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

Pfizer172 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

172

Conditions

Diabetes Mellitus, Type II

Interventions

PlaceboDRUG

Tablet, once daily for 28 days

PF-06291874DRUG

Tablet, 15 mg, once daily for 28 days

PF-06291874DRUG

Tablet, 35 mg, once daily for 28 days

PF-06291874

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

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.

Locations (19)

Anaheim Clinical Trials, LLC

Anaheim, California, United States

Profil Institute for Clinical Research, Inc.

Chula Vista, California, United States

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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).

Time frame: 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.

Data from ClinicalTrials.gov

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Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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).