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Completed

NCT Number: NCT01856595

PF-06291874 Multiple Ascending Dose Study In Type 2 Diabetes Mellitus Patients

The purpose of this study is to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of PF-06291874 in Type 2 Diabetes patients.

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Key information

Conditions

Diabetes Mellitus, Type 2 Diabetes Mellitus 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 1

Primary location

Anaheim Clinical Trials, Anaheim, California, United States

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Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Males and female subjects of non-childbearing potential between the ages of 18 and 70 years, inclusive of age at the time of the screening visit.

Female subjects of non-childbearing potential must meet at least one of the following criteria:

  • Achieved postmenopausal status, defined as: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and have a serum FSH level within the laboratory's reference range for postmenopausal females;
  • Have undergone a documented hysterectomy and/or bilateral oophorectomy;
  • Have medically confirmed ovarian failure.
  • All other female subjects (including females with tubal ligations and females that do NOT have a documented hysterectomy, bilateral oophorectomy and/or ovarian failure) will be considered to be of childbearing potential.
  • Body Mass Index (BMI) of 18.0 to 45.0 kg/m2; and a total body weight >50 kg (110 lbs).
  • An informed consent document signed and dated by the subject.
  • Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

PART A ONLY: Subjects treated with metformin monotherapy for at least 3 months at the time of the screening visit; and have been on a stable dose of metformin for at least 6 weeks prior to the first dose of study drug on Day 1. Subjects must be taking a minimum total metformin daily dose of least 1000 mg. Subjects treated with a dipeptidyl peptidase-4 inhibitor (DPP-4i), a sulfonylurea or a sodium-glucose cotransporter-2 inhibitor (SGLT-2i) in combination with metformin may be eligible if washed off the DPP-4i, sulfonylurea or SGLT-2i for a minimum of 4 weeks prior to dosing. Subjects being washed off a DPP-4i, sulfonylurea or SGLT-2i will still need to meet the fasting glucose requirements as defined in the Inclusion Criteria.

PART B ONLY: Subjects treated with metformin plus a sulfonylurea for at least 3 months at the time of the screening visit; and have been on a stable dose of metformin and a sulfonylurea for at least 6 weeks prior to first dose of study drug on Day 1. Subjects must be taking a minimum total metformin daily dose of least 1000 mg and a total daily dose of sulfonylurea that is at least the minimum recommended starting dose found in the product label. Subjects treated with a DPP-4i or SGLT-2i in combination with metformin and a sulfonylurea may be eligible if washed off the DPP-4i or SGLT-2i for a minimum of 4 weeks before dosing.

Exclusion criteria

  • History of Type 1 diabetes mellitus or secondary forms of diabetes.
  • One or more self-reported hypoglycemic episodes of severe intensity within 3 months of screening; or two or more self-reported hypoglycemic episodes of severe intensity within the last 6 months.
  • Recent [ie, within six (6) months prior to screening] evidence or medical history of unstable concurrent disease such as: clinically significant hematological, endocrine,pulmonary, gastrointestinal (including severe gastroparesis), cardiovascular, hepatic, psychiatric, neurologic, or clinically significant allergic disease (excluding treated and untreated seasonal allergies at time of dosing). Subjects who have chronic conditions other than T2DM (for example, hypercholesterolemia or hypertension) but are controlled by either diet or stable (for the last 4 weeks prior to screening) doses of medications may be included as well (for example, a subject with hypercholesterolemia on appropriate treatment is eligible).

Treatment and study plan

PF-06291874

Drug

The dosing schedule is 5, 15, 50, 100 and 150 mg QD for 14 days for the first 5 cohorts in Part A. The dosing schedule for the first cohort in Part B is 15 mg QD for 14 days and 30 mg QD for 28 days

Placebo

Drug

Placebo tablets will be administered QD in each of the cohorts for 14 days (Part A cohorts 1- 5 and Part B cohort 1) or 28 days (Part B cohort 2).

Primary outcomes

  1. Number of Participants Had Protocol-Defined Total Hypoglycemic Adverse Event (HAE) - Part A

    Time frame: Day 1 up to 7-11 days after last dose of study drug

    A hypoglycemic event (HAE) was identified by characteristic symptoms or blood glucose levels. Hypoglycaemia was assessed and reported in several categories: severe hypoglycaemia, documented symptomatic hypoglycaemia, asymptomatic hypoglycaemia, and probable hypoglycaemia.

  2. Number of Participants Had Protocol-Defined Total Hypoglycemic Adverse Event (HAE) - Part B

    Time frame: Day 1 up to 7-11 days after last dose of study drug

    A hypoglycemic event (HAE) was identified by characteristic symptoms or blood glucose levels. Hypoglycaemia was assessed and reported in several categories: severe hypoglycaemia, documented symptomatic hypoglycaemia, asymptomatic hypoglycaemia, and probable hypoglycaemia.

  3. Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A

    Time frame: Predose (0),4,6,8,12,24 hours on Days 1 and 14; 8 hours post dose on Days 3,7,11 for all Cohorts ; predose on Day 17 for Cohorts 1- 4A and 1B; predose on Days 21 and 28 for Cohorts 5A and 2B.

    ECG criteria of potential clinical concern were 1), PR interval: greater than or equal to (>=)300 milliseconds (msec); >=25 percent (%) increase when baselinegreater than (>)200 msec; or increase >=50% when baseline less than or equal to (<=)200 msec; 2), QRS interval: >=140 msec; >=50% increase from baseline; 3), QT interval: >=500 msec, QTc interval using cridericia's formula (QTcF interval): absolute value >=450 - <480 msec, >=480-<500 msec, >500 msec; absolute change 30 - <60, >=60 msec.

  4. Number of Participants With ECGs Data Met Criteria of Potential Clinical Concern - Part B

    Time frame: Predose (0),4,6,8,12,24 hours on Days 1 and 14; 8 hours post dose on Days 3,7,11 for all Cohorts ; predose on Day 17 for Cohorts 1- 4A and 1B; predose on Days 21 and 28 for Cohorts 5A and 2B.

    ECG criteria of potential clinical concern were 1), PR interval: >=300 msec; >=25% increase when baseline >200 msec; or increase >=50% when baseline <=200 msec; 2), QRS interval: >=140 msec; >=50% increase from baseline; 3), QT interval: >=500 msec, QTcF interval: absolute value >=450 - <480 msec, >=480-<500 msec, >500 msec; absolute change 30 - <60, >=60 msec.

  5. Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A

    Time frame: Predose (0),4,6,8,12,24 hours on Days 1 and 14; 8 hours post dose on Days 3,7,11 for all Cohorts ; predose on Day 17 for Cohorts 1- 4A and 1B; predose on Days 21 and 28 for Cohorts 5A and 2B.

    Vital signs included blood pressure (BP; supine, sitting and standing) and pulse rate. Vital signs criteria of potential clinical concern were 1), BP: systolic BP (SBP) greater than or equal to (>=) 30 millimeters of mercury (mm Hg) change from grand baseline in same posture, systolic less than (<) 90 mm Hg; diastolic BP (DBP) >=20 mm Hg change from grand baseline in same posture, diastolic <50 mm Hg; 2), pulse rate (supine): <40 or greater than (>) 120 beats per minute (bpm).

  6. Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part B

    Time frame: Predose (0),4,6,8,12,24 hours on Days 1 and 14; 8 hours post dose on Days 3,7,11 for all Cohorts ; predose on Day 17 for Cohorts 1- 4A and 1B; predose on Days 21 and 28 for Cohorts 5A and 2B.

    Vital signs included blood pressure (BP; supine, sitting and standing) and pulse rate. Vital signs criteria of potential clinical concern were 1), BP: SBP >= 30 mm Hg change from grand baseline in same posture, SBP < 90 mm Hg; DBP >=20 mm Hg change from grand baseline in same posture, DBP<50 mm Hg; 2), pulse rate (supine): <40 or > 120 bpm.

  7. Number of Participants With Any Abnormal Laboratory Test Results - Part A

    Time frame: Predose on Days 0,3,7,11 for all cohorts and 14 and 17 for Cohorts 1- 4A and 1B, and pre-dose on Days 21 and 28 for Cohorts 5A and 2B.

    The laboratory test included: hematology (hemoglobin, hematocrit, red blood cell count, MCV, MCH, MCHC, platelets, white blood cell count, absolute lymphocytes, absolute total neutrophils, absolute basophils, absolute eosinophils and absolute monocytes), coagulation (PPT, prothrombin), liver function(total bilirubin, AST, ALT, alkaline phosphatase, total protein and albumin), renal function (blood urea nitrogen, creatinine, uric acid), Lipids (cholesterol, HDL cholesterol, LDL cholesterol, triglycerides), Electrolytes (sodium, potassium, chloride, calcium, venous bicarbonate), clinical chemistry (glucose, glycosylated, hemoglobin, amylase, lipase), urinalysis dipstick (urine PH, urine glucose, urine ketones, urine protein, urine urobilinogen, urine bilirubin, urine nitrite, urine leukocyte, esterase), urinalysis microscopy (urine RBC, urine WBC, urine bacteria). Laboratory abnormality was determined by the investigator based on pre-defined criteria.

  8. Number of Participants With Any Abnormal Laboratory Test Results - Part B

    Time frame: Predose on Days 0,3,7,11 for all cohorts and 14 and 17 for Cohorts 1- 4A and 1B, and pre-dose on Days 21 and 28 for Cohorts 5A and 2B.

    The laboratory test included: hematology (hemoglobin, hematocrit, red blood cell count, MCV, MCH, MCHC, platelets, white blood cell count, absolute lymphocytes, absolute total neutrophils, absolute basophils, absolute eosinophils and absolute monocytes), coagulation (PPT, prothrombin), liver function(total bilirubin, AST, ALT, alkaline phosphatase, total protein and albumin), renal function (blood urea nitrogen, creatinine, uric acid), Lipids (cholesterol, HDL cholesterol, LDL cholesterol, triglycerides), Electrolytes (sodium, potassium, chloride, calcium, venous bicarbonate), clinical chemistry (glucose, glycosylated, hemoglobin, amylase, lipase), urinalysis dipstick (urine PH, urine glucose, urine ketones, urine protein, urine urobilinogen, urine bilirubin, urine nitrite, urine leukocyte, esterase), urinalysis microscopy (urine RBC, urine WBC, urine bacteria). Laboratory abnormality was determined by the investigator based on pre-defined criteria.

  9. Single Dose Maximum Plasma Concentration (Cmax) for PF-06291874 - Part A

    Time frame: 0 hour (pre-dose), 2, 4, 6, 8, 12, 19, 24 hours post-dose on Day 1

    Cmax was maximum plasma concentration. Blood samples (3 mL) to provide a minimum of approximately 1.2 mL plasma for pharmacokinetic (PK) analysis were collected at 0, 2, 4, 6, 8, 12, 19 and 24 hours post dose.

  10. Single Dose Normalized Cmax (Cmax[dn]) for PF-06291874 - Part A

    Time frame: 0 hour (pre-dose), 2, 4, 6, 8, 12, 19, 24 hours post-dose on Day 1

    Cmax (dn) was dose normalized maximum plasma concentration. Blood samples (3 mL) to provide a minimum of approximately 1.2 mL plasma for pharmacokinetic (PK) analysis were collected at 0, 2, 4, 6, 8, 12, 19 and 24 hours post dose.

  11. Single Dose Cmax for PF-06291874 - Part B

    Time frame: 0 hour (pre-dose), 2, 4, 6, 8, 12, 19, 24 hours post-dose on Day 1

    Cmax was maximum plasma concentration. Blood samples (3 mL) to provide a minimum of approximately 1.2 mL plasma for PK analysis were collected at 0, 2, 4, 6, 8, 12, 19 and 24 hours post dose.

  12. Single Dose Normalized Cmax (Cmax[dn]) for PF-06291874 - Part B

    Time frame: 0 hour (pre-dose), 2, 4, 6, 8, 12, 19, 24 hours post-dose on Day 1

    Cmax (dn) was dose normalized maximum plasma concentration. Blood samples (3 mL) to provide a minimum of approximately 1.2 mL plasma for PK analysis were collected at 0, 2, 4, 6, 8, 12, 19 and 24 hours post dose

  13. Single Dose Time at Which Cmax Occurred (Tmax) for PF-06291874 - Part A

    Time frame: 0 hour (pre-dose), 2, 4, 6, 8, 12, 19, 24 hours post-dose on Day 1

    Tmax was time at which Cmax occurred. Blood samples (3 mL) to provide a minimum of approximately 1.2 mL plasma for PK analysis were collected at 0, 2, 4, 6, 8, 12, 19, 24 hours post dose.

  14. Single Dose Tmax for PF-06291874 - Part B

    Time frame: 0 hour (pre-dose), 2, 4, 6, 8, 12, 19, 24 hours post-dose on Day 1

    Tmax was time at which Cmax occurred. Blood samples (3 mL) to provide a minimum of approximately 1.2 mL plasma for PK analysis were collected at 0, 2, 4, 6, 8, 12, 19, 24 hours post dose.

  15. Single Dose AUCtau (Area Under the Concentration-time Profile From Time Zero to Time Tau, the Dosing Interval, Where Tau = 24 Hours) for PF-06291874 - Part A

    Time frame: 0 hour (pre-dose), 2, 4, 6, 8, 12, 19, 24 hours post-dose on Day 1

    AUCtau was area under the concentration-time profile from time zero to time tau, the dosing interval, where tau = 24 hours. Blood samples (3 mL) to provide a minimum of approximately 1.2 mL plasma for PK analysis were collected at 0, 2, 4, 6, 8, 12, 19, 24 hours post dose.

  16. Single Dose AUCtau for PF-06291874 - Part B

    Time frame: 0 hour (pre-dose), 2, 4, 6, 8, 12, 19, 24 hours post-dose on Day 1

    AUCtau was area under the concentration-time profile from time zero to time tau, the dosing interval, where tau = 24 hours. Blood samples (3 mL) to provide a minimum of approximately 1.2 mL plasma for PK analysis were collected at 0, 2, 4, 6, 8, 12, 19, 24 hours post dose.

  17. Multiple Dose Cmax for PF-06291874 - Part A

    Time frame: Predose (0), 2, 4, 6, 8, 12, 19, 24 hours post dose on Day 14

    Cmax was maximum plasma concentration. Blood samples (3 mL) to provide a minimum of approximately 1.2 mL plasma for PK analysis were collected at 0, 2, 4, 6, 8, 12, 19, 24 hours post dose.

  18. Multiple Dose Cmax for PF-06291874 - Part B

    Time frame: Predose (0), 2, 4, 6, 8, 12, 19, 24 hours post dose on Day 14

    Cmax was maximum plasma concentration. Blood samples (3 mL) to provide a minimum of approximately 1.2 mL plasma for PK analysis were collected at 0, 2, 4, 6, 8, 12, 19, 24 hours post dose.

  19. Multiple Dose Tmax for PF-06291874 - Part A

    Time frame: Predose (0), 2, 4, 6, 8, 12, 19, 24 hours post dose on Day 14

    Tmax was time at which Cmax occurred. Blood samples (3 mL) to provide a minimum of approximately 1.2 mL plasma for PK analysis were collected at 0, 2, 4, 6, 8, 12, 19, 24 hours post dose.

  20. Multiple Dose Tmax for PF-06291874 - Part B

    Time frame: Predose (0), 2, 4, 6, 8, 12, 19, 24 hours post dose on Day 14

    Tmax was time at which Cmax occurred. Blood samples (3 mL) to provide a minimum of approximately 1.2 mL plasma for PK analysis were collected at 0, 2, 4, 6, 8, 12, 19, 24 hours post dose.

  21. Multiple Dose AUCtau for PF-06291874 - Part A

    Time frame: Predose (0), 2, 4, 6, 8, 12, 19, 24 hours post dose on Day 14

    AUCtau was area under the concentration-time profile from time zero to time tau, the dosing interval, where tau = 24 hours. Blood samples (3 mL) to provide a minimum of approximately 1.2 mL plasma for PK analysis were collected at 0, 2, 4, 6, 8, 12, 19, 24 hours post dose.

  22. Multiple Dose AUCtau for PF-06291874 - Part B

    Time frame: Predose (0), 2, 4, 6, 8, 12, 19, 24 hours post dose on Day 14

    AUCtau was area under the concentration-time profile from time zero to time tau, the dosing interval, where tau = 24 hours. Blood samples (3 mL) to provide a minimum of approximately 1.2 mL plasma for PK analysis were collected at 0, 2, 4, 6, 8, 12, 19, 24 hours post dose.

  23. Multiple Dose Half Life for PF-06291874

    Time frame: Predose (0), 2, 4, 6, 8, 12, 19, 24 hours post dose on Day 14

    Plasma half-life was the time measured for the plasma concentration to decrease by one half. Blood samples (3 mL) to provide a minimum of approximately 1.2 mL plasma for PK analysis were collected at 0, 2, 4, 6, 8, 12, 19, 24 hours post dose.

  24. Multiple Dose Cmin (Lowest Plasma Concentration Observed During the Dosing Interval) for PF-06291874 - Part A

    Time frame: Predose (0), 2, 4, 6, 8, 12, 19, 24 hours post dose on Day 14

    Cmin was the lowest plasma concentration observed during the dosing interval. Blood samples (3 mL) to provide a minimum of approximately 1.2 mL plasma for PK analysis were collected at 0, 2, 4, 6, 8, 12, 19, 24 hours post dose.

  25. Multiple Dose Cmin for PF-06291874 - Part B

    Time frame: Predose (0), 2, 4, 6, 8, 12, 19, 24 hours post dose on Day 14

    Cmin was the lowest plasma concentration observed during the dosing interval. Blood samples (3 mL) to provide a minimum of approximately 1.2 mL plasma for PK analysis were collected at 0, 2, 4, 6, 8, 12, 19, 24 hours post dose.

  26. Multiple Dose Apparent Clearance (CL/F) for PF-06291874 - Part A

    Time frame: on Day 14 over 2 collection periods (0-6 hours and 6-24 hours).

    CL/F was multiple dose apparent clearance. The 24-hour urine samples for PK analysis were collected on Day 14 over 2 collection periods (0-6 hours and 6-24 hours).

  27. Multiple Dose CL/F for PF-06291874 - Part B

    Time frame: on Day 14 over 2 collection periods (0-6 hours and 6-24 hours).

    CL/F was multiple dose apparent clearance. The 24-hour urine samples for PK analysis were collected on Day 14 over 2 collection periods (0-6 hours and 6-24 hours).

  28. Multiple Dose Apparent Volume of Distribution (Vz/F) for PF-06291874- Part A and Part B

    Time frame: Predose (0), 2, 4, 6, 8, 12, 19, 24 hours post dose on Day 14

    Vz/F was apparent volume of distribution. Blood samples (3 mL) to provide a minimum of approximately 1.2 mL plasma for PK analysis were collected at 0, 2, 4, 6, 8, 12, 19, 24 hours post dose.

  29. Multiple Dose Observed Accumulation Ratio (Rac) for PF-06291874 - Part A

    Time frame: Predose (0), 2, 4, 6, 8, 12, 19, 24 hours post dose on Day 14

    Rac was observed accumulation ratio. Blood samples (3 mL) to provide a minimum of approximately 1.2 mL plasma for PK analysis were collected at 0, 2, 4, 6, 8, 12, 19, 24 hours post dose.

  30. Multiple Dose Rac for PF-06291874 - Part B

    Time frame: Predose (0), 2, 4, 6, 8, 12, 19, 24 hours post dose on Day 14

    Rac was observed accumulation ratio. Blood samples (3 mL) to provide a minimum of approximately 1.2 mL plasma for PK analysis were collected at 0, 2, 4, 6, 8, 12, 19, 24 hours post dose.

  31. Multiple Dose Rac for Cmax (Rac,Cmax) for PF-06291874 - Part A

    Time frame: Predose (0), 2, 4, 6, 8, 12, 19, 24 hours post dose on Day 14

    Rac,cmax was observed accumulation ratio for Cmax. Blood samples (3 mL) to provide a minimum of approximately 1.2 mL plasma for PK analysis were collected at 0, 2, 4, 6, 8, 12, 19, 24 hours post dose.

  32. Multiple Dose Rac,Cmax for PF-06291874 - Part B

    Time frame: Predose (0), 2, 4, 6, 8, 12, 19, 24 hours post dose on Day 14

    Rac,cmax was observed accumulation ratio for Cmax. Blood samples (3 mL) to provide a minimum of approximately 1.2 mL plasma for PK analysis were collected at 0, 2, 4, 6, 8, 12, 19, 24 hours post dose.

  33. Multiple Dose Percent of Cumulative Amount of Drug Recovered Unchanged in Urine Over the Dosing Interval τ(Aetau%) for PF-06291874

    Time frame: on Day 14 over 2 collection periods (0-6 hours and 6-24 hours).

    Aetau% was percent of cumulative amount of drug recovered unchanged in urine over the dosing interval τ. The 24-hour urine samples for PK analysis were collected on Day 14 over 2 collection periods (0-6 hours and 6-24 hours).

  34. Multiple Dose Renal Clearance (CLr) for PF-06291874

    Time frame: on Day 14 over 2 collection periods (0-6 hours and 6-24 hours).

    CLr was renal clearance. The 24 hour urine samples for PK analysis were collected on Day 14 over 2 collection periods (0-6 hours and 6-24 hours)

  35. Changes From Baseline for Mean Daily Glucose (mg/dL) on Day 14 (AUC Approach) - Part A

    Time frame: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 10, 12, 15, 19 and 24 hours on Days -1 and 14 for all cohorts, and on Day 28 for PF-06291874 100 mg Part A and PF-06291874 30 mg Part B.

    A MMTT was administered on Days -1 and 14 for all cohorts. Blood samples for analysis of glucose were collected at nominal time 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 10, 12, 15, 19 and 24 hours on Days -1 and 14 for all cohorts. MDG was computed by AUC24/24 hours of the glucose values measured.

  36. Changes From Baseline for Mean Daily Glucose (mg/dL) on Day 14 (AUC Approach) - Part B

    Time frame: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 10, 12, 15, 19 and 24 hours on Days -1 and 14 for all cohorts, and on Day 28 for PF-06291874 100 mg Part A and PF-06291874 30 mg Part B.

    A MMTT was administered on Days -1 and 14 for all cohorts. Blood samples for analysis of glucose were collected at nominal time 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 10, 12, 15, 19 and 24 hours on Days -1 and 14 for all cohorts. MDG was computed by AUC24/24 hours of the glucose values measured.

  37. Changes From Baseline for Mean Daily Glucose (mg/dL) on Day 28 (AUC Approach)

    Time frame: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 10, 12, 15, 19 and 24 hours on Days -1 and 14 for all cohorts, and on Day 28 for PF-06291874 100 mg Part A and PF-06291874 30 mg Part B.

    A MMTT was administered on Days -1 for all cohorts, and on Day 28 for PF-06291874 100 mg Part A and PF-06291874 30 mg Part B. Blood samples for analysis of glucose were collected at nominal time 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 10, 12, 15, 19 and 24 hours on Days -1 and 14 for all cohorts, and on Day 28 for PF-06291874 100 mg Part A and PF-06291874 30 mg Part B. MDG was computed by AUC24/24 hours of the glucose values measured.

Secondary outcomes

  1. Changes Relative to Baseline (Ratio) of AUC0-4 for Glucose Following MMTT on Day 14 - Part A

    Time frame: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 10, 12, 15, and 19 hours on Days -1 and 14 for all cohorts, and on Day 28 for PF-06291874 100 mg Part A and PF-06291874 30 mg Part B.

    Blood samples for analysis of glucose were collected at nominal time 0, 0.25, 0.5, 1, 1.5, 2, 3, and 4 hours on Days -1 and 14 for all cohorts, and on Day 28 for PF-06291874 100 mg Part A and PF-06291874 30 mg Part B. AUC0-4 and natural log transformed AUC0-4 were calculated for each day.

  2. Changes Relative to Baseline (Ratio) of AUC0-4 for Glucose Following MMTT on Day 14 - Part B

    Time frame: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 10, 12, 15, and 19 hours on Days -1 and 14 for all cohorts, and on Day 28 for PF-06291874 100 mg Part A and PF-06291874 30 mg Part B.

    Blood samples for analysis of glucose were collected at nominal time 0, 0.25, 0.5, 1, 1.5, 2, 3, and 4 hours on Days -1 and 14 for all cohorts, and on Day 28 for PF-06291874 100 mg Part A and PF-06291874 30 mg Part B. AUC0-4 and natural log transformed AUC0-4 were calculated for each day.

  3. Changes Relative to Baseline (Ratio) of AUC0-4 for Glucose Following MMTT on Day 28

    Time frame: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 10, 12, 15, and 19 hours on Days -1 and 14 for all cohorts, and on Day 28 for PF-06291874 100 mg Part A and PF-06291874 30 mg Part B.

    Blood samples for analysis of glucose were collected at nominal time 0, 0.25, 0.5, 1, 1.5, 2, 3, and 4 hours on Days -1 and 14 for all cohorts, and on Day 28 for PF-06291874 100 mg Part A and PF-06291874 30 mg Part B. AUC0-4 and natural log transformed AUC0-4 were calculated for each day.

  4. Percent Changes From Baseline of AUC0-4 for Glucagon Following MMTT on Day 14 - Part A

    Time frame: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4 hours on Days -1 and 14 for all cohorts, and on Day 28 and follow-up visit for PF-06291874 100 mg Part A and PF-06291874 30 mg Part B.

    Blood samples for analysis of insulin, C-peptide, glucagon and glucagon-like peptide 1 (GLP-1) were collected at nominal time 0, 0.25, 0.5, 1, 1.5, 2, 3, 4 hours on Days -1 and 14 for all cohorts, and on Day 28 and follow-up visit for PF-06291874 100 mg Part A and PF-06291874 30 mg Part B. AUC0-4 and natural log transformed AUC0-4 were calculated for each day.

  5. Percent Changes From Baseline of AUC0-4 for Glucagon Following MMTT on Day 14 - Part B

    Time frame: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4 hours on Days -1 and 14 for all cohorts, and on Day 28 and follow-up visit for PF-06291874 100 mg Part A and PF-06291874 30 mg Part B.

    Blood samples for analysis of insulin, C-peptide, glucagon and glucagon-like peptide 1 (GLP-1) were collected at nominal time 0, 0.25, 0.5, 1, 1.5, 2, 3, 4 hours on Days -1 and 14 for all cohorts, and on Day 28 and follow-up visit for PF-06291874 100 mg Part A and PF-06291874 30 mg Part B. AUC0-4 and natural log transformed AUC0-4 were calculated for each day.

  6. Percent Changes From Baseline of AUC0-4 for Glucagon Following MMTT on Day 28

    Time frame: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4 hours on Days -1 and 14 for all cohorts, and on Day 28 and follow-up visit for PF-06291874 100 mg Part A and PF-06291874 30 mg Part B.

    Blood samples for analysis of insulin, C-peptide, glucagon and GLP-1 were collected at nominal time 0, 0.25, 0.5, 1, 1.5, 2, 3, 4 hours on Days -1 and 14 for all cohorts, and on Day 28 and follow-up visit for PF-06291874 100 mg Part A and PF-06291874 30 mg Part B. AUC0-4 and natural log transformed AUC0-4 were calculated for each day.

  7. Changes Relative to Baseline (Ratio) of AUC0-4 for Insulin Following MMTT on Day 14 - Part A

    Time frame: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4 hours on Days -1 and 14 for all cohorts, and on Day 28 and follow-up visit for PF-06291874 100 mg Part A and PF-06291874 30 mg Part B.

    Blood samples for analysis of insulin, C-peptide, glucagon and GLP-1 were collected at nominal time 0, 0.25, 0.5, 1, 1.5, 2, 3, 4 hours on Days -1 and 14 for all cohorts, and on Day 28 and follow-up visit for PF-06291874 100 mg Part A and PF-06291874 30 mg Part B. AUC0-4 and natural log transformed AUC0-4 were calculated for each day.

  8. Changes Relative to Baseline (Ratio) of AUC0-4 for Insulin Following MMTT on Day 14 - Part B

    Time frame: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4 hours on Days -1 and 14 for all cohorts, and on Day 28 and follow-up visit for PF-06291874 100 mg Part A and PF-06291874 30 mg Part B.

    Blood samples for analysis of insulin, C-peptide, glucagon and GLP-1 were collected at nominal time 0, 0.25, 0.5, 1, 1.5, 2, 3, 4 hours on Days -1 and 14 for all cohorts, and on Day 28 and follow-up visit for PF-06291874 100 mg Part A and PF-06291874 30 mg Part B. AUC0-4 and natural log transformed AUC0-4 were calculated for each day.

  9. Changes Relative to Baseline (Ratio) of AUC0-4 for Insulin Following MMTT on Day 28

    Time frame: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4 hours on Days -1 and 14 for all cohorts, and on Day 28 and follow-up visit for PF-06291874 100 mg Part A and PF-06291874 30 mg Part B.

    Blood samples for analysis of insulin, C-peptide, glucagon and GLP-1 were collected at nominal time 0, 0.25, 0.5, 1, 1.5, 2, 3, 4 hours on Days -1 and 14 for all cohorts, and on Day 28 and follow-up visit for PF-06291874 100 mg Part A and PF-06291874 30 mg Part B. AUC0-4 and natural log transformed AUC0-4 were calculated for each day.

  10. Changes Relative to Baseline (Ratio) of AUC0-4 for C-Peptide Following MMTT on Day 14 - Part A

    Time frame: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4 hours on Days -1 and 14 for all cohorts, and on Day 28 and follow-up visit for PF-06291874 100 mg Part A and PF-06291874 30 mg Part B.

    Blood samples for analysis of insulin, C-peptide, glucagon and GLP-1 were collected at nominal time 0, 0.25, 0.5, 1, 1.5, 2, 3, 4 hours on Days -1 and 14 for all cohorts, and on Day 28 and follow-up visit for PF-06291874 100 mg Part A and PF-06291874 30 mg Part B. AUC0-4 and natural log transformed AUC0-4 were calculated for each day.

  11. Changes Relative to Baseline (Ratio) of AUC0-4 for C-Peptide Following MMTT on Day 14 - Part B

    Time frame: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4 hours on Days -1 and 14 for all cohorts, and on Day 28 and follow-up visit for PF-06291874 100 mg Part A and PF-06291874 30 mg Part B.

    Blood samples for analysis of insulin, C-peptide, glucagon and GLP-1 were collected at nominal time 0, 0.25, 0.5, 1, 1.5, 2, 3, 4 hours on Days -1 and 14 for all cohorts, and on Day 28 and follow-up visit for PF-06291874 100 mg Part A and PF-06291874 30 mg Part B. AUC0-4 and natural log transformed AUC0-4 were calculated for each day.

  12. Changes Relative to Baseline (Ratio) of AUC0-4 for C-Peptide Following MMTT on Day 28

    Time frame: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4 hours on Days -1 and 14 for all cohorts, and on Day 28 and follow-up visit for PF-06291874 100 mg Part A and PF-06291874 30 mg Part B.

    Blood samples for analysis of insulin, C-peptide, glucagon and GLP-1 were collected at nominal time 0, 0.25, 0.5, 1, 1.5, 2, 3, 4 hours on Days -1 and 14 for all cohorts, and on Day 28 and follow-up visit for PF-06291874 100 mg Part A and PF-06291874 30 mg Part B. AUC0-4 and natural log transformed AUC0-4 were calculated for each day.

  13. Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A

    Time frame: predose on Days 0,2,7,14,15,21,28,29

    Fasting blood glucose samples were also collected on Days 0, 2, 7, and 15 for all cohorts, and on Days 21 and 29 for PF-06291874 100 mg Part A and PF-06291874 30 mg Part B.

  14. Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B

    Time frame: Days 0,2,7,14,15,21,28,29

    Fasting blood glucose samples were also collected on Days 0, 2, 7, and 15 for all cohorts, and on Days 21 and 29 for PF-06291874 100 mg Part A and PF-06291874 30 mg Part B.

  15. Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part A

    Time frame: Days -1, 14, 28

    Fasting blood insulin samples were collected on Days -1, 14 and 28 for all cohorts, and on Day 28 for PF-06291874 100 mg Part A. Baseline was defined as the value on Day -1.

  16. Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part B

    Time frame: Days -1, 14, 28

    Fasting blood insulin samples were collected on Days -1, 14 and 28 for all cohorts, and on Day 28 for PF-06291874 30 mg Part B. Baseline was defined as the value on Day -1.

  17. Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A

    Time frame: Days 0,14 and 28

    Blood samples (3.5 mL) for all lipids and 2 mL for ApoB100 were collected at Hour 0 Day 1, Day 7 prior to breakfast, Hour 0 Day 14 for all cohorts; Days 21 and 28 for PF-06291874 100 mg Part A and PF-06291874 30 mg Part B.

  18. Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part B

    Time frame: Days 0,14 and 28

    Blood samples (3.5 mL) for all lipids and 2 mL for ApoB100 were collected at Hour 0 Day 1, Day 7 prior to breakfast, Hour 0 Day 14 for all cohorts; Days 21 and 28 for PF-06291874 100 mg Part A and PF-06291874 30 mg Part B.

Sponsors and collaborators

Lead sponsor

Pfizer

Industry

Registry information

Official study title

A Phase 1, Placebo-controlled Trial To Assess The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Multiple Escalating Oral Doses Of Pf-06291874 In Adults With Type 2 Diabetes Mellitus

Important dates

Study start
2013
Primary completion
2014
Study completion
2014
First posted
May 17, 2013
Registry last updated
Nov 1, 2018

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.

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