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

• ClinicalTrials.gov Identifier: NCT03985293
• Recruitment Status: Completed
• First Posted: June 13, 2019
• Results First Posted: June 30, 2022
• Last Update Posted: June 30, 2022
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: June 11, 2019
• First Posted Date: June 13, 2019
• Results First Submitted Date: June 2, 2022
• Results First Posted Date: June 30, 2022
• Last Update Posted Date: June 30, 2022
• Actual Study Start Date: October 15, 2019
• Actual Primary Completion Date: June 8, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 2, 2022)

Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 16 [ Time Frame: Baseline, 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%.

• Original Primary Outcome Measures (submitted: June 11, 2019): Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 16 [ Time Frame: Baseline, Week 16 ]

Current Secondary Outcome Measures (submitted: June 2, 2022)

• Percentage of Participants Achieving Less Than (<) 7% Glycated Hemoglobin (HbA1c) Levels [ Time Frame: Baseline, 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%.
• Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 2 [ Time Frame: Baseline, 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%.
• Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 4 [ Time Frame: Baseline, 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%.
• Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 6 [ Time Frame: Baseline, 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%.
• Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 8 [ Time Frame: Baseline, 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%.
• Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 12 [ Time Frame: Baseline, 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%.
• Change From Baseline in Fasting Plasma Glucose at Week 2 [ Time Frame: Baseline, 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.
• Change From Baseline in Fasting Plasma Glucose at Week 4 [ Time Frame: Baseline, 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.
• Change From Baseline in Fasting Plasma Glucose at Week 6 [ Time Frame: Baseline, 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.
• Change From Baseline in Fasting Plasma Glucose at Week 8 [ Time Frame: Baseline, 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.
• Change From Baseline in Fasting Plasma Glucose at Week 12 [ Time Frame: Baseline, 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.
• Change From Baseline in Fasting Plasma Glucose at Week 16 [ Time Frame: Baseline, 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.
• Change From Baseline in Body Weight at Week 2 [ Time Frame: Baseline, 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.
• Change From Baseline in Body Weight at Week 4 [ Time Frame: Baseline, 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.
• Change From Baseline in Body Weight at Week 6 [ Time Frame: Baseline, 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.
• Change From Baseline in Body Weight at Week 8 [ Time Frame: Baseline, 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.
• Change From Baseline in Body Weight at Week 12 [ Time Frame: Baseline, 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.
• Change From Baseline in Body Weight at Week 16 [ Time Frame: Baseline, 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.
• Number of Participants With Treatment Emergent Adverse Events (Adverse Events [AEs] and Serious Adverse Events [SAEs]) [ Time Frame: Baseline up to Week 21 ]
  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.
• Number of Participants With Treatment Emergent Clinical Laboratory Abnormalities Without Regard to Baseline Abnormality [ Time Frame: Baseline Through Week 21 ]
  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).
• Number of Participants With Treatment Emergent Vital Signs Abnormalities [ Time Frame: Baseline through Week 21 ]
  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.
• Number of Participants With Treatment Emergent ECG Abnormalities [ Time Frame: Baseline Through Week 21 ]
  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.

Original Secondary Outcome Measures (submitted: June 11, 2019)

• Percentage of Participants Achieving Less Than (<) 7% Glycosylated Hemoglobin (HbA1c) Levels [ Time Frame: Baseline, Week 16 ]
• Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 2 [ Time Frame: Baseline, Week 2 ]
• Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 4 [ Time Frame: Baseline, Week 4 ]
• Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 6 [ Time Frame: Baseline, Week 6 ]
• Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 8 [ Time Frame: Baseline, Week 8 ]
• Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 12 [ Time Frame: Baseline, Week 12 ]
• Change from baseline in fasting plasma glucose at week 2 [ Time Frame: Baseline, week 2 ]
• Change from baseline in fasting plasma glucose at week 4 [ Time Frame: Baseline, week 4 ]
• Change from baseline in fasting plasma glucose at week 6 [ Time Frame: Baseline, week 6 ]
• Change from baseline in fasting plasma glucose at week 8 [ Time Frame: Baseline, week 8 ]
• Change from baseline in fasting plasma glucose at week 12 [ Time Frame: Baseline, week 12 ]
• Change from baseline in fasting plasma glucose at week 16 [ Time Frame: Baseline, week 16 ]
• Change from baseline in body weight at week 2 [ Time Frame: Baseline, week 2 ]
• Change from baseline in body weight at week 4 [ Time Frame: Baseline, week 4 ]
• Change from baseline in body weight at week 6 [ Time Frame: Baseline, week 6 ]
• Change from baseline in body weight at week 8 [ Time Frame: Baseline, week 8 ]
• Change from baseline in body weight at week 12 [ Time Frame: Baseline, week 12 ]
• Change from baseline in body weight at week 16 [ Time Frame: Baseline, week 16 ]
• Incidence of treatment emergent adverse events (AEs and SAEs) [ Time Frame: Baseline up to week 21 ]
• Incidence of treatment emergent clinical laboratory abnormalities [ Time Frame: Baseline through week 21 ]
• Incidence of treatment emergent vital signs abnormalities [ Time Frame: Baseline through week 21 ]
• Incidence of treatment emergent ECG abnormalities [ Time Frame: Baseline through week 21 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A 16 Week Study to Evaluate the Efficacy and Safety of PF-06882961 in Adults With Type 2 Diabetes Mellitus
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Diabetes Mellitus, Type 2

Intervention

• Drug: Placebo
  4 matching placebo tablets taken twice a day (BID)
• Drug: PF-06882961
  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.

Study Arms

• Placebo Comparator: Placebo
  Intervention: Drug: Placebo
• Experimental: PF-06882961 2.5 milligrams (mg)
  Intervention: Drug: PF-06882961
• Experimental: PF-06882961 10 mg
  Intervention: Drug: PF-06882961
• Experimental: PF-06882961 40 mg
  Participants will be titrated up to 2 weeks to reach desired dose level
  Intervention: Drug: PF-06882961
• Experimental: PF-06882961 80 mg
  Participants will be titrated up to 4 weeks to reach desired dose level
  Intervention: Drug: PF-06882961
• Experimental: PF-06882961 120 mg
  Participants will be titrated up to 6 weeks to reach desired dose level
  Intervention: Drug: PF-06882961

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 10, 2021): 412
• Original Estimated Enrollment (submitted: June 11, 2019): 400
• Actual Study Completion Date: July 7, 2021
• Actual Primary Completion Date: June 8, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Bulgaria, Canada, Hungary, Korea, Republic of, Poland, Slovakia, Taiwan, United States

Administrative Information

• NCT Number: NCT03985293
• Other Study ID Numbers: C3421005; 2019-000218-12 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: June 2022