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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
117
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 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).
Anaheim Clinical Trials
Anaheim, California, United States
Profil Institute for Clinical Research, Inc.
Chula Vista, California, United States
MRA Clinical Research, LLC
South Miami, Florida, United States
Number of Participants Had Protocol-Defined Total Hypoglycemic Adverse Event (HAE) - Part A
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.
Time frame: Day 1 up to 7-11 days after last dose of study drug
Number of Participants Had Protocol-Defined Total Hypoglycemic Adverse Event (HAE) - Part B
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.
Time frame: Day 1 up to 7-11 days after last dose of study drug
Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A
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.
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.
Number of Participants With ECGs Data Met Criteria of Potential Clinical Concern - Part B
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.
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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.
Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A
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).
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.
Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part B
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.
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.
Number of Participants With Any Abnormal Laboratory Test Results - Part A
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.
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.
Number of Participants With Any Abnormal Laboratory Test Results - Part B
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.
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.
Single Dose Maximum Plasma Concentration (Cmax) for PF-06291874 - Part A
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.
Time frame: 0 hour (pre-dose), 2, 4, 6, 8, 12, 19, 24 hours post-dose on Day 1
Single Dose Normalized Cmax (Cmax[dn]) for PF-06291874 - Part A
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.
Time frame: 0 hour (pre-dose), 2, 4, 6, 8, 12, 19, 24 hours post-dose on Day 1
Single Dose Cmax for PF-06291874 - Part B
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.
Time frame: 0 hour (pre-dose), 2, 4, 6, 8, 12, 19, 24 hours post-dose on Day 1
Single Dose Normalized Cmax (Cmax[dn]) for PF-06291874 - Part B
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
Time frame: 0 hour (pre-dose), 2, 4, 6, 8, 12, 19, 24 hours post-dose on Day 1
Single Dose Time at Which Cmax Occurred (Tmax) for PF-06291874 - Part A
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.
Time frame: 0 hour (pre-dose), 2, 4, 6, 8, 12, 19, 24 hours post-dose on Day 1
Single Dose Tmax for PF-06291874 - Part B
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.
Time frame: 0 hour (pre-dose), 2, 4, 6, 8, 12, 19, 24 hours post-dose on Day 1
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
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.
Time frame: 0 hour (pre-dose), 2, 4, 6, 8, 12, 19, 24 hours post-dose on Day 1
Single Dose AUCtau for PF-06291874 - Part B
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.
Time frame: 0 hour (pre-dose), 2, 4, 6, 8, 12, 19, 24 hours post-dose on Day 1
Multiple Dose Cmax for PF-06291874 - Part A
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.
Time frame: Predose (0), 2, 4, 6, 8, 12, 19, 24 hours post dose on Day 14
Multiple Dose Cmax for PF-06291874 - Part B
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.
Time frame: Predose (0), 2, 4, 6, 8, 12, 19, 24 hours post dose on Day 14
Multiple Dose Tmax for PF-06291874 - Part A
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.
Time frame: Predose (0), 2, 4, 6, 8, 12, 19, 24 hours post dose on Day 14
Multiple Dose Tmax for PF-06291874 - Part B
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.
Time frame: Predose (0), 2, 4, 6, 8, 12, 19, 24 hours post dose on Day 14
Multiple Dose AUCtau for PF-06291874 - Part A
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.
Time frame: Predose (0), 2, 4, 6, 8, 12, 19, 24 hours post dose on Day 14
Multiple Dose AUCtau for PF-06291874 - Part B
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.
Time frame: Predose (0), 2, 4, 6, 8, 12, 19, 24 hours post dose on Day 14
Multiple Dose Half Life for PF-06291874
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.
Time frame: Predose (0), 2, 4, 6, 8, 12, 19, 24 hours post dose on Day 14
Multiple Dose Cmin (Lowest Plasma Concentration Observed During the Dosing Interval) for PF-06291874 - Part A
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.
Time frame: Predose (0), 2, 4, 6, 8, 12, 19, 24 hours post dose on Day 14
Multiple Dose Cmin for PF-06291874 - Part B
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.
Time frame: Predose (0), 2, 4, 6, 8, 12, 19, 24 hours post dose on Day 14
Multiple Dose Apparent Clearance (CL/F) for PF-06291874 - Part A
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).
Time frame: on Day 14 over 2 collection periods (0-6 hours and 6-24 hours).
Multiple Dose CL/F for PF-06291874 - Part B
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).
Time frame: on Day 14 over 2 collection periods (0-6 hours and 6-24 hours).
Multiple Dose Apparent Volume of Distribution (Vz/F) for PF-06291874- Part A and Part B
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.
Time frame: Predose (0), 2, 4, 6, 8, 12, 19, 24 hours post dose on Day 14
Multiple Dose Observed Accumulation Ratio (Rac) for PF-06291874 - Part A
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.
Time frame: Predose (0), 2, 4, 6, 8, 12, 19, 24 hours post dose on Day 14
Multiple Dose Rac for PF-06291874 - Part B
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.
Time frame: Predose (0), 2, 4, 6, 8, 12, 19, 24 hours post dose on Day 14
Multiple Dose Rac for Cmax (Rac,Cmax) for PF-06291874 - Part A
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.
Time frame: Predose (0), 2, 4, 6, 8, 12, 19, 24 hours post dose on Day 14
Multiple Dose Rac,Cmax for PF-06291874 - Part B
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.
Time frame: Predose (0), 2, 4, 6, 8, 12, 19, 24 hours post dose on Day 14
Multiple Dose Percent of Cumulative Amount of Drug Recovered Unchanged in Urine Over the Dosing Interval τ(Aetau%) for PF-06291874
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).
Time frame: on Day 14 over 2 collection periods (0-6 hours and 6-24 hours).
Multiple Dose Renal Clearance (CLr) for PF-06291874
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)
Time frame: on Day 14 over 2 collection periods (0-6 hours and 6-24 hours).
Changes From Baseline for Mean Daily Glucose (mg/dL) on Day 14 (AUC Approach) - Part A
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.
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.
Changes From Baseline for Mean Daily Glucose (mg/dL) on Day 14 (AUC Approach) - 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.
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.
Changes From Baseline for Mean Daily Glucose (mg/dL) on Day 28 (AUC Approach)
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.
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.
Changes Relative to Baseline (Ratio) of AUC0-4 for Glucose Following MMTT on Day 14 - Part A
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.
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.
Changes Relative to Baseline (Ratio) of AUC0-4 for Glucose Following MMTT on Day 14 - 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.
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.
Changes Relative to Baseline (Ratio) of AUC0-4 for Glucose Following MMTT on Day 28
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.
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.
Percent Changes From Baseline of AUC0-4 for Glucagon Following MMTT on Day 14 - Part A
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.
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.
Percent Changes From Baseline of AUC0-4 for Glucagon Following MMTT on Day 14 - 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.
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.
Percent Changes From Baseline of AUC0-4 for Glucagon Following MMTT on Day 28
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.
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.
Changes Relative to Baseline (Ratio) of AUC0-4 for Insulin Following MMTT on Day 14 - Part A
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.
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.
Changes Relative to Baseline (Ratio) of AUC0-4 for Insulin Following MMTT on Day 14 - 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.
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.
Changes Relative to Baseline (Ratio) of AUC0-4 for Insulin Following MMTT on Day 28
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.
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.
Changes Relative to Baseline (Ratio) of AUC0-4 for C-Peptide Following MMTT on Day 14 - Part A
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.
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.
Changes Relative to Baseline (Ratio) of AUC0-4 for C-Peptide Following MMTT on Day 14 - 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.
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.
Changes Relative to Baseline (Ratio) of AUC0-4 for C-Peptide Following MMTT on Day 28
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.
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.
Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A
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.
Time frame: predose on Days 0,2,7,14,15,21,28,29
Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B
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.
Time frame: Days 0,2,7,14,15,21,28,29
Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part A
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.
Time frame: Days -1, 14, 28
Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part B
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.
Time frame: Days -1, 14, 28
Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A
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.
Time frame: Days 0,14 and 28
Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part B
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.
Time frame: Days 0,14 and 28