A Study to Evaluate the Effect of the Experimental GLP-1... | NCT05671653 | Trialant
NCT05671653
Sponsor
Pfizer
Status
Terminated
Last Update Posted
Jan 14, 2025Actual
Enrollment
32Actual
Phase
Phase 1
Conditions
Obesity
Interventions
PF-07081532
Semaglutide
Countries
United States
Protocol Section
Identification Module
NCT ID
NCT05671653
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
C3991040
Secondary IDs
ID
Type
Description
Link
NCT05671653
Registry Identifier
ClinicalTrials.gov
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
Acronym
Not provided
Organization
PfizerINDUSTRY
Status Module
Record Verification Date
Jan 2025
Overall Recruitment Status or Expanded Access Status
Terminated
Last Known Status
Not provided
Delayed Posting
Not provided
Why 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.
Expanded Access Info
No
Start Date
Jan 19, 2023Actual
Primary Completion Date
Nov 3, 2023Actual
Completion Date
Nov 3, 2023Actual
First Submitted Date
Dec 19, 2022
First Submission Date that Met QC Criteria
Jan 3, 2023
First Posted Date
Jan 5, 2023Actual
Results Waived
Not provided
Results First Submitted Date
Oct 28, 2024
Results First Submitted that Met QC Criteria
Oct 28, 2024
Results First Posted Date
Dec 16, 2024Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Jan 6, 2025
Last Update Posted Date
Jan 14, 2025Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
PfizerINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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.
Detailed Description
Not provided
Conditions Module
Conditions
Obesity
Keywords
Midazolam
Omeprazole
PF-07081532
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 1
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
32Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
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.
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
Drug: Semaglutide
Interventions
Name
Type
Description
Arm Group Labels
Other Names
PF-07081532
Drug
Experimental oral GLP-1 drug
Cohort 1: PF-07081532
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
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.
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.
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.
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.
Secondary Outcomes
Measure
Description
Time Frame
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.
Other Outcomes
Not provided
Eligibility Module
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)
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.
See Also Links
Label
URL
To obtain contact information for a study center near you, click here.
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.
Types
Not provided
Time Frame
Not provided
Access Criteria
Not provided
URL
Not provided
Results Section
Participant Flow Module
Pre-assignment Details
This study was a Phase 1, open-label, fixed-sequence study conducted with 2 cohorts. 16 participants were enrolled in Cohort 1 with 9 periods, 16 participants were enrolled in Cohort 2 with 4 periods.
Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.
FG001
Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2)
Periods
Title
Milestones
Reasons Not Completed
Cohort 1 Period 1 - Treatment
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Nov 8, 2022
Oct 28, 2024
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Non-Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
The overall design is randomized, open-label, fixed-sequence. Cohort 1 will consist of 9 periods while Cohort 2 will consist of 4 periods.
Primary Purpose
Basic Science
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
None (Open Label)
Masking Description
Not provided
Who Masked
Not provided
Semaglutide
Drug
Approved and marketed GLP-1 drug for subcutaneous injection.
Cohort 2: Semaglutide
Wegovy, Ozempic
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.
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
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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
Participants in Cohort 1 received SD of levonorgestrel (LE) 0.15 mg and ethinyl estradiol (EE) 0.03 mg on Day 1 of Period 2.
FG002
Cohort 1: PF-07081532 Titration up to 80 mg QD (Period 3)
Participants in Cohort 1 received PF-07081532 20 mg once daily (QD) on Day 1-7, 40 mg QD on Day 8-14, 60 mg QD on Day 15-21, 80 mg QD on Day 22-28 of Period 3.
Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.
FG004
Cohort 1: PF-07081532 80 mg QD+ LE 0.15 mg & EE 0.03 mg (Period 5)
Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.
FG005
Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6)
Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.
Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.
FG007
Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)
Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.
FG008
Cohort 1: Midazolam 2 mg (Period 9)
Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
FG009
Cohort 2: Midazolam 2 mg (Period 1)
Participants in Cohort 2 received SD of midazolam 2 mg on Day 1 of Period 1.
FG010
Cohort 2: Semaglutide Titration up to 2.4 mg QW (Period 2)
Participants in Cohort 2 received semaglutide 0.25 mg once weekly (QW) on Week 1-4, 0.5 mg QW on Week 5-8, 1.0 mg QW on Week 9-12, 1.7 mg QW on Week 13-16, 2.4 mg QW on Week 17-21 of Period 2.
Participants in Cohort 2 received semaglutide 2.4 mg QW and SD of midazolam 2 mg on Day 1 of Period 3.
FG012
Cohort 2: Midazolam 2 mg (Period 4)
Participants in Cohort 2 received SD of midazolam 2 mg on Day 1 of Period 4.
FG00016 subjects
FG0010 subjectsThis period only applies to the group "Cohort 1 Period 1".
FG0020 subjectsThis period only applies to the group "Cohort 1 Period 1".
FG0030 subjectsThis period only applies to the group "Cohort 1 Period 1".
FG0040 subjectsThis period only applies to the group "Cohort 1 Period 1".
FG0050 subjectsThis period only applies to the group "Cohort 1 Period 1".
FG0060 subjectsThis period only applies to the group "Cohort 1 Period 1".
FG0070 subjectsThis period only applies to the group "Cohort 1 Period 1".
FG0080 subjectsThis period only applies to the group "Cohort 1 Period 1".
FG0090 subjectsThis period only applies to the group "Cohort 1 Period 1".
FG0100 subjectsThis period only applies to the group "Cohort 1 Period 1".
FG0110 subjectsThis period only applies to the group "Cohort 1 Period 1".
FG0120 subjectsThis period only applies to the group "Cohort 1 Period 1".
COMPLETED
FG00016 subjects
FG0010 subjectsThis period only applies to the group "Cohort 1 Period 1".
FG0020 subjectsThis period only applies to the group "Cohort 1 Period 1".
FG0030 subjectsThis period only applies to the group "Cohort 1 Period 1".
FG0040 subjectsThis period only applies to the group "Cohort 1 Period 1".
FG0050 subjectsThis period only applies to the group "Cohort 1 Period 1".
FG0060 subjectsThis period only applies to the group "Cohort 1 Period 1".
FG0070 subjectsThis period only applies to the group "Cohort 1 Period 1".
FG0080 subjectsThis period only applies to the group "Cohort 1 Period 1".
FG0090 subjectsThis period only applies to the group "Cohort 1 Period 1".
FG0100 subjectsThis period only applies to the group "Cohort 1 Period 1".
FG0110 subjectsThis period only applies to the group "Cohort 1 Period 1".
FG0120 subjectsThis period only applies to the group "Cohort 1 Period 1".
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
Cohort 1 Period 2 - Treatment
Type
Comment
Milestone Data
STARTED
FG0000 subjectsThis period only applies to the group "Cohort 1 Period 2".
FG00116 subjects
FG0020 subjectsThis period only applies to the group "Cohort 1 Period 2".
FG0030 subjectsThis period only applies to the group "Cohort 1 Period 2".
FG0040 subjectsThis period only applies to the group "Cohort 1 Period 2".
FG0050 subjectsThis period only applies to the group "Cohort 1 Period 2".
FG0060 subjectsThis period only applies to the group "Cohort 1 Period 2".
FG0070 subjectsThis period only applies to the group "Cohort 1 Period 2".
FG0080 subjectsThis period only applies to the group "Cohort 1 Period 2".
FG0090 subjectsThis period only applies to the group "Cohort 1 Period 2".
FG0100 subjectsThis period only applies to the group "Cohort 1 Period 2".
FG0110 subjectsThis period only applies to the group "Cohort 1 Period 2".
FG0120 subjectsThis period only applies to the group "Cohort 1 Period 2".
COMPLETED
FG0000 subjectsThis period only applies to the group "Cohort 1 Period 2".
FG00116 subjects
FG0020 subjectsThis period only applies to the group "Cohort 1 Period 2".
FG003
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Cohort 1 Period 3 - Treatment
Type
Comment
Milestone Data
STARTED
FG0000 subjectsThis period only applies to the group "Cohort 1 Period 3".
FG0010 subjectsThis period only applies to the group "Cohort 1 Period 3".
FG00216 subjects
FG0030 subjectsThis period only applies to the group "Cohort 1 Period 3".
FG0040 subjectsThis period only applies to the group "Cohort 1 Period 3".
FG0050 subjectsThis period only applies to the group "Cohort 1 Period 3".
FG0060 subjectsThis period only applies to the group "Cohort 1 Period 3".
FG0070 subjectsThis period only applies to the group "Cohort 1 Period 3".
FG0080 subjectsThis period only applies to the group "Cohort 1 Period 3".
FG0090 subjectsThis period only applies to the group "Cohort 1 Period 3".
FG0100 subjectsThis period only applies to the group "Cohort 1 Period 3".
FG0110 subjectsThis period only applies to the group "Cohort 1 Period 3".
FG0120 subjectsThis period only applies to the group "Cohort 1 Period 3".
COMPLETED
FG0000 subjectsThis period only applies to the group "Cohort 1 Period 3".
FG0010 subjectsThis period only applies to the group "Cohort 1 Period 3".
FG00216 subjects
FG003
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Cohort 1 Period 4 - Treatment
Type
Comment
Milestone Data
STARTED
FG0000 subjectsThis period only applies to the group "Cohort 1 Period 4".
FG0010 subjectsThis period only applies to the group "Cohort 1 Period 4".
FG0020 subjectsThis period only applies to the group "Cohort 1 Period 4".
FG00316 subjects
FG0040 subjectsThis period only applies to the group "Cohort 1 Period 4".
FG0050 subjectsThis period only applies to the group "Cohort 1 Period 4".
FG0060 subjectsThis period only applies to the group "Cohort 1 Period 4".
FG0070 subjectsThis period only applies to the group "Cohort 1 Period 4".
FG0080 subjectsThis period only applies to the group "Cohort 1 Period 4".
FG0090 subjectsThis period only applies to the group "Cohort 1 Period 4".
FG0100 subjectsThis period only applies to the group "Cohort 1 Period 4".
FG0110 subjectsThis period only applies to the group "Cohort 1 Period 4".
FG0120 subjectsThis period only applies to the group "Cohort 1 Period 4".
COMPLETED
FG0000 subjectsThis period only applies to the group "Cohort 1 Period 4".
FG0010 subjectsThis period only applies to the group "Cohort 1 Period 4".
FG0020 subjectsThis period only applies to the group "Cohort 1 Period 4".
FG003
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Cohort 1 Period 5 - Treatment
Type
Comment
Milestone Data
STARTED
FG0000 subjectsThis period only applies to the group "Cohort 1 Period 5".
FG0010 subjectsThis period only applies to the group "Cohort 1 Period 5".
FG0020 subjectsThis period only applies to the group "Cohort 1 Period 5".
FG0030 subjectsThis period only applies to the group "Cohort 1 Period 5".
FG00416 subjects
FG0050 subjectsThis period only applies to the group "Cohort 1 Period 5".
FG0060 subjectsThis period only applies to the group "Cohort 1 Period 5".
FG0070 subjectsThis period only applies to the group "Cohort 1 Period 5".
FG0080 subjectsThis period only applies to the group "Cohort 1 Period 5".
FG0090 subjectsThis period only applies to the group "Cohort 1 Period 5".
FG0100 subjectsThis period only applies to the group "Cohort 1 Period 5".
FG0110 subjectsThis period only applies to the group "Cohort 1 Period 5".
FG0120 subjectsThis period only applies to the group "Cohort 1 Period 5".
COMPLETED
FG0000 subjectsThis period only applies to the group "Cohort 1 Period 5".
FG0010 subjectsThis period only applies to the group "Cohort 1 Period 5".
FG0020 subjectsThis period only applies to the group "Cohort 1 Period 5".
FG003
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Cohort 1 Period 6 - Treatment
Type
Comment
Milestone Data
STARTED
FG0000 subjectsThis period only applies to the group "Cohort 1 Period 6".
FG0010 subjectsThis period only applies to the group "Cohort 1 Period 6".
FG0020 subjectsThis period only applies to the group "Cohort 1 Period 6".
FG0030 subjectsThis period only applies to the group "Cohort 1 Period 6".
FG0040 subjectsThis period only applies to the group "Cohort 1 Period 6".
FG00516 subjects
FG0060 subjectsThis period only applies to the group "Cohort 1 Period 6".
FG0070 subjectsThis period only applies to the group "Cohort 1 Period 6".
FG0080 subjectsThis period only applies to the group "Cohort 1 Period 6".
FG0090 subjectsThis period only applies to the group "Cohort 1 Period 6".
FG0100 subjectsThis period only applies to the group "Cohort 1 Period 6".
FG0110 subjectsThis period only applies to the group "Cohort 1 Period 6".
FG0120 subjectsThis period only applies to the group "Cohort 1 Period 6".
COMPLETED
FG0000 subjectsThis period only applies to the group "Cohort 1 Period 6".
FG0010 subjectsThis period only applies to the group "Cohort 1 Period 6".
FG0020 subjectsThis period only applies to the group "Cohort 1 Period 6".
FG003
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Other
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Cohort 1 Period 7 - Treatment
Type
Comment
Milestone Data
STARTED
FG0000 subjectsThis period only applies to the group "Cohort 1 Period 7".
FG0010 subjectsThis period only applies to the group "Cohort 1 Period 7".
FG0020 subjectsThis period only applies to the group "Cohort 1 Period 7".
FG0030 subjectsThis period only applies to the group "Cohort 1 Period 7".
FG0040 subjectsThis period only applies to the group "Cohort 1 Period 7".
FG0050 subjectsThis period only applies to the group "Cohort 1 Period 7".
FG0068 subjects
FG0070 subjectsThis period only applies to the group "Cohort 1 Period 7".
FG0080 subjectsThis period only applies to the group "Cohort 1 Period 7".
FG0090 subjectsThis period only applies to the group "Cohort 1 Period 7".
FG0100 subjectsThis period only applies to the group "Cohort 1 Period 7".
FG0110 subjectsThis period only applies to the group "Cohort 1 Period 7".
FG0120 subjectsThis period only applies to the group "Cohort 1 Period 7".
COMPLETED
FG0000 subjectsThis period only applies to the group "Cohort 1 Period 7".
FG0010 subjectsThis period only applies to the group "Cohort 1 Period 7".
FG0020 subjectsThis period only applies to the group "Cohort 1 Period 7".
FG003
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Cohort 1 Period 8 - Treatment
Type
Comment
Milestone Data
STARTED
FG0000 subjectsThis period only applies to the group "Cohort 1 Period 8".
FG0010 subjectsThis period only applies to the group "Cohort 1 Period 8".
FG0020 subjectsThis period only applies to the group "Cohort 1 Period 8".
FG0030 subjectsThis period only applies to the group "Cohort 1 Period 8".
FG0040 subjectsThis period only applies to the group "Cohort 1 Period 8".
FG0050 subjectsThis period only applies to the group "Cohort 1 Period 8".
FG0060 subjectsThis period only applies to the group "Cohort 1 Period 8".
FG0077 subjects
FG0080 subjectsThis period only applies to the group "Cohort 1 Period 8".
FG0090 subjectsThis period only applies to the group "Cohort 1 Period 8".
FG0100 subjectsThis period only applies to the group "Cohort 1 Period 8".
FG0110 subjectsThis period only applies to the group "Cohort 1 Period 8".
FG0120 subjectsThis period only applies to the group "Cohort 1 Period 8".
COMPLETED
FG0000 subjectsThis period only applies to the group "Cohort 1 Period 8".
FG0010 subjectsThis period only applies to the group "Cohort 1 Period 8".
FG0020 subjectsThis period only applies to the group "Cohort 1 Period 8".
FG003
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Cohort 1 Period 9 - Treatment
Type
Comment
Milestone Data
STARTED
FG0000 subjectsThis period only applies to the group "Cohort 1 Period 9".
FG0010 subjectsThis period only applies to the group "Cohort 1 Period 9".
FG0020 subjectsThis period only applies to the group "Cohort 1 Period 9".
FG0030 subjectsThis period only applies to the group "Cohort 1 Period 9".
FG0040 subjectsThis period only applies to the group "Cohort 1 Period 9".
FG0050 subjectsThis period only applies to the group "Cohort 1 Period 9".
FG0060 subjectsThis period only applies to the group "Cohort 1 Period 9".
FG0070 subjectsThis period only applies to the group "Cohort 1 Period 9".
FG0088 subjects
FG0090 subjectsThis period only applies to the group "Cohort 1 Period 9".
FG0100 subjectsThis period only applies to the group "Cohort 1 Period 9".
FG0110 subjectsThis period only applies to the group "Cohort 1 Period 9".
FG0120 subjectsThis period only applies to the group "Cohort 1 Period 9".
COMPLETED
FG0000 subjectsThis period only applies to the group "Cohort 1 Period 9".
FG0010 subjectsThis period only applies to the group "Cohort 1 Period 9".
FG0020 subjectsThis period only applies to the group "Cohort 1 Period 9".
FG003
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Cohort 2 Period 1 - Treatment
Type
Comment
Milestone Data
STARTED
FG0000 subjectsThis period only applies to the group "Cohort 2 Period 1".
FG0010 subjectsThis period only applies to the group "Cohort 2 Period 1".
FG0020 subjectsThis period only applies to the group "Cohort 2 Period 1".
FG0030 subjectsThis period only applies to the group "Cohort 2 Period 1".
FG0040 subjectsThis period only applies to the group "Cohort 2 Period 1".
FG0050 subjectsThis period only applies to the group "Cohort 2 Period 1".
FG0060 subjectsThis period only applies to the group "Cohort 2 Period 1".
FG0070 subjectsThis period only applies to the group "Cohort 2 Period 1".
FG0080 subjectsThis period only applies to the group "Cohort 2 Period 1".
FG00916 subjects
FG0100 subjectsThis period only applies to the group "Cohort 2 Period 1".
FG0110 subjectsThis period only applies to the group "Cohort 2 Period 1".
FG0120 subjectsThis period only applies to the group "Cohort 2 Period 1".
COMPLETED
FG0000 subjectsThis period only applies to the group "Cohort 2 Period 1".
FG0010 subjectsThis period only applies to the group "Cohort 2 Period 1".
FG0020 subjectsThis period only applies to the group "Cohort 2 Period 1".
FG003
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Cohort 2 Period 2
Type
Comment
Milestone Data
STARTED
FG0000 subjectsThis period only applies to the group "Cohort 2 Period 2".
FG0010 subjectsThis period only applies to the group "Cohort 2 Period 2".
FG0020 subjectsThis period only applies to the group "Cohort 2 Period 2".
FG0030 subjectsThis period only applies to the group "Cohort 2 Period 2".
FG0040 subjectsThis period only applies to the group "Cohort 2 Period 2".
FG0050 subjectsThis period only applies to the group "Cohort 2 Period 2".
FG0060 subjectsThis period only applies to the group "Cohort 2 Period 2".
FG0070 subjectsThis period only applies to the group "Cohort 2 Period 2".
FG0080 subjectsThis period only applies to the group "Cohort 2 Period 2".
FG0090 subjectsThis period only applies to the group "Cohort 2 Period 2".
FG01016 subjects
FG0110 subjectsThis period only applies to the group "Cohort 2 Period 2".
FG0120 subjectsThis period only applies to the group "Cohort 2 Period 2".
COMPLETED
FG0000 subjectsThis period only applies to the group "Cohort 2 Period 2".
FG0010 subjectsThis period only applies to the group "Cohort 2 Period 2".
FG0020 subjectsThis period only applies to the group "Cohort 2 Period 2".
FG003
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Cohort 2 Period 3 - Treatment
Type
Comment
Milestone Data
STARTED
FG0000 subjectsThis period only applies to the group "Cohort 2 Period 3".
FG0010 subjectsThis period only applies to the group "Cohort 2 Period 3".
FG0020 subjectsThis period only applies to the group "Cohort 2 Period 3".
FG0030 subjectsThis period only applies to the group "Cohort 2 Period 3".
FG0040 subjectsThis period only applies to the group "Cohort 2 Period 3".
FG0050 subjectsThis period only applies to the group "Cohort 2 Period 3".
FG0060 subjectsThis period only applies to the group "Cohort 2 Period 3".
FG0070 subjectsThis period only applies to the group "Cohort 2 Period 3".
FG0080 subjectsThis period only applies to the group "Cohort 2 Period 3".
FG0090 subjectsThis period only applies to the group "Cohort 2 Period 3".
FG0100 subjectsThis period only applies to the group "Cohort 2 Period 3".
FG01111 subjects
FG0120 subjectsThis period only applies to the group "Cohort 2 Period 3".
COMPLETED
FG0000 subjectsThis period only applies to the group "Cohort 2 Period 3".
FG0010 subjectsThis period only applies to the group "Cohort 2 Period 3".
FG0020 subjectsThis period only applies to the group "Cohort 2 Period 3".
FG003
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Cohort 2 Period 4 - Treatment
Type
Comment
Milestone Data
STARTED
FG0000 subjectsThis period only applies to the group "Cohort 2 Period 4".
FG0010 subjectsThis period only applies to the group "Cohort 2 Period 4".
FG0020 subjectsThis period only applies to the group "Cohort 2 Period 4".
FG0030 subjectsThis period only applies to the group "Cohort 2 Period 4".
FG0040 subjectsThis period only applies to the group "Cohort 2 Period 4".
FG0050 subjectsThis period only applies to the group "Cohort 2 Period 4".
FG0060 subjectsThis period only applies to the group "Cohort 2 Period 4".
FG0070 subjectsThis period only applies to the group "Cohort 2 Period 4".
FG0080 subjectsThis period only applies to the group "Cohort 2 Period 4".
FG0090 subjectsThis period only applies to the group "Cohort 2 Period 4".
FG0100 subjectsThis period only applies to the group "Cohort 2 Period 4".
FG0110 subjectsThis period only applies to the group "Cohort 2 Period 4".
FG01210 subjects
COMPLETED
FG0000 subjectsThis period only applies to the group "Cohort 2 Period 4".
FG0010 subjectsThis period only applies to the group "Cohort 2 Period 4".
FG0020 subjectsThis period only applies to the group "Cohort 2 Period 4".
FG003
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
All enrolled participants who received at least 1 dose of study intervention.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Cohort 1
Reporting Group Description
BG001
Cohort 2
Reporting Group Description
BG002
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00016
BG00116
BG00232
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
Years
Title
Denominators
Categories
Mean (SD)
Title
Measurements
BG00050.8125± 13.47
BG00148.125± 13.67
BG00249.46875± 13.42
Age, Customized
Count of Participants
Participants
Title
Denominators
Categories
<18 Years
Title
Measurements
BG0000
BG0010
BG002
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00016
BG00116
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0005
BG0016
BG002
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
White
Title
Measurements
BG0009
BG0018
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
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.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanogram*hour/milliliter (ng*hr/mL)
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
Analysis done using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. Ratio (Test/Reference) and 90% confidence interval (CI) are expressed as percentages.
Primary
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.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng*hr/mL
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.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
picogram*hour/milliliter (pg*hr/mL)
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
ID
Title
Description
OG000
Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2)
Participants in Cohort 1 received SD of levonorgestrel (LE) 0.15 mg and ethinyl estradiol (EE) 0.03 mg on Day 1 of Period 2.
OG001
Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5)
Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.
OG002
Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)
Primary
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.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
pg*hr/mL
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
ID
Title
Description
OG000
Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2)
Participants in Cohort 1 received SD of levonorgestrel (LE) 0.15 mg and ethinyl estradiol (EE) 0.03 mg on Day 1 of Period 2.
OG001
Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5)
Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.
OG002
Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)
Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.
Primary
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.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng*hr/mL
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
ID
Title
Description
OG000
Cohort 2: Midazolam 2 mg (Period 1)
Participants in Cohort 2 received SD of midazolam 2 mg on Day 1 of Period 1.
Participants in Cohort 2 received semaglutide 2.4 mg QW and SD of midazolam 2 mg on Day 1 of Period 3.
Units
Counts
Participants
Secondary
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.
All participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
Posted
Count of Participants
Participants
From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1
Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.
OG001
Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2)
Participants in Cohort 1 received SD of levonorgestrel (LE) 0.15 mg and ethinyl estradiol (EE) 0.03 mg on Day 1 of Period 2.
Secondary
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.
All participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
Posted
Count of Participants
Participants
From first dose (Day 1) to follow-up telephone contact (Days 153 to 160) in Cohort 1
Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.
OG001
Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2)
Participants in Cohort 1 received SD of levonorgestrel (LE) 0.15 mg and ethinyl estradiol (EE) 0.03 mg on Day 1 of Period 2.
OG002
Cohort 1: PF-07081532 Titration up to 80 mg QD (Period 3)
Participants in Cohort 1 received PF-07081532 20 mg once daily (QD) on Day 1-7, 40 mg QD on Day 8-14, 60 mg QD on Day 15-21, 80 mg QD on Day 22-28 of Period 3.
Secondary
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.
All participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
Posted
Median
Full Range
Percentage Change
From baseline (last pre-dose measurement in Period 1) to Period 9 Day 1 (Day 124)
ID
Title
Description
OG000
All Participants
Participants underwent Period 1 to 9 and received study interventions as follows: SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1; SD of LE 0.15 mg and ethinyl estradiol (EE) 0.03 mg on Day 1 of Period 2; PF-07081532 titrated to 80 mg QD on Day 1-28 of Period 3; PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4; PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5; PF-07081532 titrated to 260 mg QD on Day 1-63 of Period 6; PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7; PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8; SD of midazolam 2 mg on Day 1 of Period 9.
Units
Counts
Participants
Secondary
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.
All participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants with evaluable C-SSRS results were analyzed.
Posted
Count of Participants
Participants
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
ID
Title
Description
OG000
All Participants
Participants underwent Period 1 to 9 and received study interventions as follows: SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1; SD of LE 0.15 mg and ethinyl estradiol (EE) 0.03 mg on Day 1 of Period 2; PF-07081532 titrated to 80 mg QD on Day 1-28 of Period 3; PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4; PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5; PF-07081532 titrated to 260 mg QD on Day 1-63 of Period 6; PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7; PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8; SD of midazolam 2 mg on Day 1 of Period 9.
Secondary
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.
All participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants with evaluable PHQ-9 results were analyzed.
Posted
Mean
Standard Deviation
Score
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
ID
Title
Description
OG000
All Participants
Participants underwent Period 1 to 9 and received study interventions as follows: SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1; SD of LE 0.15 mg and ethinyl estradiol (EE) 0.03 mg on Day 1 of Period 2; PF-07081532 titrated to 80 mg QD on Day 1-28 of Period 3; PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4; PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5; PF-07081532 titrated to 260 mg QD on Day 1-63 of Period 6; PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7; PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8; SD of midazolam 2 mg on Day 1 of Period 9.
Secondary
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.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng*hr/mL
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
ID
Title
Description
OG000
Cohort 1: Midazolam 2 mg (Period 9)
Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
Units
Counts
Participants
OG000
Secondary
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.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
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
Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.
Secondary
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.
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.
Posted
Median
Full Range
hour
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
Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.
Secondary
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.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
L/hr
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
Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.
Secondary
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.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
Liter (L)
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.
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.
Posted
Mean
Standard Deviation
hour
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
Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.
Secondary
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.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
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
Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.
Secondary
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.
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.
Posted
Median
Full Range
hour
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
Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.
Secondary
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.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
L/hr
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
Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.
Secondary
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.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
L
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. 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.
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.
Posted
Mean
Standard Deviation
hour
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
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.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
pg/mL
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
ID
Title
Description
OG000
Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2)
Participants in Cohort 1 received SD of levonorgestrel (LE) 0.15 mg and ethinyl estradiol (EE) 0.03 mg on Day 1 of Period 2.
OG001
Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5)
Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.
OG002
Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)
Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.
Secondary
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.
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.
Posted
Median
Full Range
hour
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
ID
Title
Description
OG000
Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2)
Participants in Cohort 1 received SD of levonorgestrel (LE) 0.15 mg and ethinyl estradiol (EE) 0.03 mg on Day 1 of Period 2.
OG001
Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5)
Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.
OG002
Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)
Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.
Secondary
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.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
L/hr
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
ID
Title
Description
OG000
Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2)
Participants in Cohort 1 received SD of levonorgestrel (LE) 0.15 mg and ethinyl estradiol (EE) 0.03 mg on Day 1 of Period 2.
OG001
Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5)
Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.
OG002
Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)
Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.
Secondary
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.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
L
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
ID
Title
Description
OG000
Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2)
Participants in Cohort 1 received SD of levonorgestrel (LE) 0.15 mg and ethinyl estradiol (EE) 0.03 mg on Day 1 of Period 2.
OG001
Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5)
Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.
OG002
Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)
Secondary
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.
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.
Posted
Mean
Standard Deviation
hour
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
ID
Title
Description
OG000
Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2)
Participants in Cohort 1 received SD of levonorgestrel (LE) 0.15 mg and ethinyl estradiol (EE) 0.03 mg on Day 1 of Period 2.
OG001
Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5)
Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.
OG002
Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)
Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.
Secondary
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.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
pg/mL
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
ID
Title
Description
OG000
Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2)
Participants in Cohort 1 received SD of levonorgestrel (LE) 0.15 mg and ethinyl estradiol (EE) 0.03 mg on Day 1 of Period 2.
OG001
Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5)
Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.
OG002
Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)
Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.
Secondary
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.
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.
Posted
Median
Full Range
hour
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
ID
Title
Description
OG000
Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2)
Participants in Cohort 1 received SD of levonorgestrel (LE) 0.15 mg and ethinyl estradiol (EE) 0.03 mg on Day 1 of Period 2.
OG001
Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5)
Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.
OG002
Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)
Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.
Secondary
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.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
L/hr
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
ID
Title
Description
OG000
Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2)
Participants in Cohort 1 received SD of levonorgestrel (LE) 0.15 mg and ethinyl estradiol (EE) 0.03 mg on Day 1 of Period 2.
OG001
Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5)
Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.
OG002
Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)
Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.
Secondary
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.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
L
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
ID
Title
Description
OG000
Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2)
Participants in Cohort 1 received SD of levonorgestrel (LE) 0.15 mg and ethinyl estradiol (EE) 0.03 mg on Day 1 of Period 2.
OG001
Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5)
Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.
OG002
Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)
Secondary
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.
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.
Posted
Mean
Standard Deviation
hour
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
ID
Title
Description
OG000
Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2)
Participants in Cohort 1 received SD of levonorgestrel (LE) 0.15 mg and ethinyl estradiol (EE) 0.03 mg on Day 1 of Period 2.
OG001
Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5)
Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.
OG002
Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)
Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.
Secondary
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.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
Ratio
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.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
Ratio
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.
Participants who received at least 1 dose of PF-07081532, and had at least 1 of the PK parameters of interest calculated were included in the analysis.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng*hr/mL
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
ID
Title
Description
OG000
Cohort 1: PF-07081532 Titration up to 80 mg QD (Period 3)
Participants in Cohort 1 received PF-07081532 20 mg once daily (QD) on Day 1-7, 40 mg QD on Day 8-14, 60 mg QD on Day 15-21, 80 mg QD on Day 22-28 of Period 3.
OG001
Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6)
Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.
Secondary
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.
Participants who received at least 1 dose of PF-07081532, and had at least 1 of the PK parameters of interest calculated were included in the analysis.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
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
ID
Title
Description
OG000
Cohort 1: PF-07081532 Titration up to 80 mg QD (Period 3)
Participants in Cohort 1 received PF-07081532 20 mg once daily (QD) on Day 1-7, 40 mg QD on Day 8-14, 60 mg QD on Day 15-21, 80 mg QD on Day 22-28 of Period 3.
OG001
Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6)
Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.
Secondary
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.
Participants who received at least 1 dose of PF-07081532, and had at least 1 of the PK parameters of interest calculated were included in the analysis.
Posted
Median
Full Range
hour
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
ID
Title
Description
OG000
Cohort 1: PF-07081532 Titration up to 80 mg QD (Period 3)
Participants in Cohort 1 received PF-07081532 20 mg once daily (QD) on Day 1-7, 40 mg QD on Day 8-14, 60 mg QD on Day 15-21, 80 mg QD on Day 22-28 of Period 3.
OG001
Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6)
Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.
Secondary
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.
All participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
Posted
Count of Participants
Participants
From first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2
ID
Title
Description
OG000
Cohort 2: Midazolam 2 mg (Period 1)
Participants in Cohort 2 received SD of midazolam 2 mg on Day 1 of Period 1.
OG001
Cohort 2: Semaglutide Titration up to 2.4 mg QW (Period 2)
Participants in Cohort 2 received semaglutide 0.25 mg once weekly (QW) on Week 1-4, 0.5 mg QW on Week 5-8, 1.0 mg QW on Week 9-12, 1.7 mg QW on Week 13-16, 2.4 mg QW on Week 17-21 of Period 2.
Secondary
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.
All participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
Posted
Count of Participants
Participants
From first dose (Day 1) to follow-up telephone contact (Days 193 to 200) in Cohort 2
ID
Title
Description
OG000
Cohort 2: Midazolam 2 mg (Period 1)
Participants in Cohort 2 received SD of midazolam 2 mg on Day 1 of Period 1.
OG001
Cohort 2: Semaglutide Titration up to 2.4 mg QW (Period 2)
Participants in Cohort 2 received semaglutide 0.25 mg once weekly (QW) on Week 1-4, 0.5 mg QW on Week 5-8, 1.0 mg QW on Week 9-12, 1.7 mg QW on Week 13-16, 2.4 mg QW on Week 17-21 of Period 2.
Participants in Cohort 2 received semaglutide 2.4 mg QW and SD of midazolam 2 mg on Day 1 of Period 3.
OG003
Secondary
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.
All participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
Posted
Median
Full Range
Percentage Change
From baseline (last pre-dose measurement in Period 1) to Period 4 Day 1 (Day 165)
ID
Title
Description
OG000
All Participants
Participants underwent Period 1 to 4 and received study interventions as follows: SD of midazolam 2 mg on Day 1 of Period 1; Semaglutide titrated to 2.4 mg QW on Week 1-21 of Period 2; Semaglutide 2.4 mg QW and SD of midazolam 2 mg on Day 1 of Period 3; SD of midazolam 2 mg on Day 1 of Period 4.
Units
Counts
Participants
OG000
Secondary
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.
All participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants with evaluable C-SSRS results were analyzed.
Posted
Count of Participants
Participants
Screening, D-1 (P1D-1), P2 Week 5 [W5], P2W9, P2W13, P2W17, D150 (P3D2), at follow up visit (Day 172-175)
ID
Title
Description
OG000
All Participants
Participants underwent Period 1 to 4 and received study interventions as follows: SD of midazolam 2 mg on Day 1 of Period 1; Semaglutide titrated to 2.4 mg QW on Week 1-21 of Period 2; Semaglutide 2.4 mg QW and SD of midazolam 2 mg on Day 1 of Period 3; SD of midazolam 2 mg on Day 1 of Period 4.
Units
Secondary
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.
All participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants with evaluable PHQ-9 results were analyzed.
Posted
Mean
Standard Deviation
Score
Screening, D-1 (P1D-1), P2 Week 5 [W5], P2W9, P2W13, P2W17, D150 (P3D2), at follow up visit (Day 172-175)
ID
Title
Description
OG000
All Participants
Participants underwent Period 1 to 9 and received study interventions as follows: SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1; SD of LE 0.15 mg and ethinyl estradiol (EE) 0.03 mg on Day 1 of Period 2; PF-07081532 titrated to 80 mg QD on Day 1-28 of Period 3; PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4; PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5; PF-07081532 titrated to 260 mg QD on Day 1-63 of Period 6; PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7; PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8; SD of midazolam 2 mg on Day 1 of Period 9.
1.
Secondary
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.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng*hr/mL
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
ID
Title
Description
OG000
Cohort 2: Midazolam 2 mg (Period 4)
Participants in Cohort 2 received SD of midazolam 2 mg on Day 1 of Period 4.
Units
Counts
Participants
OG000
Secondary
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.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
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
ID
Title
Description
OG000
Cohort 2: Midazolam 2 mg (Period 1)
Participants in Cohort 2 received SD of midazolam 2 mg on Day 1 of Period 1.
Participants in Cohort 2 received semaglutide 2.4 mg QW and SD of midazolam 2 mg on Day 1 of Period 3.
Units
Counts
Participants
Secondary
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.
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.
Posted
Median
Full Range
hour
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
ID
Title
Description
OG000
Cohort 2: Midazolam 2 mg (Period 1)
Participants in Cohort 2 received SD of midazolam 2 mg on Day 1 of Period 1.
Participants in Cohort 2 received semaglutide 2.4 mg QW and SD of midazolam 2 mg on Day 1 of Period 3.
Units
Counts
Participants
Secondary
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.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
L/hr
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
ID
Title
Description
OG000
Cohort 2: Midazolam 2 mg (Period 1)
Participants in Cohort 2 received SD of midazolam 2 mg on Day 1 of Period 1.
Participants in Cohort 2 received semaglutide 2.4 mg QW and SD of midazolam 2 mg on Day 1 of Period 3.
Units
Counts
Participants
Secondary
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.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
L
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
ID
Title
Description
OG000
Cohort 2: Midazolam 2 mg (Period 1)
Participants in Cohort 2 received SD of midazolam 2 mg on Day 1 of Period 1.
Participants in Cohort 2 received semaglutide 2.4 mg QW and SD of midazolam 2 mg on Day 1 of Period 3.
Units
Counts
Secondary
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.
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.
Posted
Mean
Standard Deviation
hour
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
ID
Title
Description
OG000
Cohort 2: Midazolam 2 mg (Period 1)
Participants in Cohort 2 received SD of midazolam 2 mg on Day 1 of Period 1.
Participants in Cohort 2 received semaglutide 2.4 mg QW and SD of midazolam 2 mg on Day 1 of Period 3.
Units
Counts
Participants
Secondary
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.
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.
Posted
Geometric Mean
Geometric Coefficient of Variation
Ratio
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
ID
Title
Description
OG000
Cohort 2: Midazolam 2 mg (Period 1)
Participants in Cohort 2 received SD of midazolam 2 mg on Day 1 of Period 1.
Participants in Cohort 2 received semaglutide 2.4 mg QW and SD of midazolam 2 mg on Day 1 of Period 3.
OG002
Cohort 2: Midazolam 2 mg (Period 4)
Participants in Cohort 2 received SD of midazolam 2 mg on Day 1 of Period 4.
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.
Participants in Cohort 1 received single dose (SD) of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 1.
0
16
0
16
1
16
EG001
Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2)
Participants in Cohort 1 received SD of levonorgestrel (LE) 0.15 mg and ethinyl estradiol (EE) 0.03 mg on Day 1 of Period 2.
0
16
0
16
2
16
EG002
Cohort 1: PF-07081532 Titration up to 80 mg QD (Period 3)
Participants in Cohort 1 received PF-07081532 20 mg once daily (QD) on Day 1-7, 40 mg QD on Day 8-14, 60 mg QD on Day 15-21, 80 mg QD on Day 22-28 of Period 3.
Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.
0
16
0
16
2
16
EG004
Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5)
Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.
0
16
0
16
6
16
EG005
Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6)
Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.
Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.
0
8
0
8
1
8
EG007
Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)
Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.
0
7
0
7
2
7
EG008
Cohort 1: Midazolam 2 mg (Period 9)
Participants in Cohort 1 received SD of midazolam 2 mg on Day 1 of Period 9.
0
8
0
8
2
8
EG009
Cohort 2: Midazolam 2 mg (Period 1)
Participants in Cohort 2 received SD of midazolam 2 mg on Day 1 of Period 1.
0
16
0
16
4
16
EG010
Cohort 2: Semaglutide Titration up to 2.4 mg QW (Period 2)
Participants in Cohort 2 received semaglutide 0.25 mg once weekly (QW) on Week 1-4, 0.5 mg QW on Week 5-8, 1.0 mg QW on Week 9-12, 1.7 mg QW on Week 13-16, 2.4 mg QW on Week 17-21 of Period 2.
Participants in Cohort 2 received semaglutide 2.4 mg QW and SD of midazolam 2 mg on Day 1 of Period 3.
0
11
0
11
11
11
EG012
Cohort 2: Midazolam 2 mg (Period 4)
Participants in Cohort 2 received SD of midazolam 2 mg on Day 1 of Period 4.
0
10
0
10
3
10
Serious Adverse Events
Not provided
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG0030 affected16 at risk
EG0040 affected16 at risk
EG0051 affected16 at risk
EG0061 affected8 at risk
EG0071 affected7 at risk
EG0080 affected8 at risk
EG0090 affected16 at risk
EG0101 affected16 at risk
EG0110 affected11 at risk
EG0120 affected10 at risk
Abdominal discomfort
Gastrointestinal disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0021 affected16 at risk
EG003
Abdominal distension
Gastrointestinal disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0011 affected16 at risk
EG00211 affected16 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0011 affected16 at risk
EG0020 affected16 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0026 affected16 at risk
EG003
Flatulence
Gastrointestinal disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Haemorrhoids
Gastrointestinal disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG00211 affected16 at risk
EG003
Retching
Gastrointestinal disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0011 affected16 at risk
EG0023 affected16 at risk
EG003
Early satiety
General disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0021 affected16 at risk
EG003
Non-pitting oedema
General disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Oedema peripheral
General disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Hepatic fibrosis
Hepatobiliary disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Hepatic steatosis
Hepatobiliary disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Hepatomegaly
Hepatobiliary disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Otitis externa
Infections and infestations
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Amylase increased
Investigations
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Gamma-glutamyltransferase increased
Investigations
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Lipase increased
Investigations
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0025 affected16 at risk
EG003
Musculoskeletal discomfort
Musculoskeletal and connective tissue disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Osteoarthritis
Musculoskeletal and connective tissue disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Dizziness
Nervous system disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Headache
Nervous system disorders
MedDRA v26.1
Non-systematic Assessment
EG0001 affected16 at risk
EG0010 affected16 at risk
EG0024 affected16 at risk
EG003
Syncope
Nervous system disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Abnormal dreams
Psychiatric disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0021 affected16 at risk
EG003
Restlessness
Psychiatric disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Breast tenderness
Reproductive system and breast disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Dysmenorrhoea
Reproductive system and breast disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Intermenstrual bleeding
Reproductive system and breast disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Menstruation delayed
Reproductive system and breast disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Pelvic discomfort
Reproductive system and breast disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Dermatitis contact
Skin and subcutaneous tissue disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Hyperthyroidism
Endocrine disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Hypothyroidism
Endocrine disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Aphthous ulcer
Gastrointestinal disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Change of bowel habit
Gastrointestinal disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Eructation
Gastrointestinal disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Non-cardiac chest pain
General disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Pain
General disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Viral infection
Infections and infestations
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Arthropod bite
Injury, poisoning and procedural complications
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Somnolence
Nervous system disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Renal cyst
Renal and urinary disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Haemorrhagic ovarian cyst
Reproductive system and breast disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Vaginal haemorrhage
Reproductive system and breast disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Rhinorrhoea
Respiratory, thoracic and mediastinal disorders
MedDRA v26.1
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Analysis done using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. Ratio (Test/Reference) and 90% confidence interval (CI) are expressed as percentages.
Participants in Cohort 1 received PF-07081532 260 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 7.
Analysis done using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. Ratio (Test/Reference) and 90% confidence interval (CI) are expressed as percentages.
Analysis done using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. Ratio (Test/Reference) and 90% confidence interval (CI) are expressed as percentages.
Participants in Cohort 1 received PF-07081532 260 mg QD on Day 1-5 of Period 8, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 8.
Units
Counts
Participants
OG00014
OG00116
OG0026
Title
Denominators
Categories
Title
Measurements
OG00031360± 52
OG00142120± 56
OG00260020± 63
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Reference: Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2). Test: Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5).
Ratio (%) of Adjusted Geometric Means
119.86
2-Sided
90
108.97
131.85
Other
Analysis done using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. Ratio (Test/Reference) and 90% confidence interval (CI) are expressed as percentages.
OG000
OG002
Reference: Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2). Test: Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)
Ratio (%) of Adjusted Geometric Means
185.45
2-Sided
90
108.00
318.44
Other
Analysis done using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. Ratio (Test/Reference) and 90% confidence interval (CI) are expressed as percentages.
Units
Counts
Participants
OG00016
OG00115
OG0026
Title
Denominators
Categories
Title
Measurements
OG000754.5± 37
OG001765.5± 26
OG002701.1± 29
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Reference: Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2). Test: Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5).
Ratio (%) of Adjusted Geometric Means
103.17
2-Sided
90
95.09
111.93
Other
Analysis done using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. Ratio (Test/Reference) and 90% confidence interval (CI) are expressed as percentages.
OG000
OG002
Reference: Cohort 1: LE 0.15 mg & EE 0.03 mg (Period 2). Test: Cohort 1: PF-07081532 260 mg QD + LE 0.15 mg & EE 0.03 mg (Period 8)
Ratio (%) of Adjusted Geometric Means
90.20
2-Sided
90
60.24
135.06
Other
Analysis done using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. Ratio (Test/Reference) and 90% confidence interval (CI) are expressed as percentages.
Analysis done using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. Ratio (Test/Reference) and 90% confidence interval (CI) are expressed as percentages.
OG002
Cohort 1: PF-07081532 Titration up to 80 mg QD (Period 3)
Participants in Cohort 1 received PF-07081532 20 mg once daily (QD) on Day 1-7, 40 mg QD on Day 8-14, 60 mg QD on Day 15-21, 80 mg QD on Day 22-28 of Period 3.
Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.
OG004
Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5)
Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.
OG005
Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6)
Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.
Participants in Cohort 1 received PF-07081532 80 mg QD, SD of midazolam 2 mg and omeprazole 20 mg on Day 1 of Period 4.
OG004
Cohort 1: PF-07081532 80 mg QD + LE 0.15 mg & EE 0.03 mg (Period 5)
Participants in Cohort 1 received PF-07081532 80 mg QD on Day 1-5 of Period 5, and SD of LE 0.15 mg and EE 0.03 mg on Day 1 of Period 5.
OG005
Cohort 1: PF-07081532 Titration up to 260 mg QD (Period 6)
Participants in Cohort 1 received PF-07081532 100 mg QD on Day 1-7, 120 mg QD on DAY 8-14, 140 mg QD on Day 15-21, 160 mg QD on Day 22-28, 180 mg QD on Day 29-35, 200 mg QD on Day 36-42, 220 mg QD on Day 43-49, 240 mg QD on Day 50-56, 260 mg QD on Day 57-63 of Period 6.