Back to resultsA 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
Primary Purpose
Obesity
Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
PF-07081532
Semaglutide
Sponsored by
About this trial
This is an interventional basic science trial for Obesity focused on measuring Midazolam, Omeprazole, PF-07081532
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
Sites / Locations
- Anaheim Clinical Trials, LLC
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Cohort 1: PF-07081532
Cohort 2: Semaglutide
Arm Description
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.
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
Outcomes
Primary Outcome Measures
Area Under the Curve From Time Zero Extrapolated to Infinite Time (AUCinf) for midazolam and omeprazole.
Will be calculated as permitted by the data.
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.
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
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.
Area Under the Curve From Time Zero Extrapolated to Infinite Time (AUCinf) for midazolam.
Will be calculated as permitted by the data.
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.
Secondary Outcome Measures
Number of Participants Reporting Treatment-Emergent Adverse Events
Number of Participants with Clinical Laboratory Abnormalities
Change in Body Weight
Assessment of mental health as determined by Columbia Suicide Severity Rating Scale (C-SSRS)
Assessment of mental health as determined by Patient Health Questionnaire-9P (HQ 9)
Area Under the Curve From Time Zero Extrapolated to Infinite Time (AUCinf) for midazolam
Will be calculated as permitted by the data.
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.
Area Under the Curve From Time Zero Extrapolated to Infinite Time (AUCinf) for midazolam.
Will be calculated as permitted by the data.
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.
Maximum observed plasma concentration (Cmax) for midazolam and omeprazole.
Time to Reach Maximum Observed Plasma Concentration (Tmax) for midazolam and omeprazole.
Apparent Oral Clearance (CL/F) for midazolam and omeprazole.
Will be calculated as permitted by the data.
Apparent Volume of Distribution (Vz/F) for midazolam and omeprazole.
Will be calculated as permitted by the data.
Plasma Elimination Half-Life (t1/2) for midazolam and omeprazole.
Will be calculated as permitted by the data.
Maximum observed plasma concentration (Cmax) for levonorgestrel and ethinyl estradiol.
Time to Reach Maximum Observed Plasma Concentration (Tmax) for levonorgestrel and ethinyl estradiol.
Apparent Oral Clearance (CL/F) for levonorgestrel and ethinyl estradiol
Will be calculated as permitted by the data.
Apparent Volume of Distribution (Vz/F) for levonorgestrel and ethinyl estradiol.
Will be calculated as permitted by the data.
Plasma Elimination Half-Life (t1/2) for levonorgestrel and ethinyl estradiol.
Will be calculated as permitted by the data.
Metabolite/parent ratio for midazolam (MRAUCinf [1-hydroxymidazolam AUCinf/midazolam AUCinf])
Metabolite/parent ratio for omeprazole (MRAUCinf [5-hydroxyomeprazole AUCinf/omeprazole AUCinf])
Metabolite/parent ratio for midazolam (MRAUCinf [1-hydroxymidazolam AUCinf/midazolam AUCinf])
Area under the plasma concentration-time profile from time zero to time 24 hours (AUC24) for PF-07081532.
Maximum observed plasma concentration (Cmax) for PF-07081532
Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-07081532.
Maximum observed plasma concentration (Cmax) for midazolam.
Time to Reach Maximum Observed Plasma Concentration (Tmax) for midazolam.
Apparent Oral Clearance (CL/F) for midazolam.
Will be calculated as permitted by the data.
Plasma Elimination Half-Life (t1/2) for midazolam.
Will be calculated as permitted by the data
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05671653
Brief Title
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
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 19, 2023 (Actual)
Primary Completion Date
November 4, 2023 (Anticipated)
Study Completion Date
November 4, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obesity
Keywords
Midazolam, Omeprazole, PF-07081532
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
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.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
32 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1: PF-07081532
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 2: Semaglutide
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
PF-07081532
Intervention Description
Experimental oral GLP-1 drug
Intervention Type
Drug
Intervention Name(s)
Semaglutide
Other Intervention Name(s)
Wegovy, Ozempic
Intervention Description
Approved and marketed GLP-1 drug for subcutaneous injection.
Primary Outcome Measure Information:
Title
Area Under the Curve From Time Zero Extrapolated to Infinite Time (AUCinf) for midazolam and omeprazole.
Description
Will be calculated as permitted by the data.
Time Frame
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.
Title
Area Under the Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for midazolam and omeprazole.
Description
Will be calculated if data do not permit calculation of AUCinf.
Time Frame
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.
Title
Area Under the Curve From Time Zero Extrapolated to Infinite Time (AUCinf) for levonorgestrel and ethinyl estradiol.
Description
Will be calculated as permitted by the data
Time Frame
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.
Title
Area Under the Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for levonorgestrel and ethinyl estradiol.
Description
Will be calculated if data do not permit calculation of AUCinf.
Time Frame
, 0.75, 2, 4, 8, 12, 24, 48, 72, 96, and 120 hours post dose in Periods 2, 5, and 8 for Cohort 1
Title
Area Under the Curve From Time Zero Extrapolated to Infinite Time (AUCinf) for midazolam.
Description
Will be calculated as permitted by the data.
Time Frame
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.
Title
Area Under the Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for midazolam.
Description
Will be calculated if data do not permit calculation of AUCinf.
Time Frame
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 Measure Information:
Title
Number of Participants Reporting Treatment-Emergent Adverse Events
Time Frame
Baseline through End of Study (Day 160 Cohort 1 and Day 200 Cohort 2)
Title
Number of Participants with Clinical Laboratory Abnormalities
Time Frame
Baseline through the In-patient Follow-up Visit (Day 135 Cohort 1 and Day 175 Cohort 2)
Title
Change in Body Weight
Time Frame
Baseline through the In-patient Follow-up Visit (Day 135 Cohort 1 and Day 175 Cohort 2)
Title
Assessment of mental health as determined by Columbia Suicide Severity Rating Scale (C-SSRS)
Time Frame
Baseline through the In-patient Follow-up Visit (Day 135 Cohort 1 and Day 175 Cohort 2)
Title
Assessment of mental health as determined by Patient Health Questionnaire-9P (HQ 9)
Time Frame
Baseline through the In-patient Follow-up Visit (Day 135 Cohort 1 and Day 175 Cohort 2)
Title
Area Under the Curve From Time Zero Extrapolated to Infinite Time (AUCinf) for midazolam
Description
Will be calculated as permitted by the data.
Time Frame
0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose in Period 9 for Cohort 1.
Title
Area Under the Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for midazolam.
Description
Will be calculated if data do not permit calculation of AUCinf.
Time Frame
0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose in Period 9 for Cohort 1
Title
Area Under the Curve From Time Zero Extrapolated to Infinite Time (AUCinf) for midazolam.
Description
Will be calculated as permitted by the data.
Time Frame
0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose in Period 4 for Cohort 2
Title
Area Under the Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for midazolam.
Description
Will be calculated if data do not permit calculation of AUCinf.
Time Frame
0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose in Period 4 for Cohort 2.
Title
Maximum observed plasma concentration (Cmax) for midazolam and omeprazole.
Time Frame
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.
Title
Time to Reach Maximum Observed Plasma Concentration (Tmax) for midazolam and omeprazole.
Time Frame
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
Title
Apparent Oral Clearance (CL/F) for midazolam and omeprazole.
Description
Will be calculated as permitted by the data.
Time Frame
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.
Title
Apparent Volume of Distribution (Vz/F) for midazolam and omeprazole.
Description
Will be calculated as permitted by the data.
Time Frame
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.
Title
Plasma Elimination Half-Life (t1/2) for midazolam and omeprazole.
Description
Will be calculated as permitted by the data.
Time Frame
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.
Title
Maximum observed plasma concentration (Cmax) for levonorgestrel and ethinyl estradiol.
Time Frame
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.
Title
Time to Reach Maximum Observed Plasma Concentration (Tmax) for levonorgestrel and ethinyl estradiol.
Time Frame
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.
Title
Apparent Oral Clearance (CL/F) for levonorgestrel and ethinyl estradiol
Description
Will be calculated as permitted by the data.
Time Frame
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.
Title
Apparent Volume of Distribution (Vz/F) for levonorgestrel and ethinyl estradiol.
Description
Will be calculated as permitted by the data.
Time Frame
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.
Title
Plasma Elimination Half-Life (t1/2) for levonorgestrel and ethinyl estradiol.
Description
Will be calculated as permitted by the data.
Time Frame
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.
Title
Metabolite/parent ratio for midazolam (MRAUCinf [1-hydroxymidazolam AUCinf/midazolam AUCinf])
Time Frame
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.
Title
Metabolite/parent ratio for omeprazole (MRAUCinf [5-hydroxyomeprazole AUCinf/omeprazole AUCinf])
Time Frame
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.
Title
Metabolite/parent ratio for midazolam (MRAUCinf [1-hydroxymidazolam AUCinf/midazolam AUCinf])
Time Frame
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.
Title
Area under the plasma concentration-time profile from time zero to time 24 hours (AUC24) for PF-07081532.
Time Frame
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.
Title
Maximum observed plasma concentration (Cmax) for PF-07081532
Time Frame
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.
Title
Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-07081532.
Time Frame
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.
Title
Maximum observed plasma concentration (Cmax) for midazolam.
Time Frame
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.
Title
Time to Reach Maximum Observed Plasma Concentration (Tmax) for midazolam.
Time Frame
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.
Title
Apparent Oral Clearance (CL/F) for midazolam.
Description
Will be calculated as permitted by the data.
Time Frame
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.
Title
Plasma Elimination Half-Life (t1/2) for midazolam.
Description
Will be calculated as permitted by the data
Time Frame
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.
10. Eligibility
Sex
Female
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Anaheim Clinical Trials, LLC
City
Anaheim
State/Province
California
ZIP/Postal Code
92801
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing 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.
Links:
URL
https://pmiform.com/clinical-trial-info-request?StudyID=C3991040
Description
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Learn more about this trial
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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