ObesityPhase 1NCT05671653

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 study testing PF-07081532 and Semaglutide in people with Obesity, run by Pfizer at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 18 years and older, women onlyHealthy volunteers can take part
Conditions the study is for: Obesity
What is being tested?: PF-07081532 and Semaglutide
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 32 participants
Where: 1 siteUnited States
Study dates: 19 Jan 2023to 3 Nov 2023
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
Women only
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Healthy (no clinically relevant abnormalities)
BMI 30.0-45.4 inclusive

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

Anaheim Clinical Trials, LLC
Anaheim, California, 92801

Other trials in United States

About this study

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

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.

Conditions: Obesity
Being tested: PF-07081532, Semaglutide
Keywords: Midazolam, Omeprazole, PF-07081532
Medical subject headings: Obesity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PF-07081532Drug
Experimental oral GLP-1 drug
SemaglutideDrug
Also called Wegovy, Ozempic
Approved and marketed GLP-1 drug for subcutaneous injection.

Study groups in NCT05671653
Study group	Role	What they receive
Cohort 1: PF-07081532	Experimental	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. Receives: Drug: PF-07081532
Cohort 2: Semaglutide	Experimental	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 Receives: Drug: Semaglutide

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Midazolam was given on Day 1 in Period 1, 4, 7 of Cohort 1 and blood samples were collected for midazolam pharmacokinetic (PK) at the preset time points described in the Time Frame. AUCinf calculated area under the plasma concentration-time profile from time 0 extrapolated to infinite time.
Measured: 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
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
Omeprazole was given on Day 1 in Period 1, 4, 7 of Cohort 1 and blood samples were collected for omeprazole PK at the preset time points described in the Time Frame. AUClast calculated area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration.
Measured: 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
Cohort 1: AUClast of Levonorgestrel (LE) in Periods 2, 5,and 8
LE was given on Day 1 in Period 2, 5, 8 of Cohort 1 and blood samples were collected for LE PK at the preset time points described in the Time Frame. AUClast calculated area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration.
Measured: 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
Cohort 1: AUCinf of Ethinyl Estradiol (EE) in Periods 2, 5,and 8
EE was given on Day 1 in Period 2, 5, 8 of Cohort 1 and blood samples were collected for EE PK at the preset time points described in the Time Frame. AUCinf calculated area under the plasma concentration-time profile from time 0 extrapolated to infinite time.
Measured: 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
Cohort 2: AUCinf of Midazolam in Period 1 and 3
Midazolam was given on Day 1 in Period 1 and 3 of Cohort 2 and blood samples were collected for midazolam pharmacokinetic (PK) at the preset time points described in the Time Frame. AUCinf calculated area under the plasma concentration-time profile from time 0 extrapolated to infinite time.
Measured: 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 (43)

Cohort 1: Number of Participants With All-Causality and Treatment-Related TEAEs
An adverse event (AE) was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. Treatment-related AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. Relatedness to study treatment was assessed by the investigator. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent events were events between first dose of study treatment and up to approximately 35 days that were absent before treatment or that worsened relative to pretreatment state.
Measured: From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1
Cohort 1: Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
Laboratory tests (including hematology, clinical chemistry, urinalysis) were reported and abnormalities were defined for laboratory values that met specific criteria.
Measured: From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1
Cohort 1: Percentage of Change From Baseline in Body Weight by Period 9 Day 1
Percentage of changes from Baseline in body weight of the participants were measured.
Measured: From baseline (last pre-dose measurement in Period 1) to Period 9 Day 1 (Day 124)
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
The C-SSRS is an interview-based rating scale to systematically assess suicidal ideation and suicidal behavior. C-SSRS items were mapped to the following categories: completed suicide, suicide attempt, preparatory acts towards imminent suicidal behavior, suicidal ideation, and self-injurious behavior of no suicidal intent. 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 are reported below.
Measured: 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
Cohort 1: Patient Health Quessionare-9 (PHQ-9) Total Scores
The PHQ-9 is a 9 item self-report scale for the assessment of depressive symptoms. The PHQ-9 is completed by participants and reviewed by site staff at the pre-defined time points. The total score is derived by adding the corresponding values of responses to each item. The total score ranges from 0 to 27, with the following interpretation: 1-4: Minimal depression; 5-9: Mild depression; 10-14: Moderate depression; 15-19: Moderately severe depression; 20-27: Severe depression.
Measured: 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
Cohort 1: AUCinf of Midazolam in Period 9
Midazolam was given on Day 1 in Period 9 of Cohort 1 and blood samples were collected for midazolam pharmacokinetic (PK) at the preset time points described in the Time Frame. AUCinf calculated area under the plasma concentration-time profile from time 0 extrapolated to infinite time.
Measured: 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
Cohort 1: Maximum Observed Concentration (Cmax) of Midazolam in Period 1, 4, 7
Midazolam was given on Day 1 in Period 1, 4, 7 of Cohort 1 and blood samples were collected for midazolam PK at the preset time points described in the Time Frame. Cmax was defined as maximum observed concentration and was observed directly from data.
Measured: 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
Cohort 1: Time for Cmax (Tmax) of Midazolam in Period 1, 4, 7
Midazolam was given on Day 1 in Period 1, 4, 7 of Cohort 1 and blood samples were collected for midazolam PK at the preset time points described in the Time Frame. Tmax was defined as time for Cmax and was observed directly from data.
Measured: 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
Cohort 1: Apparent Clearance (CL/F) of Midazolam in Period 1, 4, 7
Midazolam was given on Day 1 in Period 1, 4, 7 of Cohort 1 and blood samples were collected for midazolam PK at the preset time points described in the Time Frame. CL/F was defined as apparent clearance and was calculated as dose/AUCinf.
Measured: 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
Cohort 1: Apparent Volume of Distribution (Vz/F) of Midazolam in Period 1, 4, 7
Midazolam was given on Day 1 in Period 1, 4, 7 of Cohort 1 and blood samples were collected for midazolam PK at the preset time points described in the Time Frame. Vz/F was defined as apparent volume of distribution and was calculated as dose/(AUCinf*kel), where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve.
Measured: 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
Cohort 1: Terminal Half-Life (t1/2) of Midazolam in Period 1, 4, 7
Midazolam was given on Day 1 in Period 1, 4, 7 of Cohort 1 and blood samples were collected for midazolam PK at the preset time points described in the Time Frame. t1/2 was defined as terminal half life and was calculated as loge(2)/kel.
Measured: 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
Cohort 1: Cmax of Omeprazole in Period 1, 4, 7
Omeprazole was given on Day 1 in Period 1, 4, 7 of Cohort 1 and blood samples were collected for omeprazole PK at the preset time points described in the Time Frame. Cmax was defined as maximum observed concentration and was observed directly from data.
Measured: 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
Cohort 1: Tmax of Omeprazole in Period 1, 4, 7
Omeprazole was given on Day 1 in Period 1, 4, 7 of Cohort 1 and blood samples were collected for omeprazole PK at the preset time points described in the Time Frame. Tmax was defined as time for Cmax and was observed directly from data.
Measured: 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
Cohort 1: CL/F of Omeprazole in Period 1, 4, 7
Omeprazole was given on Day 1 in Period 1, 4, 7 of Cohort 1 and blood samples were collected for omeprazole PK at the preset time points described in the Time Frame. CL/F was defined as apparent clearance and was calculated as dose/AUCinf.
Measured: 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
Cohort 1: Vz/F of Omeprazole in Period 1, 4, 7
Omeprazole was given on Day 1 in Period 1, 4, 7 of Cohort 1 and blood samples were collected for omeprazole PK at the preset time points described in the Time Frame. Vz/F was defined as apparent volume of distribution and was calculated as dose/(AUCinf*kel), where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve.
Measured: 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
Cohort 1: t1/2 of Omeprazole in Period 1, 4, 7
Omeprazole was given on Day 1 in Period 1, 4, 7 of Cohort 1 and blood samples were collected for omeprazole PK at the preset time points described in the Time Frame. Vz/F was defined as apparent volume of distribution and was calculated as dose/(AUCinf ×kel), where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve.
Measured: 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
Cohort 1: Cmax of LE in Period 2, 5, 8
LE was given on Day 1 in Period 2, 5, 8 of Cohort 1 and blood samples were collected for LE PK at the preset time points described in the Time Frame. Cmax was defined as maximum observed concentration and was observed directly from data.
Measured: 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
Cohort 1: Tmax of LE in Period 2, 5, 8
LE was given on Day 1 in Period 2, 5, 8 of Cohort 1 and blood samples were collected for LE PK at the preset time points described in the Time Frame. Cmax was defined as maximum observed concentration and was observed directly from data.
Measured: 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
Cohort 1: CL/F of LE in Period 2, 5, 8
LE was given on Day 1 in Period 2, 5, 8 of Cohort 1 and blood samples were collected for LE PK at the preset time points described in the Time Frame. Cmax was defined as maximum observed concentration and was observed directly from data.
Measured: 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
Cohort 1: Vz/F of LE in Period 2, 5, 8
LE was given on Day 1 in Period 2, 5, 8 of Cohort 1 and blood samples were collected for LE PK at the preset time points described in the Time Frame. Vz/F was defined as apparent volume of distribution and was calculated as dose/(AUCinf*kel), where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve.
Measured: 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
Cohort 1: t1/2 of LE in Period 2, 5, 8
LE was given on Day 1 in Period 2, 5, 8 of Cohort 1 and blood samples were collected for LE PK at the preset time points described in the Time Frame. t1/2 was defined as terminal half life and was calculated as loge(2)/kel.
Measured: 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
Cohort 1: Cmax of EE in Period 2, 5, 8
EE was given on Day 1 in Period 2, 5, 8 of Cohort 1 and blood samples were collected for EE PK at the preset time points described in the Time Frame. Cmax was defined as maximum observed concentration and was observed directly from data.
Measured: 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
Cohort 1: Tmax of EE in Period 2, 5, 8
EE was given on Day 1 in Period 2, 5, 8 of Cohort 1 and blood samples were collected for EE PK at the preset time points described in the Time Frame. Tmax was defined as time for Cmax and was observed directly from data.
Measured: 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
Cohort 1: CL/F of EE in Period 2, 5, 8
EE was given on Day 1 in Period 2, 5, 8 of Cohort 1 and blood samples were collected for EE PK at the preset time points described in the Time Frame. CL/F was defined as apparent clearance and was calculated as dose/AUCinf.
Measured: 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
Cohort 1: Vz/F of EE in Period 2, 5, 8
EE was given on Day 1 in Period 2, 5, 8 of Cohort 1 and blood samples were collected for EE PK at the preset time points described in the Time Frame. Vz/F was defined as apparent volume of distribution and was calculated as dose/(AUCinf*kel), where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve.
Measured: 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
Cohort 1: t1/2 of EE in Period 2, 5, 8
EE was given on Day 1 in Period 2, 5, 8 of Cohort 1 and blood samples were collected for EE PK at the preset time points described in the Time Frame. t1/2 was defined as terminal half life and was calculated as loge(2)/kel.
Measured: 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
Cohort 1: Metabolite/Parent Ratio for AUCinf (MRAUCinf) of 1-Hydroxy Midazolam in Period 1, 4, 7
Midazolam was given on Day 1 in Period 1, 4, 7 of Cohort 1 and blood samples were collected for midazolam (parent) and and its metabolite 1-Hydroxy Midazolam PK at the preset time points described in the Time Frame. MRAUCinf was calculated as (AUCinf, metabolite/AUCinf, parent) * (MWparent/MWmetabolite). MW = molecular weight.
Measured: 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
Cohort 1: MRAUCinf of 5-Hydroxy Omeprazole in Period 1, 4, 7
Omeprazole was given on Day 1 in Period 1, 4, 7 of Cohort 1 and blood samples were collected for omeprazole (parent) and and its metabolite 5-Hydroxy omeprazole PK at the preset time points described in the Time Frame. MRAUCinf was calculated as (AUCinf, metabolite/AUCinf, parent) * (MWparent/MWmetabolite). MW = molecular weight.
Measured: 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
Cohort 1: Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours (AUC24) of PF-07081532 in Period 3 and 6
PF-07081532 was given titrated to 80 mg QD on Day 1-28 of Period 3, and titrated to 260 mg QD on Day 1-63 of Period 6 in Cohort 1, and blood samples were collected for PF-07081532 PK at the preset time points described in the Time Frame. AUC24 was defined as area under the plasma concentration-time profile from time 0 to 24 hours and was determined using the linear/log trapezoidal method.
Measured: 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
Cohort 1: Cmax of PF-07081532 in Period 3 and 6
PF-07081532 was given titrated to 80 mg QD on Day 1-28 of Period 3, and titrated to 260 mg QD on Day 1-63 of Period 6 in Cohort 1, and blood samples were collected for PF-07081532 PK at the preset time points described in the Time Frame. Cmax was defined as maximum observed concentration and was observed directly from data.
Measured: 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
Cohort 1: Tmax of PF-07081532 in Period 3 and 6
PF-07081532 was given titrated to 80 mg QD on Day 1-28 of Period 3, and titrated to 260 mg QD on Day 1-63 of Period 6 in Cohort 1, and blood samples were collected for PF-07081532 PK at the preset time points described in the Time Frame. Tmax was defined as time for Cmax and was observed directly from data.
Measured: 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
Cohort 2: Number of Participants With All-Causality and Treatment-Related TEAEs
An adverse event (AE) was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. Treatment-related AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. Relatedness to study treatment was assessed by the investigator. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent events were events between first dose of study treatment and up to approximately 35 days that were absent before treatment or that worsened relative to pretreatment state.
Measured: From first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2
Cohort 2: Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
Laboratory tests (including hematology, clinical chemistry, urinalysis) were reported and abnormalities were defined for laboratory values that met specific criteria.
Measured: From first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2
Cohort 2: Percentage of Change From Baseline in Body Weight by Period 4 Day 1
Percentage of changes from Baseline in body weight of the participants were measured.
Measured: From baseline (last pre-dose measurement in Period 1) to Period 4 Day 1 (Day 165)
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
The C-SSRS is an interview-based rating scale to systematically assess suicidal ideation and suicidal behavior. C-SSRS items were mapped to the following categories: completed suicide, suicide attempt, preparatory acts towards imminent suicidal behavior, suicidal ideation, and self-injurious behavior of no suicidal intent. 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 are reported below.
Measured: Screening, D-1 (P1D-1), P2 Week 5 [W5], P2W9, P2W13, P2W17, D150 (P3D2), at follow up visit (Day 172-175)
Cohort 2: PHQ-9 Total Scores
The PHQ-9 is a 9 item self-report scale for the assessment of depressive symptoms. The PHQ-9 is completed by participants and reviewed by site staff at the pre-defined time points. The total score is derived by adding the corresponding values of responses to each item. The total score ranges from 0 to 27, with the following interpretation: 1-4: Minimal depression; 5-9: Mild depression; 10-14: Moderate depression; 15-19: Moderately severe depression; 20-27: Severe depression.
Measured: Screening, D-1 (P1D-1), P2 Week 5 [W5], P2W9, P2W13, P2W17, D150 (P3D2), at follow up visit (Day 172-175)
Cohort 2: AUCinf of Midazolam in Period 4
Midazolam was given on Day 1 in Period 4 of Cohort 2 and blood samples were collected for midazolam pharmacokinetic (PK) at the preset time points described in the Time Frame. AUCinf calculated area under the plasma concentration-time profile from time 0 extrapolated to infinite time.
Measured: 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
Cohort 2: Cmax of Midazolam in Period 1 and 3
Midazolam was given on Day 1 in Period 1 and 3 of Cohort 2 and blood samples were collected for midazolam pharmacokinetic (PK) at the preset time points described in the Time Frame. Cmax was defined as maximum observed concentration and was observed directly from data.
Measured: 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
Cohort 2: Tmax of Midazolam in Period 1 and 3
Midazolam was given on Day 1 in Period 1 and 3 of Cohort 2 and blood samples were collected for midazolam pharmacokinetic (PK) at the preset time points described in the Time Frame. Tmax was defined as time for Cmax and was observed directly from data.
Measured: 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
Cohort 2: CL/F of Midazolam in Period 1 and 3
Midazolam was given on Day 1 in Period 1 and 3 of Cohort 2 and blood samples were collected for midazolam pharmacokinetic (PK) at the preset time points described in the Time Frame. CL/F was defined as apparent clearance and was calculated as dose/AUCinf.
Measured: 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
Cohort 2: Vz/F of Midazolam in Period 1 and 3
Midazolam was given on Day 1 in Period 1 and 3 of Cohort 2 and blood samples were collected for midazolam pharmacokinetic (PK) at the preset time points described in the Time Frame. Vz/F was defined as apparent volume of distribution and was calculated as dose/(AUCinf*kel), where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve.
Measured: 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
Cohort 2: t1/2 of Midazolam in Period 1 and 3
Midazolam was given on Day 1 in Period 1 and 3 of Cohort 2 and blood samples were collected for midazolam pharmacokinetic (PK) at the preset time points described in the Time Frame. t1/2 was defined as terminal half life and was calculated as loge(2)/kel.
Measured: 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
Cohort 2: MRAUCinf of 1-Hydroxy Midazolam in Period 1, 3, 4
Midazolam was given on Day 1 in Period 1, 3, 4 of Cohort 2 and blood samples were collected for midazolam (parent) and and its metabolite 1-Hydroxy Midazolam PK at the preset time points described in the Time Frame. MRAUCinf was calculated as (AUCinf, metabolite/AUCinf, parent) * (MWparent/MWmetabolite). MW = molecular weight.
Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

19 Jan 20233 Nov 2023

First posted5 Jan 2023
Study start19 Jan 2023
Primary completion3 Nov 2023
Study completion3 Nov 2023

Why it stopped: The decision to terminate clinical development of lotiglipron is based on pharmacokinetic data from Phase 1 drug-drug-interaction studies and laboratory measurements of elevated transaminases in these Phase 1 studies as well as a Phase 2 study.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for ObesityStudies of the same condition, open and under way.
More trials run by PfizerThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Parallel groups
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)
Enrolment: 32 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05671653
Sponsor's protocol ID: C3991040
Other IDs: NCT05671653
Status last verified: Jan 2025
First submitted: 19 Dec 2022
Last updated: 14 Jan 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No: 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.

Publications

Cronenberger C, Amin NB, Le VH, Carvajal-Gonzalez S, Ashworth AL, Yi EC, Schuster T, Zhang Y, Frederich RC, Friedman GS, Wang EQ, Tsamandouras N. Assessment of the Drug-Drug Interaction Potential of Lotiglipron (PF-07081532) with Midazolam, Omeprazole, Dabigatran, Rosuvastatin, and the Oral Contraceptives Levonorgestrel and Ethinyl Estradiol. J Clin Pharmacol. 2026 May;66(5):e70158. doi: 10.1002/jcph.70158.
PubMed 42053447

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Study at a glance

From the registry record, last updated by the sponsor on 14 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT05671653
Acronym / sponsor ID: C3991040
Conditions: Obesity
Keywords: Midazolam, Omeprazole, PF-07081532
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: The decision to terminate clinical development of lotiglipron is based on pharmacokinetic data from Phase 1 drug-drug-interaction studies and laboratory measurements of elevated transaminases in these Phase 1 studies as well as a Phase 2 study.
Enrolment: 32 participants (actual)
Lead sponsor: PfizerIndustry (pharma, biotech, devices)
Study start: 19 Jan 2023 (actual)
Primary completion: 3 Nov 2023 (actual)
Study completion: 3 Nov 2023 (actual)
First posted: 5 Jan 2023 (actual)
Results: Posted 16 Dec 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2
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.

Arm	Type	Receives
Cohort 1: PF-07081532	Experimental	Drug: PF-07081532Cohort 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: Semaglutide	Experimental	Drug: SemaglutideCohort 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

Who may qualify

Ages: 18 years and older
Sex: Female only
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

Healthy (no clinically relevant abnormalities)
BMI 30.0-45.4 inclusive

Key exclusion criteria (4 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PF-07081532Experimental oral GLP-1 drug	Drug	Cohort 1: PF-07081532
SemaglutideAlso: Wegovy, OzempicApproved and marketed GLP-1 drug for subcutaneous injection.	Drug	Cohort 2: Semaglutide

Primary outcome

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
Midazolam was given on Day 1 in Period 1, 4, 7 of Cohort 1 and blood samples were collected for midazolam pharmacokinetic (PK) at the preset time points described in the Time Frame. AUCinf calculated area under the plasma concentration-time profile from time 0 extrapolated to infinite time.
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
Omeprazole was given on Day 1 in Period 1, 4, 7 of Cohort 1 and blood samples were collected for omeprazole PK at the preset time points described in the Time Frame. AUClast calculated area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration.
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
LE was given on Day 1 in Period 2, 5, 8 of Cohort 1 and blood samples were collected for LE PK at the preset time points described in the Time Frame. AUClast calculated area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration.
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
EE was given on Day 1 in Period 2, 5, 8 of Cohort 1 and blood samples were collected for EE PK at the preset time points described in the Time Frame. AUCinf calculated area under the plasma concentration-time profile from time 0 extrapolated to infinite time.
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
Midazolam was given on Day 1 in Period 1 and 3 of Cohort 2 and blood samples were collected for midazolam pharmacokinetic (PK) at the preset time points described in the Time Frame. AUCinf calculated area under the plasma concentration-time profile from time 0 extrapolated to infinite time.

43 secondary outcomes

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
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
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)
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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)
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)
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)
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
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
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
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

Results and safety

Results posted to the registry on 16 Dec 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	16	16
Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2)	0	0
Cohort 1: PF-07081532 Titration up to 80 mg QD (Period 3)	0	0
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	0	0
Cohort 1: PF-07081532 80 mg QD+ LE 0.15 mg & EE 0.03 mg (Period 5)	0	0
Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6)	0	0
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	0	0
Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)	0	0
Cohort 1: Midazolam 2 mg (Period 9)	0	0
Cohort 2: Midazolam 2 mg (Period 1)	0	0
Cohort 2: Semaglutide Titration up to 2.4 mg QW (Period 2)	0	0
Cohort 2: Semaglutide 2.4 mg QW + Midazolam 2 mg (Period 3)	0	0
Cohort 2: Midazolam 2 mg (Period 4)	0	0

Primary outcome: 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. Geometric mean (Geometric Coefficient of Variation). Unit: nanogram*hour/milliliter (ng*hr/mL)

Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n = 16	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n = 13	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) n = 8
Value	39.27 (33)	33.30 (37)	28.23 (49)

Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) vs Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4): Ratio (%) of Adjusted Geometric Means: 88.85 (90% CI 80.25 to 98.38)
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) vs Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7): Ratio (%) of Adjusted Geometric Means: 70.00 (90% CI 55.21 to 88.76)

Population analysed: Participants who received at least 1 dose of midazolam, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

Primary outcome: 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. Geometric mean (Geometric Coefficient of Variation). Unit: ng*hr/mL

Measure	Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) n = 13	Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4) n = 9	Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7) n = 6
Value	956.3 (90)	620.5 (174)	602.8 (154)

Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) vs Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4): Ratio (%) of Adjusted Geometric Means: 57.19 (90% CI 39.27 to 83.29)
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1) vs Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7): Ratio (%) of Adjusted Geometric Means: 29.68 (90% CI 19.60 to 44.94)

Population analysed: Participants who received at least 1 dose of omeprazole, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

Primary outcome: 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. Geometric mean (Geometric Coefficient of Variation). Unit: picogram*hour/milliliter (pg*hr/mL)

Measure	Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2) n = 14	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) n = 16	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) n = 6
Value	31360 (52)	42120 (56)	60020 (63)

Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2) vs Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5): Ratio (%) of Adjusted Geometric Means: 119.86 (90% CI 108.97 to 131.85)
Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2) vs Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8): Ratio (%) of Adjusted Geometric Means: 185.45 (90% CI 108.00 to 318.44)

Population analysed: Participants who received at least 1 dose of LE, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

Primary outcome: 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. Geometric mean (Geometric Coefficient of Variation). Unit: pg*hr/mL

Measure	Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2) n = 16	Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5) n = 15	Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8) n = 6
Value	754.5 (37)	765.5 (26)	701.1 (29)

Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2) vs Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5): Ratio (%) of Adjusted Geometric Means: 103.17 (90% CI 95.09 to 111.93)
Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2) vs Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8): Ratio (%) of Adjusted Geometric Means: 90.20 (90% CI 60.24 to 135.06)

Population analysed: Participants who received at least 1 dose of EE, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

43 secondary outcomes are reported in the full results.

Adverse events

Time frame: From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1 and from first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort 1: Midazolam 2 mg + Omeprazole 20 mg (Period 1)	0 of 16 (0%)	1 of 16 (6.3%)	0 of 16
Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2)	0 of 16 (0%)	2 of 16 (12.5%)	0 of 16
Cohort 1: PF-07081532 Titration up to 80 mg QD (Period 3)	0 of 16 (0%)	14 of 16 (87.5%)	0 of 16
Cohort 1: PF-07081532 80 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 4)	0 of 16 (0%)	2 of 16 (12.5%)	0 of 16
Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5)	0 of 16 (0%)	6 of 16 (37.5%)	0 of 16
Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6)	0 of 16 (0%)	15 of 16 (93.8%)	0 of 16
Cohort 1: PF-07081532 260 mg QD + Midazolam 2 mg + Omeprazole 20 mg (Period 7)	0 of 8 (0%)	1 of 8 (12.5%)	0 of 8
Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)	0 of 7 (0%)	2 of 7 (28.6%)	0 of 7
Cohort 1: Midazolam 2 mg (Period 9)	0 of 8 (0%)	2 of 8 (25%)	0 of 8
Cohort 2: Midazolam 2 mg (Period 1)	0 of 16 (0%)	4 of 16 (25%)	0 of 16
Cohort 2: Semaglutide Titration up to 2.4 mg QW (Period 2)	0 of 16 (0%)	11 of 16 (68.8%)	0 of 16
Cohort 2: Semaglutide 2.4 mg QW + Midazolam 2 mg (Period 3)	0 of 11 (0%)	11 of 11 (100%)	0 of 11
Cohort 2: Midazolam 2 mg (Period 4)	0 of 10 (0%)	3 of 10 (30%)	0 of 10

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 42053447Cronenberger C, Amin NB, Le VH, Carvajal-Gonzalez S, Ashworth AL, Yi EC, Schuster T, Zhang Y, Frederich RC, Friedman GS, Wang EQ, Tsamandouras N. Assessment of the Drug-Drug Interaction Potential of Lotiglipron (PF-07081532) with Midazolam, Omeprazole, Dabigatran, Rosuvastatin, and the Oral Contraceptives Levonorgestrel and Ethinyl Estradiol. J Clin Pharmacol. 2026 May;66(5):e70158. doi: 10.1002/jcph.70158.
To obtain contact information for a study center near you, click here.Link provided by the sponsor.
Individual participant dataSharing planned: No. 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

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Pfizer

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PF-07081532 and Semaglutide in people with Obesity, run by Pfizer at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 14 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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 (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). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05671653, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2025.