Clinical trial NCT05671653: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Obesity
Keywords: Midazolam
Omeprazole
PF-07081532
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2023-01-05
Enrollment: 32
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: For Cohort 1 Periods 1, 4, and 7: At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period
measure: 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
timeFrame: For Cohort 1 Periods 1, 4, and 7: At 0 (prior to omeprazole dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period
measure: Cohort 1: AUClast of Levonorgestrel (LE) in Periods 2, 5,and 8
timeFrame: For Cohort 1 Periods 2, 5, and 8: At 0 (prior to LE dose), 0.75, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post LE dose on Day 1 of each period
measure: Cohort 1: AUCinf of Ethinyl Estradiol (EE) in Periods 2, 5,and 8
timeFrame: For Cohort 1 Periods 2, 5, and 8: At 0 (prior to EE dose), 0.75, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post LE dose on Day 1 of each period
measure: Cohort 2: AUCinf of Midazolam in Period 1 and 3
timeFrame: For Cohort 2 Periods 1 and 3: At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period
Secondary outcomes:
measure: Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs
timeFrame: From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1
measure: Cohort 1: Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
timeFrame: From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1
measure: Cohort 1: Percentage of Change From Baseline in Body Weight by Period 9 Day 1
timeFrame: From baseline (last pre-dose measurement in Period 1) to Period 9 Day 1 (Day 124)
measure: 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
timeFrame: Screening, Study Day -1 (D-1) (ie, Period 1 Day -1 [P1D-1]), D7 (P3D1), D21 (P3D15), D35 (P4D1), D54 (P6D14), D68 (P6D28), D82 (P6D42), D96 (P6D56), D103 (P6D63), D110 (P8D6) and at follow up visit D132-135
measure: Cohort 1: Patient Health Quessionare-9 (PHQ-9) Total Scores
timeFrame: Screening, Study Day -1 (D-1) (ie, Period 1 Day -1 [P1D-1]), D7 (P3D1), D21 (P3D15), D35 (P4D1), D54 (P6D14), D68 (P6D28), D82 (P6D42), D96 (P6D56), D103 (P6D63), D110 (P8D6) and at follow up visit D132-135
measure: Cohort 1: AUCinf of Midazolam in Period 9
timeFrame: For Cohort 1 Period 9: At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1
measure: Cohort 1: Maximum Observed Concentration (Cmax) of Midazolam in Period 1, 4, 7
timeFrame: For Cohort 1 Periods 1, 4, and 7: At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period
measure: Cohort 1: Time for Cmax (Tmax) of Midazolam in Period 1, 4, 7
timeFrame: For Cohort 1 Periods 1, 4, and 7: At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period
measure: Cohort 1: Apparent Clearance (CL/F) of Midazolam in Period 1, 4, 7
timeFrame: For Cohort 1 Periods 1, 4, and 7: At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period
measure: Cohort 1: Apparent Volume of Distribution (Vz/F) of Midazolam in Period 1, 4, 7
timeFrame: For Cohort 1 Periods 1, 4, and 7: At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period
measure: Cohort 1: Terminal Half-Life (t1/2) of Midazolam in Period 1, 4, 7
timeFrame: For Cohort 1 Periods 1, 4, and 7: At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period
measure: Cohort 1: Cmax of Omeprazole in Period 1, 4, 7
timeFrame: For Cohort 1 Periods 1, 4, and 7: At 0 (prior to omeprazole dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period
measure: Cohort 1: Tmax of Omeprazole in Period 1, 4, 7
timeFrame: For Cohort 1 Periods 1, 4, and 7: At 0 (prior to omeprazole dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period
measure: Cohort 1: CL/F of Omeprazole in Period 1, 4, 7
timeFrame: For Cohort 1 Periods 1, 4, and 7: At 0 (prior to omeprazole dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period
measure: Cohort 1: Vz/F of Omeprazole in Period 1, 4, 7
timeFrame: For Cohort 1 Periods 1, 4, and 7: At 0 (prior to omeprazole dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period
measure: Cohort 1: t1/2 of Omeprazole in Period 1, 4, 7
timeFrame: For Cohort 1 Periods 1, 4, and 7: At 0 (prior to omeprazole dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period
measure: Cohort 1: Cmax of LE in Period 2, 5, 8
timeFrame: For Cohort 1 Periods 2, 5, and 8: At 0 (prior to LE dose), 0.75, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post LE dose on Day 1 of each period
measure: Cohort 1: Tmax of LE in Period 2, 5, 8
timeFrame: For Cohort 1 Periods 2, 5, and 8: At 0 (prior to LE dose), 0.75, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post LE dose on Day 1 of each period
measure: Cohort 1: CL/F of LE in Period 2, 5, 8
timeFrame: For Cohort 1 Periods 2, 5, and 8: At 0 (prior to LE dose), 0.75, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post LE dose on Day 1 of each period
measure: Cohort 1: Vz/F of LE in Period 2, 5, 8
timeFrame: For Cohort 1 Periods 2, 5, and 8: At 0 (prior to LE dose), 0.75, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post LE dose on Day 1 of each period
measure: Cohort 1: t1/2 of LE in Period 2, 5, 8
timeFrame: For Cohort 1 Periods 2, 5, and 8: At 0 (prior to LE dose), 0.75, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post LE dose on Day 1 of each period
measure: Cohort 1: Cmax of EE in Period 2, 5, 8
timeFrame: For Cohort 1 Periods 2, 5, and 8: At 0 (prior to EE dose), 0.75, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post LE dose on Day 1 of each period
measure: Cohort 1: Tmax of EE in Period 2, 5, 8
timeFrame: For Cohort 1 Periods 2, 5, and 8: At 0 (prior to EE dose), 0.75, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post LE dose on Day 1 of each period
measure: Cohort 1: CL/F of EE in Period 2, 5, 8
timeFrame: For Cohort 1 Periods 2, 5, and 8: At 0 (prior to EE dose), 0.75, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post LE dose on Day 1 of each period
measure: Cohort 1: Vz/F of EE in Period 2, 5, 8
timeFrame: For Cohort 1 Periods 2, 5, and 8: At 0 (prior to EE dose), 0.75, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post LE dose on Day 1 of each period
measure: Cohort 1: t1/2 of EE in Period 2, 5, 8
timeFrame: For Cohort 1 Periods 2, 5, and 8: At 0 (prior to EE dose), 0.75, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post LE dose on Day 1 of each period
measure: Cohort 1: Metabolite/Parent Ratio for AUCinf (MRAUCinf) of 1-Hydroxy Midazolam in Period 1, 4, 7
timeFrame: For Cohort 1 Periods 1, 4, and 7: At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period
measure: Cohort 1: MRAUCinf of 5-Hydroxy Omeprazole in Period 1, 4, 7
timeFrame: For Cohort 1 Periods 1, 4, and 7: At 0 (prior to omeprazole dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period
measure: Cohort 1: Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours (AUC24) of PF-07081532 in Period 3 and 6
timeFrame: For Cohort 1 Periods 3 and 6: At 0 , 0.5, 1, 2, 4, 6, 8, 10, 14, and 24 hours post PF-07081532 dose on Day 28 of Period 3 and Day 63 of Period 6
measure: Cohort 1: Cmax of PF-07081532 in Period 3 and 6
timeFrame: For Cohort 1 Periods 3 and 6: At 0 , 0.5, 1, 2, 4, 6, 8, 10, 14, and 24 hours post PF-07081532 dose on Day 28 of Period 3 and Day 63 of Period 6
measure: Cohort 1: Tmax of PF-07081532 in Period 3 and 6
timeFrame: For Cohort 1 Periods 3 and 6: At 0 , 0.5, 1, 2, 4, 6, 8, 10, 14, and 24 hours post PF-07081532 dose on Day 28 of Period 3 and Day 63 of Period 6
measure: Cohort 2: Number of Participants With All-Causality and Treatment-Related TEAEs
timeFrame: From first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2
measure: Cohort 2: Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
timeFrame: From first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2
measure: Cohort 2: Percentage of Change From Baseline in Body Weight by Period 4 Day 1
timeFrame: From baseline (last pre-dose measurement in Period 1) to Period 4 Day 1 (Day 165)
measure: 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
timeFrame: Screening, D-1 (P1D-1), P2 Week 5 [W5], P2W9, P2W13, P2W17, D150 (P3D2), at follow up visit (Day 172-175)
measure: Cohort 2: PHQ-9 Total Scores
timeFrame: Screening, D-1 (P1D-1), P2 Week 5 [W5], P2W9, P2W13, P2W17, D150 (P3D2), at follow up visit (Day 172-175)
measure: Cohort 2: AUCinf of Midazolam in Period 4
timeFrame: For Cohort 2 Period 4: At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14 and 24 hours post midazolam dose on Day 1
measure: Cohort 2: Cmax of Midazolam in Period 1 and 3
timeFrame: For Cohort 2 Periods 1 and 3: At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period
measure: Cohort 2: Tmax of Midazolam in Period 1 and 3
timeFrame: For Cohort 2 Periods 1 and 3: At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period
measure: Cohort 2: CL/F of Midazolam in Period 1 and 3
timeFrame: For Cohort 2 Periods 1 and 3: At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period
measure: Cohort 2: Vz/F of Midazolam in Period 1 and 3
timeFrame: For Cohort 2 Periods 1 and 3: At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period
measure: Cohort 2: t1/2 of Midazolam in Period 1 and 3
timeFrame: For Cohort 2 Periods 1 and 3: At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period
measure: Cohort 2: MRAUCinf of 1-Hydroxy Midazolam in Period 1, 3, 4
timeFrame: For Cohort 2 Periods 1 and 3: At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Anaheim Clinical Trials, LLC
state: California
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: