A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of PF-06882961 in Japanese Adults With Type 2 Diabetes Mellitus

Phase 1

Completed

Conditions: Type 2 Diabetes Mellitus

Interventions: Drug: Placebo
Drug: PF-06882961

Registration Number: NCT04552470

Lead Sponsor: Pfizer

Brief Summary: This is a Phase 1, randomized, double blind (sponsor open), parallel, placebo controlled, twice daily oral dosing study of PF 06882961 in adult Japanese participants with T2DM inadequately controlled on diet and exercise alone.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 37

Inclusion Criteria

Patients with T2DM who are treated with diet and exercise
HbA1c greater than or equal to 7% and less than or equal to 10.5%
Total body weight >50 kg (110 lb) with BMI 22.5 to 45.4 kg/m^2

Exclusion Criteria

Any condition possibly affecting drug absorption
Diagnosis of Type 1 diabetes
History of myocardial infarction, unstable angina, arterial revascularization, stroke, heart failure, or transient ischemic attack within 6 months of screening
Any malignancy not considered cured
Personal or family history of MTC or MEN2, or participants with suspected MTC
Acute pancreatitis or history of chronic pancreatitis
Symptomatic gallbladder disease
Known medical history of active proliferative retinopathy and/or macular edema
Known history of HIV, hepatitis B, hepatitis C or syphilis
Supine blood pressure greater than or equal to 160 mmHg (systolic) or greater than or equal to 100 mmHg (diastolic)
Clinically relevant ECG abnormalities
Positive urine drug test

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
PF-06882961 120 mg	PF-06882961	Participants will be titrated up to 6 weeks to reach desired dose level
PF-06882961 40 mg	PF-06882961	Participants will be titrated up to 2 weeks to reach desired dose level
PF-06882961 80 mg	PF-06882961	Participants will be titrated up to 4 weeks to reach desired dose level

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	Day 1 of dosing up to approximately 4 weeks after last dose (up to maximum of approximately 12 weeks)	An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. 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 AEs were events between first dose of study drug and approximately 4 weeks after last dose of study drug, that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and all non-serious AEs.
Number of Participants With Absolute Vital Signs (SBP, DBP and Pulse Rate) Values; Increased and Decreased Vital Signs (SBP, DBP) Values From Time-Matched Baseline	Baseline (1 Day before dosing) up to last dose (maximum up to Week 8)	Supine systolic blood pressure (SBP) measured in millimeter of mercury (mmHg) had following categories: minimum of absolute SBP \<90 mmHg, maximum of SBP \>=30 mmHg decrease from baseline and maximum of SBP \>=30 mmHg increase from baseline. Supine diastolic blood pressure (DBP) measured in mmHg had following categories: minimum of absolute DBP \<50 mmHg, maximum of DBP \>20 mmHg decrease from baseline and maximum of DBP \>=20 mmHg increase from baseline. Supine pulse rate measured in beats per minute (BPM) had following categories: minimum of absolute supine pulse rate \<40 BPM and maximum of absolute supine pulse rate \>120 BPM. Baseline was defined as the time-matched value from the average of the triplicate recordings on Day -1.
Number of Participants With Clinical Laboratory Abnormalities	Day 1 of dosing up to approximately 4 weeks after last dose (up to maximum of approximately 12 weeks)	Leukocytes (10\^9/liter \[L\]) bilirubin (micromol/L), glucose (millimoles \[mmol\]/L), triacylglycerol lipase (microkatals \[microkat\]/L): greater than (\>) 1.5\upper limit normal (ULN); activated partial thromboplastin time (s): 1.1\ULN; HDL cholesterol (mmol/L), thyroid stimulating hormone (TSH) (milliunits \[mU\]/L): less than (\<) 0.8\lower limit normal (LLN); LDL cholesterol (mmol/L), urate (mmol/L): \>1.2\ULN; triglycerides: \>1.3\ULN; aspartate aminotransferase (microkat/L), alanine aminotransferase (microkat/L), gamma glutamyl transferase (microkat/L): \>3.0\ULN; cholesterol (mmol/L): \>1.3\*ULN; urine glucose, ketones urine protein, urine hemoglobin, urobilinogen, nitrite, leukocyte esterase: greater than or equal to (\>=) 1; granular casts, hyaline casts: \>1.
Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline	Baseline (1 Day before dosing) up to last dose (maximum up to Week 8)	PR interval had following categories: maximum absolute PR interval \>=300 milliseconds (msec); when baseline PR interval \>200 msec and maximum increase from baseline in PR interval \>=25 percent; when baseline PR interval less than or equal to (\<=) 200 msec and maximum increase from baseline in PR interval \>=50 percent. QRS interval had following categories: maximum absolute QRS interval \>=140 msec; maximum increase from baseline in QRS interval \>=50 percent. QTC interval with Frederica's correction (QTCF) had following categories: absolute QTCF interval \>450 msec to \<=480 msec; absolute QTCF interval \>480 msec to \<=500 msec; absolute QTCF interval \>500 msec; QTCF interval increase from baseline \>=30 msec to \<=60 msec; QTCF interval increase from baseline \>60 msec.

Secondary Outcome Measures

Name	Time	Method
Terminal Phase Half-Life (t1/2) of PF-06882961	Pre-dose (0 hour), 1, 2, 4, 6, 8, 10, 12, 14, 24, 36 and 48 hours on Day 56	t1/2 was calculated as loge (2) per kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06882961	Pre-dose (0 hour), 1, 2, 4, 6, 8, 10, 12, 14 and 24 hours post dose on Day 1; Pre-dose (0 hour), 1, 2, 4, 6, 8, 10, 12, 14, 24, 36 and 48 hours on Day 56
Area Under the Plasma Concentration-time Profile From Zero to Time 24 Hours (AUC24) of PF-06882961	Pre-dose (0 hour), 1, 2, 4, 6, 8, 10, 12, 14 and 24 hours post dose on Day 1 and 56	AUC24= Area under the plasma concentration versus time curve from time zero (pre-dose) to time 24 hours (0-24).
Maximum Plasma Concentration (Cmax) Observed of PF-06882961	Pre-dose (0 hour), 1, 2, 4, 6, 8, 10, 12, 14 and 24 hours post dose on Day 1; Pre-dose (0 hour), 1, 2, 4, 6, 8, 10, 12, 14, 24, 36 and 48 hours on Day 56