DelfaGLP-1 Atlas

← Trials/Trial dossier/NCT05671653

TerminatedPhase 1Results posted

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

Lead sponsor

Pfizer

Assets

Lotiglipron / Semaglutide

Listed sites

1

Recruiting sites

—

Enrollment

32

actual

Study population

Healthy volunteers, Obesity / overweight

Key I/E criteria

•BMI 30-45.4•Female•Healthy volunteers

Primary endpoints

•Cohort 1•Cohort 2

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT05671653
Org study IDC3991040

Timeline

Milestones

Study first posted2023-01-05actual
Study start2023-01-19actual
Primary completion2023-11-03actual
Study completion2023-11-03actual
Results first posted2024-12-16actual
Last update posted2025-01-14actual

Assets

Investigational agents

LotiglipronSemaglutide

Study populations

Who this study enrolls

Healthy volunteersObesity / overweight

Eligibility

Who can enroll

Minimum age18 Years
SexFemale
Healthy volunteersAccepted

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

Endpoints (96)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Safety / tolerability / PK
88
Weight & body composition
4
Patient-reported / QoL
4

Weight & body composition

4 endpoints
Secondary/registry result

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

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

Body weight, % change

percent change from baseline, improvement

Posted result

GroupValue (median), Percentage Change95% CI
All Participants-8.55-13.0 – -7.1
Secondary/registry result

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

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

Body weight, % change

percent change from baseline, improvement

Posted result

GroupValue (median), Percentage Change95% CI
All Participants-13.15-22.0 – -5.9
Secondary/protocol endpoint

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

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

Body weight, % change

percent change from baseline, improvement

Secondary/protocol endpoint

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

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

Body weight, % change

percent change from baseline, improvement

Patient-reported / QoL

4 endpoints
Secondary/registry result

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

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

descriptive, improvement

Posted result

GroupValue (mean), Score95% CI
All ParticipantsScreening0.3—
Period 1 Day -1 / Midazolam 2 mg + Omeprazole 20 mg0.1—
Period 3 Day 1 / PF-07081532 titration up to 80 mg QD0.1—
Period 3 Day 15 / PF-07081532 titration up to 80 mg QD1.1—
Period 4 Day 1 / PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg1.0—
Period 6 Day 14 / PF-07081532 titration up to 260 mg QD1.6—
Period 6 Day 28 / PF-07081532 titration up to 260 mg QD0.6—
Period 6 Day 42 / PF-07081532 titration up to 260 mg QD0.8—
Period 6 Day 56 / PF-07081532 titration up to 260 mg QD1.1—
Period 6 Day 63 / PF-07081532 titration up to 260 mg QD0.9—
Period 8 Day 6 / PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg0.8—
Follow Up0.1—
Secondary/registry result

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)

descriptive, improvement

Posted result

GroupValue (mean), Score95% CI
All ParticipantsScreening0.1—
Period 1 Day -1 / Midazolam 2 mg0.2—
Period 2 Week 5 / Semaglutide titration up to 2.4 mg QW0.3—
Period 2 Week 9 / Semaglutide titration up to 2.4 mg QW0.1—
Period 2 Week 13 / Semaglutide titration up to 2.4 mg QW0.2—
Period 2 Week 17 / Semaglutide titration up to 2.4 mg QW0.2—
Period 3 Day 2 / Semaglutide 2.4 mg QW + Midazolam 2 mg0.8—
Follow Up0.0—
Secondary/protocol endpoint

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

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

descriptive, improvement

Secondary/protocol endpoint

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)

change from baseline, improvement

Safety / tolerability / PK

88 endpoints
Primary/registry result

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

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

AUC₀–∞

concentration, descriptive

Posted result

GroupValue (geometric_mean), nanogram*hour/milliliter (ng*hr/mL)95% CI
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)39.27—
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)33.30—
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)28.23—
Ratio (%) of Adjusted Geometric Means88.8590% CI80.25 – 98.38

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).

Ratio (%) of Adjusted Geometric Means70.0090% CI55.21 – 88.76

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).

Primary/registry result

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

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

concentration, descriptive

Posted result

GroupValue (geometric_mean), ng*hr/mL95% CI
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)956.3—
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)620.5—
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)602.8—
Ratio (%) of Adjusted Geometric Means57.1990% CI39.27 – 83.29

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).

Ratio (%) of Adjusted Geometric Means29.6890% CI19.60 – 44.94

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).

Primary/registry result

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

concentration, descriptive

Posted result

GroupValue (geometric_mean), picogram*hour/milliliter (pg*hr/mL)95% CI
Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2)31360—
Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5)42120—
Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)60020—
Ratio (%) of Adjusted Geometric Means119.8690% CI108.97 – 131.85

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).

Ratio (%) of Adjusted Geometric Means185.4590% CI108.00 – 318.44

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)

Primary/registry result

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

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

AUC₀–∞

concentration, descriptive

Posted result

GroupValue (geometric_mean), pg*hr/mL95% CI
Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2)754.5—
Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5)765.5—
Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)701.1—
Ratio (%) of Adjusted Geometric Means103.1790% CI95.09 – 111.93

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).

Ratio (%) of Adjusted Geometric Means90.2090% CI60.24 – 135.06

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)

Primary/registry result

Cohort 2: AUCinf of Midazolam in Period 1 and 3

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

AUC₀–∞

concentration, descriptive

Posted result

GroupValue (geometric_mean), ng*hr/mL95% CI
Cohort 2: Midazolam 2 mg (Period 1)34.43—
Cohort 2: Semaglutide 2.4 mg QW + Midazolam 2 mg (Period 3)34.60—
Ratio (%) of Adjusted Geometric Means92.8890% CI79.97 – 107.87

Reference: Cohort 2: Midazolam 2 mg (Period 1). Test: Cohort 2: Semaglutide 2.4 mg QW + Midazolam 2 mg (Period 3).

Primary/protocol endpoint

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

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

AUC₀–∞

concentration, descriptive

Primary/protocol endpoint

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

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

concentration, descriptive

Primary/protocol endpoint

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

AUC₀–∞

concentration, descriptive

Primary/protocol endpoint

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

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

AUC₀–∞

concentration, descriptive

Primary/protocol endpoint

Cohort 2: AUCinf of Midazolam in Period 1 and 3

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

AUC₀–∞

concentration, descriptive

Secondary/registry result

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

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

Treatment-emergent AEs (any)

descriptive, event

Posted result

GroupValue (count_of_participants), Participants95% CI
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)Number of participants with all-causality TEAEs1—
Number of participants with all-causality SAEs0—
Number of participants with treatment-related TEAEs0—
Number of participants with treatment-related SAEs0—
Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2)Number of participants with all-causality TEAEs2—
Number of participants with all-causality SAEs0—
Number of participants with treatment-related TEAEs1—
Number of participants with treatment-related SAEs0—
Cohort 1: PF-07081532 Titration up to 80 mg QD (Period 3)Number of participants with all-causality TEAEs14—
Number of participants with all-causality SAEs0—
Number of participants with treatment-related TEAEs14—
Number of participants with treatment-related SAEs0—
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)Number of participants with all-causality TEAEs2—
Number of participants with all-causality SAEs0—
Number of participants with treatment-related TEAEs2—
Number of participants with treatment-related SAEs0—
Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5)Number of participants with all-causality TEAEs6—
Number of participants with all-causality SAEs0—
Number of participants with treatment-related TEAEs5—
Number of participants with treatment-related SAEs0—
Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6)Number of participants with all-causality TEAEs15—
Number of participants with all-causality SAEs0—
Number of participants with treatment-related TEAEs15—
Number of participants with treatment-related SAEs0—
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)Number of participants with all-causality TEAEs1—
Number of participants with all-causality SAEs0—
Number of participants with treatment-related TEAEs1—
Number of participants with treatment-related SAEs0—
Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)Number of participants with all-causality TEAEs2—
Number of participants with all-causality SAEs0—
Number of participants with treatment-related TEAEs2—
Number of participants with treatment-related SAEs0—
Cohort 1: Midazolam 2 mg (Period 9)Number of participants with all-causality TEAEs2—
Number of participants with all-causality SAEs0—
Number of participants with treatment-related TEAEs2—
Number of participants with treatment-related SAEs0—
Secondary/registry result

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

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

descriptive

Posted result

GroupValue (count_of_participants), Participants95% CI
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)0—
Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2)0—
Cohort 1: PF-07081532 Titration up to 80 mg QD (Period 3)9—
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)0—
Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5)3—
Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6)14—
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)3—
Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)6—
Cohort 1: Midazolam 2 mg (Period 9)7—
Secondary/registry result

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

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

event count, event

componentscompleted suicide, suicide attempt, preparatory acts towards imminent suicidal behavior, suicidal ideation, self injurious behavior no suicidal intent

Posted result

GroupValue (count_of_participants), Participants95% CI
All Participants0—
Secondary/registry result

Cohort 1: AUCinf of Midazolam in Period 9

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

AUC₀–∞

concentration, descriptive

Posted result

GroupValue (geometric_mean), ng*hr/mL95% CI
Cohort 1: Midazolam 2 mg (Period 9)39.80—
Secondary/registry result

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

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

Cmax

concentration, descriptive

Posted result

GroupValue (geometric_mean), ng/mL95% CI
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)6.613—
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)6.705—
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)6.804—
Secondary/registry result

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

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

Tmax

descriptive

Posted result

GroupValue (median), hour95% CI
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)1.500.500 – 3.00
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)0.5000.500 – 2.00
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)0.7670.500 – 2.00
Secondary/registry result

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

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

descriptive

Posted result

GroupValue (geometric_mean), L/hr95% CI
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)50.94—
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)60.08—
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)70.91—
Secondary/registry result

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

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

descriptive

Posted result

GroupValue (geometric_mean), Liter (L)95% CI
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)544.9—
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)605.3—
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)664.5—
Secondary/registry result

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

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

Half-life

descriptive

Posted result

GroupValue (mean), hour95% CI
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)7.539—
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)7.078—
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)6.659—
Secondary/registry result

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

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

Cmax

concentration, descriptive

Posted result

GroupValue (geometric_mean), ng/mL95% CI
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)266.4—
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)88.42—
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)169.9—
Secondary/registry result

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

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

Tmax

descriptive

Posted result

GroupValue (median), hour95% CI
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)5.992.00 – 14.3
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)8.334.00 – 23.4
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)11.16.00 – 23.4
Secondary/registry result/low confidence

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

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

descriptive

Posted result

GroupValue (geometric_mean), L/hr95% CI
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)17.19—
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)21.43—
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)17.26—
Secondary/registry result

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

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

descriptive

Posted result

GroupValue (geometric_mean), L95% CI
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)41.26—
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)49.81—
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)44.48—
Secondary/registry result

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

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

Half-life

descriptive

Posted result

GroupValue (mean), hour95% CI
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)1.793—
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)1.705—
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)1.800—
Secondary/registry result

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

Cmax

concentration, descriptive

Posted result

GroupValue (geometric_mean), pg/mL95% CI
Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2)1919—
Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5)1532—
Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)1684—
Secondary/registry result

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

Tmax

descriptive

Posted result

GroupValue (median), hour95% CI
Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2)2.000.750 – 4.00
Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5)3.020.750 – 12.0
Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)4.100.750 – 23.5
Secondary/registry result

Cohort 1: CL/F 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

descriptive

Posted result

GroupValue (geometric_mean), L/hr95% CI
Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2)6.043—
Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5)3.887—
Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)2.265—
Secondary/registry result

Cohort 1: Vz/F 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

descriptive

Posted result

GroupValue (geometric_mean), L95% CI
Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2)380.0—
Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5)251.7—
Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)133.6—
Secondary/registry result

Cohort 1: t1/2 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

Half-life

descriptive

Posted result

GroupValue (mean), hour95% CI
Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2)44.33—
Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5)45.25—
Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)41.26—
Secondary/registry result

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

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

Cmax

concentration, descriptive

Posted result

GroupValue (geometric_mean), pg/mL95% CI
Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2)42.44—
Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5)37.82—
Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)34.03—
Secondary/registry result

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

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

Tmax

descriptive

Posted result

GroupValue (median), hour95% CI
Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2)2.000.750 – 4.00
Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5)2.000.750 – 8.00
Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)2.000.750 – 4.20
Secondary/registry result

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

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

descriptive

Posted result

GroupValue (geometric_mean), L/hr95% CI
Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2)238.6—
Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5)235.3—
Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)256.9—
Secondary/registry result

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

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

descriptive

Posted result

GroupValue (geometric_mean), L95% CI
Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2)7565—
Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5)8517—
Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)7998—
Secondary/registry result

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

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

Half-life

descriptive

Posted result

GroupValue (mean), hour95% CI
Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2)22.42—
Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5)25.54—
Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)22.03—
Secondary/registry result

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

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

ratio, descriptive

Posted result

GroupValue (geometric_mean), Ratio95% CI
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)0.3143—
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)0.4480—
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)0.4314—
Secondary/registry result

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

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

ratio, descriptive

Posted result

GroupValue (geometric_mean), Ratio95% CI
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)0.3752—
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)0.4060—
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)0.3790—
Secondary/registry result

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

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

AUC₀–∞

concentration, descriptive

Posted result

GroupValue (geometric_mean), ng*hr/mL95% CI
Cohort 1: PF-07081532 Titration up to 80 mg QD (Period 3)250200—
Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6)1239000—
Secondary/registry result

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

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

Cmax

concentration, descriptive

Posted result

GroupValue (geometric_mean), ng/mL95% CI
Cohort 1: PF-07081532 Titration up to 80 mg QD (Period 3)15820—
Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6)70710—
Secondary/registry result

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

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

Tmax

descriptive

Posted result

GroupValue (median), hour95% CI
Cohort 1: PF-07081532 Titration up to 80 mg QD (Period 3)6.002.00 – 14.0
Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6)6.004.00 – 10.0
Secondary/registry result

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

Treatment-emergent AEs (any)

descriptive

Posted result

GroupValue (count_of_participants), Participants95% CI
Cohort 2: Midazolam 2 mg (Period 1)Number of participants with all-causality TEAEs4—
Number of participants with all-causality SAEs0—
Number of participants with treatment-related TEAEs0—
Number of participants with treatment-related SAEs0—
Cohort 2: Semaglutide Titration up to 2.4 mg QW (Period 2)Number of participants with all-causality TEAEs11—
Number of participants with all-causality SAEs0—
Number of participants with treatment-related TEAEs8—
Number of participants with treatment-related SAEs0—
Cohort 2: Semaglutide 2.4 mg QW + Midazolam 2 mg (Period 3)Number of participants with all-causality TEAEs11—
Number of participants with all-causality SAEs0—
Number of participants with treatment-related TEAEs11—
Number of participants with treatment-related SAEs0—
Cohort 2: Midazolam 2 mg (Period 4)Number of participants with all-causality TEAEs3—
Number of participants with all-causality SAEs0—
Number of participants with treatment-related TEAEs1—
Number of participants with treatment-related SAEs0—
Secondary/registry result

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

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

descriptive

Posted result

GroupValue (count_of_participants), Participants95% CI
Cohort 2: Midazolam 2 mg (Period 1)0—
Cohort 2: Semaglutide Titration up to 2.4 mg QW (Period 2)11—
Cohort 2: Semaglutide 2.4 mg QW + Midazolam 2 mg (Period 3)7—
Cohort 2: Midazolam 2 mg (Period 4)8—
Secondary/registry result

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)

event count, event

componentscompleted suicide, suicide attempt, preparatory acts towards imminent suicidal behavior, suicidal ideation, self injurious behavior no suicidal intent

Posted result

GroupValue (count_of_participants), Participants95% CI
All Participants0—
Secondary/registry result

Cohort 2: AUCinf of Midazolam in Period 4

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

AUC₀–∞

concentration, descriptive

Posted result

GroupValue (geometric_mean), ng*hr/mL95% CI
Cohort 2: Midazolam 2 mg (Period 4)33.67—
Secondary/registry result

Cohort 2: Cmax of Midazolam in Period 1 and 3

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

Cmax

concentration, descriptive

Posted result

GroupValue (geometric_mean), ng/mL95% CI
Cohort 2: Midazolam 2 mg (Period 1)6.234—
Cohort 2: Semaglutide 2.4 mg QW + Midazolam 2 mg (Period 3)6.483—
Secondary/registry result

Cohort 2: Tmax of Midazolam in Period 1 and 3

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

Tmax

concentration, descriptive

Posted result

GroupValue (median), hour95% CI
Cohort 2: Midazolam 2 mg (Period 1)1.000.500 – 2.08
Cohort 2: Semaglutide 2.4 mg QW + Midazolam 2 mg (Period 3)1.000.500 – 4.00
Secondary/registry result

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

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

descriptive

Posted result

GroupValue (geometric_mean), L/hr95% CI
Cohort 2: Midazolam 2 mg (Period 1)58.07—
Cohort 2: Semaglutide 2.4 mg QW + Midazolam 2 mg (Period 3)57.80—
Secondary/registry result

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

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

descriptive

Posted result

GroupValue (geometric_mean), L95% CI
Cohort 2: Midazolam 2 mg (Period 1)618.2—
Cohort 2: Semaglutide 2.4 mg QW + Midazolam 2 mg (Period 3)516.5—
Secondary/registry result

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

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

Half-life

descriptive

Posted result

GroupValue (mean), hour95% CI
Cohort 2: Midazolam 2 mg (Period 1)7.527—
Cohort 2: Semaglutide 2.4 mg QW + Midazolam 2 mg (Period 3)6.347—
Secondary/registry result

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

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

ratio, descriptive

Posted result

GroupValue (geometric_mean), Ratio95% CI
Cohort 2: Midazolam 2 mg (Period 1)0.3262—
Cohort 2: Semaglutide 2.4 mg QW + Midazolam 2 mg (Period 3)0.3818—
Cohort 2: Midazolam 2 mg (Period 4)0.3221—
Secondary/protocol endpoint

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

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

Treatment-emergent AEs (any)

event count, event

Secondary/protocol endpoint

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

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

descriptive

Secondary/protocol endpoint

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

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

event count, event

componentscompleted suicide, suicide attempt, preparatory acts towards imminent suicidal behavior, suicidal ideation, self injurious behavior no suicidal intent

Secondary/protocol endpoint

Cohort 1: AUCinf of Midazolam in Period 9

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

AUC₀–∞

concentration, descriptive

Secondary/protocol endpoint

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

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

Cmax

concentration, descriptive

Secondary/protocol endpoint

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

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

Tmax

descriptive

Secondary/protocol endpoint

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

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

AUC₀–∞

concentration, descriptive

Secondary/protocol endpoint

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

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

descriptive

Secondary/protocol endpoint

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

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

Half-life

descriptive

Secondary/protocol endpoint

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

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

Cmax

concentration, descriptive

Secondary/protocol endpoint

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

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

Tmax

concentration, descriptive

Secondary/protocol endpoint

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

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

AUC₀–∞

concentration, descriptive

Secondary/protocol endpoint

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

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

descriptive

Secondary/protocol endpoint

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

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

Half-life

descriptive

Secondary/protocol endpoint

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

Cmax

concentration, descriptive

Secondary/protocol endpoint

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

Tmax

descriptive

Secondary/protocol endpoint

Cohort 1: CL/F 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

descriptive

Secondary/protocol endpoint

Cohort 1: Vz/F 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

descriptive

Secondary/protocol endpoint

Cohort 1: t1/2 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

Half-life

descriptive

Secondary/protocol endpoint

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

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

Cmax

concentration, descriptive

Secondary/protocol endpoint

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

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

Tmax

descriptive

Secondary/protocol endpoint

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

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

descriptive

Secondary/protocol endpoint

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

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

descriptive

Secondary/protocol endpoint

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

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

Half-life

descriptive

Secondary/protocol endpoint

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

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

ratio, descriptive

Secondary/protocol endpoint

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

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

AUC₀–∞

concentration, descriptive

Secondary/protocol endpoint

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

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

AUC₀–∞

concentration, descriptive

Secondary/protocol endpoint

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

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

Cmax

concentration, descriptive

Secondary/protocol endpoint

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

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

Tmax

concentration, descriptive

Secondary/protocol endpoint

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

Treatment-emergent AEs (any)

event count, event

Secondary/protocol endpoint

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

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

descriptive, event

Secondary/protocol endpoint

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)

event count, event

componentscompleted suicide, suicide attempt, preparatory acts imminent suicidal behavior, suicidal ideation, self injurious behavior no suicidal intent

Secondary/protocol endpoint

Cohort 2: AUCinf of Midazolam in Period 4

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

AUC₀–∞

concentration, descriptive

Secondary/protocol endpoint

Cohort 2: Cmax of Midazolam in Period 1 and 3

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

Cmax

concentration, descriptive

Secondary/protocol endpoint

Cohort 2: Tmax of Midazolam in Period 1 and 3

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

Tmax

descriptive

Secondary/protocol endpoint

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

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

descriptive

Secondary/protocol endpoint

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

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

descriptive

Secondary/protocol endpoint

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

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

Half-life

descriptive

Secondary/protocol endpoint

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

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

AUC₀–∞

concentration, descriptive

Publications (1)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2
Snapshot dateJuly 1, 2026
Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)
Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.