Clinical trial NCT02175121: Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Study Of PF-06291874 As Oral Monotherapy To Treat Adults With Type 2 Diabetes Mellitus
Official title: A Phase 2, Randomized, Double-blind, Placebo-controlled, Parallel Group Trial To Assess The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Multiple Oral Doses Of Pf-06291874 Given As Monotherapy To Adults With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus, Type II
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2014-06-26
Enrollment: 172
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: This study is going to assess the safety and tolerability of PF-06291874 in adults with Type 2 Diabetes Mellitus as monotherapy, to evaluate the significance of overall glycemic control in these subjects.


Eligibility criteria: Inclusion Criteria:

* Male subjects and non-childbearing potential female subjects between the ages of 18 and 70 years old.
* Body Mass Index of 18.0 to 45.4 kg/m2; and a total body weight of \>50 kg
* HbA1c value at the screening visit meeting once of the following criteria:

  * Currently taking acceptable oral antiglycemic drug therapy within 6.5 to 9.5%
  * Not currently taking any oral antiglycemic drug therapy within 7 to 10.5%
* Fasting plasma glucose concentrations\<270mg/dL at the screening and run-in visit, confirmed by a single repeat, if deemed necessary.
* Subjects must be willing and able to perform self-tests of blood glucose at least 4 times per day, and maintain a diary for the duration of participation in the study; and therefore, subjects must be literate.

Exclusion Criteria:

* History of Type 1 diabetes mellitus or secondary forms of diabetes
* One or more self-reported hypoglycemic episodes of sever intensity within 3 months of screening; or 2 or more self-reported hypoglycemic episodes of severe intensity within the previous 6 months.
* History of myocardial infarction, unstable angina, arterial revascularization, stroke, New York Heart Association Functional Class II-IV heart failure, or transient ischemic attach within 6 months of screening.
* History or evidence of diabetic complications with significant end organ damage, such as

  * Proliferative retinopathy and/or macular edema;
  * Diabetic neuropathy complicated by neuropathic ulcers;
* Screening seated systolic blood pressure \>160 mm Hg and/or diastolic blood pressure \>100 mm Hg after at least a 5 minute seated rest. If the blood pressure exceeds this limit, the blood pressure may be repeated 2 more times following approximately 2 minutes of rest between measurements and the median of the 3 values should be used to determine subject eligibility;
* Male subjects with partners currently pregnant; or male subjects capable of conceiving children who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose of investigational product.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), or Serious Adverse Events (SAEs), or Hypoglycemic Adverse Events (HAE) or Withdrawals Due to Adverse Events (AEs)
timeFrame: Baseline up to 10-14 days after last dose of study drug, up to 42 days
measure: Number of Participants With Laboratory Test Abnormalities
timeFrame: Baseline up to 10-14 days after last dose of study drug, up to 42 days
measure: Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern
timeFrame: Baseline up to 10-14 days after last dose of study drug, up to 42 days
measure: Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern
timeFrame: Baseline up to 10-14 days after last dose of study drug, up to 42 days
Secondary outcomes:
measure: Change From Baseline in Mean Daily Glucose
timeFrame: Baseline and Day 28
measure: Change From Baseline in Fasting Plasma Glucose
timeFrame: Baseline, Day 14 and the mean of Days 28 and 29
measure: Percent Change From Baseline in Triglycerides
timeFrame: Baseline, Day 14 and the mean of Days 28 and 29
measure: Percent Change From Baseline in Total Cholesterol
timeFrame: Baseline, Day 14 and the mean of Days 28 and 29
measure: Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C)
timeFrame: Baseline, Day 14 and the mean of Days 28 and 29
measure: Percent Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C)
timeFrame: Baseline, Day 14 and the mean of Days 28 and 29
measure: Percent Change From Baseline in Non-HDL-C
timeFrame: Baseline, Day 14 and the mean of Days 28 and 29
measure: Percent Change From Baseline in Oxidized LDL
timeFrame: Baseline and the mean of Days 28 and 29
measure: Percent Change From Baseline in Large LDL Particles
timeFrame: Baseline and the mean of Days 28 and 29
measure: Percent Change From Baseline in Medium Small LDL Particles
timeFrame: Baseline and the mean of Days 28 and 29
measure: Percent Change From Baseline in Small LDL Particles
timeFrame: Baseline and the mean of Days 28 and 29
measure: Percent Change From Baseline in Very Small LDL Particles
timeFrame: Baseline and the mean of Days 28 and 29
measure: Percent Change From Baseline in Total LDL Particles
timeFrame: Baseline and the mean of Days 28 and 29
measure: Percent Change From Baseline in LDL Size
timeFrame: Baseline and the mean of Days 28 and 29
measure: Percent Change From Baseline in Apolipoprotein B100
timeFrame: Baseline and the mean of Days 28 and 29
measure: Percent Change From Baseline in Lipoprotein A
timeFrame: Baseline and the mean of Days 28 and 29
measure: Maximum Plasma Concentration (Cmax)
timeFrame: Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose)
measure: Time to Reach Cmax (Tmax)
timeFrame: Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose)
measure: Area Under the Concentration-Time Profile From Zero to Time Tau (AUCtau) (Where Tau=24 Hours)
timeFrame: Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose)
measure: Minimum Plasma Concentration (Cmin)
timeFrame: Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose)
measure: Apparent Clearance (CL/F)
timeFrame: Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose)
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Anaheim Clinical Trials, LLC
state: California
city: Chula Vista
country: United States
facility: Profil Institute for Clinical Research, Inc.
state: California
city: Walnut Creek
country: United States
facility: Diablo Clinical Research, Inc.
state: California
city: DeLand
country: United States
facility: Avail Clinical Research, LLC
state: Florida
city: Miami
country: United States
facility: SeaView Research, Inc.
state: Florida
city: Miami
country: United States
facility: SeaView Research, Inc.
state: Florida
city: Orlando
country: United States
facility: Compass Research, LLC
state: Florida
city: South Miami
country: United States
facility: Miami Research Associates, Inc.
state: Florida
city: South Miami
country: United States
facility: MRA Clinical Research, LLC
state: Florida
city: South Miami
country: United States
facility: MRA Clinical Research
state: Florida
city: Louisville
country: United States
facility: Louisville Metabolic and Atherosclerosis Research Center
state: Kentucky
city: Minneapolis
country: United States
facility: DaVita Clinical Research
state: Minnesota
city: Eatontown
country: United States
facility: Clinilabs, Inc.
state: New Jersey
city: Marlton
country: United States
facility: PRA International
state: New Jersey
city: Buffalo
country: United States
facility: Buffalo Clinical Research Center, LLC
state: New York
city: High Point
country: United States
facility: High Point Clinical Trials Center, LLC
state: North Carolina
city: Cincinnati
country: United States
facility: Community Research
state: Ohio
city: San Antonio
country: United States
facility: Clinical Trials of Texas, Inc.
state: Texas
city: Renton
country: United States
facility: Rainier Clinical Research Center, Inc.
state: Washington
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: