Study To Evaluate The Effect Of Two Steady State Doses of PF 06882961 On Rosuvastatin And Midazolam Pharmacokinetics In Otherwise Healthy Adult Participants With Obesity

Study Overview
=================
Brief Summary
-----------------
A Phase 1 Study To Evaluate The Effect Of Two Steady State Doses of PF 06882961 On Rosuvastatin And Midazolam Pharmacokinetics In Otherwise Healthy Adult Participants With Obesity

Detailed Description
-----------------
This study is designed to look at the effect of two doses of PF 06882961 (120 milligram (mg) twice a day (BID) and 200 mg BID) on the levels of one dose of rosuvastatin 10 mg and one dose of midazolam 2 mg, in otherwise healthy, adult participants with obesity. Total duration of study from screening to the telephone visit will be approximately 17 weeks, of which up to 63 days will be inpatient. All subjects take (i) Rosuvastatin alone, Midazolam alone, PF 06882961 alone (120 mg BID), PF 06882961 (120 mg BID) + Rosuvastatin, PF 06882961 (120 mg BID) + Midazolam, PF 06882961 (200 mg BID) alone, PF 06882961 (200 mg BID) + Rosuvastatin, PF 06882961 (200 mg BID)+ Midazolam in the study.

Official Title
-----------------
A PHASE 1, OPEN -LABEL, FIXED SEQUENCE STUDY TO EVALUATE THE EFFECT OF TWO STEADY STATE DOSE LEVELS OF PF-06882961 ON THE PHARMACOKINETICS OF SINGLE ORAL DOSES OF ROSUVASTATIN AND MIDAZOLAM IN OTHERWISE HEALTHY ADULT PARTICIPANTS WITH OBESITY

Conditions
-----------------
Obesity

Intervention / Treatment
-----------------
* Drug: PF-06882961
* Drug: Rosuvastatin
* Drug: Midazolam


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Body Mass Index (BMI) ≥ 30.0 kg/m2 and not more than 45.4 kg/m2 at Screening. Stable body weight, defined as <5 kg change (per participant report) for 90 days before Screening Exclusion Criteria: Known prior participation in a trial involving PF-06882961. Known intolerance or hypersensitivity to GLP-1R agonists. Known hypersensitivity to rosuvastatin or midazolam. Diagnosis of type 1 or type 2 diabetes mellitus or secondary forms of diabetes at screening. Note: prior diagnoses of gestational diabetes during pregnancy only are eligible if they meet the other eligibility criteria Any lifetime history of a suicide attempt. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing. Participation in a formal weight reduction program (eg, Weight Watchers) within 90 days prior to Screening.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Intervention Model: Crossover Assignment
Interventional Model Description: Crossover
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Period 1<br>Participants will receive the following treatments in this sequence : (i)Rosuvastatin alone (one dose of 10 mg), (ii) Midazolam alone (one dose of 2mg), (iii) PF 06882961 alone (120 mg twice daily), (iv) PF 06882961 (120 mg twice daily) + Rosuvastatin (one dose of 10mg), (v) PF 06882961 (120 mg) + Midazolam (one dose of 2 mg), (vi) PF 06882961 (200 mg) alone, (vii) PF 06882961 (200 mg) + Rosuvastatin (one dose of 10 mg), (viii) PF 06882961 (200 mg)+ Midazolam (one dose of 2 mg) in the study. | Drug: PF-06882961<br>* 120 mg and 200 mg BID<br>Drug: Rosuvastatin<br>* 10 mg single dose<br>Drug: Midazolam<br>* 2mg single dose<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Plasma Concentration-time Profile From Time 0 to Last Quantifiable Concentration (AUClast) of Rosuvastatin in Periods 1, 4 and 7 | AUClast is area under the plasma concentration-time profile from time 0 to last quantifiable concentration. | At 0 (prior to rosuvastatin dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, and 72 hours post rosuvastatin dose on Day 1 in Periods 1, 4, and 7 | 
| AUClast of Midazolam in Periods 2, 5 and 8 | AUClast is area under the plasma concentration-time profile from time 0 to last quantifiable concentration. | At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post midazolam dose on Day 1 in Periods 2, 5, and 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | An adverse event (AE) was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious adverse event (SAE) was defined as any untoward medical occurrence that, at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/incapacity; was a congenital anomaly/birth defect; or other serious situations such as important medical events. TEAEs were events between first dose of study drug and up to follow-up visit that were absent before treatment or that worsened after treatment. AEs presented below were TEAEs. The investigator was required to use clinical judgment to assess the potential relationship between investigational product and each AE, to define an treatment-related AE. | From first dose of study drug (Day 1) to telephone Follow Up (Days 89-96) (approximately up to 96 days) | 
| Number of Participants With Laboratory Abnormalities (Without Regard to Baseline [BL] Abnormality) | Safety laboratory assessments included clinical chemistry, hematology, urinalysis, and other tests. Abnormality was determined at the investigator's discretion. | From BL (Day 1, the last pre-dose measurement in Period 1) to Follow Up visit (Days 68-71) (approximately up to 71 days) | 
| Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Single, supine vital signs assessments included systolic blood pressure (BP), diastolic BP and pulse rate. Abnormality in vital signs included: pulse rate <40 beats per minute (bpm) or >120bpm; supine diastolic BP <50 millimeter of mercury (mmHg), increase and decrease in change from BL of >=20mmHg; supine systolic blood pressure <90mmHg, increase and decrease in change from BL of >=30mmHg. | From BL (Day 1, the last pre-dose measurement in Period 1) to Follow Up visit (Days 68-71) (approximately up to 71 days) | 
| Change From Baseline in Body Weight | Changes from Baseline in body weight of the participants were measured. | At BL (Period 1 Day 1), on Period 3 Days 1, 8, 15 and 22, Period 4 Day 1, Period 6 Days 1 and 9, Period 7 Day 1, Period 8 Day 2, and at Follow Up visit (Days 68-71) | 
| Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | ECG assessments included pulse rate (PR), QT, QTcF intervals and QRS complex. ECG abnormalities criteria included: PR interval value >= 300msec, or BL >200msec and >=25% increase from BL, or BL <=200msec and >=50% increase from BL; QRS interval value >= 140msec, or percent change from BL >=50%; QTcF value >400 and <=480msec, or >480 and <=500 msec, or >500msec, or change from BL>30 and <=60msec, or change from BL >60msec. | From BL (Day 1, the last pre-dose measurement in Period 1) to Follow Up visit (Days 68-71) (approximately up to 71 days) | 
| Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) | The C-SSRS was an interview-based rating scale to systematically assess suicidal ideation and suicidal behavior. C-SSRS assessed whether participant experienced any of the following 1: completed suicide, 2: suicide attempt (response of yes on actual attempt), 3: preparatory acts towards imminent suicidal behavior (yes on aborted attempt, interrupted attempt, preparatory acts/behavior), 4: suicidal ideation (yes on wish to be dead, non-specific active suicidal thoughts), 7: self-injurious behavior, no suicidal intent (yes on has participant engaged in non-suicidal self-injurious behavior). In this outcome, number of participants with positive response (response of yes) to suicidal behavior, ideation, or any self-injurious behavior were reported. | At BL (Period 1 Day 1), on Period 3 Days 1, 8, 15, and 22, Period 4 Day 1, Period 6 Days 1, 9, and 16, Period 8 Day 2, at Follow Up visit (Days 68-71) and Early Termination | 
| Number of Participants With Categorical Scores on the Patient Health Questionnaire (PHQ-9) | The PHQ-9 is a 9 item self-report scale for the assessment of depressive symptoms. The questions included little interest/pleasure in things, feeling down depressed or hopeless, trouble falling or staying asleep, feeling tired or little energy, poor appetite or overeating, feeling bad about yourself, trouble concentrating on things, moving slowly or fidgety/restless and thoughts you be better off dead. Each item was scored on scale of not at all, several days, more than half the days to nearly every day. Total score range: 0-27 (each item with scale from 0 [not at all] to 3 [nearly every day]. Higher score=greater severity). | At BL (Period 1 Day 1), on Period 3 Days 1, 8, 15, and 22, Period 4 Day 1, Period 6 Days 1, 9, and 16, Period 8 Day 2, at Follow Up visit (Days 68-71) and Early Termination | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
obesity