Clinical trial NCT02554877: A 12-week Study To Evaluate PF-06291874 Once a Day in Adults With T2DM Inadequately Controlled On Metformin
Official title: A 12-week, Phase 2, Randomized, Double-blind, Placebo-controlled, Parallel Group Study To Evaluate The Efficacy And Safety Of Once Daily Pf-06291874 Administration In Adults With Type 2 Diabetes Mellitus Inadequately Controlled On Metformin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2015-09-18
Enrollment: 206
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether PF-06291874 is effective in the treatment T2DM

Detailed description: This will be a randomized, double blind, stratified, placebo controlled, parallel group study conducted in T2DM subjects receiving background metformin therapy. Subjects will complete screening procedures to determine eligibility, followed by an 8 week metformin stabilization period prior to randomization. In addition, subjects taking other OADs, in combination with metformin, will undergo a washout during this period, in which non metformin OAD medications will be temporarily discontinued for the duration of the trial. Following confirmation of study eligibility criteria at randomization, subjects will be stratified into 2 groups based on the use of concomitant statin therapy. Each stratum will be randomized across treatment groups, such that the number of subjects taking concomitant statin therapy and those not taking statin therapy will be approximately balanced across treatment groups.

Eligibility criteria: Inclusion Criteria:

1. Males or non-childbearing potential females between the ages of 18 (or the minimum country specific age of consent if \>18) and 70 years, inclusive, at the screening visit (V1) with the diagnosis of T2DM;Female subjects who are not of childbearing potential
2. Subjects who have been on a stable dose of metformin either alone or in combination with one additional acceptable OAD
3. HbA1c at the Screen Visit (V1), as assessed by study specific central laboratory, is 7-11% if on metformin monotherapy; is 6.5-9.5% if on dual combination therapy (metformin plus 1)

Exclusion Criteria:

1. Diagnosis of type 1 diabetes mellitus or secondary forms of diabetes;
2. Fasting plasma glucose levels \>270 mg/dL (15.0 mmol/L) at the screening and run in visit, (as assessed by study specific central laboratory) confirmed by a single repeat, if deemed necessary
3. History of myocardial infarction, unstable angina, arterial revascularization, stroke, New York Heart Association Functional Class III IV heart failure, or transient ischemic attack within 6 months of screening;
4. Any medical condition possibly affecting study drug absorption (eg, gastrectomy or any area of intestinal resection, active inflammatory bowel disease or pancreatic insufficiency
5. Subjects with a creatinine clearance \<60 mL/min as determined by the Cockcroft Gault equation (listed below) using serum creatinine measured at screening, confirmed via a single repeat, if deemed necessary
6. Subject with a positive result for hepatitis B surface antigen (HBsAg), hepatitis B core antibodies (HBc Ab) or hepatitis C virus (HCV) antibodies
7. Screening seated systolic blood pressure \>160 mm Hg and/or diastolic blood pressure \>105 mm Hg after at least a 5 minute rest. Blood pressure determined as the mean of triplicate measurements collected with approximately 2 minutes of rest between measurements
8. Screening supine 12 lead ECG demonstrating a corrected QT (QTc) \>470 msec; or a QRS interval \>120 msec. If QTc exceeds 470 msec or QRS exceeds 120 msec, the ECG may be repeated 2 more times with an interval of 2-4 minutes between each measurement and the mean of the 3 values used to determine the subject's eligibility
9. Subjects with an arm circumference \>52 cm measured at the midpoint of the length of the upper arm;
10. History (within the last 6 months) of regular alcohol consumption exceeding 14 drinks per week for men and 7 drinks a week for women. (1 drink = 5 ounces of wine (150 mL) or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor);
11. Treatment with thiazolidinediones (TZDs), or subcutaneously administered anti diabetic agents (eg, insulin, exenatide, liraglutide, pramlintide) within 6 weeks prior to V1;
12. Subjects with a known hypersensitivity or intolerance to a glucagon receptor antagonist, or known prior participation in a trial involving PF 06291874;

Primary outcomes:
measure: Change From Baseline in Glycosylated Hemoglobin (HbA1c) (%) at Week 12 as Compared to Placebo
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Change From Baseline in HbA1c (%) at Weeks 2, 4, and 8
timeFrame: Baseline, Weeks 2, 4, 8
measure: Change From Baseline in Fasting Plasma Glucose at Weeks 2, 4, 8, and 12
timeFrame: Baseline, Weeks 2,4,8 and 12
measure: Percentage of Participants Achieving Glycosylated Hemoglobin (HbA1c) <7% as Well as <6.5% at Week 12.
timeFrame: Week 12
measure: Number of Participants With Laboratory Test Abnormalities
timeFrame: Baseline up to 98 days
measure: Number of Participants With Change From Baseline and Absolute Values in 12-lead Electrocardiograms (ECGs) Meeting Categorical Summarization Criteria
timeFrame: Baseline up to Day 98
measure: Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria
timeFrame: Baseline up to Day 98
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Hypoglycemic Adverse Events (HAEs).
timeFrame: Baseline up to Day 119
measure: Percent Changes From Baseline for Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Weeks 2, 4, 8 and 12
timeFrame: Baseline, Weeks 2, 4, 8 and 12
measure: Percent Changes From Baseline for Triglycerides at Weeks 2, 4, 8 and 12
timeFrame: Baseline, Weeks 2, 4, 8 and 12
measure: Percent Changes From Baseline for Total Cholesterol at Weeks 2, 4, 8 and 12
timeFrame: Baseline, Weeks 2, 4, 8 and 12
measure: Percent Changes From Baseline for High Density Lipoprotein-Cholesterol (HDL-C) at Weeks 2, 4, 8 and 12
timeFrame: Baseline, Weeks 2, 4, 8 and 12
measure: Percent Changes From Baseline for Non-High Density Lipoprotein (HDL) Cholesterol at Weeks 2, 4, 8 and 12
timeFrame: Baseline, Weeks 2, 4, 8 and 12
measure: Changes From Baseline in Body Weight at Weeks 2, 4, 8, and 12.
timeFrame: Baseline, Weeks 2, 4, 8 and 12
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Anaheim Clinical Trials, LLC
state: California
city: Los Angeles
country: United States
facility: National Research Institute
state: California
city: Orange
country: United States
facility: NRC Research Institute
state: California
city: Roseville
country: United States
facility: Sierra Clinical Research
state: California
city: Spring Valley
country: United States
facility: Encompass Clinical Research
state: California
city: Upland
country: United States
facility: Empire Clinical Research
state: California
city: Walnut Creek
country: United States
facility: Diablo Clinical Research, Inc
state: California
city: Coral Gables
country: United States
facility: Clinical Research of South Florida
state: Florida
city: DeLand
country: United States
facility: Avail Clinical Research, LLC
state: Florida
city: Miami
country: United States
facility: Suncoast Research Group, Llc
state: Florida
city: South Miami
country: United States
facility: QPS-MRA, LLC (Miami Research Associates)
state: Florida
city: West Palm Beach
country: United States
facility: Palm Beach Research Center
state: Florida
city: Sandy Springs
country: United States
facility: WR-Mount Vernon Clinical Research, LLC
state: Georgia
city: Honolulu
country: United States
facility: East-West Medical Research Institute
state: Hawaii
city: Indianapolis
country: United States
facility: Midwest Institute for Clinical Research
state: Indiana
city: Metairie
country: United States
facility: Crescent City Clinical Research Center, LLC
state: Louisiana
city: Saint Louis
country: United States
facility: St. Louis Clinical Trials, LC
state: Missouri
city: Las Vegas
country: United States
facility: ALAS Science Clinical Research
state: Nevada
city: Berlin
country: United States
facility: Comprehensive Clinical Research
state: New Jersey
city: Eatontown
country: United States
facility: Clinilabs Inc.
state: New Jersey
city: Marlton
country: United States
facility: Pharmaceutical Research Associates, Inc.
state: New Jersey
city: Trenton
country: United States
facility: TLB Research
state: New Jersey
city: Asheboro
country: United States
facility: Randolph Medical Associates
state: North Carolina
city: High Point
country: United States
facility: High Point Clinical Trials Center, LLC
state: North Carolina
city: Fargo
country: United States
facility: Lillestol Research, LLC
state: North Dakota
city: Columbus
country: United States
facility: Aventiv Research
state: Ohio
city: Houston
country: United States
facility: Juno Research, LLC
state: Texas
city: Houston
country: United States
facility: Texas Center for Drug Development, Inc.
state: Texas
city: Katy
country: United States
facility: Juno Research, LLC
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas, Inc.
state: Texas
city: Schertz
country: United States
facility: Northeast Clinical Research of San Antonio, LLC
state: Texas
city: Richmond
country: United States
facility: National Clinical Research - Richmond, Inc.
state: Virginia
city: Brampton
country: Canada
facility: Aggarwal and Associates Limited
state: Ontario
city: Thornhill
country: Canada
facility: LMC Clinical Research Inc. (Thornhill)
state: Ontario
city: Toronto
country: Canada
facility: LMC Clinical Research Inc. (Bayview)
state: Ontario
city: Toronto
country: Canada
facility: Manna Research
state: Ontario
city: Lévis
country: Canada
facility: Manna Research Inc.
state: Quebec
city: Mirabel
country: Canada
facility: Omnispec Clinical Research, Inc.
state: Quebec
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: