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

Obesity Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05671653
• Other study ID #: C3991040
• Status: Terminated
• Phase: Phase 1
• Start date: January 19, 2023
• Est. completion date: November 3, 2023

Study information

• Verified date: December 2023
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 32
• Est. completion date: November 3, 2023
• Est. primary completion date: November 3, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Obesity

Intervention

Drug:
• PF-07081532
Experimental oral GLP-1 drug
• Semaglutide
Approved and marketed GLP-1 drug for subcutaneous injection.

Locations

Country	Name	City	State
United States	Anaheim Clinical Trials, LLC	Anaheim	California

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.
Primary	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.
Primary	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
Primary	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.
Primary	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	Number of Participants Reporting Treatment-Emergent Adverse Events		Baseline through End of Study (Day 160 Cohort 1 and Day 200 Cohort 2)
Secondary	Number of Participants with Clinical Laboratory Abnormalities		Baseline through the In-patient Follow-up Visit (Day 135 Cohort 1 and Day 175 Cohort 2)
Secondary	Change in Body Weight		Baseline through the In-patient Follow-up Visit (Day 135 Cohort 1 and Day 175 Cohort 2)
Secondary	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)
Secondary	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)
Secondary	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.
Secondary	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
Secondary	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
Secondary	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.
Secondary	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.
Secondary	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
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.

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