Trial Outcomes & Findings for A Study to Evaluate the Effect of the Experimental GLP-1 Drug PF-07081532 on Blood Levels of Common Birth Control Pills, and Drugs Omeprazole and Midazolam, and Effect of GLP-1 Drug Semaglutide on Midazolam Blood Levels in Healthy Adults With Weight in the Obesity Range (NCT NCT05671653)

Last Updated: 2025-01-14

Results Overview

Midazolam was given on Day 1 in Period 1, 4, 7 of Cohort 1 and blood samples were collected for midazolam pharmacokinetic (PK) at the preset time points described in the Time Frame. AUCinf calculated area under the plasma concentration-time profile from time 0 extrapolated to infinite time.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

32 participants

Primary outcome timeframe

For Cohort 1 Periods 1, 4, and 7: At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period

Results posted on

2025-01-14

Participant Flow

This study was a Phase 1, open-label, fixed-sequence study conducted with 2 cohorts. 16 participants were enrolled in Cohort 1 with 9 periods, 16 participants were enrolled in Cohort 2 with 4 periods.

Participant milestones

Participant milestones
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2) Participants in Cohort 1 received SD of levonorgestrel (LE) 0.15 mg and ethinyl estradiol (EE) 0.03 mg on Day 1 of Period 2.	Cohort 1: PF-07081532 Titration up to 80 mg QD (Period 3) Participants in Cohort 1 received PF-07081532 20 mg once daily (QD) on Day 1-7, 40 mg QD on Day 8-14, 60 mg QD on Day 15-21, 80 mg QD on Day 22-28 of Period 3.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD+ LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.	Cohort 2: Midazolam 2 mg (Period 1) Participants in Cohort 2 received SD of midazolam 2 mg on Day 1 of Period 1.	Cohort 2: Semaglutide Titration up to 2.4 mg QW (Period 2) Participants in Cohort 2 received semaglutide 0.25 mg once weekly (QW) on Week 1-4, 0.5 mg QW on Week 5-8, 1.0 mg QW on Week 9-12, 1.7 mg QW on Week 13-16, 2.4 mg QW on Week 17-21 of Period 2.	Cohort 2: Semaglutide 2.4 mg QW + Midazolam 2 mg (Period 3) Participants in Cohort 2 received semaglutide 2.4 mg QW and SD of midazolam 2 mg on Day 1 of Period 3.	Cohort 2: Midazolam 2 mg (Period 4) Participants in Cohort 2 received SD of midazolam 2 mg on Day 1 of Period 4.
Cohort 1 Period 1 - Treatment STARTED	16	0	0	0	0	0	0	0	0	0	0	0	0
Cohort 1 Period 1 - Treatment COMPLETED	16	0	0	0	0	0	0	0	0	0	0	0	0
Cohort 1 Period 1 - Treatment NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0
Cohort 1 Period 2 - Treatment STARTED	0	16	0	0	0	0	0	0	0	0	0	0	0
Cohort 1 Period 2 - Treatment COMPLETED	0	16	0	0	0	0	0	0	0	0	0	0	0
Cohort 1 Period 2 - Treatment NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0
Cohort 1 Period 3 - Treatment STARTED	0	0	16	0	0	0	0	0	0	0	0	0	0
Cohort 1 Period 3 - Treatment COMPLETED	0	0	16	0	0	0	0	0	0	0	0	0	0
Cohort 1 Period 3 - Treatment NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0
Cohort 1 Period 4 - Treatment STARTED	0	0	0	16	0	0	0	0	0	0	0	0	0
Cohort 1 Period 4 - Treatment COMPLETED	0	0	0	16	0	0	0	0	0	0	0	0	0
Cohort 1 Period 4 - Treatment NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0
Cohort 1 Period 5 - Treatment STARTED	0	0	0	0	16	0	0	0	0	0	0	0	0
Cohort 1 Period 5 - Treatment COMPLETED	0	0	0	0	16	0	0	0	0	0	0	0	0
Cohort 1 Period 5 - Treatment NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0
Cohort 1 Period 6 - Treatment STARTED	0	0	0	0	0	16	0	0	0	0	0	0	0
Cohort 1 Period 6 - Treatment COMPLETED	0	0	0	0	0	8	0	0	0	0	0	0	0
Cohort 1 Period 6 - Treatment NOT COMPLETED	0	0	0	0	0	8	0	0	0	0	0	0	0
Cohort 1 Period 7 - Treatment STARTED	0	0	0	0	0	0	8	0	0	0	0	0	0
Cohort 1 Period 7 - Treatment COMPLETED	0	0	0	0	0	0	8	0	0	0	0	0	0
Cohort 1 Period 7 - Treatment NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0
Cohort 1 Period 8 - Treatment STARTED	0	0	0	0	0	0	0	7	0	0	0	0	0
Cohort 1 Period 8 - Treatment COMPLETED	0	0	0	0	0	0	0	7	0	0	0	0	0
Cohort 1 Period 8 - Treatment NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0
Cohort 1 Period 9 - Treatment STARTED	0	0	0	0	0	0	0	0	8	0	0	0	0
Cohort 1 Period 9 - Treatment COMPLETED	0	0	0	0	0	0	0	0	7	0	0	0	0
Cohort 1 Period 9 - Treatment NOT COMPLETED	0	0	0	0	0	0	0	0	1	0	0	0	0
Cohort 2 Period 1 - Treatment STARTED	0	0	0	0	0	0	0	0	0	16	0	0	0
Cohort 2 Period 1 - Treatment COMPLETED	0	0	0	0	0	0	0	0	0	16	0	0	0
Cohort 2 Period 1 - Treatment NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0
Cohort 2 Period 2 STARTED	0	0	0	0	0	0	0	0	0	0	16	0	0
Cohort 2 Period 2 COMPLETED	0	0	0	0	0	0	0	0	0	0	11	0	0
Cohort 2 Period 2 NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	5	0	0
Cohort 2 Period 3 - Treatment STARTED	0	0	0	0	0	0	0	0	0	0	0	11	0
Cohort 2 Period 3 - Treatment COMPLETED	0	0	0	0	0	0	0	0	0	0	0	10	0
Cohort 2 Period 3 - Treatment NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	1	0
Cohort 2 Period 4 - Treatment STARTED	0	0	0	0	0	0	0	0	0	0	0	0	10
Cohort 2 Period 4 - Treatment COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	10
Cohort 2 Period 4 - Treatment NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.	Cohort 2: Semaglutide Titration up to 2.4 mg QW (Period 2) Participants in Cohort 2 received semaglutide 0.25 mg once weekly (QW) on Week 1-4, 0.5 mg QW on Week 5-8, 1.0 mg QW on Week 9-12, 1.7 mg QW on Week 13-16, 2.4 mg QW on Week 17-21 of Period 2.	Cohort 2: Semaglutide 2.4 mg QW + Midazolam 2 mg (Period 3) Participants in Cohort 2 received semaglutide 2.4 mg QW and SD of midazolam 2 mg on Day 1 of Period 3.
Cohort 1 Period 6 - Treatment Other	1	0	0	0
Cohort 1 Period 6 - Treatment Study Terminated by Sponsor	5	0	0	0
Cohort 1 Period 6 - Treatment Adverse Event	2	0	0	0
Cohort 1 Period 9 - Treatment Adverse Event	0	1	0	0
Cohort 2 Period 2 Adverse Event	0	0	1	0
Cohort 2 Period 2 Lost to Follow-up	0	0	1	0
Cohort 2 Period 2 Pregnancy	0	0	1	0
Cohort 2 Period 2 Withdrawal by Subject	0	0	1	0
Cohort 2 Period 2 Other	0	0	1	0
Cohort 2 Period 3 - Treatment Adverse Event	0	0	0	1

Baseline Characteristics

A Study to Evaluate the Effect of the Experimental GLP-1 Drug PF-07081532 on Blood Levels of Common Birth Control Pills, and Drugs Omeprazole and Midazolam, and Effect of GLP-1 Drug Semaglutide on Midazolam Blood Levels in Healthy Adults With Weight in the Obesity Range

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 n=16 Participants Reporting Group Description	Cohort 2 n=16 Participants Reporting Group Description	Total n=32 Participants Total of all reporting groups
Age, Continuous Mean (SD)	50.8125 Years STANDARD_DEVIATION 13.47 • n=5 Participants	48.125 Years STANDARD_DEVIATION 13.67 • n=7 Participants	49.46875 Years STANDARD_DEVIATION 13.42 • n=5 Participants
Age, Customized <18 Years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Customized 18-25 Years	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Age, Customized 26-35 Years	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Age, Customized 36-45 Years	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Age, Customized >45 Years	11 Participants n=5 Participants	8 Participants n=7 Participants	19 Participants n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	16 Participants n=7 Participants	32 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	11 Participants n=5 Participants	10 Participants n=7 Participants	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Multiracial	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: For Cohort 1 Periods 1, 4, and 7: At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period

Population: Participants who received at least 1 dose of midazolam, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=16 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=13 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) n=8 Participants Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 1: Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Midazolam in Periods 1, 4 and 7	39.27 nanogramhour/milliliter (nghr/mL) Geometric Coefficient of Variation 33	33.30 nanogramhour/milliliter (nghr/mL) Geometric Coefficient of Variation 37	28.23 nanogramhour/milliliter (nghr/mL) Geometric Coefficient of Variation 49	—	—	—	—	—	—

PRIMARY outcome

Timeframe: For Cohort 1 Periods 1, 4, and 7: At 0 (prior to omeprazole dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period

Population: Participants who received at least 1 dose of omeprazole, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

Omeprazole was given on Day 1 in Period 1, 4, 7 of Cohort 1 and blood samples were collected for omeprazole PK at the preset time points described in the Time Frame. AUClast calculated area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=13 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=9 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) n=6 Participants Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 1: Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Omeprazole in Periods 1, 4 and 7	956.3 ng*hr/mL Geometric Coefficient of Variation 90	620.5 ng*hr/mL Geometric Coefficient of Variation 174	602.8 ng*hr/mL Geometric Coefficient of Variation 154	—	—	—	—	—	—

PRIMARY outcome

Timeframe: For Cohort 1 Periods 2, 5, and 8: At 0 (prior to LE dose), 0.75, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post LE dose on Day 1 of each period

Population: Participants who received at least 1 dose of LE, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

LE was given on Day 1 in Period 2, 5, 8 of Cohort 1 and blood samples were collected for LE PK at the preset time points described in the Time Frame. AUClast calculated area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=14 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=16 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) n=6 Participants Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 1: AUClast of Levonorgestrel (LE) in Periods 2, 5,and 8	31360 picogramhour/milliliter (pghr/mL) Geometric Coefficient of Variation 52	42120 picogramhour/milliliter (pghr/mL) Geometric Coefficient of Variation 56	60020 picogramhour/milliliter (pghr/mL) Geometric Coefficient of Variation 63	—	—	—	—	—	—

PRIMARY outcome

Timeframe: For Cohort 1 Periods 2, 5, and 8: At 0 (prior to EE dose), 0.75, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post LE dose on Day 1 of each period

Population: Participants who received at least 1 dose of EE, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

EE was given on Day 1 in Period 2, 5, 8 of Cohort 1 and blood samples were collected for EE PK at the preset time points described in the Time Frame. AUCinf calculated area under the plasma concentration-time profile from time 0 extrapolated to infinite time.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=16 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=15 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) n=6 Participants Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 1: AUCinf of Ethinyl Estradiol (EE) in Periods 2, 5,and 8	754.5 pg*hr/mL Geometric Coefficient of Variation 37	765.5 pg*hr/mL Geometric Coefficient of Variation 26	701.1 pg*hr/mL Geometric Coefficient of Variation 29	—	—	—	—	—	—

PRIMARY outcome

Timeframe: For Cohort 2 Periods 1 and 3: At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period

Population: Participants who received at least 1 dose of midazolam, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

Midazolam was given on Day 1 in Period 1 and 3 of Cohort 2 and blood samples were collected for midazolam pharmacokinetic (PK) at the preset time points described in the Time Frame. AUCinf calculated area under the plasma concentration-time profile from time 0 extrapolated to infinite time.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=15 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=11 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 2: AUCinf of Midazolam in Period 1 and 3	34.43 ng*hr/mL Geometric Coefficient of Variation 43	34.60 ng*hr/mL Geometric Coefficient of Variation 48	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1

Population: All participants randomly assigned to study intervention and who took at least 1 dose of study intervention.

An adverse event (AE) was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. Treatment-related AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. Relatedness to study treatment was assessed by the investigator. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent events were events between first dose of study treatment and up to approximately 35 days that were absent before treatment or that worsened relative to pretreatment state.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=16 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=16 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) n=16 Participants Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=16 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) n=16 Participants Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) n=16 Participants Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) n=8 Participants Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) n=7 Participants Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) n=8 Participants Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs Number of participants with all-causality SAEs	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs Number of participants with all-causality TEAEs	1 Participants	2 Participants	14 Participants	2 Participants	6 Participants	15 Participants	1 Participants	2 Participants	2 Participants
Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs Number of participants with treatment-related TEAEs	0 Participants	1 Participants	14 Participants	2 Participants	5 Participants	15 Participants	1 Participants	2 Participants	2 Participants
Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs Number of participants with treatment-related SAEs	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1

Population: All participants randomly assigned to study intervention and who took at least 1 dose of study intervention.

Laboratory tests (including hematology, clinical chemistry, urinalysis) were reported and abnormalities were defined for laboratory values that met specific criteria.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=16 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=16 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) n=16 Participants Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=16 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) n=16 Participants Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) n=16 Participants Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) n=8 Participants Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) n=7 Participants Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) n=8 Participants Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 1: Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)	0 Participants	0 Participants	9 Participants	0 Participants	3 Participants	14 Participants	3 Participants	6 Participants	7 Participants

SECONDARY outcome

Timeframe: From baseline (last pre-dose measurement in Period 1) to Period 9 Day 1 (Day 124)

Population: All participants randomly assigned to study intervention and who took at least 1 dose of study intervention.

Percentage of changes from Baseline in body weight of the participants were measured.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=16 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 1: Percentage of Change From Baseline in Body Weight by Period 9 Day 1	-8.55 Percentage Change Interval -13.0 to -7.1	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Screening, Study Day -1 (D-1) (ie, Period 1 Day -1 [P1D-1]), D7 (P3D1), D21 (P3D15), D35 (P4D1), D54 (P6D14), D68 (P6D28), D82 (P6D42), D96 (P6D56), D103 (P6D63), D110 (P8D6) and at follow up visit D132-135

Population: All participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants with evaluable C-SSRS results were analyzed.

The C-SSRS is an interview-based rating scale to systematically assess suicidal ideation and suicidal behavior. C-SSRS items were mapped to the following categories: completed suicide, suicide attempt, preparatory acts towards imminent suicidal behavior, suicidal ideation, and self-injurious behavior of no suicidal intent. Number of participants with completed suicide, suicide attempt, preparatory acts towards imminent suicidal behavior, suicidal ideation, or self-injurious behavior of no suicidal intent as assessed on the C-SSRS are reported below.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=16 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 1: Number of Participants With Completed Suicide, Suicide Attempt, Preparatory Acts Towards Imminent Suicidal Behavior, Suicidal Ideation, or Self-Injurious Behavior of No Suicidal Intent As Assessed on the C-SSRS	0 Participants	—	—	—	—	—	—	—	—

SECONDARY outcome

Population: All participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants with evaluable PHQ-9 results were analyzed.

The PHQ-9 is a 9 item self-report scale for the assessment of depressive symptoms. The PHQ-9 is completed by participants and reviewed by site staff at the pre-defined time points. The total score is derived by adding the corresponding values of responses to each item. The total score ranges from 0 to 27, with the following interpretation: 1-4: Minimal depression; 5-9: Mild depression; 10-14: Moderate depression; 15-19: Moderately severe depression; 20-27: Severe depression.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=16 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 1: Patient Health Quessionare-9 (PHQ-9) Total Scores Screening	0.3 Score Standard Deviation 0.79	—	—	—	—	—	—	—	—
Cohort 1: Patient Health Quessionare-9 (PHQ-9) Total Scores Period 1 Day -1 / Midazolam 2 mg + Omeprazole 20 mg	0.1 Score Standard Deviation 0.34	—	—	—	—	—	—	—	—
Cohort 1: Patient Health Quessionare-9 (PHQ-9) Total Scores Period 3 Day 1 / PF-07081532 titration up to 80 mg QD	0.1 Score Standard Deviation 0.25	—	—	—	—	—	—	—	—
Cohort 1: Patient Health Quessionare-9 (PHQ-9) Total Scores Period 3 Day 15 / PF-07081532 titration up to 80 mg QD	1.1 Score Standard Deviation 2.42	—	—	—	—	—	—	—	—
Cohort 1: Patient Health Quessionare-9 (PHQ-9) Total Scores Period 4 Day 1 / PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg	1.0 Score Standard Deviation 2.63	—	—	—	—	—	—	—	—
Cohort 1: Patient Health Quessionare-9 (PHQ-9) Total Scores Period 6 Day 14 / PF-07081532 titration up to 260 mg QD	1.6 Score Standard Deviation 4.32	—	—	—	—	—	—	—	—
Cohort 1: Patient Health Quessionare-9 (PHQ-9) Total Scores Period 6 Day 28 / PF-07081532 titration up to 260 mg QD	0.6 Score Standard Deviation 1.12	—	—	—	—	—	—	—	—
Cohort 1: Patient Health Quessionare-9 (PHQ-9) Total Scores Period 6 Day 42 / PF-07081532 titration up to 260 mg QD	0.8 Score Standard Deviation 1.63	—	—	—	—	—	—	—	—
Cohort 1: Patient Health Quessionare-9 (PHQ-9) Total Scores Period 6 Day 56 / PF-07081532 titration up to 260 mg QD	1.1 Score Standard Deviation 1.92	—	—	—	—	—	—	—	—
Cohort 1: Patient Health Quessionare-9 (PHQ-9) Total Scores Period 6 Day 63 / PF-07081532 titration up to 260 mg QD	0.9 Score Standard Deviation 1.64	—	—	—	—	—	—	—	—
Cohort 1: Patient Health Quessionare-9 (PHQ-9) Total Scores Period 8 Day 6 / PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg	0.8 Score Standard Deviation 1.39	—	—	—	—	—	—	—	—
Cohort 1: Patient Health Quessionare-9 (PHQ-9) Total Scores Follow Up	0.1 Score Standard Deviation 0.26	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: For Cohort 1 Period 9: At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1

Population: Participants who received at least 1 dose of midazolam, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

Midazolam was given on Day 1 in Period 9 of Cohort 1 and blood samples were collected for midazolam pharmacokinetic (PK) at the preset time points described in the Time Frame. AUCinf calculated area under the plasma concentration-time profile from time 0 extrapolated to infinite time.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=8 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 1: AUCinf of Midazolam in Period 9	39.80 ng*hr/mL Geometric Coefficient of Variation 35	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: For Cohort 1 Periods 1, 4, and 7: At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period

Population: Participants who received at least 1 dose of midazolam, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

Midazolam was given on Day 1 in Period 1, 4, 7 of Cohort 1 and blood samples were collected for midazolam PK at the preset time points described in the Time Frame. Cmax was defined as maximum observed concentration and was observed directly from data.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=16 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=15 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) n=8 Participants Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 1: Maximum Observed Concentration (Cmax) of Midazolam in Period 1, 4, 7	6.613 ng/mL Geometric Coefficient of Variation 38	6.705 ng/mL Geometric Coefficient of Variation 47	6.804 ng/mL Geometric Coefficient of Variation 50	—	—	—	—	—	—

SECONDARY outcome

Timeframe: For Cohort 1 Periods 1, 4, and 7: At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period

Population: Participants who received at least 1 dose of midazolam, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

Midazolam was given on Day 1 in Period 1, 4, 7 of Cohort 1 and blood samples were collected for midazolam PK at the preset time points described in the Time Frame. Tmax was defined as time for Cmax and was observed directly from data.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=16 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=15 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) n=8 Participants Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 1: Time for Cmax (Tmax) of Midazolam in Period 1, 4, 7	1.50 hour Interval 0.5 to 3.0	0.500 hour Interval 0.5 to 2.0	0.767 hour Interval 0.5 to 2.0	—	—	—	—	—	—

SECONDARY outcome

Timeframe: For Cohort 1 Periods 1, 4, and 7: At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period

Population: Participants who received at least 1 dose of midazolam, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

Midazolam was given on Day 1 in Period 1, 4, 7 of Cohort 1 and blood samples were collected for midazolam PK at the preset time points described in the Time Frame. CL/F was defined as apparent clearance and was calculated as dose/AUCinf.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=16 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=13 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) n=8 Participants Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 1: Apparent Clearance (CL/F) of Midazolam in Period 1, 4, 7	50.94 L/hr Geometric Coefficient of Variation 33	60.08 L/hr Geometric Coefficient of Variation 38	70.91 L/hr Geometric Coefficient of Variation 49	—	—	—	—	—	—

SECONDARY outcome

Timeframe: For Cohort 1 Periods 1, 4, and 7: At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period

Population: Participants who received at least 1 dose of midazolam, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

Midazolam was given on Day 1 in Period 1, 4, 7 of Cohort 1 and blood samples were collected for midazolam PK at the preset time points described in the Time Frame. Vz/F was defined as apparent volume of distribution and was calculated as dose/(AUCinf\*kel), where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=16 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=13 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) n=8 Participants Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 1: Apparent Volume of Distribution (Vz/F) of Midazolam in Period 1, 4, 7	544.9 Liter (L) Geometric Coefficient of Variation 30	605.3 Liter (L) Geometric Coefficient of Variation 28	664.5 Liter (L) Geometric Coefficient of Variation 32	—	—	—	—	—	—

SECONDARY outcome

Timeframe: For Cohort 1 Periods 1, 4, and 7: At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period

Population: Participants who received at least 1 dose of midazolam, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

Midazolam was given on Day 1 in Period 1, 4, 7 of Cohort 1 and blood samples were collected for midazolam PK at the preset time points described in the Time Frame. t1/2 was defined as terminal half life and was calculated as loge(2)/kel.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=16 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=13 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) n=8 Participants Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 1: Terminal Half-Life (t1/2) of Midazolam in Period 1, 4, 7	7.539 hour Standard Deviation 1.4445	7.078 hour Standard Deviation 1.2904	6.659 hour Standard Deviation 1.5587	—	—	—	—	—	—

SECONDARY outcome

Timeframe: For Cohort 1 Periods 1, 4, and 7: At 0 (prior to omeprazole dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period

Population: Participants who received at least 1 dose of omeprazole, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

Omeprazole was given on Day 1 in Period 1, 4, 7 of Cohort 1 and blood samples were collected for omeprazole PK at the preset time points described in the Time Frame. Cmax was defined as maximum observed concentration and was observed directly from data.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=16 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=15 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) n=8 Participants Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 1: Cmax of Omeprazole in Period 1, 4, 7	266.4 ng/mL Geometric Coefficient of Variation 112	88.42 ng/mL Geometric Coefficient of Variation 271	169.9 ng/mL Geometric Coefficient of Variation 209	—	—	—	—	—	—

SECONDARY outcome

Timeframe: For Cohort 1 Periods 1, 4, and 7: At 0 (prior to omeprazole dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period

Population: Participants who received at least 1 dose of omeprazole, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

Omeprazole was given on Day 1 in Period 1, 4, 7 of Cohort 1 and blood samples were collected for omeprazole PK at the preset time points described in the Time Frame. Tmax was defined as time for Cmax and was observed directly from data.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=16 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=15 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) n=8 Participants Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 1: Tmax of Omeprazole in Period 1, 4, 7	5.99 hour Interval 2.0 to 14.3	8.33 hour Interval 4.0 to 23.4	11.1 hour Interval 6.0 to 23.4	—	—	—	—	—	—

SECONDARY outcome

Timeframe: For Cohort 1 Periods 1, 4, and 7: At 0 (prior to omeprazole dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period

Population: Participants who received at least 1 dose of omeprazole, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

Omeprazole was given on Day 1 in Period 1, 4, 7 of Cohort 1 and blood samples were collected for omeprazole PK at the preset time points described in the Time Frame. CL/F was defined as apparent clearance and was calculated as dose/AUCinf.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=10 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=6 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) n=3 Participants Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 1: CL/F of Omeprazole in Period 1, 4, 7	17.19 L/hr Geometric Coefficient of Variation 92	21.43 L/hr Geometric Coefficient of Variation 198	17.26 L/hr Geometric Coefficient of Variation 118	—	—	—	—	—	—

SECONDARY outcome

Timeframe: For Cohort 1 Periods 1, 4, and 7: At 0 (prior to omeprazole dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period

Population: Participants who received at least 1 dose of omeprazole, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

Omeprazole was given on Day 1 in Period 1, 4, 7 of Cohort 1 and blood samples were collected for omeprazole PK at the preset time points described in the Time Frame. Vz/F was defined as apparent volume of distribution and was calculated as dose/(AUCinf\*kel), where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=10 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=6 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) n=3 Participants Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 1: Vz/F of Omeprazole in Period 1, 4, 7	41.26 L Geometric Coefficient of Variation 69	49.81 L Geometric Coefficient of Variation 150	44.48 L Geometric Coefficient of Variation 109	—	—	—	—	—	—

SECONDARY outcome

Timeframe: For Cohort 1 Periods 1, 4, and 7: At 0 (prior to omeprazole dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period

Population: Participants who received at least 1 dose of omeprazole, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

Omeprazole was given on Day 1 in Period 1, 4, 7 of Cohort 1 and blood samples were collected for omeprazole PK at the preset time points described in the Time Frame. Vz/F was defined as apparent volume of distribution and was calculated as dose/(AUCinf ×kel), where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=10 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=6 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) n=3 Participants Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 1: t1/2 of Omeprazole in Period 1, 4, 7	1.793 hour Standard Deviation 0.77789	1.705 hour Standard Deviation 0.65741	1.800 hour Standard Deviation 0.28355	—	—	—	—	—	—

SECONDARY outcome

Timeframe: For Cohort 1 Periods 2, 5, and 8: At 0 (prior to LE dose), 0.75, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post LE dose on Day 1 of each period

Population: Participants who received at least 1 dose of LE, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

LE was given on Day 1 in Period 2, 5, 8 of Cohort 1 and blood samples were collected for LE PK at the preset time points described in the Time Frame. Cmax was defined as maximum observed concentration and was observed directly from data.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=15 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=16 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) n=6 Participants Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 1: Cmax of LE in Period 2, 5, 8	1919 pg/mL Geometric Coefficient of Variation 45	1532 pg/mL Geometric Coefficient of Variation 41	1684 pg/mL Geometric Coefficient of Variation 82	—	—	—	—	—	—

SECONDARY outcome

Timeframe: For Cohort 1 Periods 2, 5, and 8: At 0 (prior to LE dose), 0.75, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post LE dose on Day 1 of each period

Population: Participants who received at least 1 dose of LE, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=15 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=16 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) n=6 Participants Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 1: Tmax of LE in Period 2, 5, 8	2.00 hour Interval 0.75 to 4.0	3.02 hour Interval 0.75 to 12.0	4.10 hour Interval 0.75 to 23.5	—	—	—	—	—	—

SECONDARY outcome

Timeframe: For Cohort 1 Periods 2, 5, and 8: At 0 (prior to LE dose), 0.75, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post LE dose on Day 1 of each period

Population: Participants who received at least 1 dose of LE, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=7 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=10 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) n=5 Participants Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 1: CL/F of LE in Period 2, 5, 8	6.043 L/hr Geometric Coefficient of Variation 51	3.887 L/hr Geometric Coefficient of Variation 52	2.265 L/hr Geometric Coefficient of Variation 54	—	—	—	—	—	—

SECONDARY outcome

Timeframe: For Cohort 1 Periods 2, 5, and 8: At 0 (prior to LE dose), 0.75, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post LE dose on Day 1 of each period

Population: Participants who received at least 1 dose of LE, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

LE was given on Day 1 in Period 2, 5, 8 of Cohort 1 and blood samples were collected for LE PK at the preset time points described in the Time Frame. Vz/F was defined as apparent volume of distribution and was calculated as dose/(AUCinf\*kel), where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=7 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=10 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) n=5 Participants Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 1: Vz/F of LE in Period 2, 5, 8	380.0 L Geometric Coefficient of Variation 44	251.7 L Geometric Coefficient of Variation 45	133.6 L Geometric Coefficient of Variation 55	—	—	—	—	—	—

SECONDARY outcome

Timeframe: For Cohort 1 Periods 2, 5, and 8: At 0 (prior to LE dose), 0.75, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post LE dose on Day 1 of each period

Population: Participants who received at least 1 dose of LE, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

LE was given on Day 1 in Period 2, 5, 8 of Cohort 1 and blood samples were collected for LE PK at the preset time points described in the Time Frame. t1/2 was defined as terminal half life and was calculated as loge(2)/kel.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=7 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=10 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) n=5 Participants Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 1: t1/2 of LE in Period 2, 5, 8	44.33 hour Standard Deviation 8.7994	45.25 hour Standard Deviation 5.9429	41.26 hour Standard Deviation 5.7709	—	—	—	—	—	—

SECONDARY outcome

Timeframe: For Cohort 1 Periods 2, 5, and 8: At 0 (prior to EE dose), 0.75, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post LE dose on Day 1 of each period

Population: Participants who received at least 1 dose of EE, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

EE was given on Day 1 in Period 2, 5, 8 of Cohort 1 and blood samples were collected for EE PK at the preset time points described in the Time Frame. Cmax was defined as maximum observed concentration and was observed directly from data.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=16 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=16 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) n=7 Participants Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 1: Cmax of EE in Period 2, 5, 8	42.44 pg/mL Geometric Coefficient of Variation 33	37.82 pg/mL Geometric Coefficient of Variation 35	34.03 pg/mL Geometric Coefficient of Variation 30	—	—	—	—	—	—

SECONDARY outcome

Timeframe: For Cohort 1 Periods 2, 5, and 8: At 0 (prior to EE dose), 0.75, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post LE dose on Day 1 of each period

Population: Participants who received at least 1 dose of EE, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

EE was given on Day 1 in Period 2, 5, 8 of Cohort 1 and blood samples were collected for EE PK at the preset time points described in the Time Frame. Tmax was defined as time for Cmax and was observed directly from data.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=16 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=16 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) n=7 Participants Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 1: Tmax of EE in Period 2, 5, 8	2.00 hour Interval 0.75 to 4.0	2.00 hour Interval 0.75 to 8.0	2.00 hour Interval 0.75 to 4.2	—	—	—	—	—	—

SECONDARY outcome

Timeframe: For Cohort 1 Periods 2, 5, and 8: At 0 (prior to EE dose), 0.75, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post LE dose on Day 1 of each period

Population: Participants who received at least 1 dose of EE, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

EE was given on Day 1 in Period 2, 5, 8 of Cohort 1 and blood samples were collected for EE PK at the preset time points described in the Time Frame. CL/F was defined as apparent clearance and was calculated as dose/AUCinf.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=16 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=15 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) n=6 Participants Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 1: CL/F of EE in Period 2, 5, 8	238.6 L/hr Geometric Coefficient of Variation 37	235.3 L/hr Geometric Coefficient of Variation 26	256.9 L/hr Geometric Coefficient of Variation 29	—	—	—	—	—	—

SECONDARY outcome

Timeframe: For Cohort 1 Periods 2, 5, and 8: At 0 (prior to EE dose), 0.75, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post LE dose on Day 1 of each period

Population: Participants who received at least 1 dose of EE, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

EE was given on Day 1 in Period 2, 5, 8 of Cohort 1 and blood samples were collected for EE PK at the preset time points described in the Time Frame. Vz/F was defined as apparent volume of distribution and was calculated as dose/(AUCinf\*kel), where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=16 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=15 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) n=6 Participants Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 1: Vz/F of EE in Period 2, 5, 8	7565 L Geometric Coefficient of Variation 32	8517 L Geometric Coefficient of Variation 34	7998 L Geometric Coefficient of Variation 25	—	—	—	—	—	—

SECONDARY outcome

Timeframe: For Cohort 1 Periods 2, 5, and 8: At 0 (prior to EE dose), 0.75, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post LE dose on Day 1 of each period

Population: Participants who received at least 1 dose of EE, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

EE was given on Day 1 in Period 2, 5, 8 of Cohort 1 and blood samples were collected for EE PK at the preset time points described in the Time Frame. t1/2 was defined as terminal half life and was calculated as loge(2)/kel.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=16 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=15 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) n=6 Participants Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 1: t1/2 of EE in Period 2, 5, 8	22.42 hour Standard Deviation 4.5451	25.54 hour Standard Deviation 4.8147	22.03 hour Standard Deviation 4.5676	—	—	—	—	—	—

SECONDARY outcome

Timeframe: For Cohort 1 Periods 1, 4, and 7: At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period

Population: Participants who received at least 1 dose of midazolam, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

Midazolam was given on Day 1 in Period 1, 4, 7 of Cohort 1 and blood samples were collected for midazolam (parent) and and its metabolite 1-Hydroxy Midazolam PK at the preset time points described in the Time Frame. MRAUCinf was calculated as (AUCinf, metabolite/AUCinf, parent) \* (MWparent/MWmetabolite). MW = molecular weight.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=12 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=11 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) n=8 Participants Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 1: Metabolite/Parent Ratio for AUCinf (MRAUCinf) of 1-Hydroxy Midazolam in Period 1, 4, 7	0.3143 Ratio Geometric Coefficient of Variation 24	0.4480 Ratio Geometric Coefficient of Variation 39	0.4314 Ratio Geometric Coefficient of Variation 49	—	—	—	—	—	—

SECONDARY outcome

Timeframe: For Cohort 1 Periods 1, 4, and 7: At 0 (prior to omeprazole dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period

Population: Participants who received at least 1 dose of omeprazole, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

Omeprazole was given on Day 1 in Period 1, 4, 7 of Cohort 1 and blood samples were collected for omeprazole (parent) and and its metabolite 5-Hydroxy omeprazole PK at the preset time points described in the Time Frame. MRAUCinf was calculated as (AUCinf, metabolite/AUCinf, parent) \* (MWparent/MWmetabolite). MW = molecular weight.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=10 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=6 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) n=3 Participants Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 1: MRAUCinf of 5-Hydroxy Omeprazole in Period 1, 4, 7	0.3752 Ratio Geometric Coefficient of Variation 93	0.4060 Ratio Geometric Coefficient of Variation 136	0.3790 Ratio Geometric Coefficient of Variation 39	—	—	—	—	—	—

SECONDARY outcome

Timeframe: For Cohort 1 Periods 3 and 6: At 0 , 0.5, 1, 2, 4, 6, 8, 10, 14, and 24 hours post PF-07081532 dose on Day 28 of Period 3 and Day 63 of Period 6

Population: Participants who received at least 1 dose of PF-07081532, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

PF-07081532 was given titrated to 80 mg QD on Day 1-28 of Period 3, and titrated to 260 mg QD on Day 1-63 of Period 6 in Cohort 1, and blood samples were collected for PF-07081532 PK at the preset time points described in the Time Frame. AUC24 was defined as area under the plasma concentration-time profile from time 0 to 24 hours and was determined using the linear/log trapezoidal method.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=15 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=8 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 1: Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours (AUC24) of PF-07081532 in Period 3 and 6	250200 ng*hr/mL Geometric Coefficient of Variation 31	1239000 ng*hr/mL Geometric Coefficient of Variation 49	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: For Cohort 1 Periods 3 and 6: At 0 , 0.5, 1, 2, 4, 6, 8, 10, 14, and 24 hours post PF-07081532 dose on Day 28 of Period 3 and Day 63 of Period 6

Population: Participants who received at least 1 dose of PF-07081532, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

PF-07081532 was given titrated to 80 mg QD on Day 1-28 of Period 3, and titrated to 260 mg QD on Day 1-63 of Period 6 in Cohort 1, and blood samples were collected for PF-07081532 PK at the preset time points described in the Time Frame. Cmax was defined as maximum observed concentration and was observed directly from data.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=15 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=8 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 1: Cmax of PF-07081532 in Period 3 and 6	15820 ng/mL Geometric Coefficient of Variation 29	70710 ng/mL Geometric Coefficient of Variation 40	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: For Cohort 1 Periods 3 and 6: At 0 , 0.5, 1, 2, 4, 6, 8, 10, 14, and 24 hours post PF-07081532 dose on Day 28 of Period 3 and Day 63 of Period 6

Population: Participants who received at least 1 dose of PF-07081532, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

PF-07081532 was given titrated to 80 mg QD on Day 1-28 of Period 3, and titrated to 260 mg QD on Day 1-63 of Period 6 in Cohort 1, and blood samples were collected for PF-07081532 PK at the preset time points described in the Time Frame. Tmax was defined as time for Cmax and was observed directly from data.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=15 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=8 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 1: Tmax of PF-07081532 in Period 3 and 6	6.00 hour Interval 2.0 to 14.0	6.00 hour Interval 4.0 to 10.0	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2

Population: All participants randomly assigned to study intervention and who took at least 1 dose of study intervention.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=16 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=16 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) n=11 Participants Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=10 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 2: Number of Participants With All-Causality and Treatment-Related TEAEs Number of participants with all-causality SAEs	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—
Cohort 2: Number of Participants With All-Causality and Treatment-Related TEAEs Number of participants with all-causality TEAEs	4 Participants	11 Participants	11 Participants	3 Participants	—	—	—	—	—
Cohort 2: Number of Participants With All-Causality and Treatment-Related TEAEs Number of participants with treatment-related TEAEs	0 Participants	8 Participants	11 Participants	1 Participants	—	—	—	—	—
Cohort 2: Number of Participants With All-Causality and Treatment-Related TEAEs Number of participants with treatment-related SAEs	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—

SECONDARY outcome

Timeframe: From first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2

Population: All participants randomly assigned to study intervention and who took at least 1 dose of study intervention.

Laboratory tests (including hematology, clinical chemistry, urinalysis) were reported and abnormalities were defined for laboratory values that met specific criteria.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=16 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=16 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) n=11 Participants Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=10 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 2: Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)	0 Participants	11 Participants	7 Participants	8 Participants	—	—	—	—	—

SECONDARY outcome

Timeframe: From baseline (last pre-dose measurement in Period 1) to Period 4 Day 1 (Day 165)

Population: All participants randomly assigned to study intervention and who took at least 1 dose of study intervention.

Percentage of changes from Baseline in body weight of the participants were measured.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=16 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 2: Percentage of Change From Baseline in Body Weight by Period 4 Day 1	-13.15 Percentage Change Interval -22.0 to -5.9	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Screening, D-1 (P1D-1), P2 Week 5 [W5], P2W9, P2W13, P2W17, D150 (P3D2), at follow up visit (Day 172-175)

Population: All participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants with evaluable C-SSRS results were analyzed.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=16 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 2: Number of Participants With Completed Suicide, Suicide Attempt, Preparatory Acts Towards Imminent Suicidal Behavior, Suicidal Ideation, or Self-Injurious Behavior of No Suicidal Intent As Assessed on the C-SSRS	0 Participants	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Screening, D-1 (P1D-1), P2 Week 5 [W5], P2W9, P2W13, P2W17, D150 (P3D2), at follow up visit (Day 172-175)

Population: All participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants with evaluable PHQ-9 results were analyzed.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=16 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 2: PHQ-9 Total Scores Screening	0.1 Score Standard Deviation 0.25	—	—	—	—	—	—	—	—
Cohort 2: PHQ-9 Total Scores Period 1 Day -1 / Midazolam 2 mg	0.2 Score Standard Deviation 0.40	—	—	—	—	—	—	—	—
Cohort 2: PHQ-9 Total Scores Period 2 Week 5 / Semaglutide titration up to 2.4 mg QW	0.3 Score Standard Deviation 0.46	—	—	—	—	—	—	—	—
Cohort 2: PHQ-9 Total Scores Period 2 Week 9 / Semaglutide titration up to 2.4 mg QW	0.1 Score Standard Deviation 0.35	—	—	—	—	—	—	—	—
Cohort 2: PHQ-9 Total Scores Period 2 Week 13 / Semaglutide titration up to 2.4 mg QW	0.2 Score Standard Deviation 0.43	—	—	—	—	—	—	—	—
Cohort 2: PHQ-9 Total Scores Period 2 Week 17 / Semaglutide titration up to 2.4 mg QW	0.2 Score Standard Deviation 0.43	—	—	—	—	—	—	—	—
Cohort 2: PHQ-9 Total Scores Period 3 Day 2 / Semaglutide 2.4 mg QW + Midazolam 2 mg	0.8 Score Standard Deviation 1.33	—	—	—	—	—	—	—	—
Cohort 2: PHQ-9 Total Scores Follow Up	0.0 Score Standard Deviation 0.00	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: For Cohort 2 Period 4: At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14 and 24 hours post midazolam dose on Day 1

Population: Participants who received at least 1 dose of midazolam, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

Midazolam was given on Day 1 in Period 4 of Cohort 2 and blood samples were collected for midazolam pharmacokinetic (PK) at the preset time points described in the Time Frame. AUCinf calculated area under the plasma concentration-time profile from time 0 extrapolated to infinite time.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=10 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 2: AUCinf of Midazolam in Period 4	33.67 ng*hr/mL Geometric Coefficient of Variation 38	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: For Cohort 2 Periods 1 and 3: At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period

Population: Participants who received at least 1 dose of midazolam, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

Midazolam was given on Day 1 in Period 1 and 3 of Cohort 2 and blood samples were collected for midazolam pharmacokinetic (PK) at the preset time points described in the Time Frame. Cmax was defined as maximum observed concentration and was observed directly from data.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=16 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=11 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 2: Cmax of Midazolam in Period 1 and 3	6.234 ng/mL Geometric Coefficient of Variation 32	6.483 ng/mL Geometric Coefficient of Variation 40	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: For Cohort 2 Periods 1 and 3: At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period

Population: Participants who received at least 1 dose of midazolam, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

Midazolam was given on Day 1 in Period 1 and 3 of Cohort 2 and blood samples were collected for midazolam pharmacokinetic (PK) at the preset time points described in the Time Frame. Tmax was defined as time for Cmax and was observed directly from data.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=16 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=11 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 2: Tmax of Midazolam in Period 1 and 3	1.00 hour Interval 0.5 to 2.08	1.00 hour Interval 0.5 to 4.0	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: For Cohort 2 Periods 1 and 3: At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period

Population: Participants who received at least 1 dose of midazolam, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

Midazolam was given on Day 1 in Period 1 and 3 of Cohort 2 and blood samples were collected for midazolam pharmacokinetic (PK) at the preset time points described in the Time Frame. CL/F was defined as apparent clearance and was calculated as dose/AUCinf.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=15 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=11 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 2: CL/F of Midazolam in Period 1 and 3	58.07 L/hr Geometric Coefficient of Variation 43	57.80 L/hr Geometric Coefficient of Variation 48	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: For Cohort 2 Periods 1 and 3: At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period

Population: Participants who received at least 1 dose of midazolam, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

Midazolam was given on Day 1 in Period 1 and 3 of Cohort 2 and blood samples were collected for midazolam pharmacokinetic (PK) at the preset time points described in the Time Frame. Vz/F was defined as apparent volume of distribution and was calculated as dose/(AUCinf\*kel), where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=15 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=11 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 2: Vz/F of Midazolam in Period 1 and 3	618.2 L Geometric Coefficient of Variation 37	516.5 L Geometric Coefficient of Variation 37	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: For Cohort 2 Periods 1 and 3: At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period

Population: Participants who received at least 1 dose of midazolam, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

Midazolam was given on Day 1 in Period 1 and 3 of Cohort 2 and blood samples were collected for midazolam pharmacokinetic (PK) at the preset time points described in the Time Frame. t1/2 was defined as terminal half life and was calculated as loge(2)/kel.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=15 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=11 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 2: t1/2 of Midazolam in Period 1 and 3	7.527 hour Standard Deviation 1.6147	6.347 hour Standard Deviation 1.4305	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: For Cohort 2 Periods 1 and 3: At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period

Population: Participants who received at least 1 dose of midazolam, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

Midazolam was given on Day 1 in Period 1, 3, 4 of Cohort 2 and blood samples were collected for midazolam (parent) and and its metabolite 1-Hydroxy Midazolam PK at the preset time points described in the Time Frame. MRAUCinf was calculated as (AUCinf, metabolite/AUCinf, parent) \* (MWparent/MWmetabolite). MW = molecular weight.

Outcome measures

Outcome measures
Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=13 Participants Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=10 Participants Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) n=8 Participants Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.	Cohort 1: Midazolam 2 mg (Period 9) Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Cohort 2: MRAUCinf of 1-Hydroxy Midazolam in Period 1, 3, 4	0.3262 Ratio Geometric Coefficient of Variation 42	0.3818 Ratio Geometric Coefficient of Variation 52	0.3221 Ratio Geometric Coefficient of Variation 35	—	—	—	—	—	—

Adverse Events

Cohort 1: Midazolam 2 mg (Period 9)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Cohort 2: Midazolam 2 mg (Period 1)

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Cohort 2: Semaglutide Titration up to 2.4 mg QW (Period 2)

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Cohort 2: Semaglutide 2.4 mg QW + Midazolam 2 mg (Period 3)

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Cohort 2: Midazolam 2 mg (Period 4)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Cohort 1: PF-07081532 Titration up to 80 mg QD (Period 3)

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5)

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6)

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Cohort 1: Midazolam 2 mg (Period 9) n=8 participants at risk Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.	Cohort 2: Midazolam 2 mg (Period 1) n=16 participants at risk Participants in Cohort 2 received SD of midazolam 2 mg on Day 1 of Period 1.	Cohort 2: Semaglutide Titration up to 2.4 mg QW (Period 2) n=16 participants at risk Participants in Cohort 2 received semaglutide 0.25 mg once weekly (QW) on Week 1-4, 0.5 mg QW on Week 5-8, 1.0 mg QW on Week 9-12, 1.7 mg QW on Week 13-16, 2.4 mg QW on Week 17-21 of Period 2.	Cohort 2: Semaglutide 2.4 mg QW + Midazolam 2 mg (Period 3) n=11 participants at risk Participants in Cohort 2 received semaglutide 2.4 mg QW and SD of midazolam 2 mg on Day 1 of Period 3.	Cohort 2: Midazolam 2 mg (Period 4) n=10 participants at risk Participants in Cohort 2 received SD of midazolam 2 mg on Day 1 of Period 4.	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n=16 participants at risk Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.	Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2) n=16 participants at risk Participants in Cohort 1 received SD of levonorgestrel (LE) 0.15 mg and ethinyl estradiol (EE) 0.03 mg on Day 1 of Period 2.	Cohort 1: PF-07081532 Titration up to 80 mg QD (Period 3) n=16 participants at risk Participants in Cohort 1 received PF-07081532 20 mg once daily (QD) on Day 1-7, 40 mg QD on Day 8-14, 60 mg QD on Day 15-21, 80 mg QD on Day 22-28 of Period 3.	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n=16 participants at risk Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) n=16 participants at risk Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.	Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6) n=16 participants at risk Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) n=8 participants at risk Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) n=7 participants at risk Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.
General disorders Non-cardiac chest pain	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Blood and lymphatic system disorders Anaemia	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	12.5% 1/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	14.3% 1/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	12.5% 2/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	14.3% 1/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Gastrointestinal disorders Abdominal distension	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	12.5% 2/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Gastrointestinal disorders Constipation	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	31.2% 5/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	68.8% 11/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	12.5% 2/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	43.8% 7/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	14.3% 1/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Gastrointestinal disorders Diarrhoea	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	9.1% 1/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	18.8% 3/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Gastrointestinal disorders Dyspepsia	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	37.5% 6/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	31.2% 5/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Gastrointestinal disorders Flatulence	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Gastrointestinal disorders Haemorrhoids	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Gastrointestinal disorders Nausea	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	18.8% 3/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	68.8% 11/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	12.5% 2/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	56.2% 9/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Gastrointestinal disorders Retching	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Gastrointestinal disorders Vomiting	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	18.8% 3/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	25.0% 4/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	12.5% 1/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
General disorders Early satiety	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	12.5% 2/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
General disorders Non-pitting oedema	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	12.5% 1/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
General disorders Oedema peripheral	12.5% 1/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Hepatobiliary disorders Hepatic fibrosis	12.5% 1/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Hepatobiliary disorders Hepatic steatosis	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	14.3% 1/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Hepatobiliary disorders Hepatomegaly	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	14.3% 1/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Infections and infestations Otitis externa	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Investigations Alanine aminotransferase increased	12.5% 1/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	31.2% 5/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Investigations Amylase increased	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	14.3% 1/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Investigations Aspartate aminotransferase increased	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	31.2% 5/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Investigations Gamma-glutamyltransferase increased	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Investigations Lipase increased	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	10.0% 1/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	14.3% 1/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	12.5% 2/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	31.2% 5/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	25.0% 4/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Musculoskeletal and connective tissue disorders Musculoskeletal discomfort	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Nervous system disorders Dizziness	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	12.5% 2/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	9.1% 1/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	25.0% 4/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Nervous system disorders Headache	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	18.8% 3/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	10.0% 1/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	25.0% 4/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	37.5% 6/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Nervous system disorders Syncope	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	9.1% 1/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Psychiatric disorders Abnormal dreams	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Psychiatric disorders Insomnia	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Psychiatric disorders Restlessness	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Reproductive system and breast disorders Breast tenderness	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Reproductive system and breast disorders Dysmenorrhoea	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Reproductive system and breast disorders Intermenstrual bleeding	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Reproductive system and breast disorders Menstruation delayed	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Reproductive system and breast disorders Pelvic discomfort	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Skin and subcutaneous tissue disorders Dermatitis contact	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Endocrine disorders Hyperthyroidism	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	10.0% 1/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Endocrine disorders Hypothyroidism	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Gastrointestinal disorders Aphthous ulcer	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Gastrointestinal disorders Change of bowel habit	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Gastrointestinal disorders Eructation	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
General disorders Pain	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Infections and infestations Viral infection	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	9.1% 1/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Nervous system disorders Somnolence	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	100.0% 11/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Renal and urinary disorders Renal cyst	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Reproductive system and breast disorders Haemorrhagic ovarian cyst	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Reproductive system and breast disorders Vaginal haemorrhage	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	6.2% 1/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/11 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/10 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/16 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/8 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.	0.00% 0/7 • From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.

Additional Information

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