Single + Multiple Ascending Dose and Food Effect Study of... | NCT02303574

ID	Type	Description	Link
2014-004043-13	EudraCT Number

Label	Type	Description	Intervention Names
AZD7986, single and mulltiple doses	Experimental	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
Placebo, single and multiple doses	Placebo Comparator	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

Name	Type	Description	Arm Group Labels	Other Names
AZD7986, oral solution, 1 to 50 mg/mL	Drug	Starting dose in single ascending dose part: 5 mg	AZD7986, single and mulltiple doses

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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)	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)	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
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	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	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)
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	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	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
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

Secondary Outcomes

Measure	Description	Time Frame
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	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

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Provision of signed and dated written informed consent prior to any study specific procedures.
Healthy male or female subjects aged 18 to 50 years (inclusive) at screening with suitable veins for cannulation or repeated venepuncture.
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.
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).
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.

Name	Affiliation	Role
Annelize Koch, Dr	PAREXEL Early Phase Clinical Unit, Level 7, Northwick Park Hospital, Watford Road, Harrow, Middlesex, HA1 3UJ, United Kingdom	Principal Investigator
Bengt Larsson	AstraZeneca	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Harrow		HA1 3UJ	United Kingdom

ID	Title	Description
FG000	AZD7986 5 mg (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 5mg on Day 1 in fasted state.
FG001	AZD7986 15 mg (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 15mg on Day 1in fasted state.

Arm/Group Information

ID	Title	Description
BG000	AZD7986 5 mg (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 5mg on Day 1 in fasted state.
BG001	AZD7986 15 mg (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 15mg on Day 1in fasted state.
BG002	AZD7986 35 mg (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 35mg on Day 1 in fasted state.
BG003	AZD7986 50 mg (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 50mg on Day 1 in fasted state.
BG004	AZD7986 65 mg (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 65mg on Day 1 in fasted state.
BG005	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.
BG006	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.
BG007	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.
BG008	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.
BG009	Placebo - Part 1a (Fasted)	Randomized participants received orally AZD7986 matching placebo oral solution on Day 1 in fasted state.
BG010	Placebo - Part 1b (Fed State)	Randomized participants received orally AZD7986 matching placebo oral solution on Day 1 in fed state.
BG011	Placebo - Part 2	Randomized participants received orally AZD7986 matching placebo oral solution for 28 days (fasted/fed state, based on part 1b results).
BG012	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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)

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)

All randomized subjects who received at least one dose of IMP were included in the safety analysis for the study.

Posted

Number

Participants

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

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.
OG003	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
OG004	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.
OG005	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.

Units	Counts
Participants	OG00030 OG0015 OG00224 OG003

Title

Denominators

Categories

Any AE

Title	Measurements
	OG0008 OG0012 OG00223 OG003

Primary

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

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

The pharmacokinetic analysis (PK) analysis set consisted of all subjects in the safety analysis set who received at least 1 dose of AZD7986 and had evaluable PK data.

Posted

Geometric Mean

Geometric Coefficient of Variation

h·nmol/L

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)

ID	Title	Description
OG000	AZD7986 5mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 5mg on Day 1 in fasted state.
OG001	AZD7986 15mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 15mg on Day 1.
OG002	AZD7986 35mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 35mg on Day 1 in fasted state.

Primary

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

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

The pharmacokinetic analysis (PK) analysis set consisted of all subjects in the safety analysis set who received at least 1 dose of AZD7986 and had evaluable PK data.

Posted

Geometric Mean

Geometric Coefficient of Variation

h·nmol/L

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

ID	Title	Description
OG000	AZD7986 10mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 10mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG001	AZD7986 25mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 25mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG002	AZD7986 40mg - Day 1 - Part 2 - MAD

Primary

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

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.

The pharmacokinetic analysis (PK) analysis set consisted of all subjects in the safety analysis set who received at least 1 dose of AZD7986 and had evaluable PK data.

Posted

Geometric Mean

Geometric Coefficient of Variation

h·nmol/L

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)

ID	Title	Description
OG000	AZD7986 5mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 5mg on Day 1 in fasted state.
OG001	AZD7986 15mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 15mg on Day 1.
OG002	AZD7986 35mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 35mg on Day 1 in fasted state.

Primary

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

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

The pharmacokinetic analysis (PK) analysis set consisted of all subjects in the safety analysis set who received at least 1 dose of AZD7986 and had evaluable PK data.

Posted

Geometric Mean

Geometric Coefficient of Variation

h·nmol/L

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

ID	Title	Description
OG000	AZD7986 10mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 10mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG001	AZD7986 25mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 25mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG002	AZD7986 40mg - Day 1 - Part 2 - MAD

Primary

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

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

The pharmacokinetic analysis (PK) analysis set consisted of all subjects in the safety analysis set who received at least 1 dose of AZD7986 and had evaluable PK data.

Posted

Geometric Mean

Geometric Coefficient of Variation

h·nmol/L

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

ID	Title	Description
OG000	AZD7986 10mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 10mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG001	AZD7986 25mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 25mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG002	AZD7986 40mg - Day 1 - Part 2 - MAD

Primary

Rate and Extent of Absorption AZD7986 by Assessment of the Observed Maximum Plasma Concentration (Cmax) for Part 1a and 1b - SAD

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

The pharmacokinetic analysis (PK) analysis set consisted of all subjects in the safety analysis set who received at least 1 dose of AZD7986 and had evaluable PK data.

Posted

Geometric Mean

Geometric Coefficient of Variation

nmol/L

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)

ID	Title	Description
OG000	AZD7986 5mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 5mg on Day 1 in fasted state.
OG001	AZD7986 15mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 15mg on Day 1.
OG002	AZD7986 35mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 35mg on Day 1 in fasted state.
OG003

Primary

Rate and Extent of Absorption of AZD7986 by Assessment of the Observed Maximum Plasma Concentration (Cmax) for Part 2 - MAD

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

The pharmacokinetic analysis (PK) analysis set consisted of all subjects in the safety analysis set who received at least 1 dose of AZD7986 and had evaluable PK data.

Posted

Geometric Mean

Geometric Coefficient of Variation

nmol/L

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

ID	Title	Description
OG000	AZD7986 10mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 10mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG001	AZD7986 25mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 25mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG002	AZD7986 40mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 40mg on Day 1 and daily dosing on Days 21 or 28 I fasted state.

Primary

Rate and Extent of Absorption AZD7986 by Assessment of the Time to Reach Maximum Observed Concentration (Tmax) for Part 1a and 1b - SAD

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

The pharmacokinetic analysis (PK) analysis set consisted of all subjects in the safety analysis set who received at least 1 dose of AZD7986 and had evaluable PK data.

Posted

Median

Full Range

Hour

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)

ID	Title	Description
OG000	AZD7986 5mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 5mg on Day 1 in fasted state.
OG001	AZD7986 15mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 15mg on Day 1.
OG002	AZD7986 35mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 35mg on Day 1 in fasted state.
OG003

Primary

Rate and Extent of Absorption of AZD7986 by Assessment of the Time to Reach Maximum Observed Concentration (Tmax) for Part 2 - MAD

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

The pharmacokinetic analysis (PK) analysis set consisted of all subjects in the safety analysis set who received at least 1 dose of AZD7986 and had evaluable PK data.

Posted

Median

Full Range

Hour

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

ID	Title	Description
OG000	AZD7986 10mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 10mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG001	AZD7986 25mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 25mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG002	AZD7986 40mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 40mg on Day 1 and daily dosing on Days 21 or 28 I fasted state.

Primary

Rate and Extent of Absorption AZD7986 by Assessment of the Apparent Terminal Elimination Half-life (t½.λz) for Part 1a and 1b - SAD

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

The pharmacokinetic analysis (PK) analysis set consisted of all subjects in the safety analysis set who received at least 1 dose of AZD7986 and had evaluable PK data.

Posted

Mean

Standard Deviation

Hour

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)

ID	Title	Description
OG000	AZD7986 5mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 5mg on Day 1 in fasted state.
OG001	AZD7986 15mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 15mg on Day 1.
OG002	AZD7986 35mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 35mg on Day 1 in fasted state.
OG003

Primary

Rate and Extent of Absorption of AZD7986 by Assessment of the Apparent Terminal Elimination Half-life (t½.λz) for Part 2 - MAD

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

The pharmacokinetic analysis (PK) analysis set consisted of all subjects in the safety analysis set who received at least 1 dose of AZD7986 and had evaluable PK data.

Posted

Mean

Standard Deviation

Hour

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

ID	Title	Description
OG000	AZD7986 10mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 10mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG001	AZD7986 25mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 25mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG002	AZD7986 40mg - Day 1 - Part 2 - MAD

Primary

Rate and Extent of Absorption AZD7986 by Assessment of the Mean Residence Time (MRT) for Part 1a and 1b - SAD

To assess the mean residence time (MRT) for Part 1a (fasted state) and 1b (fed state) - SAD

The pharmacokinetic analysis (PK) analysis set consisted of all subjects in the safety analysis set who received at least 1 dose of AZD7986 and had evaluable PK data.

Posted

Mean

Standard Deviation

Hour

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)

ID	Title	Description
OG000	AZD7986 5mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 5mg on Day 1 in fasted state.
OG001	AZD7986 15mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 15mg on Day 1.
OG002	AZD7986 35mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 35mg on Day 1 in fasted state.
OG003	AZD7986 50mg - Part 1a (Fasted State) - SAD

Primary

Rate and Extent of Absorption of AZD7986 by Assessment of Mean Residence Time (MRT) for Part 2 - MAD

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

The pharmacokinetic analysis (PK) analysis set consisted of all subjects in the safety analysis set who received at least 1 dose of AZD7986 and had evaluable PK data.

Posted

Mean

Standard Deviation

Hour

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

ID	Title	Description
OG000	AZD7986 10mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 10mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG001	AZD7986 25mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 25mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG002	AZD7986 40mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 40mg on Day 1 and daily dosing on Days 21 or 28 I fasted state.

Primary

Rate and Extent of Absorption AZD7986 by Assessment of the Apparent Clearance (CL/F) for Part 1a and 1b - SAD

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

The pharmacokinetic analysis (PK) analysis set consisted of all subjects in the safety analysis set who received at least 1 dose of AZD7986 and had evaluable PK data.

Posted

Mean

Standard Deviation

Litre/Hour

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)

ID	Title	Description
OG000	AZD7986 5mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 5mg on Day 1 in fasted state.
OG001	AZD7986 15mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 15mg on Day 1.
OG002	AZD7986 35mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 35mg on Day 1 in fasted state.
OG003	AZD7986 50mg - Part 1a (Fasted State) - SAD

Primary

Rate and Extent of Absorption of AZD7986 by Assessment of the Apparent Clearance (CL/F) for Part 2 - MAD

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

The pharmacokinetic analysis (PK) analysis set consisted of all subjects in the safety analysis set who received at least 1 dose of AZD7986 and had evaluable PK data.

Posted

Mean

Standard Deviation

Litre/Hour

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

ID	Title	Description
OG000	AZD7986 10mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 10mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG001	AZD7986 25mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 25mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG002	AZD7986 40mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 40mg on Day 1 and daily dosing on Days 21 or 28 I fasted state.

Primary

Rate and Extent of Absorption AZD7986 by Assessment of the Apparent Volume of Distribution (Vz/F) for Part 1a and 1b - SAD

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

The pharmacokinetic analysis (PK) analysis set consisted of all subjects in the safety analysis set who received at least 1 dose of AZD7986 and had evaluable PK data.

Posted

Mean

Standard Deviation

Litre

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)

ID	Title	Description
OG000	AZD7986 5mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 5mg on Day 1 in fasted state.
OG001	AZD7986 15mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 15mg on Day 1.
OG002	AZD7986 35mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 35mg on Day 1 in fasted state.

Primary

Rate and Extent of Absorption of AZD7986 by Assessment of the Apparent Volume of Distribution (Vz/F) for Part 2 - MAD

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

The pharmacokinetic analysis (PK) analysis set consisted of all subjects in the safety analysis set who received at least 1 dose of AZD7986 and had evaluable PK data.

Posted

Mean

Standard Deviation

Litre

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

ID	Title	Description
OG000	AZD7986 10mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 10mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG001	AZD7986 25mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 25mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG002	AZD7986 40mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 40mg on Day 1 and daily dosing on Days 21 or 28 I fasted state.

Primary

Rate and Extent of Absorption of AZD7986 by Assessment of the Accumulation Ratio for (Rac(AUC(0-τ)) for Part 2 - MAD

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

The pharmacokinetic analysis (PK) analysis set consisted of all subjects in the safety analysis set who received at least 1 dose of AZD7986 and had evaluable PK data.

Posted

Mean

Standard Deviation

Ratio

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

ID	Title	Description
OG000	AZD7986 10mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 10mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG001	AZD7986 25mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 25mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG002	AZD7986 40mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 40mg on Day 1 and daily dosing on Days 21 or 28 I fasted state.

Primary

Rate and Extent of Absorption of AZD7986 by Assessment of the Accumulation Ratio for Cmax (Rac(Cmax)) for Part 2 - MAD

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

The pharmacokinetic analysis (PK) analysis set consisted of all subjects in the safety analysis set who received at least 1 dose of AZD7986 and had evaluable PK data.

Posted

Mean

Standard Deviation

Ratio

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

ID	Title	Description
OG000	AZD7986 10mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 10mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG001	AZD7986 25mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 25mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG002	AZD7986 40mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 40mg on Day 1 and daily dosing on Days 21 or 28 I fasted state.

Primary

Rate and Extent of Absorption of AZD7986 by Assessment of the Temporal Change Parameter (TCP) for Part 2 - MAD

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%

The pharmacokinetic analysis (PK) analysis set consisted of all subjects in the safety analysis set who received at least 1 dose of AZD7986 and had evaluable PK data.

Posted

Mean

Standard Deviation

Ratio

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

ID	Title	Description
OG000	AZD7986 10mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 10mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG001	AZD7986 25mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 25mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG002	AZD7986 40mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 40mg on Day 1 and daily dosing on Days 21 or 28 I fasted state.

Primary

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

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)

The pharmacokinetic analysis (PK) analysis set consisted of all subjects in the safety analysis set who received at least 1 dose of AZD7986 and had evaluable PK data.

Posted

Mean

Standard Deviation

nmol

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)

ID	Title	Description
OG000	AZD7986 5mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 5mg on Day 1 in fasted state.
OG001	AZD7986 15mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 15mg on Day 1.
OG002	AZD7986 35mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 35mg on Day 1 in fasted state.

Primary

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

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)

The pharmacokinetic analysis (PK) analysis set consisted of all subjects in the safety analysis set who received at least 1 dose of AZD7986 and had evaluable PK data.

Posted

Mean

Standard Deviation

Percentage of dose excreted unchanged

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)

ID	Title	Description
OG000	AZD7986 5mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 5mg on Day 1 in fasted state.
OG001	AZD7986 15mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 15mg on Day 1.
OG002	AZD7986 35mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 35mg on Day 1 in fasted state.

Primary

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

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)

The pharmacokinetic analysis (PK) analysis set consisted of all subjects in the safety analysis set who received at least 1 dose of AZD7986 and had evaluable PK data.

Posted

Mean

Standard Deviation

Liter/hour

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)

ID	Title	Description
OG000	AZD7986 5mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 5mg on Day 1 in fasted state.
OG001	AZD7986 15mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 15mg on Day 1.
OG002	AZD7986 35mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 35mg on Day 1 in fasted state.

Primary

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

To assess cumulative amount of analyte excreted from 0 to 24 hours (CumAe0-24) for Part 2

The pharmacokinetic analysis (PK) analysis set consisted of all subjects in the safety analysis set who received at least 1 dose of AZD7986 and had evaluable PK data.

Posted

Mean

Standard Deviation

nmol

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

ID	Title	Description
OG000	AZD7986 10mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 10mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG001	AZD7986 25mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 25mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG002	AZD7986 40mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 40mg on Day 1 and daily dosing on Days 21 or 28 I fasted state.

Secondary

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

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

The pharmacokinetic analysis (PK) analysis set consisted of all subjects in the safety analysis set who received at least 1 dose of AZD7986 and had evaluable PK data.

Posted

Geometric Mean

Geometric Coefficient of Variation

h·nmol/L

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)

ID	Title	Description
OG000	AZD7986 35mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 35mg on Day 1 in fasted state.
OG001	AZD7986 35mg - Part 1b (Fed State) - SAD	Participants received single dose of oral solution of AZD7986 35mg on Day 1.

Units	Counts

Secondary

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

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.

The pharmacokinetic analysis (PK) analysis set consisted of all subjects in the safety analysis set who received at least 1 dose of AZD7986 and had evaluable PK data.

Posted

Geometric Mean

Geometric Coefficient of Variation

h·nmol/L

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)

ID	Title	Description
OG000	AZD7986 35mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 35mg on Day 1 in fasted state.
OG001	AZD7986 35mg - Part 1b (Fed State) - SAD	Participants received single dose of oral solution of AZD7986 35mg on Day 1.

Units	Counts

Secondary

Effect of Food on Absorption AZD7986 by Assessment of the Observed Maximum Plasma Concentration (Cmax) for Part 1a and 1b - SAD

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

The pharmacokinetic analysis (PK) analysis set consisted of all subjects in the safety analysis set who received at least 1 dose of AZD7986 and had evaluable PK data.

Posted

Geometric Mean

Geometric Coefficient of Variation

nmol/L

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)

ID	Title	Description
OG000	AZD7986 35mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 35mg on Day 1 in fasted state.
OG001	AZD7986 35mg - Part 1b (Fed State) - SAD	Participants received single dose of oral solution of AZD7986 35mg on Day 1.

Units	Counts
Participants

Secondary

Effect of Food on Absorption AZD7986 by Assessment of the Time to Reach Maximum Observed Concentration (Tmax) for Part 1a and 1b - SAD

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

The pharmacokinetic analysis (PK) analysis set consisted of all subjects in the safety analysis set who received at least 1 dose of AZD7986 and had evaluable PK data.

Posted

Median

Full Range

Hour

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)

ID	Title	Description
OG000	AZD7986 35mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 35mg on Day 1 in fasted state.
OG001	AZD7986 35mg - Part 1b (Fed State) - SAD	Participants received single dose of oral solution of AZD7986 35mg on Day 1.

Units	Counts
Participants

Secondary

Effect of Food on Absorption AZD7986 by Assessment of the Apparent Terminal Elimination Half-life (t½.λz) for Part 1a and 1b - SAD

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

The pharmacokinetic analysis (PK) analysis set consisted of all subjects in the safety analysis set who received at least 1 dose of AZD7986 and had evaluable PK data.

Posted

Mean

Standard Deviation

Hour

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)

ID	Title	Description
OG000	AZD7986 35mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 35mg on Day 1 in fasted state.
OG001	AZD7986 35mg - Part 1b (Fed State) - SAD	Participants received single dose of oral solution of AZD7986 35mg on Day 1.

Units	Counts
Participants

Secondary

Effect of Food on Absorption AZD7986 by Assessment of the Mean Residence Time (MRT) for Part 1a and 1b - SAD

To assess the effect of food by evaluating the mean residence time (MRT) for Part 1a (fasted state) and 1b (fed state) - SAD

The pharmacokinetic analysis (PK) analysis set consisted of all subjects in the safety analysis set who received at least 1 dose of AZD7986 and had evaluable PK data.

Posted

Mean

Standard Deviation

Hour

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)

ID	Title	Description
OG000	AZD7986 35mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 35mg on Day 1 in fasted state.
OG001	AZD7986 35mg - Part 1b (Fed State) - SAD	Participants received single dose of oral solution of AZD7986 35mg on Day 1.

Units	Counts
Participants	OG000

Secondary

Effect of Food on Absorption AZD7986 by Assessment of the Apparent Clearance (CL/F) for Part 1a and 1b - SAD

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

The pharmacokinetic analysis (PK) analysis set consisted of all subjects in the safety analysis set who received at least 1 dose of AZD7986 and had evaluable PK data.

Posted

Mean

Standard Deviation

Litre/Hour

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)

ID	Title	Description
OG000	AZD7986 35mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 35mg on Day 1 in fasted state.
OG001	AZD7986 35mg - Part 1b (Fed State) - SAD	Participants received single dose of oral solution of AZD7986 35mg on Day 1.

Units	Counts
Participants

Secondary

Effect of Food on Absorption AZD7986 by Assessment of the Apparent Volume of Distribution (Vz/F) for Part 1a and 1b - SAD

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

The pharmacokinetic analysis (PK) analysis set consisted of all subjects in the safety analysis set who received at least 1 dose of AZD7986 and had evaluable PK data.

Posted

Mean

Standard Deviation

Litre

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)

ID	Title	Description
OG000	AZD7986 35mg - Part 1a (Fasted State) - SAD	Participants received single dose of oral solution of AZD7986 35mg on Day 1 in fasted state.
OG001	AZD7986 35mg - Part 1b (Fed State) - SAD	Participants received single dose of oral solution of AZD7986 35mg on Day 1.

Units	Counts
Participants

Secondary

Assessment of Mean Normalized Relative Neutrophil Elastase (NE) Activity in All Cohorts of Part 2

Absolute neutrophil count (ANC) was evaluated as part of the safety laboratory assessments and to evaluate the pharmacodynamics (PD) marker

All participants who receiving at least 1 dose of AZD7986 or placebo and who had at least 1 pre-dose and 1 post-dose measurement for either NE (NE1 or NE2), and who had no major protocol deviations thought to impact on the analysis of the PD data

Posted

Mean

Standard Deviation

Percentage change in NE activity

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

ID	Title	Description
OG000	AZD7986 10mg - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 10mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG001	AZD7986 25mg - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 25mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG002	AZD7986 40mg - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 40mg on Day 1 and daily dosing on Days 21 or 28 I fasted state.

Secondary

Assessment of Absolute Neutrophil Count (ANC) in All Cohorts of Part 2

Absolute neutrophil count (ANC) was evaluated as part of the safety laboratory assessments and to evaluate the pharmacodynamics (PD) marker

Posted

Mean

Standard Deviation

10^9 neutrophils/L

At Day 12 (pre-dose, 6 hours and 12 hours)

ID	Title	Description
OG000	AZD7986 10mg - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 10mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG001	AZD7986 25mg - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 25mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG002	AZD7986 40mg - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 40mg on Day 1 and daily dosing on Days 21 or 28 I fasted state.
OG003

Primary

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

To assess percentage of dose excreted unchanged into the urine from 0 to 24 hours (Cumfe0 24) for Part 2

The pharmacokinetic analysis (PK) analysis set consisted of all subjects in the safety analysis set who received at least 1 dose of AZD7986 and had evaluable PK data.

Posted

Mean

Standard Deviation

Percentage of dose excreted unchanged

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

ID	Title	Description
OG000	AZD7986 10mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 10mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG001	AZD7986 25mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 25mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG002	AZD7986 40mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 40mg on Day 1 and daily dosing on Days 21 or 28 I fasted state.

Primary

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

To assess renal clearance from 0 to 24 hours (CLR0-24) for Part 2

The pharmacokinetic analysis (PK) analysis set consisted of all subjects in the safety analysis set who received at least 1 dose of AZD7986 and had evaluable PK data.

Posted

Mean

Standard Deviation

Liter/hour

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

ID	Title	Description
OG000	AZD7986 10mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 10mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG001	AZD7986 25mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 25mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG002	AZD7986 40mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 40mg on Day 1 and daily dosing on Days 21 or 28 I fasted state.

Primary

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

To assess Cumulative amount of analyte excreted from 0 to 48 hours (CumAe0-48)) for Part 2

The pharmacokinetic analysis (PK) analysis set consisted of all subjects in the safety analysis set who received at least 1 dose of AZD7986 and had evaluable PK data.

Posted

Mean

Standard Deviation

nmol

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

ID	Title	Description
OG000	AZD7986 10mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 10mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG001	AZD7986 25mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 25mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG002	AZD7986 40mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 40mg on Day 1 and daily dosing on Days 21 or 28 I fasted state.

Primary

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

To assess Percentage of dose excreted unchanged into the urine from 0 to 48 hours (Cumfe0 48) for Part 2

The pharmacokinetic analysis (PK) analysis set consisted of all subjects in the safety analysis set who received at least 1 dose of AZD7986 and had evaluable PK data.

Posted

Mean

Standard Deviation

Percentage of dose excreted unchanged

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

ID	Title	Description
OG000	AZD7986 10mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 10mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG001	AZD7986 25mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 25mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG002	AZD7986 40mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 40mg on Day 1 and daily dosing on Days 21 or 28 I fasted state.

Primary

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

To assess Percentage of dose excreted unchanged into the urine from 0 to 48 hours (Cumfe0 48) for Part 2

The pharmacokinetic analysis (PK) analysis set consisted of all subjects in the safety analysis set who received at least 1 dose of AZD7986 and had evaluable PK data.

Posted

Mean

Standard Deviation

Liter/hour

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

ID	Title	Description
OG000	AZD7986 10mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 10mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG001	AZD7986 25mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 25mg on Day 1 and daily dosing on Days 21 or 28 in fasted state.
OG002	AZD7986 40mg - Day 1 - Part 2 - MAD	Participants received single dose of oral solution of AZD7986 40mg on Day 1 and daily dosing on Days 21 or 28 I fasted state.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain	Gastrointestinal disorders	MedDRA v19.0	Non-systematic Assessment	EG0001 affected30 at risk EG0010 affected5 at risk EG0020 affected24 at risk EG0031 affected15 at risk EG0040 affected3 at risk EG0050 affected12 at risk
Dry mouth	Gastrointestinal disorders	MedDRA v19.0	Non-systematic Assessment	EG0001 affected30 at risk EG0010 affected5 at risk EG0020 affected24 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA v19.0	Non-systematic Assessment	EG0001 affected30 at risk EG0010 affected5 at risk EG0020 affected24 at risk EG003
Rectal haemorrhage	Gastrointestinal disorders	MedDRA v19.0	Non-systematic Assessment	EG0001 affected30 at risk EG0010 affected5 at risk EG0020 affected24 at risk EG003
Gingival bleeding	Gastrointestinal disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0011 affected5 at risk EG0023 affected24 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0024 affected24 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0022 affected24 at risk EG003
Lip dry	Gastrointestinal disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0022 affected24 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0022 affected24 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0021 affected24 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0021 affected24 at risk EG003
Gingival pain	Gastrointestinal disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0021 affected24 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0021 affected24 at risk EG003
Aphthous ulcer	Gastrointestinal disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0020 affected24 at risk EG003
Headache	Nervous system disorders	MedDRA v19.0	Non-systematic Assessment	EG0003 affected30 at risk EG0012 affected5 at risk EG0026 affected24 at risk EG003
Dizziness	Nervous system disorders	MedDRA v19.0	Non-systematic Assessment	EG0001 affected30 at risk EG0010 affected5 at risk EG0022 affected24 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0020 affected24 at risk EG003
Dizziness postural	Nervous system disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0021 affected24 at risk EG003
Fatigue	General disorders	MedDRA v19.0	Non-systematic Assessment	EG0001 affected30 at risk EG0010 affected5 at risk EG0022 affected24 at risk EG003
Pain	General disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0022 affected24 at risk EG003
Axillary pain	General disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0021 affected24 at risk EG003
Catheter site related reaction	General disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0021 affected24 at risk EG003
Chest discomfort	General disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0021 affected24 at risk EG003
Asthenia	General disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0020 affected24 at risk EG003
Feeling hot	General disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0020 affected24 at risk EG003
Vessel puncture site pain	General disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0020 affected24 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA v19.0	Non-systematic Assessment	EG0001 affected30 at risk EG0010 affected5 at risk EG0023 affected24 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA v19.0	Non-systematic Assessment	EG0001 affected30 at risk EG0010 affected5 at risk EG0023 affected24 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0020 affected24 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0011 affected5 at risk EG0020 affected24 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0011 affected5 at risk EG0020 affected24 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0022 affected24 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0020 affected24 at risk EG003
Insomnia	Psychiatric disorders	MedDRA v19.0	Non-systematic Assessment	EG0001 affected30 at risk EG0010 affected5 at risk EG0020 affected24 at risk EG003
Skin irritation	Skin and subcutaneous tissue disorders	MedDRA v19.0	Non-systematic Assessment	EG0001 affected30 at risk EG0010 affected5 at risk EG0020 affected24 at risk EG003
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0011 affected5 at risk EG0022 affected24 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0023 affected24 at risk EG003
Dermatitis atopic	Skin and subcutaneous tissue disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0021 affected24 at risk EG003
Drug eruption	Skin and subcutaneous tissue disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0021 affected24 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0021 affected24 at risk EG003
Hyperkeratosis	Skin and subcutaneous tissue disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0021 affected24 at risk EG003
Skin exfoliation	Skin and subcutaneous tissue disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0021 affected24 at risk EG003
Skin hypertrophy	Skin and subcutaneous tissue disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0021 affected24 at risk EG003
Night sweats	Skin and subcutaneous tissue disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0020 affected24 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0020 affected24 at risk EG003
Palpitations	Cardiac disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0021 affected24 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0020 affected24 at risk EG003
Hot flush	Vascular disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0020 affected24 at risk EG003
Systolic hypertension	Vascular disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0020 affected24 at risk EG003
Weight decreased	Investigations	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0020 affected24 at risk EG003
Skin papilloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0021 affected24 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0020 affected24 at risk EG003
Seasonal allergy	Immune system disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0021 affected24 at risk EG003
Excessive cerumen production	Ear and labyrinth disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0021 affected24 at risk EG003
Laceration	Injury, poisoning and procedural complications	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0021 affected24 at risk EG003
Arthropod bite	General disorders	MedDRA v19.0	Non-systematic Assessment	EG0000 affected30 at risk EG0010 affected5 at risk EG0021 affected24 at risk EG003

ID	Term
C000619932	brensocatib
D012996	Solutions

ID	Title	Description	Deaths (At Risk)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.	30	30	8	30
EG001	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.	5	5	2	5
EG002	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.	24	24	23	24
EG003	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	15	15	8	15
EG004	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.	3	3	1	3
EG005	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.	12	12	8	12