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
Overview
- Phase
- Phase 2
- Intervention
- Placebo
- Conditions
- Diabetes Mellitus, Type II
- Sponsor
- Pfizer
- Enrollment
- 172
- Locations
- 18
- Primary Endpoint
- 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)
- Status
- Completed
- Last Updated
- 9 years ago
Overview
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.
Investigators
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.
Arms & Interventions
Treatment A- Placebo
Intervention: Placebo
Treatment B- PF-06291874
Intervention: PF-06291874
Treatment C- PF-06291874
Intervention: PF-06291874
Treatment D- PF-06291874
Intervention: PF-06291874
Treatment E- PF-06291874
Intervention: PF-06291874
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)
Time Frame: Baseline up to 10-14 days after last dose of study drug, up to 42 days
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
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
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
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 Outcomes
- Change From Baseline in Mean Daily Glucose(Baseline and Day 28)
- Change From Baseline in Fasting Plasma Glucose(Baseline, Day 14 and the mean of Days 28 and 29)
- Percent Change From Baseline in Triglycerides(Baseline, Day 14 and the mean of Days 28 and 29)
- Percent Change From Baseline in Total Cholesterol(Baseline, Day 14 and the mean of Days 28 and 29)
- Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C)(Baseline, Day 14 and the mean of Days 28 and 29)
- Percent Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C)(Baseline, Day 14 and the mean of Days 28 and 29)
- Percent Change From Baseline in Non-HDL-C(Baseline, Day 14 and the mean of Days 28 and 29)
- Percent Change From Baseline in Oxidized LDL(Baseline and the mean of Days 28 and 29)
- Percent Change From Baseline in Large LDL Particles(Baseline and the mean of Days 28 and 29)
- Percent Change From Baseline in Medium Small LDL Particles(Baseline and the mean of Days 28 and 29)
- Percent Change From Baseline in Small LDL Particles(Baseline and the mean of Days 28 and 29)
- Percent Change From Baseline in Very Small LDL Particles(Baseline and the mean of Days 28 and 29)
- Percent Change From Baseline in Total LDL Particles(Baseline and the mean of Days 28 and 29)
- Percent Change From Baseline in LDL Size(Baseline and the mean of Days 28 and 29)
- Percent Change From Baseline in Apolipoprotein B100(Baseline and the mean of Days 28 and 29)
- Percent Change From Baseline in Lipoprotein A(Baseline and the mean of Days 28 and 29)
- Maximum Plasma Concentration (Cmax)(Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose))
- Time to Reach Cmax (Tmax)(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)(Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose))
- Minimum Plasma Concentration (Cmin)(Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose))
- Apparent Clearance (CL/F)(Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose))