A 16 Week Study to Evaluate the Efficacy and Safety of PF-06882961 in Adults With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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This multicenter, randomized, double-blind, placebo controlled, parallel group study is being conducted to provide data on efficacy, safety, tolerability and pharmacokinetics (PK) of multiple dose levels of PF-06882961 in adults with type 2 diabetes mellitus (T2DM) inadequately controlled on metformin and/or diet and exercise. In addition, the study is intended to enable selection of efficacious doses for future clinical development of PF-06882961.

Official Title
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A 16-WEEK, PHASE 2B, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL GROUP STUDY TO EVALUATE THE EFFICACY AND SAFETY OF TWICE DAILY PF-06882961 ADMINISTRATION IN ADULTS WITH TYPE 2 DIABETES MELLITUS INADEQUATELY CONTROLLED ON METFORMIN OR DIET AND EXERCISE

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Placebo
* Drug: PF-06882961


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with T2DM who are treated with metformin and/or 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 24.5 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 medical history of active liver disease, including chronic active hepatitis B or C, or primary biliary cirrhosis Known history of HIV 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* 4 matching placebo tablets taken twice a day (BID)<br>|
| Experimental: PF-06882961 2.5 milligrams (mg)<br> | Drug: PF-06882961<br>* Participants will be randomized to one of 5 active doses (2.5, 10, 40, 80, or 120 mg), taking 4 tablets twice daily for 16 weeks.<br>|
| Experimental: PF-06882961 10 mg<br> | Drug: PF-06882961<br>* Participants will be randomized to one of 5 active doses (2.5, 10, 40, 80, or 120 mg), taking 4 tablets twice daily for 16 weeks.<br>|
| Experimental: PF-06882961 40 mg<br>Participants will be titrated up to 2 weeks to reach desired dose level | Drug: PF-06882961<br>* Participants will be randomized to one of 5 active doses (2.5, 10, 40, 80, or 120 mg), taking 4 tablets twice daily for 16 weeks.<br>|
| Experimental: PF-06882961 80 mg<br>Participants will be titrated up to 4 weeks to reach desired dose level | Drug: PF-06882961<br>* Participants will be randomized to one of 5 active doses (2.5, 10, 40, 80, or 120 mg), taking 4 tablets twice daily for 16 weeks.<br>|
| Experimental: PF-06882961 120 mg<br>Participants will be titrated up to 6 weeks to reach desired dose level | Drug: PF-06882961<br>* Participants will be randomized to one of 5 active doses (2.5, 10, 40, 80, or 120 mg), taking 4 tablets twice daily for 16 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 16 | HbA1c can be used as a diagnostic test for diabetes. The target HbA1c level for people with diabetes is usually less than 7%. | Baseline, Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Less Than (<) 7% Glycated Hemoglobin (HbA1c) Levels | HbA1c can be used as a diagnostic test for diabetes. The target HbA1c level for people with diabetes is usually less than 7%. | Baseline, Week 16 | 
| Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 2 | HbA1c can be used as a diagnostic test for diabetes. The target HbA1c level for people with diabetes is usually less than 7%. | Baseline, Week 2 | 
| Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 4 | HbA1c can be used as a diagnostic test for diabetes. The target HbA1c level for people with diabetes is usually less than 7%. | Baseline, Week 4 | 
| Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 6 | HbA1c can be used as a diagnostic test for diabetes. The target HbA1c level for people with diabetes is usually less than 7%. | Baseline, Week 6 | 
| Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 8 | HbA1c can be used as a diagnostic test for diabetes. The target HbA1c level for people with diabetes is usually less than 7%. | Baseline, Week 8 | 
| Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 12 | HbA1c can be used as a diagnostic test for diabetes. The target HbA1c level for people with diabetes is usually less than 7%. | Baseline, Week 12 | 
| Change From Baseline in Fasting Plasma Glucose at Week 2 | The fasting plasma glucose test measures the levels of glucose (sugar) in the blood, with a normal range of 70 milligram per deciliter (mg/dL) to 99 mg/dL. | Baseline, Week 2 | 
| Change From Baseline in Fasting Plasma Glucose at Week 4 | The fasting plasma glucose test measures the levels of glucose (sugar) in the blood, with a normal range of 70 mg/dL to 99 mg/dL. | Baseline, Week 4 | 
| Change From Baseline in Fasting Plasma Glucose at Week 6 | The fasting plasma glucose test measures the levels of glucose (sugar) in the blood, with a normal range of 70 mg/dL to 99 mg/dL. | Baseline, Week 6 | 
| Change From Baseline in Fasting Plasma Glucose at Week 8 | The fasting plasma glucose test measures the levels of glucose (sugar) in the blood, with a normal range of 70 mg/dL to 99 mg/dL. | Baseline, Week 8 | 
| Change From Baseline in Fasting Plasma Glucose at Week 12 | The fasting plasma glucose test measures the levels of glucose (sugar) in the blood, with a normal range of 70 mg/dL to 99 mg/dL. | Baseline, Week 12 | 
| Change From Baseline in Fasting Plasma Glucose at Week 16 | The fasting plasma glucose test measures the levels of glucose (sugar) in the blood, with a normal range of 70 mg/dL to 99 mg/dL. | Baseline, Week 16 | 
| Change From Baseline in Body Weight at Week 2 | Weight was recorded using a calibrated scale (with the same scale used if possible for the duration of the study) reporting weight in kilograms (kg), and accuracy to the nearest 0.1 kg. | Baseline, Week 2 | 
| Change From Baseline in Body Weight at Week 4 | Weight was recorded using a calibrated scale (with the same scale used if possible for the duration of the study) reporting weight in kilograms (kg), and accuracy to the nearest 0.1 kg. | Baseline, Week 4 | 
| Change From Baseline in Body Weight at Week 6 | Weight was recorded using a calibrated scale (with the same scale used if possible for the duration of the study) reporting weight in kilograms (kg), and accuracy to the nearest 0.1 kg. | Baseline, Week 6 | 
| Change From Baseline in Body Weight at Week 8 | Weight was recorded using a calibrated scale (with the same scale used if possible for the duration of the study) reporting weight in kilograms (kg), and accuracy to the nearest 0.1 kg. | Baseline, Week 8 | 
| Change From Baseline in Body Weight at Week 12 | Weight was recorded using a calibrated scale (with the same scale used if possible for the duration of the study) reporting weight in kilograms (kg), and accuracy to the nearest 0.1 kg. | Baseline, Week 12 | 
| Change From Baseline in Body Weight at Week 16 | Weight was recorded using a calibrated scale (with the same scale used if possible for the duration of the study) reporting weight in kilograms (kg), and accuracy to the nearest 0.1 kg. | Baseline, Week 16 | 
| Number of Participants With Treatment Emergent Adverse Events (Adverse Events [AEs] and Serious Adverse Events [SAEs]) | An adverse event (AE) was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. A serious AE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening; initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. Any such events with initial onset or increasing in severity after the first dose of study treatment were counted as treatment-emergent. | Baseline up to Week 21 | 
| Number of Participants With Treatment Emergent Clinical Laboratory Abnormalities Without Regard to Baseline Abnormality | Following laboratory parameters were assessed against pre-defined abnormality criteria: hematology (hemoglobin, hematocrit, erythrocytes, reticulocytes, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils, monocytes, activated partial thromboplastin time, prothrombin time, PT/INR, reticulocytes); chemistry (indirect bilirubin, direct bilirubin, protein, albumin, blood urea nitrogen, creatinine, creatine kinase, urate, calcium, sodium, potassium, chloride, bicarbonate, urine urobilinogen); urinalysis (pH, urine glucose, urine ketones, urine protein, urine hemoglobin, nitrites, leukocyte esterase, urine erythrocytes, urine leukocytes, urine hyaline casts, urine bilirubin); lipid panel (low density lipoprotein cholesterol, high density lipoprotein cholesterol). | Baseline Through Week 21 | 
| Number of Participants With Treatment Emergent Vital Signs Abnormalities | Vital signs abnormality criteria: 1) supine systolic blood pressure (SBP) <90 millimeters of mercury (mmHg); 2) supine diastolic blood pressure (DBP) <50 mmHg; 3) supine pulse rate <40 or >120 beats per minute (bpm); 4) change from baseline (increase or decrease) in supine SBP greater than or equal to (>=) 30 mmHg; 5) change from baseline (increase or decrease) in supine DBP >= 20 mmHg. | Baseline through Week 21 | 
| Number of Participants With Treatment Emergent ECG Abnormalities | ECG categorical abnormality criteria: 1. PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization): a) greater than or equal to (>=) 300 millisecond (msec), b) >=25% increase when baseline is > 200 msec or >=50% increase when baseline is less than or equal to (<=) 200 msec. 2. QRS interval (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization): a) >=140 msec, b) >=50% increase from baseline. 3. QTcF interval (QT corrected using the Fridericia formula): a) >450 msec and <=480 msec, b) >480 msec and <=500 msec, c) >500 msec, d) >30 msec and <=60 msec increase from baseline, e) >60 msec increase from baseline. | Baseline Through Week 21 |