Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Study Of PF-06291874 As Oral Monotherapy To Treat Adults With Type 2 Diabetes Mellitus

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT02175121
First received: June 24, 2014
Last updated: May 10, 2016
Last verified: May 2016
  Purpose
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.

Condition Intervention Phase
Diabetes Mellitus, Type II
Drug: Placebo
Drug: PF-06291874
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • 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) [ Time Frame: Baseline up to 10-14 days after last dose of study drug, up to 42 days ] [ Designated as safety issue: Yes ]
    An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. An HAE was identified by characteristic symptoms or blood glucose levels. TEAEs are events between first dose of study drug and up to 10-14 days after last dose of study drug that were absent before treatment or that worsened relative to pre-treatment state.

  • Number of Participants With Laboratory Test Abnormalities [ Time Frame: Baseline up to 10-14 days after last dose of study drug, up to 42 days ] [ Designated as safety issue: Yes ]
    The total number of participants with laboratory test abnormalities (without regard to baseline abnormality) was assessed. Clinical laboratory tests included hematology, chemistry, urinalysis, and some other tests.

  • Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern [ Time Frame: Baseline up to 10-14 days after last dose of study drug, up to 42 days ] [ Designated as safety issue: Yes ]
    Vital Signs included seated supine systolic and diastolic blood pressure (BP) and pulse rate. Vital signs criteria of potential clinical concern were 1), BP: systolic (SBP) greater than or equal to (>=) 30 millimeters of mercury (mm Hg) change from baseline, systolic less than (<) 90 mm Hg; diastolic BP (DBP) >=20 mm Hg change from baseline, diastolic <50 mm Hg; 2), pulse rate <40 or greater than (>) 120 beats per minute (bpm).

  • Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern [ Time Frame: Baseline up to 10-14 days after last dose of study drug, up to 42 days ] [ Designated as safety issue: Yes ]
    ECG criteria of potential clinical concern were 1), time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization (QRS interval): >=140 msec; >=50% increase from baseline; 2), 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 (PR interval): >=300 milliseconds (msec); >=25 percent (%) increase when baseline >200 msec; or increase >=50% when baseline less than or equal to (<=)200 msec; 3), time from ECG Q wave to the end of the T wave corresponding to electrical systole corrected for heart rate using Fridericia's formula (QTcF interval): absolute value >=450 - <480 msec, >=480-<500 msec, >=500 msec; increase from baseline >=30 - <60, >=60 msec.


Secondary Outcome Measures:
  • Change From Baseline in Mean Daily Glucose [ Time Frame: Baseline and Day 28 ] [ Designated as safety issue: No ]
    The mean daily glucose was determined from the area under the concentration (AUC) of the glucose concentrations measured at nominal times 0, 0.5, 1, 1.5, 2, 4, 6, 10, 12, 15 and 24 hours post dose. Mean daily glucose change from baseline (defined as Day 0) on Day 28.

  • Change From Baseline in Fasting Plasma Glucose [ Time Frame: Baseline, Day 14 and the mean of Days 28 and 29 ] [ Designated as safety issue: No ]
    Fasting plasma glucose response change from baseline (defined as the mean of Day 0 and Day 1 pre-dose) on Day 14, and the mean of Days 28 and 29.

  • Percent Change From Baseline in Triglycerides [ Time Frame: Baseline, Day 14 and the mean of Days 28 and 29 ] [ Designated as safety issue: No ]
    Triglycerides percent change from baseline (defined as the mean of Day 0 and Day 1 pre-dose) on Day 14, and the mean of Days 28 and 29.

  • Percent Change From Baseline in Total Cholesterol [ Time Frame: Baseline, Day 14 and the mean of Days 28 and 29 ] [ Designated as safety issue: No ]
    Total cholesterol percent change from baseline (defined as the mean of Day 0 and Day 1 pre-dose) on Day 14, and the mean of Days 28 and 29.

  • Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) [ Time Frame: Baseline, Day 14 and the mean of Days 28 and 29 ] [ Designated as safety issue: No ]
    LDL-C percent change from baseline (defined as the mean of Day 0 and Day 1 pre-dose) on Day 14, and the mean of Days 28 and 29.

  • Percent Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C) [ Time Frame: Baseline, Day 14 and the mean of Days 28 and 29 ] [ Designated as safety issue: No ]
    HDL-C percent change from baseline (defined as the mean of Day 0 and Day 1 pre-dose) on Day 14, and the mean of Days 28 and 29.

  • Percent Change From Baseline in Non-HDL-C [ Time Frame: Baseline, Day 14 and the mean of Days 28 and 29 ] [ Designated as safety issue: No ]
    Non-HDL-C percent change from baseline (defined as the mean of Day 0 and Day 1 pre-dose) on Day 14, and the mean of Days 28 and 29.

  • Percent Change From Baseline in Oxidized LDL [ Time Frame: Baseline and the mean of Days 28 and 29 ] [ Designated as safety issue: No ]
    Oxidized LDL percent change from baseline (defined as the mean of Day 0 and Day 1 pre-dose) on Day 28 (the mean of Days 28 and 29).

  • Percent Change From Baseline in Large LDL Particles [ Time Frame: Baseline and the mean of Days 28 and 29 ] [ Designated as safety issue: No ]
    Large LDL particles percent change from baseline (defined as the mean of Day 0 and Day 1 pre-dose) on Day 28 (the mean of Days 28 and 29).

  • Percent Change From Baseline in Medium Small LDL Particles [ Time Frame: Baseline and the mean of Days 28 and 29 ] [ Designated as safety issue: No ]
    Medium small LDL particles percent change from baseline (defined as the mean of Day 0 and Day 1 pre-dose) on Day 28 (the mean of Days 28 and 29).

  • Percent Change From Baseline in Small LDL Particles [ Time Frame: Baseline and the mean of Days 28 and 29 ] [ Designated as safety issue: No ]
    Small LDL particles percent change from baseline (defined as the mean of Day 0 and Day 1 pre-dose) on Day 28 (the mean of Days 28 and 29).

  • Percent Change From Baseline in Very Small LDL Particles [ Time Frame: Baseline and the mean of Days 28 and 29 ] [ Designated as safety issue: No ]
    Very small LDL particles percent change from baseline (defined as the mean of Day 0 and Day 1 pre-dose) on Day 28 (the mean of Days 28 and 29).

  • Percent Change From Baseline in Total LDL Particles [ Time Frame: Baseline and the mean of Days 28 and 29 ] [ Designated as safety issue: No ]
    Total LDL particles percent change from baseline (defined as the mean of Day 0 and Day 1 pre-dose) on Day 28 (the mean of Days 28 and 29).

  • Percent Change From Baseline in LDL Size [ Time Frame: Baseline and the mean of Days 28 and 29 ] [ Designated as safety issue: No ]
    The LDL size percent change from baseline (defined as the mean of Day 0 and Day 1 pre-dose) on Day 28 (the mean of Days 28 and 29).

  • Percent Change From Baseline in Apolipoprotein B100 [ Time Frame: Baseline and the mean of Days 28 and 29 ] [ Designated as safety issue: No ]
    The Apolipoprotein B100 was calculated as the difference between total Apolipoprotein B and Apolipoprotein B48 and analyzed the percent change from baseline (defined as mean of Day 0 and Day 1) on Day 28 (mean of Days 28 and 29).

  • Percent Change From Baseline in Lipoprotein A [ Time Frame: Baseline and the mean of Days 28 and 29 ] [ Designated as safety issue: No ]
    The Lipoprotein A percent change from baseline (defined as the mean of Day 0 and Day 1 pre-dose) on Day 28 (mean of Days 28 and 29).

  • Maximum Plasma Concentration (Cmax) [ Time Frame: Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose) ] [ Designated as safety issue: No ]
    Maximum PF-06291874 plasma concentration.

  • Time to Reach Cmax (Tmax) [ Time Frame: Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose) ] [ Designated as safety issue: No ]
    Time to maximum PF-06291874 plasma concentration.

  • Area Under the Concentration-Time Profile From Zero to Time Tau (AUCtau) (Where Tau=24 Hours) [ Time Frame: Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose) ] [ Designated as safety issue: No ]
    Area under the PF-06291874 plasma concentration-time profile from time zero to time tau, the dosing interval, where tau=24 hours.

  • Minimum Plasma Concentration (Cmin) [ Time Frame: Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose) ] [ Designated as safety issue: No ]
    Minimum PF-06291874 plasma concentration.

  • Apparent Clearance (CL/F) [ Time Frame: Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose) ] [ Designated as safety issue: No ]
    Apparent oral clearance of PF-06291874.


Enrollment: 172
Study Start Date: August 2014
Study Completion Date: March 2015
Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Treatment A- Placebo Drug: Placebo
Tablet, once daily for 28 days
Experimental: Treatment B- PF-06291874 Drug: PF-06291874
Tablet, 15 mg, once daily for 28 days
Experimental: Treatment C- PF-06291874 Drug: PF-06291874
Tablet, 35 mg, once daily for 28 days
Experimental: Treatment D- PF-06291874 Drug: PF-06291874
Tablet, 75 mg, once daily for 28 days
Experimental: Treatment E- PF-06291874 Drug: PF-06291874
Tablet, 150 mg, once daily for 28 days

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02175121

Locations
United States, California
Anaheim Clinical Trials, LLC
Anaheim, California, United States, 92801
Profil Institute for Clinical Research, Inc.
Chula Vista, California, United States, 91911
Diablo Clinical Research, Inc.
Walnut Creek, California, United States, 94598
United States, Florida
Avail Clinical Research, LLC
DeLand, Florida, United States, 32720
SeaView Research, Inc.
Miami, Florida, United States, 33125
SeaView Research, Inc.
Miami, Florida, United States, 33126
Compass Research, LLC
Orlando, Florida, United States, 32806
Miami Research Associates, Inc.
South Miami, Florida, United States, 33143
MRA Clinical Research, LLC
South Miami, Florida, United States, 33143
MRA Clinical Research
South Miami, Florida, United States, 33143
United States, Kentucky
Louisville Metabolic and Atherosclerosis Research Center
Louisville, Kentucky, United States, 40213
United States, Minnesota
DaVita Clinical Research
Minneapolis, Minnesota, United States, 55404
United States, New Jersey
Clinilabs, Inc.
Eatontown, New Jersey, United States, 07724
PRA International
Marlton, New Jersey, United States, 08053
United States, New York
Buffalo Clinical Research Center, LLC
Buffalo, New York, United States, 14202
United States, North Carolina
High Point Clinical Trials Center, LLC
High Point, North Carolina, United States, 27265
United States, Ohio
Community Research
Cincinnati, Ohio, United States, 45255
United States, Texas
Clinical Trials of Texas, Inc.
San Antonio, Texas, United States, 78229
United States, Washington
Rainier Clinical Research Center, Inc.
Renton, Washington, United States, 98057
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02175121     History of Changes
Other Study ID Numbers: B4801011 
Study First Received: June 24, 2014
Results First Received: February 19, 2016
Last Updated: May 10, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on July 21, 2016