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

Phase 1

Conditions: TYPE 2 DIABETES MELLITUS INADEQUATELY CONTROLLED ON METFORMIN OR DIET AND EXERCISE
MedDRA version: 20.1Level: LLTClassification code 10063624Term: Type II diabetes mellitus inadequate controlSystem Organ Class: 100000004861
Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Registration Number: EUCTR2019-000218-12-PL

Lead Sponsor: Pfizer Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 400

Inclusion Criteria

Age and Sex:
1.Male or female participants between the ages of 18 (or the minimum country specific age of consent if >18) and 75 years, inclusive, at Visit 1.
•Refer to Appendix 4 of the protocol for reproductive criteria for male (Section 10.4.1 of the protocol) and female (Section 10.4.2 of the protocol) participants.
Type of Participant and Disease Characteristics:
2.Patients with T2DM who are treated with metformin and/or diet and exercise.
•For participants taking metformin, the metformin dose must have been stable for at least 60 days prior to the screening visit (Visit 1).
•Enrollment of participants on diet and exercise only (ie, no anti diabetic medications) will be limited to =20% of total participant population.
3.HbA1c =7% and =10.5% at screening (Visit 1) as assessed by the study specific laboratory and confirmed by a single repeat test, if deemed necessary.
4.Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures, including the ability to perform self-tests of blood sugar regularly (see Section 8.2.5.1 of the protocol) for the duration of the study and maintenance of study specific glucose logs for the duration of participation in the study.
Body Mass Index (BMI) and Weight:
5.Total body weight >50 kg (110 lb) with BMI of 24.5 to 45.4 kg/m2 (for sites in North America and Europe) or BMI 22.5 to 45.4 kg/m2 (for sites in Asia). Body weight must have been stable (<5% change) for 90 days prior to screening (Visit 1) as per participant report.
Informed Consent:
6.Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the informed consent document (ICD) and in this protocol.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 320
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 80

Exclusion Criteria

Medical Conditions:
1.Any acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or IP administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
2.Any condition possibly affecting drug absorption.
3.Diagnosis of type 1 diabetes mellitus or secondary forms of diabetes.
4.History of myocardial infarction, unstable angina, arterial revascularization, stroke, New York Heart Association Functional Class II IV heart failure, or transient ischemic attack within 6 months of screening (Visit 1).
5.Any malignancy not considered cured (except basal cell carcinoma and squamous cell carcinoma of the skin); a subject is considered cured if there has been no evidence of cancer recurrence in the previous 5 years.
6.Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2), or subjects with suspected MTC per the investigator’s judgment.
7.Acute pancreatitis or history of chronic pancreatitis.
8.Symptomatic gallbladder disease.
9.Participants with a known medical history of active proliferative retinopathy and/or macular edema.
10.Participants with a known medical history of active liver disease (other than non-alcoholic hepatic steatosis), including chronic active hepatitis B or C, or primary biliary cirrhosis.
11.Participants with known history of human immunodeficiency virus.
Prior/Concomitant Therapy:
12.See Appendix 8 for details regarding prohibited prior/concomitant medications.
Prior/Concurrent Clinical Study Experience:
13.Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half lives preceding the first dose of IP used in this study.
14.Known prior participation in a trial involving PF 06882961 or known intolerance to a GLP 1R agonist.
Diagnostic Assessments:
15.Screening supine blood pressure =180 mmHg (systolic) or =105 mmHg (diastolic), following at least 5 minutes of supine rest. BP should be measured in triplicate and the average of the 3 BP values should be used to determine the participant’s eligibility. Note: Participants with an arm circumference greater than the largest cuff size or those with a mid-arm circumference >52 cm are not eligible.
16.Screening 12 lead electrocardiogram that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, baseline corrected QT interval>450 msec, complete left bundle branch block , signs of an acute or indeterminate age myocardial infarction, ST T interval changes suggestive of myocardial ischemia, second or third degree atrioventricular [AV] block, or serious bradyarrhythmias or tachyarrhythmias).
•If QTcF exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more times and the average of the 3 QTcF or QRS values should be used to determine the participant’s eligibility.
17.A positive urine drug test. Note: may be allowed to participate with notification to the sponsor in case of medically prescribed opiates/opioids or benzodiazepines
18.Participants with ANY of the following abnormalities in clinical laboratory tests at screening:
•Aspartate aminotransferase (AST) or alanin

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare the effect of multiple dose levels of PF 06882961 versus placebo on glycated hemoglobin (HbA1c) in participants with T2DM on stable doses of metformin and/or diet and exercise.;Secondary Objective: 1.To compare the effect of multiple dose levels of PF 06882961 versus placebo on glycemic control in participants with T2DM on stable doses of metformin and/or diet and exercise.<br>2.To compare the effect of multiple dose levels of PF 06882961 versus placebo on body weight in participants with T2DM on stable doses of metformin and/or diet and exercise.<br>3.To characterize the safety and tolerability of multiple dose levels of PF 06882961 administered to participants with T2DM on stable doses of metformin and/or diet and exercise.<br>;Primary end point(s): Change from baseline in HbA1c at Week 16.;Timepoint(s) of evaluation of this end point: Week 16.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1.A Response as defined by an HbA1c <7% at Week 16.<br> B Change from baseline in HbA1c at Weeks 2, 4, 6, 8 and 12<br> C Change from baseline in fasting plasma glucose at Weeks, 2, 4, 6, 8, 12 and 16.<br>2.Change from baseline in body weight at Weeks 2, 4, 6, 8, 12 and 16.<br>3.Incidence of treatment emergent adverse events [adverse events (AEs) and serious adverse events (SAEs)], clinical laboratory abnormalities, vital signs (blood pressure and pulse rate) and electrocardiogram (ECG) parameters (heart rate, QT, QTcF, PR and QRS intervals).<br>;Timepoint(s) of evaluation of this end point: Individual timepoints are included in each bullet point above.

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