Skip to main content
OpenTrials
Completed

NCT Number: NCT02175121

Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Study Of PF-06291874 As Oral Monotherapy To Treat 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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Diabetes Mellitus, Type II Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Anaheim Clinical Trials, LLC, Anaheim, California, United States

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Placebo

Drug

Tablet, once daily for 28 days

PF-06291874

Drug

Tablet, 15 mg, once daily for 28 days

Primary outcomes

  1. 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.

  2. 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.

  3. 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).

  4. 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

  1. Change From Baseline in Mean Daily Glucose

    Time frame: Baseline and Day 28

    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.

  2. Change From Baseline in Fasting Plasma Glucose

    Time frame: Baseline, Day 14 and the mean of Days 28 and 29

    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.

  3. Percent Change From Baseline in Triglycerides

    Time frame: Baseline, Day 14 and the mean of Days 28 and 29

    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.

  4. Percent Change From Baseline in Total Cholesterol

    Time frame: Baseline, Day 14 and the mean of Days 28 and 29

    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.

  5. Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C)

    Time frame: Baseline, Day 14 and the mean of Days 28 and 29

    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.

  6. Percent Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C)

    Time frame: Baseline, Day 14 and the mean of Days 28 and 29

    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.

  7. Percent Change From Baseline in Non-HDL-C

    Time frame: Baseline, Day 14 and the mean of Days 28 and 29

    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.

  8. Percent Change From Baseline in Oxidized LDL

    Time frame: Baseline and the mean of Days 28 and 29

    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).

  9. Percent Change From Baseline in Large LDL Particles

    Time frame: Baseline and the mean of Days 28 and 29

    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).

  10. Percent Change From Baseline in Medium Small LDL Particles

    Time frame: Baseline and the mean of Days 28 and 29

    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).

  11. Percent Change From Baseline in Small LDL Particles

    Time frame: Baseline and the mean of Days 28 and 29

    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).

  12. Percent Change From Baseline in Very Small LDL Particles

    Time frame: Baseline and the mean of Days 28 and 29

    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).

  13. Percent Change From Baseline in Total LDL Particles

    Time frame: Baseline and the mean of Days 28 and 29

    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).

  14. Percent Change From Baseline in LDL Size

    Time frame: Baseline and the mean of Days 28 and 29

    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).

  15. Percent Change From Baseline in Apolipoprotein B100

    Time frame: Baseline and the mean of Days 28 and 29

    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).

  16. Percent Change From Baseline in Lipoprotein A

    Time frame: Baseline and the mean of Days 28 and 29

    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).

  17. Maximum Plasma Concentration (Cmax)

    Time frame: Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose)

    Maximum PF-06291874 plasma concentration.

  18. Time to Reach Cmax (Tmax)

    Time frame: Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose)

    Time to maximum PF-06291874 plasma concentration.

  19. 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)

    Area under the PF-06291874 plasma concentration-time profile from time zero to time tau, the dosing interval, where tau=24 hours.

  20. Minimum Plasma Concentration (Cmin)

    Time frame: Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose)

    Minimum PF-06291874 plasma concentration.

  21. Apparent Clearance (CL/F)

    Time frame: Day 28 (samples taken at 0, 2, 4, 8 and 24 hours after Day 28 dose)

    Apparent oral clearance of PF-06291874.

Sponsors and collaborators

Lead sponsor

Pfizer

Industry

Registry information

Official study 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

Important dates

Study start
2014
Primary completion
2015
Study completion
2015
First posted
Jun 26, 2014
Registry last updated
Jun 15, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.