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

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.

Study Overview

• Status: Terminated
• Conditions: Obesity
• Intervention / Treatment: Drug: PF-07081532; Drug: Semaglutide

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: PF-07081532; Cohort 1 is an open-label, 9 period, fixed-sequence design to evaluate the effect of 2 steady state dose levels of PF-07081532 on the SD pharmacokinetics of midazolam and omeprazole, administered simultaneously, and an OC (LE/EE) in otherwise healthy obese adult female participants with a BMI ≥30 kg/m2.	Drug: PF-07081532; Experimental oral GLP-1 drug
Experimental: Cohort 2: Semaglutide; Cohort 2 is an open label, 4-period, fixed-sequence design to evaluate the effect of steady state semaglutide on the SD PK of midazolam in obese adult female participants with a BMI ≥30 kg/m2	Drug: Semaglutide; Approved and marketed GLP-1 drug for subcutaneous injection.; Other Names: Wegovy, Ozempic

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve From Time Zero Extrapolated to Infinite Time (AUCinf) for midazolam and omeprazole.	Will be calculated as permitted by the data.	0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose in Periods 1, 4, and 7 for Cohort 1.
Area Under the Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for midazolam and omeprazole.	Will be calculated if data do not permit calculation of AUCinf.	0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose in Periods 1, 4, and 7 for Cohort 1.
Area Under the Curve From Time Zero Extrapolated to Infinite Time (AUCinf) for levonorgestrel and ethinyl estradiol.	Will be calculated as permitted by the data	0, 0.75, 2, 4, 8, 12, 24, 48, 72, 96, and 120 hours post dose in Periods 2, 5, and 8 for Cohort 1.
Area Under the Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for levonorgestrel and ethinyl estradiol.	Will be calculated if data do not permit calculation of AUCinf.	, 0.75, 2, 4, 8, 12, 24, 48, 72, 96, and 120 hours post dose in Periods 2, 5, and 8 for Cohort 1
Area Under the Curve From Time Zero Extrapolated to Infinite Time (AUCinf) for midazolam.	Will be calculated as permitted by the data.	0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose in Periods 1 and 3 for Cohort 2.
Area Under the Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for midazolam.	Will be calculated if data do not permit calculation of AUCinf.	0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose in Periods 1 and 3 for Cohort 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Reporting Treatment-Emergent Adverse Events		Baseline through End of Study (Day 160 Cohort 1 and Day 200 Cohort 2)
Number of Participants with Clinical Laboratory Abnormalities		Baseline through the In-patient Follow-up Visit (Day 135 Cohort 1 and Day 175 Cohort 2)
Change in Body Weight		Baseline through the In-patient Follow-up Visit (Day 135 Cohort 1 and Day 175 Cohort 2)
Assessment of mental health as determined by Columbia Suicide Severity Rating Scale (C-SSRS)		Baseline through the In-patient Follow-up Visit (Day 135 Cohort 1 and Day 175 Cohort 2)
Assessment of mental health as determined by Patient Health Questionnaire-9P (HQ 9)		Baseline through the In-patient Follow-up Visit (Day 135 Cohort 1 and Day 175 Cohort 2)
Area Under the Curve From Time Zero Extrapolated to Infinite Time (AUCinf) for midazolam	Will be calculated as permitted by the data.	0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose in Period 9 for Cohort 1.
Area Under the Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for midazolam.	Will be calculated if data do not permit calculation of AUCinf.	0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose in Period 9 for Cohort 1
Area Under the Curve From Time Zero Extrapolated to Infinite Time (AUCinf) for midazolam.	Will be calculated as permitted by the data.	0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose in Period 4 for Cohort 2
Area Under the Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for midazolam.	Will be calculated if data do not permit calculation of AUCinf.	0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose in Period 4 for Cohort 2.
Maximum observed plasma concentration (Cmax) for midazolam and omeprazole.		0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose in Periods 1, 4, and 7 for Cohort 1.
Time to Reach Maximum Observed Plasma Concentration (Tmax) for midazolam and omeprazole.		0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose in Periods 1, 4, and 7 for Cohort 1
Apparent Oral Clearance (CL/F) for midazolam and omeprazole.	Will be calculated as permitted by the data.	0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose in Periods 1, 4, and 7 for Cohort 1.
Apparent Volume of Distribution (Vz/F) for midazolam and omeprazole.	Will be calculated as permitted by the data.	0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose in Periods 1, 4, and 7 for Cohort 1.
Plasma Elimination Half-Life (t1/2) for midazolam and omeprazole.	Will be calculated as permitted by the data.	0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose in Periods 1, 4, and 7 for Cohort 1.
Maximum observed plasma concentration (Cmax) for levonorgestrel and ethinyl estradiol.		0, 0.75, 2, 4, 8, 12, 24, 48, 72, 96, and 120 hours post dose in Periods 2, 5, and 8 for Cohort 1.
Time to Reach Maximum Observed Plasma Concentration (Tmax) for levonorgestrel and ethinyl estradiol.		0, 0.75, 2, 4, 8, 12, 24, 48, 72, 96, and 120 hours post dose in Periods 2, 5, and 8 for Cohort 1.
Apparent Oral Clearance (CL/F) for levonorgestrel and ethinyl estradiol	Will be calculated as permitted by the data.	0, 0.75, 2, 4, 8, 12, 24, 48, 72, 96, and 120 hours post dose in Periods 2, 5, and 8 for Cohort 1.
Apparent Volume of Distribution (Vz/F) for levonorgestrel and ethinyl estradiol.	Will be calculated as permitted by the data.	0, 0.75, 2, 4, 8, 12, 24, 48, 72, 96, and 120 hours post dose in Periods 2, 5, and 8 for Cohort 1.
Plasma Elimination Half-Life (t1/2) for levonorgestrel and ethinyl estradiol.	Will be calculated as permitted by the data.	0, 0.75, 2, 4, 8, 12, 24, 48, 72, 96, and 120 hours post dose in Periods 2, 5, and 8 for Cohort 1.
Metabolite/parent ratio for midazolam (MRAUCinf [1-hydroxymidazolam AUCinf/midazolam AUCinf])		0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose in Periods 1, 4, and 7 for Cohort 1.
Metabolite/parent ratio for omeprazole (MRAUCinf [5-hydroxyomeprazole AUCinf/omeprazole AUCinf])		0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose in Periods 1, 4, and 7 for Cohort 1.
Metabolite/parent ratio for midazolam (MRAUCinf [1-hydroxymidazolam AUCinf/midazolam AUCinf])		0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose in Periods 1 and 3 for Cohort 2.
Area under the plasma concentration-time profile from time zero to time 24 hours (AUC24) for PF-07081532.		0, 0.5, 1, 2, 4, 6, 8, 10, 14, and 24 hours post dose in Period 3 Day 28 and Period 6 Day 63.
Maximum observed plasma concentration (Cmax) for PF-07081532		0, 0.5, 1, 2, 4, 6, 8, 10, 14, and 24 hours post dose in Period 3 Day 28 and Period 6 Day 63.
Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-07081532.		0, 0.5, 1, 2, 4, 6, 8, 10, 14, and 24 hours post dose in Period 3 Day 28 and Period 6 Day 63.
Maximum observed plasma concentration (Cmax) for midazolam.		0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose in Periods 1 and 3 for Cohort 2.
Time to Reach Maximum Observed Plasma Concentration (Tmax) for midazolam.		0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose in Periods 1 and 3 for Cohort 2.
Apparent Oral Clearance (CL/F) for midazolam.	Will be calculated as permitted by the data.	0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose in Periods 1 and 3 for Cohort 2.
Plasma Elimination Half-Life (t1/2) for midazolam.	Will be calculated as permitted by the data	0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose in Periods 1 and 3 for Cohort 2.

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2023
• Primary Completion (Actual): November 3, 2023
• Study Completion (Actual): November 3, 2023

Study Registration Dates

• First Submitted: December 19, 2022
• First Submitted That Met QC Criteria: January 3, 2023
• First Posted (Actual): January 5, 2023

Study Record Updates

• Last Update Posted (Actual): December 26, 2023
• Last Update Submitted That Met QC Criteria: December 19, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Midazolam; Omeprazole; PF-07081532
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity
• Other Study ID Numbers: C3991040

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No