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

Phase 1

Completed

Conditions: Obesity

Interventions: Drug: PF-06882961
Drug: Rosuvastatin
Drug: Midazolam

Registration Number: NCT04621227

Lead Sponsor: Pfizer

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 16

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Period 1	Rosuvastatin	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.
Period 1	Midazolam	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.
Period 1	PF-06882961	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.

Primary Outcome Measures

Name	Time	Method
AUClast of Midazolam in Periods 2, 5 and 8	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	AUClast is area under the plasma concentration-time profile from time 0 to last quantifiable concentration.
Area Under the Plasma Concentration-time Profile From Time 0 to Last Quantifiable Concentration (AUClast) of Rosuvastatin in Periods 1, 4 and 7	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 is area under the plasma concentration-time profile from time 0 to last quantifiable concentration.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Laboratory Abnormalities (Without Regard to Baseline [BL] Abnormality)	From BL (Day 1, the last pre-dose measurement in Period 1) to Follow Up visit (Days 68-71) (approximately up to 71 days)	Safety laboratory assessments included clinical chemistry, hematology, urinalysis, and other tests. Abnormality was determined at the investigator's discretion.
Change From Baseline in Body Weight	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)	Changes from Baseline in body weight of the participants were measured.
Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS)	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	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.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	From first dose of study drug (Day 1) to telephone Follow Up (Days 89-96) (approximately up to 96 days)	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.
Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria	From BL (Day 1, the last pre-dose measurement in Period 1) to Follow Up visit (Days 68-71) (approximately up to 71 days)	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.
Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria	From BL (Day 1, the last pre-dose measurement in Period 1) to Follow Up visit (Days 68-71) (approximately up to 71 days)	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.
Number of Participants With Categorical Scores on the Patient Health Questionnaire (PHQ-9)	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	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).