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

A PHASE 1, OPEN-LABEL, FIXED-SEQUENCE STUDY TO EVALUATE THE EFFECT OF TWO STEADY-STATE DOSE LEVELS OF PF-07081532 ON THE PHARMACOKINETICS OF SINGLE-DOSE MIDAZOLAM, OMEPRAZOLE AND AN ORAL CONTRACEPTIVE, AND THE EFFECT OF STEADY-STATE SEMAGLUTIDE ON THE PHARMACOKINETICS OF SINGLE-DOSE MIDAZOLAM, IN OBESE ADULT FEMALE PARTICIPANTS

Status

Terminated

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05671653

Enrollment

Registered

2023-01-05

Start date

2023-01-19

Completion date

2023-11-03

Last updated

2025-01-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Obesity

Keywords

Midazolam, Omeprazole, PF-07081532

Brief summary

Two different groups of healthy volunteers will be chronically treated with GLP-1 drugs PF-07081532 or alternatively Semaglutide. The effect of these GLP-1 drugs on a single dose of the common sedative medication midazolam blood levels will be measured. The effect of chronic PF-07081532 on single doses of the common stomach acid medication omeprazole, and common birth control medication blood levels will also be measured. The hypothesis is that chronic administration of the GLP-1 drugs will minimally affect blood levels from these common medications.

Interventions

DRUGPF-07081532

Experimental oral GLP-1 drug

DRUGSemaglutide

Approved and marketed GLP-1 drug for subcutaneous injection.

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

BASIC_SCIENCE

Masking

NONE

Intervention model description

The overall design is randomized, open-label, fixed-sequence. Cohort 1 will consist of 9 periods while Cohort 2 will consist of 4 periods.

Eligibility

Sex/Gender

FEMALE

Age

18 Years to No maximum

Healthy volunteers

Yes

Inclusion criteria

* Healthy (no clinically relevant abnormalities) * BMI 30.0-45.4 inclusive

Exclusion criteria

* Current or history of significant clinical condition * Use of prescription or nonprescription drugs and dietary and herbal supplements within 7 or 14 days or 5 half-lives (whichever is longer) * Pregnant * Breast feeding

Design outcomes

Primary

Measure	Time frame	Description
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	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	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.
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	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	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.
Cohort 1: AUClast of Levonorgestrel (LE) in Periods 2, 5,and 8	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	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.
Cohort 1: AUCinf of Ethinyl Estradiol (EE) in Periods 2, 5,and 8	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	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.
Cohort 2: AUCinf of Midazolam in Period 1 and 3	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	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.

Secondary

Measure	Time frame	Description
Cohort 1: Patient Health Quessionare-9 (PHQ-9) Total Scores	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	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.
Cohort 1: AUCinf of Midazolam in Period 9	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	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.
Cohort 1: Maximum Observed Concentration (Cmax) of Midazolam in Period 1, 4, 7	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	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.
Cohort 1: Time for Cmax (Tmax) of Midazolam in Period 1, 4, 7	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	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.
Cohort 1: Apparent Clearance (CL/F) of Midazolam in Period 1, 4, 7	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	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.
Cohort 1: Apparent Volume of Distribution (Vz/F) of Midazolam in Period 1, 4, 7	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	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.
Cohort 1: Terminal Half-Life (t1/2) of Midazolam in Period 1, 4, 7	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	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.
Cohort 1: Cmax of Omeprazole in Period 1, 4, 7	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	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.
Cohort 1: Tmax of Omeprazole in Period 1, 4, 7	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	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.
Cohort 1: CL/F of Omeprazole in Period 1, 4, 7	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	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.
Cohort 1: Vz/F of Omeprazole in Period 1, 4, 7	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	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.
Cohort 1: t1/2 of Omeprazole in Period 1, 4, 7	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	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.
Cohort 1: Cmax of LE in Period 2, 5, 8	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	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.
Cohort 1: CL/F of LE in Period 2, 5, 8	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	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.
Cohort 1: Vz/F of LE in Period 2, 5, 8	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	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.
Cohort 1: t1/2 of LE in Period 2, 5, 8	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	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.
Cohort 1: Cmax of EE in Period 2, 5, 8	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	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.
Cohort 1: Tmax of EE in Period 2, 5, 8	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	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.
Cohort 1: CL/F of EE in Period 2, 5, 8	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	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.
Cohort 1: Vz/F of EE in Period 2, 5, 8	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	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.
Cohort 1: t1/2 of EE in Period 2, 5, 8	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	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.
Cohort 1: Metabolite/Parent Ratio for AUCinf (MRAUCinf) of 1-Hydroxy Midazolam in Period 1, 4, 7	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	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.
Cohort 1: MRAUCinf of 5-Hydroxy Omeprazole in Period 1, 4, 7	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	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.
Cohort 1: Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours (AUC24) of PF-07081532 in Period 3 and 6	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	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.
Cohort 1: Cmax of PF-07081532 in Period 3 and 6	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	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.
Cohort 1: Tmax of PF-07081532 in Period 3 and 6	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	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.
Cohort 2: Number of Participants With All-Causality and Treatment-Related TEAEs	From first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2	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.
Cohort 2: Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)	From first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2	Laboratory tests (including hematology, clinical chemistry, urinalysis) were reported and abnormalities were defined for laboratory values that met specific criteria.
Cohort 2: Percentage of Change From Baseline in Body Weight by Period 4 Day 1	From baseline (last pre-dose measurement in Period 1) to Period 4 Day 1 (Day 165)	Percentage of changes from Baseline in body weight of the participants were measured.
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	Screening, D-1 (P1D-1), P2 Week 5 [W5], P2W9, P2W13, P2W17, D150 (P3D2), at follow up visit (Day 172-175)	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.
Cohort 2: PHQ-9 Total Scores	Screening, D-1 (P1D-1), P2 Week 5 [W5], P2W9, P2W13, P2W17, D150 (P3D2), at follow up visit (Day 172-175)	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.
Cohort 2: AUCinf of Midazolam in Period 4	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	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.
Cohort 2: Cmax of Midazolam in Period 1 and 3	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	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.
Cohort 2: Tmax of Midazolam in Period 1 and 3	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	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.
Cohort 2: CL/F of Midazolam in Period 1 and 3	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	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.
Cohort 2: Vz/F of Midazolam in Period 1 and 3	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	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.
Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs	From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1	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.
Cohort 2: MRAUCinf of 1-Hydroxy Midazolam in Period 1, 3, 4	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	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.
Cohort 2: t1/2 of Midazolam in Period 1 and 3	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	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.
Cohort 1: Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)	From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1	Laboratory tests (including hematology, clinical chemistry, urinalysis) were reported and abnormalities were defined for laboratory values that met specific criteria.
Cohort 1: Percentage of Change From Baseline in Body Weight by Period 9 Day 1	From baseline (last pre-dose measurement in Period 1) to Period 9 Day 1 (Day 124)	Percentage of changes from Baseline in body weight of the participants were measured.
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	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	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.
Cohort 1: Tmax of LE in Period 2, 5, 8	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	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.

Countries

United States

Participant flow

Pre-assignment details

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.

Participants by arm

Arm	Count
Cohort 1 Reporting Group Description	16
Cohort 2 Reporting Group Description	16
Total	32

Withdrawals & dropouts

Period	Reason	FG005	FG008	FG010	FG011
Cohort 1 Period 6 - Treatment	Adverse Event	2	0	0	0
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 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	Other	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 3 - Treatment	Adverse Event	0	0	0	1

Baseline characteristics

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

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk	EG009 affected / at risk	EG010 affected / at risk	EG011 affected / at risk	EG012 affected / at risk
deaths Total, all-cause mortality	0 / 16	0 / 16	0 / 16	0 / 16	0 / 16	0 / 16	0 / 8	0 / 7	0 / 8	0 / 16	0 / 16	0 / 11	0 / 10
other Total, other adverse events	1 / 16	2 / 16	14 / 16	2 / 16	6 / 16	15 / 16	1 / 8	2 / 7	2 / 8	4 / 16	11 / 16	11 / 11	3 / 10
serious Total, serious adverse events	0 / 16	0 / 16	0 / 16	0 / 16	0 / 16	0 / 16	0 / 8	0 / 7	0 / 8	0 / 16	0 / 16	0 / 11	0 / 10

Outcome results

Primary

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

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.

Time frame: 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.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	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
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	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	33.30 nanogramhour/milliliter (nghr/mL)	Geometric Coefficient of Variation 37
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	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	28.23 nanogramhour/milliliter (nghr/mL)	Geometric Coefficient of Variation 49

Comparison: Reference: Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1). Test: Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4).90% CI: [80.25, 98.38]

Comparison: Reference: Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1). Test: Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7).90% CI: [55.21, 88.76]

Primary

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

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.

Time frame: 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.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	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
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	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	620.5 ng*hr/mL	Geometric Coefficient of Variation 174
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	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	602.8 ng*hr/mL	Geometric Coefficient of Variation 154

Comparison: Reference: Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1). Test: Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4).90% CI: [39.27, 83.29]

Comparison: Reference: Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1). Test: Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7).90% CI: [19.6, 44.94]

Primary

Cohort 1: AUCinf of Ethinyl Estradiol (EE) in Periods 2, 5,and 8

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.

Time frame: 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.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 1: AUCinf of Ethinyl Estradiol (EE) in Periods 2, 5,and 8	754.5 pg*hr/mL	Geometric Coefficient of Variation 37
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 1: AUCinf of Ethinyl Estradiol (EE) in Periods 2, 5,and 8	765.5 pg*hr/mL	Geometric Coefficient of Variation 26
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 1: AUCinf of Ethinyl Estradiol (EE) in Periods 2, 5,and 8	701.1 pg*hr/mL	Geometric Coefficient of Variation 29

Comparison: Reference: Cohort 1: LE 0.15 mg \& EE 0.03 mg (Period 2). Test: Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg \& EE 0.03 mg (Period 5).90% CI: [95.09, 111.93]

Comparison: Reference: Cohort 1: LE 0.15 mg \& EE 0.03 mg (Period 2). Test: Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg \& EE 0.03 mg (Period 8)90% CI: [60.24, 135.06]

Primary

Cohort 1: AUClast of Levonorgestrel (LE) in Periods 2, 5,and 8

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.

Time frame: 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.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 1: AUClast of Levonorgestrel (LE) in Periods 2, 5,and 8	31360 picogramhour/milliliter (pghr/mL)	Geometric Coefficient of Variation 52
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 1: AUClast of Levonorgestrel (LE) in Periods 2, 5,and 8	42120 picogramhour/milliliter (pghr/mL)	Geometric Coefficient of Variation 56
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 1: AUClast of Levonorgestrel (LE) in Periods 2, 5,and 8	60020 picogramhour/milliliter (pghr/mL)	Geometric Coefficient of Variation 63

Comparison: Reference: Cohort 1: LE 0.15 mg \& EE 0.03 mg (Period 2). Test: Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg \& EE 0.03 mg (Period 5).90% CI: [108.97, 131.85]

Comparison: Reference: Cohort 1: LE 0.15 mg \& EE 0.03 mg (Period 2). Test: Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg \& EE 0.03 mg (Period 8)90% CI: [108, 318.44]

Primary

Cohort 2: AUCinf of Midazolam in Period 1 and 3

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.

Time frame: 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.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 2: AUCinf of Midazolam in Period 1 and 3	34.43 ng*hr/mL	Geometric Coefficient of Variation 43
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 2: AUCinf of Midazolam in Period 1 and 3	34.60 ng*hr/mL	Geometric Coefficient of Variation 48

Comparison: Reference: Cohort 2: Midazolam 2 mg (Period 1). Test: Cohort 2: Semaglutide 2.4 mg QW + Midazolam 2 mg (Period 3).90% CI: [79.97, 107.87]

Secondary

Cohort 1: Apparent Clearance (CL/F) of Midazolam in Period 1, 4, 7

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.

Time frame: 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.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 1: Apparent Clearance (CL/F) of Midazolam in Period 1, 4, 7	50.94 L/hr	Geometric Coefficient of Variation 33
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 1: Apparent Clearance (CL/F) of Midazolam in Period 1, 4, 7	60.08 L/hr	Geometric Coefficient of Variation 38
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 1: Apparent Clearance (CL/F) of Midazolam in Period 1, 4, 7	70.91 L/hr	Geometric Coefficient of Variation 49

Secondary

Cohort 1: Apparent Volume of Distribution (Vz/F) of Midazolam in Period 1, 4, 7

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.

Time frame: 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.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 1: Apparent Volume of Distribution (Vz/F) of Midazolam in Period 1, 4, 7	544.9 Liter (L)	Geometric Coefficient of Variation 30
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 1: Apparent Volume of Distribution (Vz/F) of Midazolam in Period 1, 4, 7	605.3 Liter (L)	Geometric Coefficient of Variation 28
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 1: Apparent Volume of Distribution (Vz/F) of Midazolam in Period 1, 4, 7	664.5 Liter (L)	Geometric Coefficient of Variation 32

Secondary

Cohort 1: Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours (AUC24) of PF-07081532 in Period 3 and 6

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.

Time frame: 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.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	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
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 1: Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours (AUC24) of PF-07081532 in Period 3 and 6	1239000 ng*hr/mL	Geometric Coefficient of Variation 49

Secondary

Cohort 1: AUCinf of Midazolam in Period 9

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.

Time frame: 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.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 1: AUCinf of Midazolam in Period 9	39.80 ng*hr/mL	Geometric Coefficient of Variation 35

Secondary

Cohort 1: CL/F of EE in Period 2, 5, 8

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.

Time frame: 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.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 1: CL/F of EE in Period 2, 5, 8	238.6 L/hr	Geometric Coefficient of Variation 37
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 1: CL/F of EE in Period 2, 5, 8	235.3 L/hr	Geometric Coefficient of Variation 26
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 1: CL/F of EE in Period 2, 5, 8	256.9 L/hr	Geometric Coefficient of Variation 29

Secondary

Cohort 1: CL/F of LE in Period 2, 5, 8

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.

Time frame: 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.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 1: CL/F of LE in Period 2, 5, 8	6.043 L/hr	Geometric Coefficient of Variation 51
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 1: CL/F of LE in Period 2, 5, 8	3.887 L/hr	Geometric Coefficient of Variation 52
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 1: CL/F of LE in Period 2, 5, 8	2.265 L/hr	Geometric Coefficient of Variation 54

Secondary

Cohort 1: CL/F of Omeprazole in Period 1, 4, 7

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.

Time frame: 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.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 1: CL/F of Omeprazole in Period 1, 4, 7	17.19 L/hr	Geometric Coefficient of Variation 92
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 1: CL/F of Omeprazole in Period 1, 4, 7	21.43 L/hr	Geometric Coefficient of Variation 198
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 1: CL/F of Omeprazole in Period 1, 4, 7	17.26 L/hr	Geometric Coefficient of Variation 118

Secondary

Cohort 1: Cmax of EE in Period 2, 5, 8

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.

Time frame: 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.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 1: Cmax of EE in Period 2, 5, 8	42.44 pg/mL	Geometric Coefficient of Variation 33
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 1: Cmax of EE in Period 2, 5, 8	37.82 pg/mL	Geometric Coefficient of Variation 35
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 1: Cmax of EE in Period 2, 5, 8	34.03 pg/mL	Geometric Coefficient of Variation 30

Secondary

Cohort 1: Cmax of LE in Period 2, 5, 8

Time frame: 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.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 1: Cmax of LE in Period 2, 5, 8	1919 pg/mL	Geometric Coefficient of Variation 45
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 1: Cmax of LE in Period 2, 5, 8	1532 pg/mL	Geometric Coefficient of Variation 41
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 1: Cmax of LE in Period 2, 5, 8	1684 pg/mL	Geometric Coefficient of Variation 82

Secondary

Cohort 1: Cmax of Omeprazole in Period 1, 4, 7

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.

Time frame: 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.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 1: Cmax of Omeprazole in Period 1, 4, 7	266.4 ng/mL	Geometric Coefficient of Variation 112
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 1: Cmax of Omeprazole in Period 1, 4, 7	88.42 ng/mL	Geometric Coefficient of Variation 271
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 1: Cmax of Omeprazole in Period 1, 4, 7	169.9 ng/mL	Geometric Coefficient of Variation 209

Secondary

Cohort 1: Cmax of PF-07081532 in Period 3 and 6

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.

Time frame: 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.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 1: Cmax of PF-07081532 in Period 3 and 6	15820 ng/mL	Geometric Coefficient of Variation 29
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 1: Cmax of PF-07081532 in Period 3 and 6	70710 ng/mL	Geometric Coefficient of Variation 40

Secondary

Cohort 1: Maximum Observed Concentration (Cmax) of Midazolam in Period 1, 4, 7

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.

Time frame: 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.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 1: Maximum Observed Concentration (Cmax) of Midazolam in Period 1, 4, 7	6.613 ng/mL	Geometric Coefficient of Variation 38
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 1: Maximum Observed Concentration (Cmax) of Midazolam in Period 1, 4, 7	6.705 ng/mL	Geometric Coefficient of Variation 47
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 1: Maximum Observed Concentration (Cmax) of Midazolam in Period 1, 4, 7	6.804 ng/mL	Geometric Coefficient of Variation 50

Secondary

Cohort 1: Metabolite/Parent Ratio for AUCinf (MRAUCinf) of 1-Hydroxy Midazolam in Period 1, 4, 7

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.

Time frame: 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.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	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
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 1: Metabolite/Parent Ratio for AUCinf (MRAUCinf) of 1-Hydroxy Midazolam in Period 1, 4, 7	0.4480 Ratio	Geometric Coefficient of Variation 39
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 1: Metabolite/Parent Ratio for AUCinf (MRAUCinf) of 1-Hydroxy Midazolam in Period 1, 4, 7	0.4314 Ratio	Geometric Coefficient of Variation 49

Secondary

Cohort 1: MRAUCinf of 5-Hydroxy Omeprazole in Period 1, 4, 7

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.

Time frame: 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.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 1: MRAUCinf of 5-Hydroxy Omeprazole in Period 1, 4, 7	0.3752 Ratio	Geometric Coefficient of Variation 93
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 1: MRAUCinf of 5-Hydroxy Omeprazole in Period 1, 4, 7	0.4060 Ratio	Geometric Coefficient of Variation 136
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 1: MRAUCinf of 5-Hydroxy Omeprazole in Period 1, 4, 7	0.3790 Ratio	Geometric Coefficient of Variation 39

Secondary

Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs

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.

Time frame: 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.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with treatment-related TEAEs	0 Participants
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with all-causality TEAEs	1 Participants
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with treatment-related SAEs	0 Participants
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with all-causality SAEs	0 Participants
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with all-causality SAEs	0 Participants
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with treatment-related SAEs	0 Participants
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with all-causality TEAEs	2 Participants
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with treatment-related TEAEs	1 Participants
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with treatment-related TEAEs	14 Participants
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with all-causality TEAEs	14 Participants
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with all-causality SAEs	0 Participants
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with treatment-related SAEs	0 Participants
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with treatment-related SAEs	0 Participants
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with all-causality SAEs	0 Participants
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with treatment-related TEAEs	2 Participants
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with all-causality TEAEs	2 Participants
Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5)	Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with treatment-related SAEs	0 Participants
Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5)	Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with all-causality TEAEs	6 Participants
Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5)	Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with treatment-related TEAEs	5 Participants
Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5)	Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with all-causality SAEs	0 Participants
Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6)	Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with treatment-related SAEs	0 Participants
Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6)	Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with all-causality SAEs	0 Participants
Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6)	Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with all-causality TEAEs	15 Participants
Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6)	Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with treatment-related TEAEs	15 Participants
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with all-causality SAEs	0 Participants
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with all-causality TEAEs	1 Participants
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with treatment-related TEAEs	1 Participants
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with treatment-related SAEs	0 Participants
Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)	Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with treatment-related SAEs	0 Participants
Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)	Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with all-causality SAEs	0 Participants
Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)	Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with all-causality TEAEs	2 Participants
Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)	Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with treatment-related TEAEs	2 Participants
Cohort 1: Midazolam 2 mg (Period 9)	Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with all-causality SAEs	0 Participants
Cohort 1: Midazolam 2 mg (Period 9)	Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with treatment-related TEAEs	2 Participants
Cohort 1: Midazolam 2 mg (Period 9)	Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with treatment-related SAEs	0 Participants
Cohort 1: Midazolam 2 mg (Period 9)	Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with all-causality TEAEs	2 Participants

Secondary

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

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.

Time frame: 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.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	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

Cohort 1: Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)

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

Time frame: 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.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 1: Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)	0 Participants
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 1: Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)	0 Participants
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 1: Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)	9 Participants
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 1: Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)	0 Participants
Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5)	Cohort 1: Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)	3 Participants
Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6)	Cohort 1: Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)	14 Participants
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 1: Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)	3 Participants
Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)	Cohort 1: Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)	6 Participants
Cohort 1: Midazolam 2 mg (Period 9)	Cohort 1: Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)	7 Participants

Secondary

Cohort 1: Patient Health Quessionare-9 (PHQ-9) Total Scores

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.

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.

Arm	Measure	Group	Value (MEAN)	Dispersion
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 1: Patient Health Quessionare-9 (PHQ-9) Total Scores	Screening	0.3 Score	Standard Deviation 0.79
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	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: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	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: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	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: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	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: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	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: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	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: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	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: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	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: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	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: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	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: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 1: Patient Health Quessionare-9 (PHQ-9) Total Scores	Follow Up	0.1 Score	Standard Deviation 0.26

Secondary

Cohort 1: Percentage of Change From Baseline in Body Weight by Period 9 Day 1

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

Time frame: 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.

Arm	Measure	Value (MEDIAN)
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 1: Percentage of Change From Baseline in Body Weight by Period 9 Day 1	-8.55 Percentage Change

Secondary

Cohort 1: t1/2 of EE in Period 2, 5, 8

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.

Time frame: 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.

Arm	Measure	Value (MEAN)	Dispersion
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 1: t1/2 of EE in Period 2, 5, 8	22.42 hour	Standard Deviation 4.5451
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 1: t1/2 of EE in Period 2, 5, 8	25.54 hour	Standard Deviation 4.8147
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 1: t1/2 of EE in Period 2, 5, 8	22.03 hour	Standard Deviation 4.5676

Secondary

Cohort 1: t1/2 of LE in Period 2, 5, 8

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.

Time frame: 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.

Arm	Measure	Value (MEAN)	Dispersion
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 1: t1/2 of LE in Period 2, 5, 8	44.33 hour	Standard Deviation 8.7994
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 1: t1/2 of LE in Period 2, 5, 8	45.25 hour	Standard Deviation 5.9429
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 1: t1/2 of LE in Period 2, 5, 8	41.26 hour	Standard Deviation 5.7709

Secondary

Cohort 1: t1/2 of Omeprazole in Period 1, 4, 7

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.

Time frame: 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.

Arm	Measure	Value (MEAN)	Dispersion
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 1: t1/2 of Omeprazole in Period 1, 4, 7	1.793 hour	Standard Deviation 0.77789
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 1: t1/2 of Omeprazole in Period 1, 4, 7	1.705 hour	Standard Deviation 0.65741
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 1: t1/2 of Omeprazole in Period 1, 4, 7	1.800 hour	Standard Deviation 0.28355

Secondary

Cohort 1: Terminal Half-Life (t1/2) of Midazolam in Period 1, 4, 7

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.

Time frame: 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.

Arm	Measure	Value (MEAN)	Dispersion
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 1: Terminal Half-Life (t1/2) of Midazolam in Period 1, 4, 7	7.539 hour	Standard Deviation 1.4445
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 1: Terminal Half-Life (t1/2) of Midazolam in Period 1, 4, 7	7.078 hour	Standard Deviation 1.2904
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 1: Terminal Half-Life (t1/2) of Midazolam in Period 1, 4, 7	6.659 hour	Standard Deviation 1.5587

Secondary

Cohort 1: Time for Cmax (Tmax) of Midazolam in Period 1, 4, 7

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.

Time frame: 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.

Arm	Measure	Value (MEDIAN)
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 1: Time for Cmax (Tmax) of Midazolam in Period 1, 4, 7	1.50 hour
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 1: Time for Cmax (Tmax) of Midazolam in Period 1, 4, 7	0.500 hour
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 1: Time for Cmax (Tmax) of Midazolam in Period 1, 4, 7	0.767 hour

Secondary

Cohort 1: Tmax of EE in Period 2, 5, 8

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.

Time frame: 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.

Arm	Measure	Value (MEDIAN)
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 1: Tmax of EE in Period 2, 5, 8	2.00 hour
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 1: Tmax of EE in Period 2, 5, 8	2.00 hour
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 1: Tmax of EE in Period 2, 5, 8	2.00 hour

Secondary

Cohort 1: Tmax of LE in Period 2, 5, 8

Time frame: 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.

Arm	Measure	Value (MEDIAN)
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 1: Tmax of LE in Period 2, 5, 8	2.00 hour
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 1: Tmax of LE in Period 2, 5, 8	3.02 hour
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 1: Tmax of LE in Period 2, 5, 8	4.10 hour

Secondary

Cohort 1: Tmax of Omeprazole in Period 1, 4, 7

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.

Time frame: 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.

Arm	Measure	Value (MEDIAN)
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 1: Tmax of Omeprazole in Period 1, 4, 7	5.99 hour
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 1: Tmax of Omeprazole in Period 1, 4, 7	8.33 hour
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 1: Tmax of Omeprazole in Period 1, 4, 7	11.1 hour

Secondary

Cohort 1: Tmax of PF-07081532 in Period 3 and 6

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.

Time frame: 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.

Arm	Measure	Value (MEDIAN)
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 1: Tmax of PF-07081532 in Period 3 and 6	6.00 hour
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 1: Tmax of PF-07081532 in Period 3 and 6	6.00 hour

Secondary

Cohort 1: Vz/F of EE in Period 2, 5, 8

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.

Time frame: 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.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 1: Vz/F of EE in Period 2, 5, 8	7565 L	Geometric Coefficient of Variation 32
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 1: Vz/F of EE in Period 2, 5, 8	8517 L	Geometric Coefficient of Variation 34
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 1: Vz/F of EE in Period 2, 5, 8	7998 L	Geometric Coefficient of Variation 25

Secondary

Cohort 1: Vz/F of LE in Period 2, 5, 8

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.

Time frame: 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.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 1: Vz/F of LE in Period 2, 5, 8	380.0 L	Geometric Coefficient of Variation 44
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 1: Vz/F of LE in Period 2, 5, 8	251.7 L	Geometric Coefficient of Variation 45
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 1: Vz/F of LE in Period 2, 5, 8	133.6 L	Geometric Coefficient of Variation 55

Secondary

Cohort 1: Vz/F of Omeprazole in Period 1, 4, 7

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.

Time frame: 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.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 1: Vz/F of Omeprazole in Period 1, 4, 7	41.26 L	Geometric Coefficient of Variation 69
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 1: Vz/F of Omeprazole in Period 1, 4, 7	49.81 L	Geometric Coefficient of Variation 150
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 1: Vz/F of Omeprazole in Period 1, 4, 7	44.48 L	Geometric Coefficient of Variation 109

Secondary

Cohort 2: AUCinf of Midazolam in Period 4

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.

Time frame: 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.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 2: AUCinf of Midazolam in Period 4	33.67 ng*hr/mL	Geometric Coefficient of Variation 38

Secondary

Cohort 2: CL/F of Midazolam in Period 1 and 3

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.

Time frame: 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.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 2: CL/F of Midazolam in Period 1 and 3	58.07 L/hr	Geometric Coefficient of Variation 43
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 2: CL/F of Midazolam in Period 1 and 3	57.80 L/hr	Geometric Coefficient of Variation 48

Secondary

Cohort 2: Cmax of Midazolam in Period 1 and 3

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.

Time frame: 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.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 2: Cmax of Midazolam in Period 1 and 3	6.234 ng/mL	Geometric Coefficient of Variation 32
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 2: Cmax of Midazolam in Period 1 and 3	6.483 ng/mL	Geometric Coefficient of Variation 40

Secondary

Cohort 2: MRAUCinf of 1-Hydroxy Midazolam in Period 1, 3, 4

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.

Time frame: 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.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 2: MRAUCinf of 1-Hydroxy Midazolam in Period 1, 3, 4	0.3262 Ratio	Geometric Coefficient of Variation 42
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 2: MRAUCinf of 1-Hydroxy Midazolam in Period 1, 3, 4	0.3818 Ratio	Geometric Coefficient of Variation 52
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 2: MRAUCinf of 1-Hydroxy Midazolam in Period 1, 3, 4	0.3221 Ratio	Geometric Coefficient of Variation 35

Secondary

Cohort 2: Number of Participants With All-Causality and Treatment-Related TEAEs

Time frame: 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.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 2: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with all-causality TEAEs	4 Participants
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 2: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with all-causality SAEs	0 Participants
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 2: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with treatment-related SAEs	0 Participants
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 2: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with treatment-related TEAEs	0 Participants
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 2: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with all-causality SAEs	0 Participants
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 2: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with treatment-related SAEs	0 Participants
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 2: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with treatment-related TEAEs	8 Participants
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 2: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with all-causality TEAEs	11 Participants
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 2: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with all-causality TEAEs	11 Participants
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 2: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with treatment-related SAEs	0 Participants
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 2: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with treatment-related TEAEs	11 Participants
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 2: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with all-causality SAEs	0 Participants
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 2: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with treatment-related SAEs	0 Participants
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 2: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with all-causality TEAEs	3 Participants
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 2: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with all-causality SAEs	0 Participants
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 2: Number of Participants With All-Causality and Treatment-Related TEAEs	Number of participants with treatment-related TEAEs	1 Participants

Secondary

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

Time frame: 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.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	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

Cohort 2: Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)

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

Time frame: 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.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 2: Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)	0 Participants
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 2: Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)	11 Participants
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	Cohort 2: Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)	7 Participants
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 2: Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)	8 Participants

Secondary

Cohort 2: Percentage of Change From Baseline in Body Weight by Period 4 Day 1

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

Time frame: 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.

Arm	Measure	Value (MEDIAN)
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 2: Percentage of Change From Baseline in Body Weight by Period 4 Day 1	-13.15 Percentage Change

Secondary

Cohort 2: PHQ-9 Total Scores

Time frame: 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.

Arm	Measure	Group	Value (MEAN)	Dispersion
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 2: PHQ-9 Total Scores	Screening	0.1 Score	Standard Deviation 0.25
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 2: PHQ-9 Total Scores	Period 1 Day -1 / Midazolam 2 mg	0.2 Score	Standard Deviation 0.4
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	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 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	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 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	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 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	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 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	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 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 2: PHQ-9 Total Scores	Follow Up	0.0 Score	Standard Deviation 0

Secondary

Cohort 2: t1/2 of Midazolam in Period 1 and 3

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.

Time frame: 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.

Arm	Measure	Value (MEAN)	Dispersion
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 2: t1/2 of Midazolam in Period 1 and 3	7.527 hour	Standard Deviation 1.6147
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 2: t1/2 of Midazolam in Period 1 and 3	6.347 hour	Standard Deviation 1.4305

Secondary

Cohort 2: Tmax of Midazolam in Period 1 and 3

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.

Time frame: 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.

Arm	Measure	Value (MEDIAN)
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 2: Tmax of Midazolam in Period 1 and 3	1.00 hour
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 2: Tmax of Midazolam in Period 1 and 3	1.00 hour

Secondary

Cohort 2: Vz/F of Midazolam in Period 1 and 3

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.

Time frame: 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.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	Cohort 2: Vz/F of Midazolam in Period 1 and 3	618.2 L	Geometric Coefficient of Variation 37
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	Cohort 2: Vz/F of Midazolam in Period 1 and 3	516.5 L	Geometric Coefficient of Variation 37

Source: ClinicalTrials.gov · Data processed: May 1, 2026

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

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Intervention model description

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Secondary

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Participant flow

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

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

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

Cohort 1: AUCinf of Ethinyl Estradiol (EE) in Periods 2, 5,and 8

Cohort 1: AUClast of Levonorgestrel (LE) in Periods 2, 5,and 8

Cohort 2: AUCinf of Midazolam in Period 1 and 3

Cohort 1: Apparent Clearance (CL/F) of Midazolam in Period 1, 4, 7

Cohort 1: Apparent Volume of Distribution (Vz/F) of Midazolam in Period 1, 4, 7

Cohort 1: Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours (AUC24) of PF-07081532 in Period 3 and 6

Cohort 1: AUCinf of Midazolam in Period 9

Cohort 1: CL/F of EE in Period 2, 5, 8

Cohort 1: CL/F of LE in Period 2, 5, 8

Cohort 1: CL/F of Omeprazole in Period 1, 4, 7

Cohort 1: Cmax of EE in Period 2, 5, 8

Cohort 1: Cmax of LE in Period 2, 5, 8

Cohort 1: Cmax of Omeprazole in Period 1, 4, 7

Cohort 1: Cmax of PF-07081532 in Period 3 and 6

Cohort 1: Maximum Observed Concentration (Cmax) of Midazolam in Period 1, 4, 7

Cohort 1: Metabolite/Parent Ratio for AUCinf (MRAUCinf) of 1-Hydroxy Midazolam in Period 1, 4, 7

Cohort 1: MRAUCinf of 5-Hydroxy Omeprazole in Period 1, 4, 7

Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs

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

Cohort 1: Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)

Cohort 1: Patient Health Quessionare-9 (PHQ-9) Total Scores

Cohort 1: Percentage of Change From Baseline in Body Weight by Period 9 Day 1

Cohort 1: t1/2 of EE in Period 2, 5, 8

Cohort 1: t1/2 of LE in Period 2, 5, 8

Cohort 1: t1/2 of Omeprazole in Period 1, 4, 7

Cohort 1: Terminal Half-Life (t1/2) of Midazolam in Period 1, 4, 7

Cohort 1: Time for Cmax (Tmax) of Midazolam in Period 1, 4, 7

Cohort 1: Tmax of EE in Period 2, 5, 8

Cohort 1: Tmax of LE in Period 2, 5, 8

Cohort 1: Tmax of Omeprazole in Period 1, 4, 7

Cohort 1: Tmax of PF-07081532 in Period 3 and 6

Cohort 1: Vz/F of EE in Period 2, 5, 8

Cohort 1: Vz/F of LE in Period 2, 5, 8

Cohort 1: Vz/F of Omeprazole in Period 1, 4, 7

Cohort 2: AUCinf of Midazolam in Period 4

Cohort 2: CL/F of Midazolam in Period 1 and 3

Cohort 2: Cmax of Midazolam in Period 1 and 3

Cohort 2: MRAUCinf of 1-Hydroxy Midazolam in Period 1, 3, 4

Cohort 2: Number of Participants With All-Causality and Treatment-Related TEAEs

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

Cohort 2: Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)

Cohort 2: Percentage of Change From Baseline in Body Weight by Period 4 Day 1

Cohort 2: PHQ-9 Total Scores

Cohort 2: t1/2 of Midazolam in Period 1 and 3

Cohort 2: Tmax of Midazolam in Period 1 and 3

Cohort 2: Vz/F of Midazolam in Period 1 and 3