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

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type II
• Intervention / Treatment: Drug: Placebo; Drug: PF-06291874; Drug: PF-06291874; Drug: PF-06291874; Drug: PF-06291874

• Study Type: Interventional
• Enrollment (Actual): 172
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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; Drug: PF-06291874; Tablet, 35 mg, once daily for 28 days; Drug: PF-06291874; Tablet, 75 mg, once daily for 28 days; Drug: PF-06291874; Tablet, 150 mg, once daily for 28 days
Experimental: Treatment C- PF-06291874	Drug: PF-06291874; Tablet, 15 mg, once daily for 28 days; Drug: PF-06291874; Tablet, 35 mg, once daily for 28 days; Drug: PF-06291874; Tablet, 75 mg, once daily for 28 days; Drug: PF-06291874; Tablet, 150 mg, once daily for 28 days
Experimental: Treatment D- PF-06291874	Drug: PF-06291874; Tablet, 15 mg, once daily for 28 days; Drug: PF-06291874; Tablet, 35 mg, once daily for 28 days; Drug: PF-06291874; Tablet, 75 mg, once daily for 28 days; Drug: PF-06291874; Tablet, 150 mg, once daily for 28 days
Experimental: Treatment E- PF-06291874	Drug: PF-06291874; Tablet, 15 mg, once daily for 28 days; Drug: PF-06291874; Tablet, 35 mg, once daily for 28 days; Drug: PF-06291874; Tablet, 75 mg, once daily for 28 days; Drug: PF-06291874; Tablet, 150 mg, once daily for 28 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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.	Baseline up to 10-14 days after last dose of study drug, up to 42 days
Number of Participants With Laboratory Test Abnormalities	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.	Baseline up to 10-14 days after last dose of study drug, up to 42 days
Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern	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).	Baseline up to 10-14 days after last dose of study drug, up to 42 days
Number of Participants With Electrocardiogram (ECG) Data Meeting Criteria of Potential Clinical Concern	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.	Baseline up to 10-14 days after last dose of study drug, up to 42 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean Daily Glucose	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.	Baseline and Day 28
Change From Baseline in Fasting Plasma Glucose	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.	Baseline, Day 14 and the mean of Days 28 and 29
Percent Change From Baseline in Triglycerides	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.	Baseline, Day 14 and the mean of Days 28 and 29
Percent Change From Baseline in Total Cholesterol	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.	Baseline, Day 14 and the mean of Days 28 and 29
Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C)	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.	Baseline, Day 14 and the mean of Days 28 and 29
Percent Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C)	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.	Baseline, Day 14 and the mean of Days 28 and 29
Percent Change From Baseline in Non-HDL-C	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.	Baseline, Day 14 and the mean of Days 28 and 29
Percent Change From Baseline in Oxidized LDL	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).	Baseline and the mean of Days 28 and 29
Percent Change From Baseline in Large LDL Particles	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).	Baseline and the mean of Days 28 and 29
Percent Change From Baseline in Medium Small LDL Particles	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).	Baseline and the mean of Days 28 and 29
Percent Change From Baseline in Small LDL Particles	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).	Baseline and the mean of Days 28 and 29
Percent Change From Baseline in Very Small LDL Particles	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).	Baseline and the mean of Days 28 and 29
Percent Change From Baseline in Total LDL Particles	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).	Baseline and the mean of Days 28 and 29
Percent Change From Baseline in LDL Size	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).	Baseline and the mean of Days 28 and 29
Percent Change From Baseline in Apolipoprotein B100	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).	Baseline and the mean of Days 28 and 29
Percent Change From Baseline in Lipoprotein A	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).	Baseline and the mean of Days 28 and 29
Maximum Plasma Concentration (Cmax)	Maximum PF-06291874 plasma concentration.	Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose)
Time to Reach Cmax (Tmax)	Time to maximum PF-06291874 plasma concentration.	Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose)
Area Under the Concentration-Time Profile From Zero to Time Tau (AUCtau) (Where Tau=24 Hours)	Area under the PF-06291874 plasma concentration-time profile from time zero to time tau, the dosing interval, where tau=24 hours.	Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose)
Minimum Plasma Concentration (Cmin)	Minimum PF-06291874 plasma concentration.	Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose)
Apparent Clearance (CL/F)	Apparent oral clearance of PF-06291874.	Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose)

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: June 24, 2014
• First Submitted That Met QC Criteria: June 24, 2014
• First Posted (Estimate): June 26, 2014

Study Record Updates

• Last Update Posted (Estimate): June 15, 2016
• Last Update Submitted That Met QC Criteria: May 10, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: B4801011