia, Indonesia
• Oral body temperature of > 37.7°C on Day -1, or as judged by the Investigator.
• Blood neutrophil count < 1.7 x109/L (Screening and Day -1 morning sample).
• Is in high risk-group for HIV infection within the last 6 months (i.e., men who have had unprotected sex with men, women who have had sex without a condom with men who have sex with men, people who have had sex without a condom with a person who has lived or travelled in Africa, people who inject drugs, people who have had sex without a condom with somebody who has injected drugs, people who have caught another sexually transmitted infection, people who have received a blood transfusion while in Africa, eastern Europe, the countries of the former Soviet Union, Asia or central and southern America).
• Other latent or chronic infections (e.g., recurrent sinusitis, genital or ocular herpes, urinary tract infection) or at risk of infection (surgery, trauma, or significant infection) within 90 days of screening, or history of skin abscesses within 90 days of screening.
• Clinically significant lower respiratory tract infection not resolved within 4 weeks prior to screening, as determined by the Investigator.
• Volunteers with active malignancy or neoplastic disease in the previous 5 years other than superficial basal cell carcinoma.
• Disease history suggesting abnormal immune function.
• Volunteers who have received live or live-attenuated vaccine in the 4 weeks prior to dosing.
• High-sensitivity C-reactive protein above upper limit of laboratory reference range at screening and on Day -1.
- Some subjects lacking functional dipeptidyl peptidase 1 (DPP1) enzyme have been described to have periodontitis and palmoplantar hyperkeratosis:
• For Part 1a and Part 1b: Subjects with signs of current gingivitis/periodontitis. Gingival evaluation (by inspection) will be performed by a dental hygienist or trained study physician.
• For Part 2: Subjects with a history of recurring gingivitis/periodontitis or signs of current gingivitis/periodontitis. Gingival evaluation will be performed by a dental hygienist or trained study physician. Evaluation of bleeding propensity due to gingivitis will be performed by using dental hygienist instrumentation. Exact measurement of gum pockets is not needed.
• Subjects with a history of hyperkeratosis or erythema in palms or soles.

Location

Research Site

Harrow, United Kingdom, HA1 3UJ

Arms	Assigned Interventions
Experimental: AZD7986, single and mulltiple doses In Part 1 up to 8 cohorts with single doses starting with 5 mg AZD7986 as oral solution. In Part 2 up to 5 cohorts with multiple doses of AZD7986 as oral solution	Drug: AZD7986, oral solution, 1 to 50 mg/mL Starting dose in single ascending dose part: 5 mg
Placebo Comparator: Placebo, single and multiple doses In Part 1 up to 8 cohorts and in Part 2 up to 5 cohorts with matching placebo to AZD7986 as oral solution	Drug: Placebo, oral solution Matching placebo

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This study was conducted at PAREXEL Early Phase Clinical Unit London, Level 7, Northwick Park Hospital in London. Healthy male and female participants were enrolled.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
In Part 1 and Part 2, participants underwent a screening visit within 28 days before receiving the first dose of investigational medicinal product (IMP). Participants were admitted to the study centre 1 day before administration of the IMP (Day -1).

Reporting Groups

	Description
AZD7986 5 mg (Fasted state) - SAD	Participants received single dose of oral solution of AZD7986 5mg on Day 1 in fasted state.
AZD7986 15 mg (Fasted state) - SAD	Participants received single dose of oral solution of AZD7986 15mg on Day 1in fasted state.
AZD7986 35 mg (Fasted state) - SAD	Participants received single dose of oral solution of AZD7986 35mg on Day 1 in fasted state.
AZD7986 50 mg (Fasted state) - SAD	Participants received single dose of oral solution of AZD7986 50mg on Day 1 in fasted state.
AZD7986 65 mg (Fasted state) - SAD	Participants received single dose of oral solution of AZD7986 65mg on Day 1 in fasted state.
AZD7986 35 mg (Fed state) - SAD	Participants of Cohorts 3 from Part 1a received single dose of oral solution of AZD7986 35 mg on Day 1 in fed state after a washout of at least 7 days.
AZD7986 10 mg - MAD	Participants received single dose (morning) of oral solution of AZD7986 10 mg for 28 days (fasted or fed state, depending on Part 1b results). Participants were fasted until 1 hour after dosing when a light breakfast was provided.
AZD7986 25 mg - MAD	Participants received single dose (morning) of oral solution of AZD7986 25 mg for 28 days (fasted or fed state, depending on Part 1b results). Participants were fasted until 1 hour after dosing when a light breakfast was provided.
AZD7986 40 mg - MAD	Participants received single dose (morning) of oral solution of AZD7986 40 mg for 28 days (fasted or fed state, depending on Part 1b results). Participants were fasted until 1 hour after dosing when a light breakfast was provided.
Placebo	Randomized participants received orally AZD7986 matching placebo oral solution.

Participant Flow for 3 periods

Period 1: Part 1a (Fasted state)- SAD

	AZD7986 5 mg (Fasted state) - SAD	AZD7986 15 mg (Fasted state) - SAD	AZD7986 35 mg (Fasted state) - SAD	AZD7986 50 mg (Fasted state) - SAD	AZD7986 65 mg (Fasted state) - SAD	Placebo
STARTED	6	6	6	6	6	15^[1]
COMPLETED	6	6	5	6	6	15
NOT COMPLETED	0	0	1	0	0	0
Withdrawal by Subject	0	0	1	0	0	0

[1]	Participants received AZD7986 matching placebo on Day 1 in fasted state.

Period 2: Part 1b (Fed state) - SAD

	AZD7986 35 mg (Fed state) - SAD	Placebo
STARTED	5	3^[1]
COMPLETED	5	3
NOT COMPLETED	0	0

[1]	Participants received AZD7986 matching placebo on Day 1 in fed state.

Period 3: Part 2 - Multiple ascending dose (MAD)

	AZD7986 10 mg - MAD	AZD7986 25 mg - MAD	AZD7986 40 mg - MAD	Placebo
STARTED	6	8	10	12^[1]
COMPLETED	6	7	10	12
NOT COMPLETED	0	1	0	0
Adverse Event	0	1	0	0

[1]	Participants took AZD7986 matching placebo for 28 days (fasted/fed state, based on part 1b results)

Baseline Characteristics

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

Reporting Groups

	Description
AZD7986 5 mg (Fasted state) - SAD	Participants received single dose of oral solution of AZD7986 5mg on Day 1 in fasted state.
AZD7986 15 mg (Fasted state) - SAD	Participants received single dose of oral solution of AZD7986 15mg on Day 1in fasted state.
AZD7986 35 mg (Fasted state) - SAD	Participants received single dose of oral solution of AZD7986 35mg on Day 1 in fasted state.
AZD7986 50 mg (Fasted state) - SAD	Participants received single dose of oral solution of AZD7986 50mg on Day 1 in fasted state.
AZD7986 65 mg (Fasted state) - SAD	Participants received single dose of oral solution of AZD7986 65mg on Day 1 in fasted state.
AZD7986 35 mg (Fed state) - SAD	Participants of Cohorts 3 from Part 1a received single dose of oral solution of AZD7986 35 mg on Day 1 in fed state after a washout of at least 7 days.
AZD7986 10 mg - MAD	Participants received single dose (morning) of oral solution of AZD7986 10 mg for 28 days (fasted or fed state, depending on Part 1b results). Participants were fasted until 1 hour after dosing when a light breakfast was provided.
AZD7986 25 mg - MAD	Participants received single dose (morning) of oral solution of AZD7986 25 mg for 28 days (fasted or fed state, depending on Part 1b results). Participants were fasted until 1 hour after dosing when a light breakfast was provided.
AZD7986 40 mg - MAD	Participants received single dose (morning) of oral solution of AZD7986 40 mg for 28 days (fasted or fed state, depending on Part 1b results). Participants were fasted until 1 hour after dosing when a light breakfast was provided.
Placebo - Part 1a (Fasted)	Randomized participants received orally AZD7986 matching placebo oral solution on Day 1 in fasted state.
Placebo - Part 1b (Fed state)	Randomized participants received orally AZD7986 matching placebo oral solution on Day 1 in fed state.
Placebo - Part 2	Randomized participants received orally AZD7986 matching placebo oral solution for 28 days (fasted/fed state, based on part 1b results).

Baseline Measures

	AZD7986 5 mg (Fasted state) - SAD	AZD7986 15 mg (Fasted state) - SAD	AZD7986 35 mg (Fasted state) - SAD	AZD7986 50 mg (Fasted state) - SAD	AZD7986 65 mg (Fasted state) - SAD	AZD7986 35 mg (Fed state) - SAD	AZD7986 10 mg - MAD	AZD7986 25 mg - MAD	AZD7986 40 mg - MAD	Placebo - Part 1a (Fasted)	Placebo - Part 1b (Fed state)	Placebo - Part 2	Total
Number of Participants [units: Participants]	6	6	6	6	6	5	6	8	10	15	3	12	89
Age Continuous [units: Years] Mean ± Standard Deviation
Part 1a	28.5 ± 5.39	29.7 ± 8.78	26.2 ± 3.66	32.2 ± 10.5	29.7 ± 6.65								29.2 ± 7.14
Part 1b						26.6 ± 3.91							26.6 ± 3.91
Part 2							30.7 ± 5.65	38.4 ± 7.25	34.4 ± 9.17				34.8 ± 8.05
Part 1a Placebo										29.9 ± 7.24			29.9 ± 7.24
Part 1b Placebo											28.7 ± 8.5		28.7 ± 8.5
Part 2 Placebo												36.2 ± 7.2	36.2 ± 7.2
Sex: Female, Male [units: participants]
Part 1a
Female	0	0	0	0	0	0	0	0	0	0	0	0	0
Male	6	6	6	6	6	0	0	0	0	15	0	0	45
Part 1b
Female	0	0	0	0	0	0	0	0	0	0	0	0	0
Male	0	0	0	0	0	5	0	0	0	0	3	0	8
Part 2
Female	0	0	0	0	0	0	0	0	0	0	0	0	0
Male	0	0	0	0	0	0	6	8	10	0	0	12	36

Outcome Measures

1. Primary Outcome Measure: Safety and tolerability of AZD7986 by assessment of the number of adverse events (AEs) following administration of oral solution in single ascending dose (SAD - Part 1a and 1b) and multiple ascending doses (MAD -Part 2) [ Time Frame: Part 1a and 1b: Day -1, Day 1 to Day 3 (spontaneous, at pre-dose, 3, 12, 24, 48 and 72 hours [h] post-dose), Day 4, Day 5 and follow-up (7-10 days after dosing [not for participants included in Part 1b]); Part 2: Day -1, Day 1 to Day 21/28 and follow-up ]

Measure Type	Primary
Measure Name	Safety and tolerability of AZD7986 by assessment of the number of adverse events (AEs) following administration of oral solution in single ascending dose (SAD - Part 1a and 1b) and multiple ascending doses (MAD -Part 2)
Measure Description	To investigate the safety and tolerability of AZD7986 by assessment of AEs (non-serious and serious) following administration of oral solution in SAD (Part 1a - fasted state and 1b - fed state) and MAD (Part 2)
Time Frame	Part 1a and 1b: Day -1, Day 1 to Day 3 (spontaneous, at pre-dose, 3, 12, 24, 48 and 72 hours [h] post-dose), Day 4, Day 5 and follow-up (7-10 days after dosing [not for participants included in Part 1b]); Part 2: Day -1, Day 1 to Day 21/28 and follow-up
Safety Issue?	Yes

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: Yes

2. Primary Outcome Measure: Rate and extent of absorption AZD7986 by assessment of the area under the plasma concentration versus time curve, from time zero to the time of the last quantifiable concentration (AUC(0-last)) for Part 1a and 1b - SAD [ Time Frame: At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 h); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h) ]

Measure Type	Primary
Measure Name	Rate and extent of absorption AZD7986 by assessment of the area under the plasma concentration versus time curve, from time zero to the time of the last quantifiable concentration (AUC(0-last)) for Part 1a and 1b - SAD
Measure Description	To assess the area under the plasma concentration versus time curve, from time zero to the time of the last quantifiable analyte concentration (AUC(0-last)) for Part 1a (fasted state) and 1b (fed state) - SAD
Time Frame	At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 h); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h)
Safety Issue?	No

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

3. Primary Outcome Measure: Rate and extent of absorption of AZD7986 by assessment of the area under the plasma concentration versus time curve, from time zero to the time of the last quantifiable analyte concentration (AUC(0-last)) for Part 2 - MAD [ Time Frame: Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24 h); Day 21 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24, 72, 96 h) and Day 28 ]

Measure Type	Primary
Measure Name	Rate and extent of absorption of AZD7986 by assessment of the area under the plasma concentration versus time curve, from time zero to the time of the last quantifiable analyte concentration (AUC(0-last)) for Part 2 - MAD
Measure Description	To assess the area under the plasma concentration versus time curve, from time zero to the time of the last quantifiable analyte concentration (AUC(0-last)) following a single AZD7986 dose on Day 1 and daily dosing on Days 21 or 28 at 10, 25 and 40 mg in Part 2
Time Frame	Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24 h); Day 21 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24, 72, 96 h) and Day 28
Safety Issue?	No

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

4. Primary Outcome Measure: Rate and extent of absorption AZD7986 by assessment of the area under plasma concentration-time curve from zero extrapolated to infinity (AUC) for Part 1a and 1b - SAD [ Time Frame: At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 h); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h) ]

Measure Type	Primary
Measure Name	Rate and extent of absorption AZD7986 by assessment of the area under plasma concentration-time curve from zero extrapolated to infinity (AUC) for Part 1a and 1b - SAD
Measure Description	To assess the area under plasma concentration-time curve from zero extrapolated to infinity (AUC) for Part 1a (fasted state) and 1b (fed state) - SAD. AUC was estimated by AUC(0 last) + Clast/λz where Clast was the last observed quantifiable concentration.
Time Frame	At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 h); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h)
Safety Issue?	No

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

5. Primary Outcome Measure: Rate and extent of absorption of AZD7986 by assessment of the area under plasma concentration-time curve from zero extrapolated to infinity (AUC) for Part 2 - MAD [ Time Frame: Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24 h); Day 21 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24, 72, 96 h) and Day 28 ]

Measure Type	Primary
Measure Name	Rate and extent of absorption of AZD7986 by assessment of the area under plasma concentration-time curve from zero extrapolated to infinity (AUC) for Part 2 - MAD
Measure Description	To assess the area under plasma concentration-time curve from zero extrapolated to infinity (AUC) following a single AZD7986 dose on Day 1 and daily dosing on Days 21 or 28 at 10, 25 and 40 mg in Part 2. Note: Day 1 data calculated over a 24 hour period and was therefore not comparable with the Day 21 and Day 28 data
Time Frame	Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24 h); Day 21 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24, 72, 96 h) and Day 28
Safety Issue?	No

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

6. Primary Outcome Measure: Rate and extent of absorption of AZD7986 by assessment of area under the plasma concentration-time curve from time zero to the end of the dosing interval (AUCτ) for Part 2 - MAD [ Time Frame: Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24 h); Day 21 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24, 72, 96 h) and Day 28 ]

Measure Type	Primary
Measure Name	Rate and extent of absorption of AZD7986 by assessment of area under the plasma concentration-time curve from time zero to the end of the dosing interval (AUCτ) for Part 2 - MAD
Measure Description	To assess area under the plasma concentration-time curve from time zero to the end of the dosing interval (AUCτ) following a single AZD7986 dose on Day 1 and daily dosing on Days 21 or 28 at 10, 25 and 40 mg in Part 2. AUCτ: AUC from time zero to 24 hours post-dose presented on Day1
Time Frame	Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24 h); Day 21 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24, 72, 96 h) and Day 28
Safety Issue?	No

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

7. Primary Outcome Measure: Rate and extent of absorption AZD7986 by assessment of the observed maximum plasma concentration (Cmax) for Part 1a and 1b - SAD [ Time Frame: At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 h); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h) ]

Measure Type	Primary
Measure Name	Rate and extent of absorption AZD7986 by assessment of the observed maximum plasma concentration (Cmax) for Part 1a and 1b - SAD
Measure Description	To assess the observed maximum plasma concentration (Cmax) for Part 1a (fasted state) and 1b (fed state) - SAD. Cmax was taken directly from the individual concentration-time curve
Time Frame	At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 h); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h)
Safety Issue?	No

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

8. Primary Outcome Measure: Rate and extent of absorption of AZD7986 by assessment of the observed maximum plasma concentration (Cmax) for Part 2 - MAD [ Time Frame: Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24 h); Day 21 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24, 72, 96 h) and Day 28 ]

Measure Type	Primary
Measure Name	Rate and extent of absorption of AZD7986 by assessment of the observed maximum plasma concentration (Cmax) for Part 2 - MAD
Measure Description	To assessthe observed maximum plasma concentration (Cmax) following a single AZD7986 dose on Day 1 and daily dosing on Days 21 or 28 at 10, 25 and 40 mg in Part 2. Cmax was taken directly from the individual concentration-time curve
Time Frame	Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24 h); Day 21 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24, 72, 96 h) and Day 28
Safety Issue?	No

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

9. Primary Outcome Measure: Rate and extent of absorption AZD7986 by assessment of the time to reach maximum observed concentration (tmax) for Part 1a and 1b - SAD [ Time Frame: At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 h); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h) ]

Measure Type	Primary
Measure Name	Rate and extent of absorption AZD7986 by assessment of the time to reach maximum observed concentration (tmax) for Part 1a and 1b - SAD
Measure Description	To assess the time to reach maximum observed concentration (tmax) for Part 1a (fasted state) and 1b (fed state) - SAD; tmax was taken directly from the individual concentration-time curve
Time Frame	At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 h); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h)
Safety Issue?	No

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

10. Primary Outcome Measure: Rate and extent of absorption of AZD7986 by assessment of the time to reach maximum observed concentration (tmax) for Part 2 - MAD [ Time Frame: Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24 h); Day 21 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24, 72, 96 h) and Day 28 ]

Measure Type	Primary
Measure Name	Rate and extent of absorption of AZD7986 by assessment of the time to reach maximum observed concentration (tmax) for Part 2 - MAD
Measure Description	To assess the time to reach maximum observed concentration (tmax) following a single AZD7986 dose on Day 1 and daily dosing on Days 21 or 28 at 10, 25 and 40 mg in Part 2; tmax was taken directly from the individual concentration-time curve
Time Frame	Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24 h); Day 21 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24, 72, 96 h) and Day 28
Safety Issue?	No

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

11. Primary Outcome Measure: Rate and extent of absorption AZD7986 by assessment of the apparent terminal elimination half-life (t½.λz) for Part 1a and 1b - SAD [ Time Frame: At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 h); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h) ]

Measure Type	Primary
Measure Name	Rate and extent of absorption AZD7986 by assessment of the apparent terminal elimination half-life (t½.λz) for Part 1a and 1b - SAD
Measure Description	To assess the half life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½.λz) for Part 1a (fasted state) and 1b (fed state) - SAD
Time Frame	At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 h); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h)
Safety Issue?	No

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

12. Primary Outcome Measure: Rate and extent of absorption of AZD7986 by assessment of the apparent terminal elimination half-life (t½.λz) for Part 2 - MAD [ Time Frame: Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24 h); Day 21 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24, 72, 96 h) and Day 28 ]

Measure Type	Primary
Measure Name	Rate and extent of absorption of AZD7986 by assessment of the apparent terminal elimination half-life (t½.λz) for Part 2 - MAD
Measure Description	To assess the apparent terminal elimination half-life (t½.λz) following a single AZD7986 dose on Day 1 and daily dosing on Days 21 or 28 at 10, 25 and 40 mg in Part 2; tmax was taken directly from the individual concentration-time curve. Note: Day 1 data were calculated over a 24 hour period and was therefore not comparable with the Day 21 and Day 28 data
Time Frame	Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24 h); Day 21 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24, 72, 96 h) and Day 28
Safety Issue?	No

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

13. Primary Outcome Measure: Rate and extent of absorption AZD7986 by assessment of the mean residence time (MRT) for Part 1a and 1b - SAD [ Time Frame: At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 h); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h) ]

Measure Type	Primary
Measure Name	Rate and extent of absorption AZD7986 by assessment of the mean residence time (MRT) for Part 1a and 1b - SAD
Measure Description	To assess the mean residence time (MRT) for Part 1a (fasted state) and 1b (fed state) - SAD
Time Frame	At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 h); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h)
Safety Issue?	No

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

14. Primary Outcome Measure: Rate and extent of absorption of AZD7986 by assessment of mean residence time (MRT) for Part 2 - MAD [ Time Frame: Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24 h); Day 21 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24, 72, 96 h) and Day 28 ]

Measure Type	Primary
Measure Name	Rate and extent of absorption of AZD7986 by assessment of mean residence time (MRT) for Part 2 - MAD
Measure Description	To assess the mean residence time (MRT) following a single AZD7986 dose on Day 1 and daily dosing on Days 21 or 28 at 10, 25 and 40 mg in Part 2
Time Frame	Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24 h); Day 21 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24, 72, 96 h) and Day 28
Safety Issue?	No

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

15. Primary Outcome Measure: Rate and extent of absorption AZD7986 by assessment of the apparent clearance (CL/F) for Part 1a and 1b - SAD [ Time Frame: At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 h); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h) ]

Measure Type	Primary
Measure Name	Rate and extent of absorption AZD7986 by assessment of the apparent clearance (CL/F) for Part 1a and 1b - SAD
Measure Description	To assess the apparent clearance (CL/F) for Part 1a (fasted state) and 1b (fed state) - SAD; CL/F for parent drug was estimated as dose divided by AUC
Time Frame	At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 h); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h)
Safety Issue?	No

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

16. Primary Outcome Measure: Rate and extent of absorption of AZD7986 by assessment of the apparent clearance (CL/F) for Part 2 - MAD [ Time Frame: Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24 h); Day 21 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24, 72, 96 h) and Day 28 ]

Measure Type	Primary
Measure Name	Rate and extent of absorption of AZD7986 by assessment of the apparent clearance (CL/F) for Part 2 - MAD
Measure Description	To assess the apparent clearance (CL/F) following a single AZD7986 dose on Day 1 and daily dosing on Days 21 or 28 at 10, 25 and 40 mg in Part 2; CL/F for parent drug was estimated as dose divided by AUC
Time Frame	Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24 h); Day 21 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24, 72, 96 h) and Day 28
Safety Issue?	No

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

17. Primary Outcome Measure: Rate and extent of absorption AZD7986 by assessment of the apparent volume of distribution (Vz/F) for Part 1a and 1b - SAD [ Time Frame: At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 h); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h) ]

Measure Type	Primary
Measure Name	Rate and extent of absorption AZD7986 by assessment of the apparent volume of distribution (Vz/F) for Part 1a and 1b - SAD
Measure Description	To assess the apparent volume of distribution (Vz/F) for Part 1a (fasted state) and 1b (fed state) - SAD; Vz/F at terminal phase (extravascular administration) was estimated by dividing the apparent clearance (CL/F) by λz
Time Frame	At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 h); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h)
Safety Issue?	No

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

18. Primary Outcome Measure: Rate and extent of absorption of AZD7986 by assessment of the apparent volume of distribution (Vz/F) for Part 2 - MAD [ Time Frame: Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24 h); Day 21 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24, 72, 96 h) and Day 28 ]

Measure Type	Primary
Measure Name	Rate and extent of absorption of AZD7986 by assessment of the apparent volume of distribution (Vz/F) for Part 2 - MAD
Measure Description	To assess the the apparent volume of distribution (Vz/F) following a single AZD7986 dose on Day 1 and daily dosing on Days 21 or 28 at 10, 25 and 40 mg in Part 2; Vz/F at terminal phase (extravascular administration) was estimated by dividing the apparent clearance (CL/F) by λz
Time Frame	Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24 h); Day 21 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24, 72, 96 h) and Day 28
Safety Issue?	No

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

19. Primary Outcome Measure: Rate and extent of absorption of AZD7986 by assessment of the accumulation ratio for (Rac(AUC(0-τ)) for Part 2 - MAD [ Time Frame: Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24 h); Day 21 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24, 72, 96 h) and Day 28 ]

Measure Type	Primary
Measure Name	Rate and extent of absorption of AZD7986 by assessment of the accumulation ratio for (Rac(AUC(0-τ)) for Part 2 - MAD
Measure Description	To assess the accumulation ratio for (Rac(AUC(0-τ)) following a single AZD7986 dose on Day 1 and daily dosing on Days 21 or 28 at 10, 25 and 40 mg in Part 2; estimated as AUC(0-τ) Day 21/AUC(0-24) Day 1
Time Frame	Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24 h); Day 21 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24, 72, 96 h) and Day 28
Safety Issue?	No

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

20. Primary Outcome Measure: Rate and extent of absorption of AZD7986 by assessment of the accumulation ratio for Cmax (Rac(Cmax)) for Part 2 - MAD [ Time Frame: Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24 h); Day 21 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24, 72, 96 h) and Day 28 ]

Measure Type	Primary
Measure Name	Rate and extent of absorption of AZD7986 by assessment of the accumulation ratio for Cmax (Rac(Cmax)) for Part 2 - MAD
Measure Description	To assess the accumulation ratio for Cmax (Rac(Cmax)) following a single AZD7986 dose on Day 1 and daily dosing on Days 21 or 28 at 10, 25 and 40 mg in Part 2; estimated as Cmax Day 21/Cmax Day 1
Time Frame	Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24 h); Day 21 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24, 72, 96 h) and Day 28
Safety Issue?	No

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

21. Primary Outcome Measure: Rate and extent of absorption of AZD7986 by assessment of the temporal change parameter (TCP) for Part 2 - MAD [ Time Frame: Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24 h); Day 21 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24, 72, 96 h) and Day 28 ]

Measure Type	Primary
Measure Name	Rate and extent of absorption of AZD7986 by assessment of the temporal change parameter (TCP) for Part 2 - MAD
Measure Description	To assess the temporal change parameter (TCP) following a single AZD7986 dose on Day 1 and daily dosing on Days 21 or 28 at 10, 25 and 40 mg in Part 2; estimated as AUC(0-τ) Day 21/AUC Day 1, if extrapolated part was less than 20%
Time Frame	Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24 h); Day 21 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24, 72, 96 h) and Day 28
Safety Issue?	No

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

22. Primary Outcome Measure: Rate and extent of absorption of AZD7986 by assessment of urine PK parameter (cumulative amount of analyte excreted from 0 to 48 hours (CumAe0-48)) following administration of single dose oral solution for Part 1a and 1b - SAD [ Time Frame: At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 h); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h) ]

Measure Type	Primary
Measure Name	Rate and extent of absorption of AZD7986 by assessment of urine PK parameter (cumulative amount of analyte excreted from 0 to 48 hours (CumAe0-48)) following administration of single dose oral solution for Part 1a and 1b - SAD
Measure Description	To assess cumulative amount of analyte excreted from 0 to 48 hours (CumAe0-48) after single dose administration of AZD7986 oral solution in Part 1a (fasted state) and 1b (fed state)
Time Frame	At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 h); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h)
Safety Issue?	No

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

23. Primary Outcome Measure: Rate and extent of absorption of AZD7986 by assessment of urine PK parameter (percentage of dose excreted unchanged into the urine from 0 to 48 hours (Cumfe0-48)) following administration of single dose oral solution for Part 1a and 1b - SAD [ Time Frame: At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 h); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h) ]

Measure Type	Primary
Measure Name	Rate and extent of absorption of AZD7986 by assessment of urine PK parameter (percentage of dose excreted unchanged into the urine from 0 to 48 hours (Cumfe0-48)) following administration of single dose oral solution for Part 1a and 1b - SAD
Measure Description	To assess percentage of dose excreted unchanged into the urine from 0 to 48 hours (Cumfe0-48) after single dose administration of AZD7986 oral solution in Part 1a (fasted state) and 1b (fed state)
Time Frame	At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 h); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h)
Safety Issue?	No

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

24. Primary Outcome Measure: Rate and extent of absorption of AZD7986 by assessment of urine PK parameter (renal clearance from 0 to 48 hours (CLR0-48)) following administration of single dose oral solution for Part 1a and 1b - SAD [ Time Frame: At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 h); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h) ]

Measure Type	Primary
Measure Name	Rate and extent of absorption of AZD7986 by assessment of urine PK parameter (renal clearance from 0 to 48 hours (CLR0-48)) following administration of single dose oral solution for Part 1a and 1b - SAD
Measure Description	To assess renal clearance from 0 to 48 hours (CLR0-48) after single dose administration of AZD7986 oral solution in Part 1a (fasted state) and 1b (fed state)
Time Frame	At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 h); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h)
Safety Issue?	No

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

25. Primary Outcome Measure: Rate and extent of absorption of AZD7986 by assessment of urine PK (cumulative amount of analyte excreted from 0 to 24 hours (CumAe0-24)) parameters for Part 2 - MAD [ Time Frame: Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24 h); Day 21 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24, 72, 96 h) and Day 28 ]

Measure Type	Primary
Measure Name	Rate and extent of absorption of AZD7986 by assessment of urine PK (cumulative amount of analyte excreted from 0 to 24 hours (CumAe0-24)) parameters for Part 2 - MAD
Measure Description	To assess cumulative amount of analyte excreted from 0 to 24 hours (CumAe0-24) for Part 2
Time Frame	Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24 h); Day 21 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24, 72, 96 h) and Day 28
Safety Issue?	No

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

26. Primary Outcome Measure: Rate and extent of absorption of AZD7986 by assessment of urine PK (percentage of dose excreted unchanged into the urine from 0 to 24 hours (Cumfe0-24)) parameter for Part 2 - MAD [ Time Frame: Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24 h); Day 21 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24, 72, 96 h) and Day 28 ]

Measure Type	Primary
Measure Name	Rate and extent of absorption of AZD7986 by assessment of urine PK (percentage of dose excreted unchanged into the urine from 0 to 24 hours (Cumfe0-24)) parameter for Part 2 - MAD
Measure Description	To assess percentage of dose excreted unchanged into the urine from 0 to 24 hours (Cumfe0 24) for Part 2
Time Frame	Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24 h); Day 21 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24, 72, 96 h) and Day 28
Safety Issue?	No

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

27. Primary Outcome Measure: Rate and extent of absorption of AZD7986 by assessment of urine PK (renal clearance from 0 to 24 hours (CLR0-24)) parameter for Part 2 - MAD [ Time Frame: Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24 h); Day 21 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24, 72, 96 h) and Day 28 ]

Measure Type	Primary
Measure Name	Rate and extent of absorption of AZD7986 by assessment of urine PK (renal clearance from 0 to 24 hours (CLR0-24)) parameter for Part 2 - MAD
Measure Description	To assess renal clearance from 0 to 24 hours (CLR0-24) for Part 2
Time Frame	Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24 h); Day 21 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24, 72, 96 h) and Day 28
Safety Issue?	No

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

28. Primary Outcome Measure: Rate and extent of absorption of AZD7986 by assessment of urine PK (Cumulative amount of analyte excreted from 0 to 48 hours (CumAe0-48)) parameter for Part 2 - MAD [ Time Frame: Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24 h); Day 21 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24, 72, 96 h) and Day 28 ]

Measure Type	Primary
Measure Name	Rate and extent of absorption of AZD7986 by assessment of urine PK (Cumulative amount of analyte excreted from 0 to 48 hours (CumAe0-48)) parameter for Part 2 - MAD
Measure Description	To assess Cumulative amount of analyte excreted from 0 to 48 hours (CumAe0-48)) for Part 2
Time Frame	Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24 h); Day 21 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24, 72, 96 h) and Day 28
Safety Issue?	No

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

29. Primary Outcome Measure: Rate and extent of absorption of AZD7986 by assessment of urine PK (Percentage of dose excreted unchanged into the urine from 0 to 48 hours (Cumfe0 48)) parameter for Part 2 - MAD [ Time Frame: Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24 h); Day 21 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24, 72, 96 h) and Day 28 ]

Measure Type	Primary
Measure Name	Rate and extent of absorption of AZD7986 by assessment of urine PK (Percentage of dose excreted unchanged into the urine from 0 to 48 hours (Cumfe0 48)) parameter for Part 2 - MAD
Measure Description	To assess Percentage of dose excreted unchanged into the urine from 0 to 48 hours (Cumfe0 48) for Part 2
Time Frame	Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24 h); Day 21 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24, 72, 96 h) and Day 28
Safety Issue?	No

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

30. Primary Outcome Measure: Rate and extent of absorption of AZD7986 by assessment of urine PK (renal clearance from 0 to 48 hours (CLR0-48)) parameter for Part 2 - MAD [ Time Frame: Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24 h); Day 21 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24, 72, 96 h) and Day 28 ]

Measure Type	Primary
Measure Name	Rate and extent of absorption of AZD7986 by assessment of urine PK (renal clearance from 0 to 48 hours (CLR0-48)) parameter for Part 2 - MAD
Measure Description	To assess Percentage of dose excreted unchanged into the urine from 0 to 48 hours (Cumfe0 48) for Part 2
Time Frame	Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24 h); Day 21 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, 9, 12, 24, 72, 96 h) and Day 28
Safety Issue?	No

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

31. Secondary Outcome Measure: Effect of food on absorption AZD7986 by assessment of the area under the plasma concentration versus time curve, from time zero to the time of the last quantifiable concentration (AUC(0-last)) for Part 1a and 1b - SAD [ Time Frame: At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 hours); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h) ]

Measure Type	Secondary
Measure Name	Effect of food on absorption AZD7986 by assessment of the area under the plasma concentration versus time curve, from time zero to the time of the last quantifiable concentration (AUC(0-last)) for Part 1a and 1b - SAD
Measure Description	To assess the effect of food by evaluating the area under the plasma concentration versus time curve, from time zero to the time of the last quantifiable analyte concentration (AUC(0-last)) for Part 1a (fasted state) and 1b (fed state) - SAD
Time Frame	At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 hours); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h)
Safety Issue?	No

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

32. Secondary Outcome Measure: Effect of food on absorption AZD7986 by assessment of the area under plasma concentration-time curve from zero extrapolated to infinity (AUC) for Part 1a and 1b - SAD [ Time Frame: At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 hours); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h) ]

Measure Type	Secondary
Measure Name	Effect of food on absorption AZD7986 by assessment of the area under plasma concentration-time curve from zero extrapolated to infinity (AUC) for Part 1a and 1b - SAD
Measure Description	To assess the effect of food by evaluating the area under plasma concentration-time curve from zero extrapolated to infinity (AUC) for Part 1a (fasted state) and 1b (fed state) - SAD. AUC was estimated by AUC(0 last) + Clast/λz where Clast was the last observed quantifiable concentration.
Time Frame	At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 hours); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h)
Safety Issue?	No

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

33. Secondary Outcome Measure: Effect of food on absorption AZD7986 by assessment of the observed maximum plasma concentration (Cmax) for Part 1a and 1b - SAD [ Time Frame: At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 hours); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h) ]

Measure Type	Secondary
Measure Name	Effect of food on absorption AZD7986 by assessment of the observed maximum plasma concentration (Cmax) for Part 1a and 1b - SAD
Measure Description	To assess the effect of food by evaluating the observed maximum plasma concentration (Cmax) for Part 1a (fasted state) and 1b (fed state) - SAD. Cmax was taken directly from the individual concentration-time curve
Time Frame	At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 hours); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h)
Safety Issue?	No

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

34. Secondary Outcome Measure: Effect of food on absorption AZD7986 by assessment of the time to reach maximum observed concentration (tmax) for Part 1a and 1b - SAD [ Time Frame: At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 hours); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h) ]

Measure Type	Secondary
Measure Name	Effect of food on absorption AZD7986 by assessment of the time to reach maximum observed concentration (tmax) for Part 1a and 1b - SAD
Measure Description	To assess the effect of food by evaluating the time to reach maximum observed concentration (tmax) for Part 1a (fasted state) and 1b (fed state) - SAD; tmax was taken directly from the individual concentration-time curve
Time Frame	At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 hours); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h)
Safety Issue?	No

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

35. Secondary Outcome Measure: Effect of food on absorption AZD7986 by assessment of the apparent terminal elimination half-life (t½.λz) for Part 1a and 1b - SAD [ Time Frame: At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 hours); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h) ]

Measure Type	Secondary
Measure Name	Effect of food on absorption AZD7986 by assessment of the apparent terminal elimination half-life (t½.λz) for Part 1a and 1b - SAD
Measure Description	To assess the effect of food by evaluating the half life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½.λz) for Part 1a (fasted state) and 1b (fed state) - SAD
Time Frame	At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 hours); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h)
Safety Issue?	No

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

36. Secondary Outcome Measure: Effect of food on absorption AZD7986 by assessment of the mean residence time (MRT) for Part 1a and 1b - SAD [ Time Frame: At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 hours); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h) ]

Measure Type	Secondary
Measure Name	Effect of food on absorption AZD7986 by assessment of the mean residence time (MRT) for Part 1a and 1b - SAD
Measure Description	To assess the effect of food by evaluating the mean residence time (MRT) for Part 1a (fasted state) and 1b (fed state) - SAD
Time Frame	At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 hours); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h)
Safety Issue?	No

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

37. Secondary Outcome Measure: Effect of food on absorption AZD7986 by assessment of the apparent clearance (CL/F) for Part 1a and 1b - SAD [ Time Frame: At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 hours); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h) ]

Measure Type	Secondary
Measure Name	Effect of food on absorption AZD7986 by assessment of the apparent clearance (CL/F) for Part 1a and 1b - SAD
Measure Description	To assess the effect of food by evaluating the apparent clearance (CL/F) for Part 1a (fasted state) and 1b (fed state) - SAD; CL/F for parent drug was estimated as dose divided by AUC
Time Frame	At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 hours); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h)
Safety Issue?	No

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

38. Secondary Outcome Measure: Effect of food on absorption AZD7986 by assessment of the apparent volume of distribution (Vz/F) for Part 1a and 1b - SAD [ Time Frame: At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 hours); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h) ]

Measure Type	Secondary
Measure Name	Effect of food on absorption AZD7986 by assessment of the apparent volume of distribution (Vz/F) for Part 1a and 1b - SAD
Measure Description	To assess the effect of food by evaluating the apparent volume of distribution (Vz/F) for Part 1a (fasted state) and 1b (fed state) - SAD; Vz/F at terminal phase (extravascular administration) was estimated by dividing the apparent clearance (CL/F) by λz
Time Frame	At Day 1 (Pre-dose, 0.5, 1, 2, 3, 4, 5, 7, 8, 9, 12 hours); Day 2 (24 h); Day 3 (48 h); Day 4 (72 h) and Day 5 (96 h)
Safety Issue?	No

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

39. Secondary Outcome Measure: Assessment of mean normalized relative neutrophil elastase (NE) activity in all cohorts of Part 2 [ Time Frame: At Day 16, 21 ((last dosing day in Cohort 1), 25, 28 (last sampling day in Cohort 1 and last dosing day in Cohorts 2 and 3), 32, 38, 41 and 52 ]

Measure Type	Secondary
Measure Name	Assessment of mean normalized relative neutrophil elastase (NE) activity in all cohorts of Part 2
Measure Description	Absolute neutrophil count (ANC) was evaluated as part of the safety laboratory assessments and to evaluate the pharmacodynamics (PD) marker
Time Frame	At Day 16, 21 ((last dosing day in Cohort 1), 25, 28 (last sampling day in Cohort 1 and last dosing day in Cohorts 2 and 3), 32, 38, 41 and 52
Safety Issue?	Yes

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: Yes

40. Secondary Outcome Measure: Assessment of absolute neutrophil count (ANC) in all cohorts of Part 2 [ Time Frame: At Day 12 (pre-dose, 6 hours and 12 hours) ]

Measure Type	Secondary
Measure Name	Assessment of absolute neutrophil count (ANC) in all cohorts of Part 2
Measure Description	Absolute neutrophil count (ANC) was evaluated as part of the safety laboratory assessments and to evaluate the pharmacodynamics (PD) marker
Time Frame	At Day 12 (pre-dose, 6 hours and 12 hours)
Safety Issue?	Yes

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: Yes

Serious Adverse Events

Time Frame	Part 1a and 1b: Day -1, Day 1 to Day 3 (spontaneous, at pre-dose, 3, 12, 24, 48 and 72 hours [h] post-dose), Day 4, Day 5 and follow-up (7-10 days after dosing [not for participants included in Part 1b]); Part 2: Day -1, Day 1 to Day 21/28 and follow-up
Additional Description	All randomized participants who received at least 1 dose of IMP were included in the safety analysis. Adverse events (AEs - serious / non-serious), an undesirable medical condition occurring at any time after the participant had signed informed consent, including run-in or washout periods, even if no specific treatment has been administered.

Reporting Groups

	Description
Part 1a (Fasted state) - Single ascending dose (SAD)	Participants received single dose of oral solution of AZD7986 at 5 ascending doses (5mg, 15mg, 35mg, 50mg and 65mg) on Day 1 in fasted state with 6 participants in each dose level.
Part 1b (Fed state) - SAD	5 Participants of Cohort 3 from Part 1a received single dose of oral solution of AZD7986 35mg on Day 1 in fed state after a washout of at least 7 days.
Part 2 - Multiple ascending dose (MAD)	24 participants (6 in Cohort 1-10mg, 8 in Cohort 2- 25mg and 10 in Cohort 3-40mg) received once daily dose of oral solution of AZD7986 in the morning for 28 days. Participants were fasted until 1 hour after dosing when a light breakfast was provided.
Placebo - Part 1a (Fasted state)- SAD	3 participants per dose level received single dose of oral solution of placebo in Part 1a in fasted state on Day 1
Placebo - Part 1b (Fed state) - SAD	3 participants of Cohort 3 from Part 1a received single dose of oral solution of placebo 35mg on Day 1 in fed state after a washout of at least 7 days.
Placebo - Part 2 - MAD	12 participants (randomized 6:3, 8:3 and 10:4/10:6/12:4) received once daily dose of oral solution of Placebo in the morning for 28 days. Participants were fasted until 1 hour after dosing when a light breakfast was provided.

Serious Adverse Events

	Part 1a (Fasted state) - Single ascending dose (SAD)	Part 1b (Fed state) - SAD	Part 2 - Multiple ascending dose (MAD)	Placebo - Part 1a (Fasted state)- SAD	Placebo - Part 1b (Fed state) - SAD	Placebo - Part 2 - MAD
Total, serious adverse events
# participants affected / at risk	0/30 (0.00%)	0/5 (0.00%)	0/24 (0.00%)	0/15 (0.00%)	0/3 (0.00%)	0/12 (0.00%)

Other Adverse Events

Time Frame	Part 1a and 1b: Day -1, Day 1 to Day 3 (spontaneous, at pre-dose, 3, 12, 24, 48 and 72 hours [h] post-dose), Day 4, Day 5 and follow-up (7-10 days after dosing [not for participants included in Part 1b]); Part 2: Day -1, Day 1 to Day 21/28 and follow-up
Additional Description	All randomized participants who received at least 1 dose of IMP were included in the safety analysis. Adverse events (AEs - serious / non-serious), an undesirable medical condition occurring at any time after the participant had signed informed consent, including run-in or washout periods, even if no specific treatment has been administered.

Frequency Threshold

Threshold above which other adverse events are reported	0%

Reporting Groups

	Description
Part 1a (Fasted state) - Single ascending dose (SAD)	Participants received single dose of oral solution of AZD7986 at 5 ascending doses (5mg, 15mg, 35mg, 50mg and 65mg) on Day 1 in fasted state with 6 participants in each dose level.
Part 1b (Fed state) - SAD	5 Participants of Cohort 3 from Part 1a received single dose of oral solution of AZD7986 35mg on Day 1 in fed state after a washout of at least 7 days.
Part 2 - Multiple ascending dose (MAD)	24 participants (6 in Cohort 1-10mg, 8 in Cohort 2- 25mg and 10 in Cohort 3-40mg) received once daily dose of oral solution of AZD7986 in the morning for 28 days. Participants were fasted until 1 hour after dosing when a light breakfast was provided.
Placebo - Part 1a (Fasted state)- SAD	3 participants per dose level received single dose of oral solution of placebo in Part 1a in fasted state on Day 1
Placebo - Part 1b (Fed state) - SAD	3 participants of Cohort 3 from Part 1a received single dose of oral solution of placebo 35mg on Day 1 in fed state after a washout of at least 7 days.
Placebo - Part 2 - MAD	12 participants (randomized 6:3, 8:3 and 10:4/10:6/12:4) received once daily dose of oral solution of Placebo in the morning for 28 days. Participants were fasted until 1 hour after dosing when a light breakfast was provided.

Other Adverse Events

Part 1a (Fasted state) - Single ascending dose (SAD)

Part 1b (Fed state) - SAD

Part 2 - Multiple ascending dose (MAD)

Placebo - Part 1a (Fasted state)- SAD

Placebo - Part 1b (Fed state) - SAD

Placebo - Part 2 - MAD

Total, other (not including serious) adverse events

# participants affected / at risk

8/30 (26.67%)

2/5 (40.00%)

23/24 (95.83%)

8/15 (53.33%)

1/3 (33.33%)

8/12 (66.67%)

Gastrointestinal disorders

Abdominal pain¹

# participants affected / at risk

1/30 (3.33%)

0/5 (0.00%)

0/24 (0.00%)

1/15 (6.67%)

0/3 (0.00%)

0/12 (0.00%)

Gastrointestinal disorders

Dry mouth¹

# participants affected / at risk

1/30 (3.33%)

0/5 (0.00%)

0/24 (0.00%)

0/15 (0.00%)

0/3 (0.00%)

0/12 (0.00%)

Gastrointestinal disorders

Dyspepsia¹

# participants affected / at risk

1/30 (3.33%)

0/5 (0.00%)

0/24 (0.00%)

0/15 (0.00%)

0/3 (0.00%)

0/12 (0.00%)

Gastrointestinal disorders

Rectal haemorrhage¹

# participants affected / at risk

1/30 (3.33%)

0/5 (0.00%)

0/24 (0.00%)

0/15 (0.00%)

0/3 (0.00%)

0/12 (0.00%)

Gastrointestinal disorders

Gingival bleeding¹

# participants affected / at risk

0/30 (0.00%)

1/5 (20.00%)

3/24 (12.50%)

1/15 (6.67%)

1/3 (33.33%)

2/12 (16.67%)

Gastrointestinal disorders

Constipation¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

4/24 (16.67%)

0/15 (0.00%)

0/3 (0.00%)

2/12 (16.67%)

Gastrointestinal disorders

Abdominal discomfort¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

2/24 (8.33%)

0/15 (0.00%)

0/3 (0.00%)

1/12 (8.33%)

Gastrointestinal disorders

Lip dry¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

2/24 (8.33%)

0/15 (0.00%)

0/3 (0.00%)

0/12 (0.00%)

Gastrointestinal disorders

Nausea¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

2/24 (8.33%)

0/15 (0.00%)

0/3 (0.00%)

1/12 (8.33%)

Gastrointestinal disorders

Diarrhoea¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

1/24 (4.17%)

0/15 (0.00%)

0/3 (0.00%)

0/12 (0.00%)

Gastrointestinal disorders

Flatulence¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

1/24 (4.17%)

0/15 (0.00%)

0/3 (0.00%)

0/12 (0.00%)

Gastrointestinal disorders

Gingival pain¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

1/24 (4.17%)

0/15 (0.00%)

0/3 (0.00%)

1/12 (8.33%)

Gastrointestinal disorders

Vomiting¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

1/24 (4.17%)

0/15 (0.00%)

0/3 (0.00%)

0/12 (0.00%)

Gastrointestinal disorders

Aphthous ulcer¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

0/24 (0.00%)

0/15 (0.00%)

0/3 (0.00%)

1/12 (8.33%)

Nervous system disorders

Headache¹

# participants affected / at risk

3/30 (10.00%)

2/5 (40.00%)

6/24 (25.00%)

2/15 (13.33%)

0/3 (0.00%)

1/12 (8.33%)

Nervous system disorders

Dizziness¹

# participants affected / at risk

1/30 (3.33%)

0/5 (0.00%)

2/24 (8.33%)

1/15 (6.67%)

0/3 (0.00%)

2/12 (16.67%)

Nervous system disorders

Paraesthesia¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

0/24 (0.00%)

1/15 (6.67%)

0/3 (0.00%)

0/12 (0.00%)

Nervous system disorders

Dizziness postural¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

1/24 (4.17%)

0/15 (0.00%)

0/3 (0.00%)

1/12 (8.33%)

General disorders

Fatigue¹

# participants affected / at risk

1/30 (3.33%)

0/5 (0.00%)

2/24 (8.33%)

0/15 (0.00%)

0/3 (0.00%)

1/12 (8.33%)

General disorders

Pain¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

2/24 (8.33%)

0/15 (0.00%)

0/3 (0.00%)

0/12 (0.00%)

General disorders

Axillary pain¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

1/24 (4.17%)

0/15 (0.00%)

0/3 (0.00%)

0/12 (0.00%)

General disorders

Catheter site related reaction¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

1/24 (4.17%)

0/15 (0.00%)

0/3 (0.00%)

0/12 (0.00%)

General disorders

Chest discomfort¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

1/24 (4.17%)

0/15 (0.00%)

0/3 (0.00%)

0/12 (0.00%)

General disorders

Asthenia¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

0/24 (0.00%)

0/15 (0.00%)

0/3 (0.00%)

1/12 (8.33%)

General disorders

Feeling hot¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

0/24 (0.00%)

0/15 (0.00%)

0/3 (0.00%)

2/12 (16.67%)

General disorders

Vessel puncture site pain¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

0/24 (0.00%)

0/15 (0.00%)

0/3 (0.00%)

1/12 (8.33%)

Infections and infestations

Nasopharyngitis¹

# participants affected / at risk

1/30 (3.33%)

0/5 (0.00%)

3/24 (12.50%)

0/15 (0.00%)

0/3 (0.00%)

1/12 (8.33%)

Respiratory, thoracic and mediastinal disorders

Oropharyngeal pain¹

# participants affected / at risk

1/30 (3.33%)

0/5 (0.00%)

3/24 (12.50%)

1/15 (6.67%)

0/3 (0.00%)

2/12 (16.67%)

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

0/24 (0.00%)

1/15 (6.67%)

0/3 (0.00%)

0/12 (0.00%)

Respiratory, thoracic and mediastinal disorders

Epistaxis¹

# participants affected / at risk

0/30 (0.00%)

1/5 (20.00%)

0/24 (0.00%)

0/15 (0.00%)

0/3 (0.00%)

0/12 (0.00%)

Respiratory, thoracic and mediastinal disorders

Nasal congestion¹

# participants affected / at risk

0/30 (0.00%)

1/5 (20.00%)

0/24 (0.00%)

0/15 (0.00%)

0/3 (0.00%)

2/12 (16.67%)

Respiratory, thoracic and mediastinal disorders

Cough¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

2/24 (8.33%)

0/15 (0.00%)

0/3 (0.00%)

0/12 (0.00%)

Respiratory, thoracic and mediastinal disorders

Productive cough¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

0/24 (0.00%)

0/15 (0.00%)

0/3 (0.00%)

1/12 (8.33%)

Psychiatric disorders

Insomnia¹

# participants affected / at risk

1/30 (3.33%)

0/5 (0.00%)

0/24 (0.00%)

1/15 (6.67%)

0/3 (0.00%)

0/12 (0.00%)

Skin and subcutaneous tissue disorders

Skin irritation¹

# participants affected / at risk

1/30 (3.33%)

0/5 (0.00%)

0/24 (0.00%)

1/15 (6.67%)

0/3 (0.00%)

1/12 (8.33%)

Skin and subcutaneous tissue disorders

Dermatitis contact¹

# participants affected / at risk

0/30 (0.00%)

1/5 (20.00%)

2/24 (8.33%)

0/15 (0.00%)

0/3 (0.00%)

0/12 (0.00%)

Skin and subcutaneous tissue disorders

Dry skin¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

3/24 (12.50%)

0/15 (0.00%)

0/3 (0.00%)

0/12 (0.00%)

Skin and subcutaneous tissue disorders

Dermatitis atopic¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

1/24 (4.17%)

0/15 (0.00%)

0/3 (0.00%)

1/12 (8.33%)

Skin and subcutaneous tissue disorders

Drug eruption¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

1/24 (4.17%)

0/15 (0.00%)

0/3 (0.00%)

0/12 (0.00%)

Skin and subcutaneous tissue disorders

Erythema¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

1/24 (4.17%)

0/15 (0.00%)

0/3 (0.00%)

1/12 (8.33%)

Skin and subcutaneous tissue disorders

Hyperkeratosis¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

1/24 (4.17%)

0/15 (0.00%)

0/3 (0.00%)

0/12 (0.00%)

Skin and subcutaneous tissue disorders

Skin exfoliation¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

1/24 (4.17%)

0/15 (0.00%)

0/3 (0.00%)

1/12 (8.33%)

Skin and subcutaneous tissue disorders

Skin hypertrophy¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

1/24 (4.17%)

0/15 (0.00%)

0/3 (0.00%)

0/12 (0.00%)

Skin and subcutaneous tissue disorders

Night sweats¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

0/24 (0.00%)

0/15 (0.00%)

0/3 (0.00%)

1/12 (8.33%)

Skin and subcutaneous tissue disorders

Pruritus¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

0/24 (0.00%)

0/15 (0.00%)

0/3 (0.00%)

1/12 (8.33%)

Cardiac disorders

Palpitations¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

1/24 (4.17%)

1/15 (6.67%)

0/3 (0.00%)

0/12 (0.00%)

Cardiac disorders

Sinus tachycardia¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

0/24 (0.00%)

1/15 (6.67%)

0/3 (0.00%)

0/12 (0.00%)

Vascular disorders

Hot flush¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

0/24 (0.00%)

1/15 (6.67%)

0/3 (0.00%)

1/12 (8.33%)

Vascular disorders

Systolic hypertension¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

0/24 (0.00%)

1/15 (6.67%)

0/3 (0.00%)

0/12 (0.00%)

Investigations

Weight decreased¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

0/24 (0.00%)

0/15 (0.00%)

0/3 (0.00%)

1/12 (8.33%)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Skin papilloma¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

1/24 (4.17%)

0/15 (0.00%)

0/3 (0.00%)

0/12 (0.00%)

Musculoskeletal and connective tissue disorders

Neck pain¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

0/24 (0.00%)

0/15 (0.00%)

0/3 (0.00%)

1/12 (8.33%)

Immune system disorders

Seasonal allergy¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

1/24 (4.17%)

0/15 (0.00%)

0/3 (0.00%)

0/12 (0.00%)

Ear and labyrinth disorders

Excessive cerumen production¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

1/24 (4.17%)

0/15 (0.00%)

0/3 (0.00%)

0/12 (0.00%)

Injury, poisoning and procedural complications

Laceration¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

1/24 (4.17%)

0/15 (0.00%)

0/3 (0.00%)

0/12 (0.00%)

General disorders

Arthropod bite¹

# participants affected / at risk

0/30 (0.00%)

0/5 (0.00%)

1/24 (4.17%)

0/15 (0.00%)

0/3 (0.00%)

0/12 (0.00%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA v19.0

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: All clinical study findings and documents will be regarded as confidential. The investigator and members of his/her research team must not disclose such information without prior written approval from the sponsor.