Diabetes Mellitus, Type 2
Conditions
Brief summary
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.
Interventions
DRUGPF-06291874
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
DRUGPlacebo
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).
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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: 1. 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; 2. Have undergone a documented hysterectomy and/or bilateral oophorectomy; 3. Have medically confirmed ovarian failure. 4. 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes From Baseline for Mean Daily Glucose (mg/dL) on Day 28 (AUC Approach) | 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. |
| Multiple Dose Cmax for PF-06291874 - Part B | 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. |
| Multiple Dose Tmax for PF-06291874 - Part A | 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. |
| Multiple Dose AUCtau for PF-06291874 - Part A | 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. |
| Multiple Dose AUCtau for PF-06291874 - Part B | 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. |
| Multiple Dose Half Life for PF-06291874 | 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. |
| Multiple Dose Cmin (Lowest Plasma Concentration Observed During the Dosing Interval) for PF-06291874 - Part A | 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. |
| Multiple Dose Cmin for PF-06291874 - Part B | 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. |
| Multiple Dose Apparent Clearance (CL/F) for PF-06291874 - Part A | 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). |
| Multiple Dose CL/F for PF-06291874 - Part B | 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). |
| Multiple Dose Apparent Volume of Distribution (Vz/F) for PF-06291874- Part A and Part B | 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. |
| Multiple Dose Observed Accumulation Ratio (Rac) for PF-06291874 - Part A | 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. |
| Multiple Dose Rac for PF-06291874 - Part B | 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. |
| Multiple Dose Rac for Cmax (Rac,Cmax) for PF-06291874 - Part A | 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. |
| Multiple Dose Rac,Cmax for PF-06291874 - Part B | 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. |
| Multiple Dose Percent of Cumulative Amount of Drug Recovered Unchanged in Urine Over the Dosing Interval τ(Aetau%) for PF-06291874 | 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). |
| Multiple Dose Renal Clearance (CLr) for PF-06291874 | 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) |
| Changes From Baseline for Mean Daily Glucose (mg/dL) on Day 14 (AUC Approach) - Part A | 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. |
| Changes From Baseline for Mean Daily Glucose (mg/dL) on Day 14 (AUC Approach) - Part B | 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. |
| Number of Participants Had Protocol-Defined Total Hypoglycemic Adverse Event (HAE) - Part A | 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. |
| Number of Participants Had Protocol-Defined Total Hypoglycemic Adverse Event (HAE) - Part B | 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. |
| Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | 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. |
| Number of Participants With ECGs Data Met Criteria of Potential Clinical Concern - Part B | 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. |
| Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | 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). |
| Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part B | 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. |
| Multiple Dose Tmax for PF-06291874 - Part B | 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. |
| Number of Participants With Any Abnormal Laboratory Test Results - Part A | 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. |
| Number of Participants With Any Abnormal Laboratory Test Results - Part B | 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. |
| Single Dose Maximum Plasma Concentration (Cmax) for PF-06291874 - Part A | 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. |
| Single Dose Normalized Cmax (Cmax[dn]) for PF-06291874 - Part A | 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. |
| Single Dose Cmax for PF-06291874 - Part B | 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. |
| Single Dose Normalized Cmax (Cmax[dn]) for PF-06291874 - Part B | 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 |
| Single Dose Time at Which Cmax Occurred (Tmax) for PF-06291874 - Part A | 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. |
| Single Dose Tmax for PF-06291874 - Part B | 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. |
| 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 | 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. |
| Single Dose AUCtau for PF-06291874 - Part B | 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. |
| Multiple Dose Cmax for PF-06291874 - Part A | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes Relative to Baseline (Ratio) of AUC0-4 for Glucose Following MMTT on Day 14 - Part B | 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. |
| Changes Relative to Baseline (Ratio) of AUC0-4 for Glucose Following MMTT on Day 28 | 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. |
| Percent Changes From Baseline of AUC0-4 for Glucagon Following MMTT on Day 14 - Part A | 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. |
| Percent Changes From Baseline of AUC0-4 for Glucagon Following MMTT on Day 14 - Part B | 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. |
| Percent Changes From Baseline of AUC0-4 for Glucagon Following MMTT on Day 28 | 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. |
| Changes Relative to Baseline (Ratio) of AUC0-4 for Insulin Following MMTT on Day 14 - Part A | 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. |
| Changes Relative to Baseline (Ratio) of AUC0-4 for Insulin Following MMTT on Day 14 - Part B | 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. |
| Changes Relative to Baseline (Ratio) of AUC0-4 for Insulin Following MMTT on Day 28 | 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. |
| Changes Relative to Baseline (Ratio) of AUC0-4 for C-Peptide Following MMTT on Day 14 - Part A | 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. |
| Changes Relative to Baseline (Ratio) of AUC0-4 for C-Peptide Following MMTT on Day 14 - Part B | 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. |
| Changes Relative to Baseline (Ratio) of AUC0-4 for C-Peptide Following MMTT on Day 28 | 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. |
| Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | 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. |
| Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | 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. |
| Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part A | 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. |
| Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part B | 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. |
| Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | 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. |
| Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part B | 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. |
| Changes Relative to Baseline (Ratio) of AUC0-4 for Glucose Following MMTT on Day 14 - Part A | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part A: Placebo Participants received placebo matched to PF-06291874 orally once daily for 14 or 28 days | 18 |
| Part A: PF-06291874 5 mg Participants received PF-06291874 5 milligram (mg) orally once daily for 14 days | 12 |
| Part A: PF-06291874 15 mg Participants received PF-06291874 15 mg orally once daily for 14 days | 12 |
| Part A: PF-06291874 50 mg Participants received PF-06291874 50 mg orally once daily for 14 days | 12 |
| Part A: PF-06291874 100 mg Participants received PF-06291874 100 mg orally once daily for 28 days | 14 |
| Part A: PF-06291874 150 mg Participants received PF-06291874 150 mg orally once daily for 14 days | 12 |
| Part B: Placebo Participants received placebo matched to PF-06291874 orally once daily for 14 or 28 days | 13 |
| Part B: PF-06291874 15 mg Participants received PF-06291874 15 mg orally once daily for 14 days | 10 |
| Part B: PF-06291874 30 mg Participants received PF-06291874 30 mg orally once daily for 28 days | 14 |
| Total | 117 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Part A: Placebo | Part A: PF-06291874 5 mg | Part A: PF-06291874 15 mg | Part A: PF-06291874 50 mg | Part A: PF-06291874 100 mg | Part A: PF-06291874 150 mg | Part B: Placebo | Part B: PF-06291874 15 mg | Part B: PF-06291874 30 mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 58.9 years STANDARD_DEVIATION 5.1 | 58.9 years STANDARD_DEVIATION 5 | 53.8 years STANDARD_DEVIATION 5.9 | 56.2 years STANDARD_DEVIATION 7.7 | 54 years STANDARD_DEVIATION 10.8 | 56.1 years STANDARD_DEVIATION 6.7 | 56.3 years STANDARD_DEVIATION 7.6 | 54.2 years STANDARD_DEVIATION 8.7 | 55 years STANDARD_DEVIATION 10 | 56.1 years STANDARD_DEVIATION 7.7 |
| Sex: Female, Male Female | 8 Participants | 7 Participants | 9 Participants | 4 Participants | 7 Participants | 3 Participants | 4 Participants | 3 Participants | 2 Participants | 47 Participants |
| Sex: Female, Male Male | 10 Participants | 5 Participants | 3 Participants | 8 Participants | 7 Participants | 9 Participants | 9 Participants | 7 Participants | 12 Participants | 70 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 10 / 18 | 7 / 12 | 4 / 12 | 6 / 12 | 5 / 14 | 3 / 12 | 8 / 13 | 5 / 10 | 5 / 14 | 53 / 117 |
| serious Total, serious adverse events | 0 / 18 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 14 | 0 / 12 | 0 / 13 | 0 / 10 | 0 / 14 | 0 / 117 |
Outcome results
Primary
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.
Population: All subjects administered PF-06291874 or placebo were included in PD analysis. Placebo subjects within each cohort in Part A or B were pooled into a single placebo group for the inpatient portion of the study. Data collected from placebo subjects during the outpatient portion of study (Day 28) were also pooled separately for Parts A and B.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Changes From Baseline for Mean Daily Glucose (mg/dL) on Day 14 (AUC Approach) - Part A | -11.54 mg/dL | 90% Confidence Interval 58 |
| PF-06291874 5 mg | Changes From Baseline for Mean Daily Glucose (mg/dL) on Day 14 (AUC Approach) - Part A | -14.31 mg/dL | 90% Confidence Interval 28 |
| PF-06291874 15 mg | Changes From Baseline for Mean Daily Glucose (mg/dL) on Day 14 (AUC Approach) - Part A | -33.18 mg/dL | 90% Confidence Interval 38 |
| PF-06291874 50 mg | Changes From Baseline for Mean Daily Glucose (mg/dL) on Day 14 (AUC Approach) - Part A | -38.13 mg/dL | 90% Confidence Interval 178 |
| PF-06291874 100 mg | Changes From Baseline for Mean Daily Glucose (mg/dL) on Day 14 (AUC Approach) - Part A | -43.86 mg/dL | 90% Confidence Interval 47 |
| PF-06291874 150 mg | Changes From Baseline for Mean Daily Glucose (mg/dL) on Day 14 (AUC Approach) - Part A | -53.92 mg/dL | — |
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: 0.745790% CI: [-16.93, 11.38]ANCOVA
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: 0.010890% CI: [-35.47, -7.81]ANCOVA
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: 0.001890% CI: [-40.38, -12.8]ANCOVA
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: 0.000190% CI: [-45.66, -18.99]ANCOVA
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: <0.000190% CI: [-56.23, -28.55]ANCOVA
Primary
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.
Population: All subjects administered PF-06291874 or placebo were included in PD analysis. Placebo subjects within each cohort in Part A or B were pooled into a single placebo group for the inpatient portion of the study. Data collected from placebo subjects during the outpatient portion of study (Day 28) were also pooled separately for Parts A and B.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Changes From Baseline for Mean Daily Glucose (mg/dL) on Day 14 (AUC Approach) - Part B | -20.85 ng/mL | 90% Confidence Interval 32 |
| PF-06291874 5 mg | Changes From Baseline for Mean Daily Glucose (mg/dL) on Day 14 (AUC Approach) - Part B | -50.65 ng/mL | 90% Confidence Interval 217 |
| PF-06291874 15 mg | Changes From Baseline for Mean Daily Glucose (mg/dL) on Day 14 (AUC Approach) - Part B | -31.32 ng/mL | — |
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: 0.27990% CI: [-5.5, 26.43]ANCOVA
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: 0.029990% CI: [-33.89, -4.76]ANCOVA
Primary
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.
Population: All subjects administered PF-06291874 or placebo were included in PD analysis. Placebo subjects within each cohort in Part A or B were pooled into a single placebo group for the inpatient portion of the study. Data collected from placebo subjects during the outpatient portion of study (Day 28) were also pooled separately for Parts A and B.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Changes From Baseline for Mean Daily Glucose (mg/dL) on Day 28 (AUC Approach) | -6.99 mg/dL | 90% Confidence Interval 58 |
| PF-06291874 5 mg | Changes From Baseline for Mean Daily Glucose (mg/dL) on Day 28 (AUC Approach) | -36.42 mg/dL | 90% Confidence Interval 28 |
| PF-06291874 15 mg | Changes From Baseline for Mean Daily Glucose (mg/dL) on Day 28 (AUC Approach) | -30.10 mg/dL | 90% Confidence Interval 38 |
| PF-06291874 50 mg | Changes From Baseline for Mean Daily Glucose (mg/dL) on Day 28 (AUC Approach) | -42.00 mg/dL | 90% Confidence Interval 178 |
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: 0.000590% CI: [-42.28, -16.57]ANCOVA
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: 0.113390% CI: [-24.26, 0.48]ANCOVA
Primary
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).
Population: This PK Parameter Analysis Set was defined as all participants randomized and treated who have at least 1 of the PK parameters of interest. The number of participants analyzed was the number of participants contributing to the summary statistics.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Multiple Dose Apparent Clearance (CL/F) for PF-06291874 - Part A | 1.315 L/hr | Geometric Coefficient of Variation 42 |
| PF-06291874 5 mg | Multiple Dose Apparent Clearance (CL/F) for PF-06291874 - Part A | 1.275 L/hr | Geometric Coefficient of Variation 19 |
| PF-06291874 15 mg | Multiple Dose Apparent Clearance (CL/F) for PF-06291874 - Part A | 1.264 L/hr | Geometric Coefficient of Variation 30 |
| PF-06291874 50 mg | Multiple Dose Apparent Clearance (CL/F) for PF-06291874 - Part A | 1.258 L/hr | Geometric Coefficient of Variation 32 |
| PF-06291874 100 mg | Multiple Dose Apparent Clearance (CL/F) for PF-06291874 - Part A | 1.422 L/hr | Geometric Coefficient of Variation 37 |
Primary
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
Population: This PK Parameter Analysis Set was defined as all participants randomized and treated who have at least 1 of the PK parameters of interest. This parameter was not calculated for treatment groups with only 24-hour sampling on Day 14(A: 100 mg and B: 30 mg), since the terminal phase was not well characterized.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Multiple Dose Apparent Volume of Distribution (Vz/F) for PF-06291874- Part A and Part B | 38.37 L | Geometric Coefficient of Variation 20 |
| PF-06291874 5 mg | Multiple Dose Apparent Volume of Distribution (Vz/F) for PF-06291874- Part A and Part B | 35.54 L | Geometric Coefficient of Variation 21 |
| PF-06291874 15 mg | Multiple Dose Apparent Volume of Distribution (Vz/F) for PF-06291874- Part A and Part B | 40.47 L | Geometric Coefficient of Variation 25 |
| PF-06291874 50 mg | Multiple Dose Apparent Volume of Distribution (Vz/F) for PF-06291874- Part A and Part B | 41.88 L | Geometric Coefficient of Variation 29 |
| PF-06291874 100 mg | Multiple Dose Apparent Volume of Distribution (Vz/F) for PF-06291874- Part A and Part B | 42.20 L | Geometric Coefficient of Variation 14 |
Primary
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
Population: This PK Parameter Analysis Set was defined as all participants randomized and treated who had at least 1 of the PK parameters of interest. The number of participants analyzed was the number of participants contributing to the summary statistics.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Multiple Dose AUCtau for PF-06291874 - Part A | 3800 ng.hr/mL | Geometric Coefficient of Variation 42 |
| PF-06291874 5 mg | Multiple Dose AUCtau for PF-06291874 - Part A | 11760 ng.hr/mL | Geometric Coefficient of Variation 19 |
| PF-06291874 15 mg | Multiple Dose AUCtau for PF-06291874 - Part A | 39560 ng.hr/mL | Geometric Coefficient of Variation 30 |
| PF-06291874 50 mg | Multiple Dose AUCtau for PF-06291874 - Part A | 79550 ng.hr/mL | Geometric Coefficient of Variation 32 |
| PF-06291874 100 mg | Multiple Dose AUCtau for PF-06291874 - Part A | 105400 ng.hr/mL | Geometric Coefficient of Variation 37 |
Primary
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
Population: This PK Parameter Analysis Set was defined as all participants randomized and treated who have at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Multiple Dose AUCtau for PF-06291874 - Part B | 11530 ng.hr/mL | Geometric Coefficient of Variation 23 |
| PF-06291874 5 mg | Multiple Dose AUCtau for PF-06291874 - Part B | 19270 ng.hr/mL | Geometric Coefficient of Variation 34 |
Primary
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).
Population: This PK Parameter Analysis Set was defined as all participants randomized and treated who have at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Multiple Dose CL/F for PF-06291874 - Part B | 1.300 L/hr | Geometric Coefficient of Variation 23 |
| PF-06291874 5 mg | Multiple Dose CL/F for PF-06291874 - Part B | 1.555 L/hr | Geometric Coefficient of Variation 34 |
Primary
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
Population: This PK Parameter Analysis Set was defined as all participants randomized and treated who had at least 1 of the PK parameters of interest. The number of participants analyzed was the number of participants contributing to the summary statistics.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Multiple Dose Cmax for PF-06291874 - Part A | 213.4 ng/mL | Geometric Coefficient of Variation 27 |
| PF-06291874 5 mg | Multiple Dose Cmax for PF-06291874 - Part A | 669.1 ng/mL | Geometric Coefficient of Variation 17 |
| PF-06291874 15 mg | Multiple Dose Cmax for PF-06291874 - Part A | 2220 ng/mL | Geometric Coefficient of Variation 31 |
| PF-06291874 50 mg | Multiple Dose Cmax for PF-06291874 - Part A | 4362 ng/mL | Geometric Coefficient of Variation 30 |
| PF-06291874 100 mg | Multiple Dose Cmax for PF-06291874 - Part A | 5957 ng/mL | Geometric Coefficient of Variation 29 |
Primary
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
Population: This PK Parameter Analysis Set was defined as all participants randomized and treated who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Multiple Dose Cmax for PF-06291874 - Part B | 663.1 ng/mL | Geometric Coefficient of Variation 19 |
| PF-06291874 5 mg | Multiple Dose Cmax for PF-06291874 - Part B | 1108 ng/mL | Geometric Coefficient of Variation 26 |
Primary
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
Population: This PK Parameter Analysis Set was defined as all participants randomized and treated who have at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Multiple Dose Cmin for PF-06291874 - Part B | 339.5 ng/mL | Geometric Coefficient of Variation 32 |
| PF-06291874 5 mg | Multiple Dose Cmin for PF-06291874 - Part B | 411.5 ng/mL | Geometric Coefficient of Variation 217 |
Primary
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
Population: This PK Parameter Analysis Set was defined as all participants randomized and treated who have at least 1 of the PK parameters of interest. The number of participants analyzed was the number of participants contributing to the summary statistics.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Multiple Dose Cmin (Lowest Plasma Concentration Observed During the Dosing Interval) for PF-06291874 - Part A | 117.8 ng/mL | Geometric Coefficient of Variation 58 |
| PF-06291874 5 mg | Multiple Dose Cmin (Lowest Plasma Concentration Observed During the Dosing Interval) for PF-06291874 - Part A | 350.5 ng/mL | Geometric Coefficient of Variation 28 |
| PF-06291874 15 mg | Multiple Dose Cmin (Lowest Plasma Concentration Observed During the Dosing Interval) for PF-06291874 - Part A | 1132 ng/mL | Geometric Coefficient of Variation 38 |
| PF-06291874 50 mg | Multiple Dose Cmin (Lowest Plasma Concentration Observed During the Dosing Interval) for PF-06291874 - Part A | 1747 ng/mL | Geometric Coefficient of Variation 178 |
| PF-06291874 100 mg | Multiple Dose Cmin (Lowest Plasma Concentration Observed During the Dosing Interval) for PF-06291874 - Part A | 3096 ng/mL | Geometric Coefficient of Variation 47 |
Primary
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
Population: This PK Parameter Analysis Set was defined as all participants randomized and treated who have at least 1 of the PK parameters of interest. The number of participants analyzed was the number of participants contributing to the summary statistics. This parameter was not calculated for group: 100 mg Part A, 30 mg Part B.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Multiple Dose Half Life for PF-06291874 | 20.96 hr | Standard Deviation 5.6029 |
| PF-06291874 5 mg | Multiple Dose Half Life for PF-06291874 | 19.68 hr | Standard Deviation 4.2407 |
| PF-06291874 15 mg | Multiple Dose Half Life for PF-06291874 | 22.24 hr | Standard Deviation 3.2605 |
| PF-06291874 50 mg | Multiple Dose Half Life for PF-06291874 | 20.83 hr | Standard Deviation 4.1134 |
| PF-06291874 100 mg | Multiple Dose Half Life for PF-06291874 | 22.74 hr | Standard Deviation 3.4699 |
Primary
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
Population: This PK Parameter Analysis Set was defined as all participants randomized and treated who have at least 1 of the PK parameters of interest. The number of participants analyzed was the number of participants contributing to the summary statistics.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Multiple Dose Observed Accumulation Ratio (Rac) for PF-06291874 - Part A | 1.766 ratio | Geometric Coefficient of Variation 38 |
| PF-06291874 5 mg | Multiple Dose Observed Accumulation Ratio (Rac) for PF-06291874 - Part A | 1.724 ratio | Geometric Coefficient of Variation 17 |
| PF-06291874 15 mg | Multiple Dose Observed Accumulation Ratio (Rac) for PF-06291874 - Part A | 1.915 ratio | Geometric Coefficient of Variation 17 |
| PF-06291874 50 mg | Multiple Dose Observed Accumulation Ratio (Rac) for PF-06291874 - Part A | 1.847 ratio | Geometric Coefficient of Variation 22 |
| PF-06291874 100 mg | Multiple Dose Observed Accumulation Ratio (Rac) for PF-06291874 - Part A | 2.032 ratio | Geometric Coefficient of Variation 16 |
Primary
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).
Population: This PK Parameter Analysis Set was defined as all participants randomized and treated who have at least 1 of the PK parameters of interest. For treatment groups with dose\< 50 mg, all urine concentrations were below the lower limit of quantification (\<50.0 ng/mL) and hence no urine parameter was calculated including Aetau%.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Placebo | Multiple Dose Percent of Cumulative Amount of Drug Recovered Unchanged in Urine Over the Dosing Interval τ(Aetau%) for PF-06291874 | 0.0000 percentage of dose | Full Range 19 |
| PF-06291874 5 mg | Multiple Dose Percent of Cumulative Amount of Drug Recovered Unchanged in Urine Over the Dosing Interval τ(Aetau%) for PF-06291874 | 0.0000 percentage of dose | Full Range 25 |
| PF-06291874 15 mg | Multiple Dose Percent of Cumulative Amount of Drug Recovered Unchanged in Urine Over the Dosing Interval τ(Aetau%) for PF-06291874 | 0.0000 percentage of dose | Full Range 18 |
Primary
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
Population: This PK Parameter Analysis Set was defined as all participants randomized and treated who have at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Multiple Dose Rac,Cmax for PF-06291874 - Part B | 1.775 ratio | Geometric Coefficient of Variation 22 |
| PF-06291874 5 mg | Multiple Dose Rac,Cmax for PF-06291874 - Part B | 1.610 ratio | Geometric Coefficient of Variation 16 |
Primary
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
Population: This PK Parameter Analysis Set was defined as all participants randomized and treated who have at least 1 of the PK parameters of interest. The number of participants analyzed was the number of participants contributing to the summary statistics.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Multiple Dose Rac for Cmax (Rac,Cmax) for PF-06291874 - Part A | 1.575 ratio | Geometric Coefficient of Variation 26 |
| PF-06291874 5 mg | Multiple Dose Rac for Cmax (Rac,Cmax) for PF-06291874 - Part A | 1.567 ratio | Geometric Coefficient of Variation 23 |
| PF-06291874 15 mg | Multiple Dose Rac for Cmax (Rac,Cmax) for PF-06291874 - Part A | 1.698 ratio | Geometric Coefficient of Variation 19 |
| PF-06291874 50 mg | Multiple Dose Rac for Cmax (Rac,Cmax) for PF-06291874 - Part A | 1.690 ratio | Geometric Coefficient of Variation 25 |
| PF-06291874 100 mg | Multiple Dose Rac for Cmax (Rac,Cmax) for PF-06291874 - Part A | 1.812 ratio | Geometric Coefficient of Variation 18 |
Primary
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
Population: This PK Parameter Analysis Set was defined as all participants randomized and treated who have at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Multiple Dose Rac for PF-06291874 - Part B | 1.780 ratio | Geometric Coefficient of Variation 17 |
| PF-06291874 5 mg | Multiple Dose Rac for PF-06291874 - Part B | 1.709 ratio | Geometric Coefficient of Variation 22 |
Primary
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).
Population: This PK Parameter Analysis Set was defined as all participants randomized and treated who have at least 1 of the PK parameters of interest. For treatment groups with dose\< 50 mg, all urine concentrations were below the lower limit of quantification (\<50.0 ng/mL) and hence no urine parameter was calculated including CLr.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Placebo | Multiple Dose Renal Clearance (CLr) for PF-06291874 | 0.0000 mL/hr | Full Range 19 |
| PF-06291874 5 mg | Multiple Dose Renal Clearance (CLr) for PF-06291874 | 0.0000 mL/hr | Full Range 25 |
| PF-06291874 15 mg | Multiple Dose Renal Clearance (CLr) for PF-06291874 | 0.0000 mL/hr | Full Range 18 |
Primary
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
Population: This PK Parameter Analysis Set was defined as all participants randomized and treated who had at least 1 of the PK parameters of interest. The number of participants analyzed was the number of participants contributing to the summary statistics.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Multiple Dose Tmax for PF-06291874 - Part A | 5.98 hour |
| PF-06291874 5 mg | Multiple Dose Tmax for PF-06291874 - Part A | 5.00 hour |
| PF-06291874 15 mg | Multiple Dose Tmax for PF-06291874 - Part A | 4.02 hour |
| PF-06291874 50 mg | Multiple Dose Tmax for PF-06291874 - Part A | 6.00 hour |
| PF-06291874 100 mg | Multiple Dose Tmax for PF-06291874 - Part A | 5.00 hour |
Primary
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
Population: This PK Parameter Analysis Set was defined as all participants randomized and treated who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Placebo | Multiple Dose Tmax for PF-06291874 - Part B | 4.00 hr | Full Range 19 |
| PF-06291874 5 mg | Multiple Dose Tmax for PF-06291874 - Part B | 6.00 hr | Full Range 26 |
Primary
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
Population: The Safety Analysis Set was defined as all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants Had Protocol-Defined Total Hypoglycemic Adverse Event (HAE) - Part A | 2 participants |
| PF-06291874 5 mg | Number of Participants Had Protocol-Defined Total Hypoglycemic Adverse Event (HAE) - Part A | 2 participants |
| PF-06291874 15 mg | Number of Participants Had Protocol-Defined Total Hypoglycemic Adverse Event (HAE) - Part A | 1 participants |
| PF-06291874 50 mg | Number of Participants Had Protocol-Defined Total Hypoglycemic Adverse Event (HAE) - Part A | 1 participants |
| PF-06291874 100 mg | Number of Participants Had Protocol-Defined Total Hypoglycemic Adverse Event (HAE) - Part A | 1 participants |
| PF-06291874 150 mg | Number of Participants Had Protocol-Defined Total Hypoglycemic Adverse Event (HAE) - Part A | 2 participants |
Primary
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
Population: The Safety Analysis Set was defined as all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants Had Protocol-Defined Total Hypoglycemic Adverse Event (HAE) - Part B | 7 participants |
| PF-06291874 5 mg | Number of Participants Had Protocol-Defined Total Hypoglycemic Adverse Event (HAE) - Part B | 4 participants |
| PF-06291874 15 mg | Number of Participants Had Protocol-Defined Total Hypoglycemic Adverse Event (HAE) - Part B | 13 participants |
Primary
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.
Population: The Safety Analysis Set was defined as all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Any Abnormal Laboratory Test Results - Part A | 17 participants |
| PF-06291874 5 mg | Number of Participants With Any Abnormal Laboratory Test Results - Part A | 10 participants |
| PF-06291874 15 mg | Number of Participants With Any Abnormal Laboratory Test Results - Part A | 11 participants |
| PF-06291874 50 mg | Number of Participants With Any Abnormal Laboratory Test Results - Part A | 12 participants |
| PF-06291874 100 mg | Number of Participants With Any Abnormal Laboratory Test Results - Part A | 13 participants |
| PF-06291874 150 mg | Number of Participants With Any Abnormal Laboratory Test Results - Part A | 8 participants |
Primary
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.
Population: The Safety Analysis Set was defined as all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Any Abnormal Laboratory Test Results - Part B | 8 participants |
| PF-06291874 5 mg | Number of Participants With Any Abnormal Laboratory Test Results - Part B | 12 participants |
| PF-06291874 15 mg | Number of Participants With Any Abnormal Laboratory Test Results - Part B | 11 participants |
Primary
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.
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.
Population: The Safety Analysis Set was defined as all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With ECGs Data Met Criteria of Potential Clinical Concern - Part B | PR interval increase ≥25%/50% | 0 participants |
| Placebo | Number of Participants With ECGs Data Met Criteria of Potential Clinical Concern - Part B | QTcF interval 450-480 msec | 1 participants |
| Placebo | Number of Participants With ECGs Data Met Criteria of Potential Clinical Concern - Part B | QRS interval >=140 msec | 0 participants |
| Placebo | Number of Participants With ECGs Data Met Criteria of Potential Clinical Concern - Part B | QTcF interval >=500 msec | 0 participants |
| Placebo | Number of Participants With ECGs Data Met Criteria of Potential Clinical Concern - Part B | QTcF interval 480-500 msec | 0 participants |
| Placebo | Number of Participants With ECGs Data Met Criteria of Potential Clinical Concern - Part B | QTcF increase 30-60 msec | 1 participants |
| Placebo | Number of Participants With ECGs Data Met Criteria of Potential Clinical Concern - Part B | PR interval >=300 msec | 0 participants |
| Placebo | Number of Participants With ECGs Data Met Criteria of Potential Clinical Concern - Part B | QRS interval increase >=50% | 0 participants |
| Placebo | Number of Participants With ECGs Data Met Criteria of Potential Clinical Concern - Part B | QT interval >=500 msec | 0 participants |
| Placebo | Number of Participants With ECGs Data Met Criteria of Potential Clinical Concern - Part B | QTcF increase >=60 msec | 0 participants |
| PF-06291874 5 mg | Number of Participants With ECGs Data Met Criteria of Potential Clinical Concern - Part B | QTcF interval 480-500 msec | 0 participants |
| PF-06291874 5 mg | Number of Participants With ECGs Data Met Criteria of Potential Clinical Concern - Part B | QTcF increase 30-60 msec | 0 participants |
| PF-06291874 5 mg | Number of Participants With ECGs Data Met Criteria of Potential Clinical Concern - Part B | PR interval >=300 msec | 0 participants |
| PF-06291874 5 mg | Number of Participants With ECGs Data Met Criteria of Potential Clinical Concern - Part B | QRS interval >=140 msec | 0 participants |
| PF-06291874 5 mg | Number of Participants With ECGs Data Met Criteria of Potential Clinical Concern - Part B | QT interval >=500 msec | 0 participants |
| PF-06291874 5 mg | Number of Participants With ECGs Data Met Criteria of Potential Clinical Concern - Part B | QTcF interval 450-480 msec | 1 participants |
| PF-06291874 5 mg | Number of Participants With ECGs Data Met Criteria of Potential Clinical Concern - Part B | QTcF interval >=500 msec | 0 participants |
| PF-06291874 5 mg | Number of Participants With ECGs Data Met Criteria of Potential Clinical Concern - Part B | PR interval increase ≥25%/50% | 0 participants |
| PF-06291874 5 mg | Number of Participants With ECGs Data Met Criteria of Potential Clinical Concern - Part B | QRS interval increase >=50% | 0 participants |
| PF-06291874 5 mg | Number of Participants With ECGs Data Met Criteria of Potential Clinical Concern - Part B | QTcF increase >=60 msec | 0 participants |
| PF-06291874 15 mg | Number of Participants With ECGs Data Met Criteria of Potential Clinical Concern - Part B | QT interval >=500 msec | 0 participants |
| PF-06291874 15 mg | Number of Participants With ECGs Data Met Criteria of Potential Clinical Concern - Part B | PR interval >=300 msec | 0 participants |
| PF-06291874 15 mg | Number of Participants With ECGs Data Met Criteria of Potential Clinical Concern - Part B | PR interval increase ≥25%/50% | 0 participants |
| PF-06291874 15 mg | Number of Participants With ECGs Data Met Criteria of Potential Clinical Concern - Part B | QRS interval >=140 msec | 0 participants |
| PF-06291874 15 mg | Number of Participants With ECGs Data Met Criteria of Potential Clinical Concern - Part B | QTcF increase >=60 msec | 0 participants |
| PF-06291874 15 mg | Number of Participants With ECGs Data Met Criteria of Potential Clinical Concern - Part B | QRS interval increase >=50% | 0 participants |
| PF-06291874 15 mg | Number of Participants With ECGs Data Met Criteria of Potential Clinical Concern - Part B | QTcF interval 480-500 msec | 0 participants |
| PF-06291874 15 mg | Number of Participants With ECGs Data Met Criteria of Potential Clinical Concern - Part B | QTcF interval 450-480 msec | 2 participants |
| PF-06291874 15 mg | Number of Participants With ECGs Data Met Criteria of Potential Clinical Concern - Part B | QTcF increase 30-60 msec | 1 participants |
| PF-06291874 15 mg | Number of Participants With ECGs Data Met Criteria of Potential Clinical Concern - Part B | QTcF interval >=500 msec | 0 participants |
Primary
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.
Population: The Safety Analysis Set was defined as all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | PR interval >=300 msec | 0 participants |
| Placebo | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QT interval >=500 msec | 0 participants |
| Placebo | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QTcF increase >=60 msec | 0 participants |
| Placebo | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QTcF increase 30-60 msec | 0 participants |
| Placebo | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QRS interval >=140 msec | 0 participants |
| Placebo | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QRS interval increase >=50% | 0 participants |
| Placebo | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QTcF interval 480-500 msec | 0 participants |
| Placebo | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QTcF interval >=500 msec | 0 participants |
| Placebo | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | PR interval increase ≥25%/50% | 0 participants |
| Placebo | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QTcF interval 450-480 msec | 1 participants |
| PF-06291874 5 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | PR interval >=300 msec | 0 participants |
| PF-06291874 5 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | PR interval increase ≥25%/50% | 0 participants |
| PF-06291874 5 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QTcF interval >=500 msec | 0 participants |
| PF-06291874 5 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QTcF increase >=60 msec | 0 participants |
| PF-06291874 5 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QRS interval increase >=50% | 0 participants |
| PF-06291874 5 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QRS interval >=140 msec | 0 participants |
| PF-06291874 5 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QTcF increase 30-60 msec | 0 participants |
| PF-06291874 5 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QT interval >=500 msec | 0 participants |
| PF-06291874 5 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QTcF interval 450-480 msec | 0 participants |
| PF-06291874 5 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QTcF interval 480-500 msec | 0 participants |
| PF-06291874 15 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | PR interval increase ≥25%/50% | 0 participants |
| PF-06291874 15 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QT interval >=500 msec | 0 participants |
| PF-06291874 15 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QRS interval increase >=50% | 0 participants |
| PF-06291874 15 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QTcF interval 480-500 msec | 0 participants |
| PF-06291874 15 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QTcF interval 450-480 msec | 1 participants |
| PF-06291874 15 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QRS interval >=140 msec | 0 participants |
| PF-06291874 15 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QTcF increase >=60 msec | 0 participants |
| PF-06291874 15 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QTcF interval >=500 msec | 0 participants |
| PF-06291874 15 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QTcF increase 30-60 msec | 1 participants |
| PF-06291874 15 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | PR interval >=300 msec | 0 participants |
| PF-06291874 50 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QTcF interval 480-500 msec | 0 participants |
| PF-06291874 50 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QT interval >=500 msec | 0 participants |
| PF-06291874 50 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QTcF increase 30-60 msec | 1 participants |
| PF-06291874 50 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | PR interval >=300 msec | 0 participants |
| PF-06291874 50 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QRS interval >=140 msec | 0 participants |
| PF-06291874 50 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QTcF interval 450-480 msec | 0 participants |
| PF-06291874 50 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QTcF interval >=500 msec | 0 participants |
| PF-06291874 50 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | PR interval increase ≥25%/50% | 1 participants |
| PF-06291874 50 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QRS interval increase >=50% | 0 participants |
| PF-06291874 50 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QTcF increase >=60 msec | 0 participants |
| PF-06291874 100 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QTcF interval 480-500 msec | 0 participants |
| PF-06291874 100 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | PR interval increase ≥25%/50% | 0 participants |
| PF-06291874 100 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QTcF interval 450-480 msec | 0 participants |
| PF-06291874 100 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QTcF increase >=60 msec | 0 participants |
| PF-06291874 100 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QRS interval increase >=50% | 0 participants |
| PF-06291874 100 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QRS interval >=140 msec | 0 participants |
| PF-06291874 100 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QTcF increase 30-60 msec | 0 participants |
| PF-06291874 100 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | PR interval >=300 msec | 0 participants |
| PF-06291874 100 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QTcF interval >=500 msec | 0 participants |
| PF-06291874 100 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QT interval >=500 msec | 0 participants |
| PF-06291874 150 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QTcF interval 480-500 msec | 0 participants |
| PF-06291874 150 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QTcF increase >=60 msec | 0 participants |
| PF-06291874 150 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | PR interval >=300 msec | 0 participants |
| PF-06291874 150 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | PR interval increase ≥25%/50% | 0 participants |
| PF-06291874 150 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QTcF interval 450-480 msec | 1 participants |
| PF-06291874 150 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QT interval >=500 msec | 0 participants |
| PF-06291874 150 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QTcF increase 30-60 msec | 0 participants |
| PF-06291874 150 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QTcF interval >=500 msec | 0 participants |
| PF-06291874 150 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QRS interval increase >=50% | 0 participants |
| PF-06291874 150 mg | Number of Participants With Electrocardiograms (ECGs) Data Met Criteria of Potential Clinical Concern - Part A | QRS interval >=140 msec | 0 participants |
Primary
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.
Population: The Safety Analysis Set was defined as all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Increase:supine SBP≥30 mm Hg | 0 participants |
| Placebo | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Supine pulse rate >120 bpm | 3 participants |
| Placebo | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Increase:supine DBP≥20 mm Hg | 3 participants |
| Placebo | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Decrease:supine SBP≥30 mm Hg | 2 participants |
| Placebo | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Supine SBP <90 mm Hg | 1 participants |
| Placebo | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Decrease:supine DBP≥20 mm Hg | 1 participants |
| Placebo | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Supine DBP <50 mm Hg | 0 participants |
| Placebo | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Supine pulse rate <40 bpm | 0 participants |
| PF-06291874 5 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Decrease:supine DBP≥20 mm Hg | 3 participants |
| PF-06291874 5 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Increase:supine SBP≥30 mm Hg | 0 participants |
| PF-06291874 5 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Supine SBP <90 mm Hg | 0 participants |
| PF-06291874 5 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Decrease:supine SBP≥30 mm Hg | 1 participants |
| PF-06291874 5 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Supine DBP <50 mm Hg | 0 participants |
| PF-06291874 5 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Supine pulse rate >120 bpm | 2 participants |
| PF-06291874 5 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Increase:supine DBP≥20 mm Hg | 0 participants |
| PF-06291874 5 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Supine pulse rate <40 bpm | 0 participants |
| PF-06291874 15 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Supine pulse rate <40 bpm | 0 participants |
| PF-06291874 15 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Increase:supine SBP≥30 mm Hg | 1 participants |
| PF-06291874 15 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Decrease:supine SBP≥30 mm Hg | 0 participants |
| PF-06291874 15 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Supine SBP <90 mm Hg | 0 participants |
| PF-06291874 15 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Decrease:supine DBP≥20 mm Hg | 1 participants |
| PF-06291874 15 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Increase:supine DBP≥20 mm Hg | 0 participants |
| PF-06291874 15 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Supine pulse rate >120 bpm | 1 participants |
| PF-06291874 15 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Supine DBP <50 mm Hg | 0 participants |
| PF-06291874 50 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Supine SBP <90 mm Hg | 0 participants |
| PF-06291874 50 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Decrease:supine DBP≥20 mm Hg | 2 participants |
| PF-06291874 50 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Supine DBP <50 mm Hg | 0 participants |
| PF-06291874 50 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Supine pulse rate <40 bpm | 0 participants |
| PF-06291874 50 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Increase:supine SBP≥30 mm Hg | 0 participants |
| PF-06291874 50 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Increase:supine DBP≥20 mm Hg | 0 participants |
| PF-06291874 50 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Decrease:supine SBP≥30 mm Hg | 0 participants |
| PF-06291874 50 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Supine pulse rate >120 bpm | 3 participants |
| PF-06291874 100 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Decrease:supine DBP≥20 mm Hg | 0 participants |
| PF-06291874 100 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Supine DBP <50 mm Hg | 0 participants |
| PF-06291874 100 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Supine pulse rate >120 bpm | 1 participants |
| PF-06291874 100 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Decrease:supine SBP≥30 mm Hg | 0 participants |
| PF-06291874 100 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Supine SBP <90 mm Hg | 1 participants |
| PF-06291874 100 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Increase:supine DBP≥20 mm Hg | 7 participants |
| PF-06291874 100 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Increase:supine SBP≥30 mm Hg | 0 participants |
| PF-06291874 100 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Supine pulse rate <40 bpm | 0 participants |
| PF-06291874 150 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Supine pulse rate <40 bpm | 0 participants |
| PF-06291874 150 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Decrease:supine SBP≥30 mm Hg | 0 participants |
| PF-06291874 150 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Supine SBP <90 mm Hg | 0 participants |
| PF-06291874 150 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Decrease:supine DBP≥20 mm Hg | 0 participants |
| PF-06291874 150 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Increase:supine DBP≥20 mm Hg | 2 participants |
| PF-06291874 150 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Supine DBP <50 mm Hg | 0 participants |
| PF-06291874 150 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Increase:supine SBP≥30 mm Hg | 0 participants |
| PF-06291874 150 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part A | Supine pulse rate >120 bpm | 0 participants |
Primary
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.
Population: The Safety Analysis Set was defined as all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part B | Supine DBP <50 mm Hg | 0 participants |
| Placebo | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part B | Supine pulse rate <40 bpm | 0 participants |
| Placebo | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part B | Increase:supine DBP≥20 mm Hg | 2 participants |
| Placebo | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part B | Supine SBP <90 mm Hg | 1 participants |
| Placebo | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part B | Increase:supine SBP≥30 mm Hg | 0 participants |
| Placebo | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part B | Decrease:supine SBP≥30 mm Hg | 3 participants |
| Placebo | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part B | Supine pulse rate >120 bpm | 0 participants |
| Placebo | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part B | Decrease:supine DBP≥20 mm Hg | 0 participants |
| PF-06291874 5 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part B | Supine SBP <90 mm Hg | 0 participants |
| PF-06291874 5 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part B | Decrease:supine DBP≥20 mm Hg | 1 participants |
| PF-06291874 5 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part B | Increase:supine DBP≥20 mm Hg | 0 participants |
| PF-06291874 5 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part B | Supine DBP <50 mm Hg | 0 participants |
| PF-06291874 5 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part B | Supine pulse rate >120 bpm | 1 participants |
| PF-06291874 5 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part B | Supine pulse rate <40 bpm | 0 participants |
| PF-06291874 5 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part B | Increase:supine SBP≥30 mm Hg | 0 participants |
| PF-06291874 5 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part B | Decrease:supine SBP≥30 mm Hg | 0 participants |
| PF-06291874 15 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part B | Increase:supine DBP≥20 mm Hg | 3 participants |
| PF-06291874 15 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part B | Supine SBP <90 mm Hg | 0 participants |
| PF-06291874 15 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part B | Supine DBP <50 mm Hg | 1 participants |
| PF-06291874 15 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part B | Supine pulse rate <40 bpm | 0 participants |
| PF-06291874 15 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part B | Decrease:supine SBP≥30 mm Hg | 2 participants |
| PF-06291874 15 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part B | Decrease:supine DBP≥20 mm Hg | 0 participants |
| PF-06291874 15 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part B | Supine pulse rate >120 bpm | 0 participants |
| PF-06291874 15 mg | Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern - Part B | Increase:supine SBP≥30 mm Hg | 0 participants |
Primary
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
Population: This PK Parameter Analysis Set was defined as all participants randomized and treated who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 | 2181 ng.hr/mL | Geometric Coefficient of Variation 27 |
| PF-06291874 5 mg | 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 | 6821 ng.hr/mL | Geometric Coefficient of Variation 20 |
| PF-06291874 15 mg | 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 | 20650 ng.hr/mL | Geometric Coefficient of Variation 27 |
| PF-06291874 50 mg | 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 | 43040 ng.hr/mL | Geometric Coefficient of Variation 20 |
| PF-06291874 100 mg | 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 | 51860 ng.hr/mL | Geometric Coefficient of Variation 34 |
Primary
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
Population: This PK Parameter Analysis Set was defined as all participants randomized and treated who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Single Dose AUCtau for PF-06291874 - Part B | 6486 ng.hr/mL | Geometric Coefficient of Variation 14 |
| PF-06291874 5 mg | Single Dose AUCtau for PF-06291874 - Part B | 11280 ng.hr/mL | Geometric Coefficient of Variation 35 |
Primary
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
Population: This PK Parameter Analysis Set was defined as all participants randomized and treated who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Single Dose Cmax for PF-06291874 - Part B | 373.6 ng/mL | Geometric Coefficient of Variation 16 |
| PF-06291874 5 mg | Single Dose Cmax for PF-06291874 - Part B | 687.6 ng/mL | Geometric Coefficient of Variation 34 |
Primary
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
Population: This PK Parameter Analysis Set was defined as all participants randomized and treated who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Single Dose Maximum Plasma Concentration (Cmax) for PF-06291874 - Part A | 137.0 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 17 |
| PF-06291874 5 mg | Single Dose Maximum Plasma Concentration (Cmax) for PF-06291874 - Part A | 427.1 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 22 |
| PF-06291874 15 mg | Single Dose Maximum Plasma Concentration (Cmax) for PF-06291874 - Part A | 1308 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 26 |
| PF-06291874 50 mg | Single Dose Maximum Plasma Concentration (Cmax) for PF-06291874 - Part A | 2582 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 19 |
| PF-06291874 100 mg | Single Dose Maximum Plasma Concentration (Cmax) for PF-06291874 - Part A | 3288 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 32 |
Primary
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
Population: This PK Parameter Analysis Set was defined as all participants randomized and treated who had at least 1 of the PK parameters of interest
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Single Dose Normalized Cmax (Cmax[dn]) for PF-06291874 - Part A | 27.40 ng/mL/mg | Geometric Coefficient of Variation 17 |
| PF-06291874 5 mg | Single Dose Normalized Cmax (Cmax[dn]) for PF-06291874 - Part A | 28.46 ng/mL/mg | Geometric Coefficient of Variation 22 |
| PF-06291874 15 mg | Single Dose Normalized Cmax (Cmax[dn]) for PF-06291874 - Part A | 26.15 ng/mL/mg | Geometric Coefficient of Variation 26 |
| PF-06291874 50 mg | Single Dose Normalized Cmax (Cmax[dn]) for PF-06291874 - Part A | 25.82 ng/mL/mg | Geometric Coefficient of Variation 19 |
| PF-06291874 100 mg | Single Dose Normalized Cmax (Cmax[dn]) for PF-06291874 - Part A | 21.90 ng/mL/mg | Geometric Coefficient of Variation 32 |
Primary
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
Population: This PK Parameter Analysis Set was defined as all participants randomized and treated who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Single Dose Normalized Cmax (Cmax[dn]) for PF-06291874 - Part B | 24.90 ng/mL/mg | Geometric Coefficient of Variation 16 |
| PF-06291874 5 mg | Single Dose Normalized Cmax (Cmax[dn]) for PF-06291874 - Part B | 22.92 ng/mL/mg | Geometric Coefficient of Variation 34 |
Primary
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
Population: This PK Parameter Analysis Set was defined as all participants randomized and treated who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Placebo | Single Dose Time at Which Cmax Occurred (Tmax) for PF-06291874 - Part A | 6.00 hr | Full Range 17 |
| PF-06291874 5 mg | Single Dose Time at Which Cmax Occurred (Tmax) for PF-06291874 - Part A | 5.00 hr | Full Range 22 |
| PF-06291874 15 mg | Single Dose Time at Which Cmax Occurred (Tmax) for PF-06291874 - Part A | 6.00 hr | Full Range 26 |
| PF-06291874 50 mg | Single Dose Time at Which Cmax Occurred (Tmax) for PF-06291874 - Part A | 6.07 hr | Full Range 19 |
| PF-06291874 100 mg | Single Dose Time at Which Cmax Occurred (Tmax) for PF-06291874 - Part A | 4.00 hr | Full Range 32 |
Primary
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
Population: This PK Parameter Analysis Set was defined as all participants randomized and treated who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Placebo | Single Dose Tmax for PF-06291874 - Part B | 6.02 hr | Full Range 16 |
| PF-06291874 5 mg | Single Dose Tmax for PF-06291874 - Part B | 6.00 hr | Full Range 34 |
Secondary
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
Population: All subjects administered PF-06291874 or placebo were included in PD analysis. Placebo subjects within each cohort in Part A or B were pooled into a single placebo group for the inpatient portion of the study. Data collected from placebo subjects during the outpatient portion of study (Day 28) were also pooled separately for Parts A and B.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 21 changes from baseline | 1.1 mg/dL | Standard Deviation 30.57 |
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 14 absolute value | 150.9 mg/dL | Standard Deviation 33.95 |
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 7 changes from baseline | -5.4 mg/dL | Standard Deviation 18.14 |
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 28 absolute value | 163.7 mg/dL | Standard Deviation 26.9 |
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 15 changes from baseline | -10.4 mg/dL | Standard Deviation 27.51 |
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 28 changes from baseline | 3.6 mg/dL | Standard Deviation 22.52 |
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 29 absolute value | 166.5 mg/dL | Standard Deviation 31.56 |
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 29 changes from baseline | 6.4 mg/dL | Standard Deviation 21.17 |
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Baseline | 165.8 mg/dL | Standard Deviation 31.61 |
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 15 absolute value | 155.4 mg/dL | Standard Deviation 33.08 |
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 2 absolute value | 167.0 mg/dL | Standard Deviation 35.06 |
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 21 absolute value | 161.2 mg/dL | Standard Deviation 38.22 |
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 14 changes from baseline | -14.8 mg/dL | Standard Deviation 29.96 |
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 2 changes from baseline | 1.2 mg/dL | Standard Deviation 16.6 |
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 7 absolute value | 161.4 mg/dL | Standard Deviation 33.3 |
| PF-06291874 5 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Baseline | 163.6 mg/dL | Standard Deviation 32.43 |
| PF-06291874 5 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 2 absolute value | 158.7 mg/dL | Standard Deviation 32.08 |
| PF-06291874 5 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 7 changes from baseline | -9.1 mg/dL | Standard Deviation 22.57 |
| PF-06291874 5 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 15 changes from baseline | -16.2 mg/dL | Standard Deviation 21.64 |
| PF-06291874 5 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 14 absolute value | 144.4 mg/dL | Standard Deviation 33.67 |
| PF-06291874 5 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 14 changes from baseline | -19.2 mg/dL | Standard Deviation 21.45 |
| PF-06291874 5 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 7 absolute value | 154.5 mg/dL | Standard Deviation 32.07 |
| PF-06291874 5 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 2 changes from baseline | -4.9 mg/dL | Standard Deviation 14.37 |
| PF-06291874 5 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 15 absolute value | 150.9 mg/dL | Standard Deviation 37.64 |
| PF-06291874 15 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 2 changes from baseline | -20.8 mg/dL | Standard Deviation 13.54 |
| PF-06291874 15 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 15 changes from baseline | -41.5 mg/dL | Standard Deviation 33.08 |
| PF-06291874 15 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 14 changes from baseline | -39.8 mg/dL | Standard Deviation 34.07 |
| PF-06291874 15 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 14 absolute value | 133.3 mg/dL | Standard Deviation 39.57 |
| PF-06291874 15 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 15 absolute value | 131.6 mg/dL | Standard Deviation 25.96 |
| PF-06291874 15 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 7 changes from baseline | -25.2 mg/dL | Standard Deviation 25.83 |
| PF-06291874 15 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 2 absolute value | 152.3 mg/dL | Standard Deviation 31.59 |
| PF-06291874 15 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 7 absolute value | 147.9 mg/dL | Standard Deviation 27.04 |
| PF-06291874 15 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Baseline | 173.1 mg/dL | Standard Deviation 38.28 |
| PF-06291874 50 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 15 absolute value | 132.7 mg/dL | Standard Deviation 31.67 |
| PF-06291874 50 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Baseline | 173.9 mg/dL | Standard Deviation 45.67 |
| PF-06291874 50 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 2 absolute value | 150.0 mg/dL | Standard Deviation 31.71 |
| PF-06291874 50 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 2 changes from baseline | -23.9 mg/dL | Standard Deviation 23.36 |
| PF-06291874 50 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 7 absolute value | 138.5 mg/dL | Standard Deviation 33.56 |
| PF-06291874 50 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 7 changes from baseline | -37.4 mg/dL | Standard Deviation 25.1 |
| PF-06291874 50 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 14 absolute value | 131.5 mg/dL | Standard Deviation 28.68 |
| PF-06291874 50 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 14 changes from baseline | -42.4 mg/dL | Standard Deviation 29.56 |
| PF-06291874 50 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 15 changes from baseline | -44.2 mg/dL | Standard Deviation 33.1 |
| PF-06291874 100 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 7 absolute value | 122.5 mg/dL | Standard Deviation 16.38 |
| PF-06291874 100 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Baseline | 150.6 mg/dL | Standard Deviation 29.45 |
| PF-06291874 100 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 29 changes from baseline | -24.2 mg/dL | Standard Deviation 21.52 |
| PF-06291874 100 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 29 absolute value | 129.6 mg/dL | Standard Deviation 23.47 |
| PF-06291874 100 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 28 changes from baseline | -28.2 mg/dL | Standard Deviation 15.99 |
| PF-06291874 100 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 15 absolute value | 120.4 mg/dL | Standard Deviation 22.15 |
| PF-06291874 100 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 28 absolute value | 122.4 mg/dL | Standard Deviation 20.54 |
| PF-06291874 100 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 21 changes from baseline | -24.2 mg/dL | Standard Deviation 31.4 |
| PF-06291874 100 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 21 absolute value | 128.5 mg/dL | Standard Deviation 26.19 |
| PF-06291874 100 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 7 changes from baseline | -35.6 mg/dL | Standard Deviation 21.67 |
| PF-06291874 100 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 2 changes from baseline | -14.4 mg/dL | Standard Deviation 32.29 |
| PF-06291874 100 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 14 absolute value | 112.9 mg/dL | Standard Deviation 17.54 |
| PF-06291874 100 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 2 absolute value | 139.4 mg/dL | Standard Deviation 42.05 |
| PF-06291874 100 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 15 changes from baseline | -33.4 mg/dL | Standard Deviation 24.46 |
| PF-06291874 100 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 14 changes from baseline | -37.7 mg/dL | Standard Deviation 19.46 |
| PF-06291874 150 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 2 changes from baseline | -35.3 mg/dL | Standard Deviation 14.64 |
| PF-06291874 150 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 15 absolute value | 122.7 mg/dL | Standard Deviation 30.61 |
| PF-06291874 150 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 15 changes from baseline | -47.7 mg/dL | Standard Deviation 19.31 |
| PF-06291874 150 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 14 changes from baseline | -49.1 mg/dL | Standard Deviation 18.29 |
| PF-06291874 150 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 14 absolute value | 121.3 mg/dL | Standard Deviation 30.03 |
| PF-06291874 150 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 2 absolute value | 135.1 mg/dL | Standard Deviation 31.46 |
| PF-06291874 150 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 7 absolute value | 116.5 mg/dL | Standard Deviation 21.59 |
| PF-06291874 150 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Baseline | 170.4 mg/dL | Standard Deviation 41.86 |
| PF-06291874 150 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at at Days 2, 7, 14, 15, 21, 28 and 29 - Part A | Day 7 changes from baseline | -38.4 mg/dL | Standard Deviation 15.37 |
Secondary
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
Population: All subjects administered PF-06291874 or placebo were included in PD analysis. Placebo subjects within each cohort in Part A or B were pooled into a single placebo group for the inpatient portion of the study. Data collected from placebo subjects during the outpatient portion of study (Day 28) were also pooled separately for Parts A and B.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Day 14 absolute value | 118.3 mg/dL | Standard Deviation 40.08 |
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Day 2 changes from baseline | -11.8 mg/dL | Standard Deviation 10.79 |
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Day 21 absolute value | 136.9 mg/dL | Standard Deviation 34.54 |
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Day 14 changes from baseline | -31.0 mg/dL | Standard Deviation 35.02 |
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Baseline | 156.0 mg/dL | Standard Deviation 37.72 |
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Day 15 changes from baseline | -24.6 mg/dL | Standard Deviation 33.01 |
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Day 15 absolute value | 124.7 mg/dL | Standard Deviation 37.44 |
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Day 2 absolute value | 133.9 mg/dL | Standard Deviation 26.73 |
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Day 28 changes from baseline | -16.4 mg/dL | Standard Deviation 33.19 |
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Day 7 absolute value | 125.9 mg/dL | Standard Deviation 32.13 |
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Day 29 changes from baseline | -12.8 mg/dL | Standard Deviation 11.53 |
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Day 28 absolute value | 124.3 mg/dL | Standard Deviation 21.84 |
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Day 7 changes from baseline | -23.0 mg/dL | Standard Deviation 25.32 |
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Day 29 absolute value | 127.9 mg/dL | Standard Deviation 15.87 |
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Day 21 changes from baseline | -3.8 mg/dL | Standard Deviation 26.23 |
| PF-06291874 5 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Day 14 changes from baseline | -35.3 mg/dL | Standard Deviation 18.32 |
| PF-06291874 5 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Baseline | 163.9 mg/dL | Standard Deviation 31.43 |
| PF-06291874 5 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Day 2 absolute value | 147.6 mg/dL | Standard Deviation 32.25 |
| PF-06291874 5 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Day 2 changes from baseline | -16.3 mg/dL | Standard Deviation 9.05 |
| PF-06291874 5 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Day 7 absolute value | 134.4 mg/dL | Standard Deviation 32.15 |
| PF-06291874 5 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Day 7 changes from baseline | -29.5 mg/dL | Standard Deviation 15.47 |
| PF-06291874 5 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Day 14 absolute value | 128.6 mg/dL | Standard Deviation 36.04 |
| PF-06291874 5 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Day 15 absolute value | 133.4 mg/dL | Standard Deviation 36.28 |
| PF-06291874 5 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Day 15 changes from baseline | -30.5 mg/dL | Standard Deviation 19.31 |
| PF-06291874 15 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Day 14 changes from baseline | -45.3 mg/dL | Standard Deviation 32.4 |
| PF-06291874 15 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Day 29 changes from baseline | -26.1 mg/dL | Standard Deviation 28.74 |
| PF-06291874 15 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Day 15 changes from baseline | -38.8 mg/dL | Standard Deviation 33.39 |
| PF-06291874 15 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Day 14 absolute value | 108.9 mg/dL | Standard Deviation 24.64 |
| PF-06291874 15 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Day 21 absolute value | 131.5 mg/dL | Standard Deviation 34.2 |
| PF-06291874 15 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Day 7 changes from baseline | -41.6 mg/dL | Standard Deviation 36.31 |
| PF-06291874 15 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Day 21 changes from baseline | -18.3 mg/dL | Standard Deviation 37.27 |
| PF-06291874 15 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Day 7 absolute value | 114.4 mg/dL | Standard Deviation 20.67 |
| PF-06291874 15 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Day 28 absolute value | 113.3 mg/dL | Standard Deviation 34.71 |
| PF-06291874 15 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Day 2 changes from baseline | -29.7 mg/dL | Standard Deviation 18.11 |
| PF-06291874 15 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Day 28 changes from baseline | -41.0 mg/dL | Standard Deviation 44.01 |
| PF-06291874 15 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Day 2 absolute value | 129.7 mg/dL | Standard Deviation 28.13 |
| PF-06291874 15 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Day 29 absolute value | 127.5 mg/dL | Standard Deviation 28.8 |
| PF-06291874 15 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Baseline | 154.3 mg/dL | Standard Deviation 38.79 |
| PF-06291874 15 mg | Absolute Values and Changes From Baseline in Fasting Plasma Glucose at Days 2, 7, 14, 15, 21, 28 and 29 - Part B | Day 15 absolute value | 115.4 mg/dL | Standard Deviation 32.53 |
Secondary
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
Population: All subjects administered PF-06291874 or placebo were included in PD analysis. Placebo subjects within each cohort in Part A or B were pooled into a single placebo group for the inpatient portion of the study. Data collected from placebo subjects during the outpatient portion of study (Day 28) were also pooled separately for Parts A and B.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part A | Baseline | 7.82 µIU/mL | Standard Deviation 3.26 |
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part A | Day 14 absolute value | 6.93 µIU/mL | Standard Deviation 3.91 |
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part A | Day 28 changes from baseline | -0.82 µIU/mL | Standard Deviation 4.35 |
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part A | Day 28 absolute value | 8.53 µIU/mL | Standard Deviation 4.2 |
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part A | Day 14 changes from baseline | -0.88 µIU/mL | Standard Deviation 2.81 |
| PF-06291874 5 mg | Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part A | Day 14 changes from baseline | 0.00 µIU/mL | Standard Deviation 3.86 |
| PF-06291874 5 mg | Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part A | Baseline | 9.84 µIU/mL | Standard Deviation 5.12 |
| PF-06291874 5 mg | Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part A | Day 14 absolute value | 9.83 µIU/mL | Standard Deviation 4.01 |
| PF-06291874 15 mg | Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part A | Day 14 absolute value | 10.33 µIU/mL | Standard Deviation 4.96 |
| PF-06291874 15 mg | Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part A | Baseline | 11.04 µIU/mL | Standard Deviation 6.06 |
| PF-06291874 15 mg | Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part A | Day 14 changes from baseline | -0.37 µIU/mL | Standard Deviation 3.46 |
| PF-06291874 50 mg | Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part A | Day 14 absolute value | 5.61 µIU/mL | Standard Deviation 2.72 |
| PF-06291874 50 mg | Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part A | Baseline | 7.34 µIU/mL | Standard Deviation 3.6 |
| PF-06291874 50 mg | Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part A | Day 14 changes from baseline | -1.73 µIU/mL | Standard Deviation 1.52 |
| PF-06291874 100 mg | Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part A | Day 28 changes from baseline | -1.46 µIU/mL | Standard Deviation 3.2 |
| PF-06291874 100 mg | Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part A | Baseline | 10.77 µIU/mL | Standard Deviation 6.62 |
| PF-06291874 100 mg | Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part A | Day 14 absolute value | 9.09 µIU/mL | Standard Deviation 4.27 |
| PF-06291874 100 mg | Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part A | Day 14 changes from baseline | -1.68 µIU/mL | Standard Deviation 3.43 |
| PF-06291874 100 mg | Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part A | Day 28 absolute value | 9.30 µIU/mL | Standard Deviation 3.43 |
| PF-06291874 150 mg | Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part A | Baseline | 9.64 µIU/mL | Standard Deviation 5.61 |
| PF-06291874 150 mg | Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part A | Day 14 absolute value | 8.98 µIU/mL | Standard Deviation 5.02 |
| PF-06291874 150 mg | Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part A | Day 14 changes from baseline | -0.66 µIU/mL | Standard Deviation 2.72 |
Secondary
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
Population: All subjects administered PF-06291874 or placebo were included in PD analysis. Placebo subjects within each cohort in Part A or B were pooled into a single placebo group for the inpatient portion of the study. Data collected from placebo subjects during the outpatient portion of study (Day 28) were also pooled separately for Parts A and B.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part B | Baseline | 8.66 µIU/mL | Standard Deviation 2.59 |
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part B | Day 14 absolute value | 8.08 µIU/mL | Standard Deviation 3.81 |
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part B | Day 14 changes from baseline | -0.49 µIU/mL | Standard Deviation 2.96 |
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part B | Day 28 absolute value | 7.96 µIU/mL | Standard Deviation 3.58 |
| Placebo | Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part B | Day 28 changes from baseline | -0.44 µIU/mL | Standard Deviation 2.92 |
| PF-06291874 5 mg | Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part B | Day 14 absolute value | 12.57 µIU/mL | Standard Deviation 8.63 |
| PF-06291874 5 mg | Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part B | Day 14 changes from baseline | -1.13 µIU/mL | Standard Deviation 1.75 |
| PF-06291874 5 mg | Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part B | Baseline | 14.49 µIU/mL | Standard Deviation 9.7 |
| PF-06291874 15 mg | Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part B | Day 14 changes from baseline | -0.25 µIU/mL | Standard Deviation 4.07 |
| PF-06291874 15 mg | Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part B | Day 14 absolute value | 9.82 µIU/mL | Standard Deviation 4.18 |
| PF-06291874 15 mg | Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part B | Baseline | 9.69 µIU/mL | Standard Deviation 4.94 |
| PF-06291874 15 mg | Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part B | Day 28 absolute value | 10.43 µIU/mL | Standard Deviation 4.5 |
| PF-06291874 15 mg | Absolute Values and Changes From Baseline in Fasting Plasma Insulin at Days 14 and 28 - Part B | Day 28 changes from baseline | 1.41 µIU/mL | Standard Deviation 4.52 |
Secondary
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.
Population: All subjects administered PF-06291874 or placebo were included in PD analysis. Placebo subjects within each cohort in Part A or B were pooled into a single placebo group for the inpatient portion of the study. Data collected from placebo subjects during the outpatient portion of study (Day 28) were also pooled separately for Parts A and B.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Changes Relative to Baseline (Ratio) of AUC0-4 for C-Peptide Following MMTT on Day 14 - Part A | 0.96 ratio |
| PF-06291874 5 mg | Changes Relative to Baseline (Ratio) of AUC0-4 for C-Peptide Following MMTT on Day 14 - Part A | 1.01 ratio |
| PF-06291874 15 mg | Changes Relative to Baseline (Ratio) of AUC0-4 for C-Peptide Following MMTT on Day 14 - Part A | 0.94 ratio |
| PF-06291874 50 mg | Changes Relative to Baseline (Ratio) of AUC0-4 for C-Peptide Following MMTT on Day 14 - Part A | 0.89 ratio |
| PF-06291874 100 mg | Changes Relative to Baseline (Ratio) of AUC0-4 for C-Peptide Following MMTT on Day 14 - Part A | 0.95 ratio |
| PF-06291874 150 mg | Changes Relative to Baseline (Ratio) of AUC0-4 for C-Peptide Following MMTT on Day 14 - Part A | 1.03 ratio |
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: 0.96790% CI: [0.88, 1.13]ANCOVA
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: 0.31990% CI: [0.95, 1.23]ANCOVA
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: 0.457990% CI: [0.93, 1.2]ANCOVA
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: 0.814490% CI: [0.87, 1.11]ANCOVA
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: 0.342590% CI: [0.81, 1.06]ANCOVA
Secondary
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.
Population: All subjects administered PF-06291874 or placebo were included in PD analysis. Placebo subjects within each cohort in Part A or B were pooled into a single placebo group for the inpatient portion of the study. Data collected from placebo subjects during the outpatient portion of study (Day 28) were also pooled separately for Parts A and B.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Changes Relative to Baseline (Ratio) of AUC0-4 for C-Peptide Following MMTT on Day 14 - Part B | 1.19 Ratio | 90% Confidence Interval 32 |
| PF-06291874 5 mg | Changes Relative to Baseline (Ratio) of AUC0-4 for C-Peptide Following MMTT on Day 14 - Part B | 1.13 Ratio | 90% Confidence Interval 217 |
| PF-06291874 15 mg | Changes Relative to Baseline (Ratio) of AUC0-4 for C-Peptide Following MMTT on Day 14 - Part B | 1.05 Ratio | — |
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: 0.161790% CI: [0.98, 1.32]ANCOVA
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: 0.370390% CI: [0.94, 1.23]ANCOVA
Secondary
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.
Population: All subjects administered PF-06291874 or placebo were included in PD analysis. Placebo subjects within each cohort in Part A or B were pooled into a single placebo group for the inpatient portion of the study. Data collected from placebo subjects during the outpatient portion of study (Day 28) were also pooled separately for Parts A and B.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Changes Relative to Baseline (Ratio) of AUC0-4 for C-Peptide Following MMTT on Day 28 | 0.95 Ratio | 90% Confidence Interval 58 |
| PF-06291874 5 mg | Changes Relative to Baseline (Ratio) of AUC0-4 for C-Peptide Following MMTT on Day 28 | 0.91 Ratio | 90% Confidence Interval 28 |
| PF-06291874 15 mg | Changes Relative to Baseline (Ratio) of AUC0-4 for C-Peptide Following MMTT on Day 28 | 0.79 Ratio | 90% Confidence Interval 38 |
| PF-06291874 50 mg | Changes Relative to Baseline (Ratio) of AUC0-4 for C-Peptide Following MMTT on Day 28 | 0.93 Ratio | 90% Confidence Interval 178 |
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: 0.683390% CI: [0.79, 1.15]ANCOVA
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: 0.131890% CI: [0.98, 1.41]ANCOVA
Secondary
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.
Population: All subjects administered PF-06291874 or placebo were included in PD analysis. Placebo subjects within each cohort in Part A or B were pooled into a single placebo group for the inpatient portion of the study. Data collected from placebo subjects during the outpatient portion of study (Day 28) were also pooled separately for Parts A and B.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Changes Relative to Baseline (Ratio) of AUC0-4 for Glucose Following MMTT on Day 14 - Part A | 0.88 ratio |
| PF-06291874 5 mg | Changes Relative to Baseline (Ratio) of AUC0-4 for Glucose Following MMTT on Day 14 - Part A | 0.87 ratio |
| PF-06291874 15 mg | Changes Relative to Baseline (Ratio) of AUC0-4 for Glucose Following MMTT on Day 14 - Part A | 0.75 ratio |
| PF-06291874 50 mg | Changes Relative to Baseline (Ratio) of AUC0-4 for Glucose Following MMTT on Day 14 - Part A | 0.74 ratio |
| PF-06291874 100 mg | Changes Relative to Baseline (Ratio) of AUC0-4 for Glucose Following MMTT on Day 14 - Part A | 0.72 ratio |
| PF-06291874 150 mg | Changes Relative to Baseline (Ratio) of AUC0-4 for Glucose Following MMTT on Day 14 - Part A | 0.67 ratio |
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: 0.85390% CI: [0.89, 1.1]ANCOVA
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: 0.017290% CI: [0.77, 0.95]ANCOVA
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: 0.010690% CI: [0.77, 0.94]ANCOVA
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: 0.001290% CI: [0.74, 0.9]ANCOVA
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: <0.000190% CI: [0.69, 0.85]ANCOVA
Secondary
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.
Population: All subjects administered PF-06291874 or placebo were included in PD analysis. Placebo subjects within each cohort in Part A or B were pooled into a single placebo group for the inpatient portion of the study. Data collected from placebo subjects during the outpatient portion of study (Day 28) were also pooled separately for Parts A and B.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Changes Relative to Baseline (Ratio) of AUC0-4 for Glucose Following MMTT on Day 14 - Part B | 0.81 ratio | 90% Confidence Interval 32 |
| PF-06291874 5 mg | Changes Relative to Baseline (Ratio) of AUC0-4 for Glucose Following MMTT on Day 14 - Part B | 0.74 ratio | 90% Confidence Interval 217 |
| PF-06291874 15 mg | Changes Relative to Baseline (Ratio) of AUC0-4 for Glucose Following MMTT on Day 14 - Part B | 0.83 ratio | — |
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: 0.780490% CI: [0.87, 1.1]ANCOVA
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: 0.090890% CI: [0.77, 1]ANCOVA
Secondary
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.
Population: All subjects administered PF-06291874 or placebo were included in PD analysis. Placebo subjects within each cohort in Part A or B were pooled into a single placebo group for the inpatient portion of the study. Data collected from placebo subjects during the outpatient portion of study (Day 28) were also pooled separately for Parts A and B.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Changes Relative to Baseline (Ratio) of AUC0-4 for Glucose Following MMTT on Day 28 | 1.02 ratio | 90% Confidence Interval 58 |
| PF-06291874 5 mg | Changes Relative to Baseline (Ratio) of AUC0-4 for Glucose Following MMTT on Day 28 | 0.79 ratio | 90% Confidence Interval 28 |
| PF-06291874 15 mg | Changes Relative to Baseline (Ratio) of AUC0-4 for Glucose Following MMTT on Day 28 | 0.89 ratio | 90% Confidence Interval 38 |
| PF-06291874 50 mg | Changes Relative to Baseline (Ratio) of AUC0-4 for Glucose Following MMTT on Day 28 | 0.78 ratio | 90% Confidence Interval 178 |
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: 0.002790% CI: [0.68, 0.88]ANCOVA
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: 0.090890% CI: [0.77, 1]ANCOVA
Secondary
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.
Population: All subjects administered PF-06291874 or placebo were included in PD analysis. Placebo subjects within each cohort in Part A or B were pooled into a single placebo group for the inpatient portion of the study. The number of participants analyzed was the number of participants contributing to the summary statistics.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Changes Relative to Baseline (Ratio) of AUC0-4 for Insulin Following MMTT on Day 14 - Part A | 1.02 ratio |
| PF-06291874 5 mg | Changes Relative to Baseline (Ratio) of AUC0-4 for Insulin Following MMTT on Day 14 - Part A | 1.01 ratio |
| PF-06291874 15 mg | Changes Relative to Baseline (Ratio) of AUC0-4 for Insulin Following MMTT on Day 14 - Part A | 0.95 ratio |
| PF-06291874 50 mg | Changes Relative to Baseline (Ratio) of AUC0-4 for Insulin Following MMTT on Day 14 - Part A | 0.85 ratio |
| PF-06291874 100 mg | Changes Relative to Baseline (Ratio) of AUC0-4 for Insulin Following MMTT on Day 14 - Part A | 0.91 ratio |
| PF-06291874 150 mg | Changes Relative to Baseline (Ratio) of AUC0-4 for Insulin Following MMTT on Day 14 - Part A | 1.00 ratio |
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: 0.872390% CI: [0.81, 1.19]ANCOVA
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: 0.515890% CI: [0.76, 1.13]ANCOVA
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: 0.125890% CI: [0.68, 1.01]ANCOVA
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: 0.288390% CI: [0.74, 1.07]ANCOVA
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: 0.843790% CI: [0.81, 1.18]ANCOVA
Secondary
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.
Population: All subjects administered PF-06291874 or placebo were included in PD analysis. Placebo subjects within each cohort in Part A or B were pooled into a single placebo group for the inpatient portion of the study. Data collected from placebo subjects during the outpatient portion of study (Day 28) were also pooled separately for Parts A and B.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Changes Relative to Baseline (Ratio) of AUC0-4 for Insulin Following MMTT on Day 14 - Part B | 1.13 Ratio | 90% Confidence Interval 32 |
| PF-06291874 5 mg | Changes Relative to Baseline (Ratio) of AUC0-4 for Insulin Following MMTT on Day 14 - Part B | 1.10 Ratio | 90% Confidence Interval 217 |
| PF-06291874 15 mg | Changes Relative to Baseline (Ratio) of AUC0-4 for Insulin Following MMTT on Day 14 - Part B | 1.01 Ratio | — |
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: 0.440590% CI: [0.88, 1.42]ANCOVA
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: 0.517890% CI: [0.87, 1.37]ANCOVA
Secondary
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.
Population: All subjects administered PF-06291874 or placebo were included in PD analysis. Placebo subjects within each cohort in Part A or B were pooled into a single placebo group for the inpatient portion of the study. Data collected from placebo subjects during the outpatient portion of study (Day 28) were also pooled separately for Parts A and B.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Changes Relative to Baseline (Ratio) of AUC0-4 for Insulin Following MMTT on Day 28 | 1.22 Ratio | 90% Confidence Interval 58 |
| PF-06291874 5 mg | Changes Relative to Baseline (Ratio) of AUC0-4 for Insulin Following MMTT on Day 28 | 0.85 Ratio | 90% Confidence Interval 28 |
| PF-06291874 15 mg | Changes Relative to Baseline (Ratio) of AUC0-4 for Insulin Following MMTT on Day 28 | 0.77 Ratio | 90% Confidence Interval 38 |
| PF-06291874 50 mg | Changes Relative to Baseline (Ratio) of AUC0-4 for Insulin Following MMTT on Day 28 | 0.93 Ratio | 90% Confidence Interval 178 |
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: 0.03490% CI: [0.52, 0.92]ANCOVA
Comparison: Placebo was the Reference and each of the active doses was the Test.p-value: 0.251990% CI: [0.92, 1.58]ANCOVA
Secondary
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
Population: All subjects administered PF-06291874 or placebo were included in PD analysis. Placebo subjects within each cohort in Part A or B were pooled into a single placebo group for the inpatient portion of the study. Data collected from placebo subjects during the outpatient portion of study (Day 28) were also pooled separately for Parts A and B.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | HDL Cholesterol -Day 14 Mean Percent Change | -5.4 percentage of change | Standard Deviation 5.6 |
| Placebo | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | LDL Cholesterol -Day28 Mean Percent Change | 1.8 percentage of change | Standard Deviation 16.8 |
| Placebo | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | ApoB100 -Day 28 Mean Percent Change | 0.7 percentage of change | Standard Deviation 12.6 |
| Placebo | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | HDL Cholesterol -Day28 Mean Percent Change | -4.3 percentage of change | Standard Deviation 8.5 |
| Placebo | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | Total Cholesterol-Day 14 Mean Percent Change | -8.6 percentage of change | Standard Deviation 6.7 |
| Placebo | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | Triglycerides -Day28 Mean Percent Change | 3.8 percentage of change | Standard Deviation 24.5 |
| Placebo | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | LDL Cholesterol -Day 14 Mean Percent Change | -9.6 percentage of change | Standard Deviation 12.6 |
| Placebo | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | ApoB100 -Day 14 Mean Percent Change | -7.2 percentage of change | Standard Deviation 6.8 |
| Placebo | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | Triglycerides -Day 14 Mean Percent Change | -13.9 percentage of change | Standard Deviation 15.2 |
| Placebo | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | Total Cholesterol-Day28 Mean Percent Change | 1.4 percentage of change | Standard Deviation 13 |
| PF-06291874 5 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | Triglycerides -Day 14 Mean Percent Change | 6.4 percentage of change | Standard Deviation 21.4 |
| PF-06291874 5 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | ApoB100 -Day 14 Mean Percent Change | -5.6 percentage of change | Standard Deviation 9.9 |
| PF-06291874 5 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | LDL Cholesterol -Day 14 Mean Percent Change | -9.4 percentage of change | Standard Deviation 10.8 |
| PF-06291874 5 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | Total Cholesterol-Day 14 Mean Percent Change | -5.6 percentage of change | Standard Deviation 6.6 |
| PF-06291874 5 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | HDL Cholesterol -Day 14 Mean Percent Change | -5.2 percentage of change | Standard Deviation 11.3 |
| PF-06291874 15 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | ApoB100 -Day 14 Mean Percent Change | -6.1 percentage of change | Standard Deviation 14.8 |
| PF-06291874 15 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | Triglycerides -Day 14 Mean Percent Change | 10.3 percentage of change | Standard Deviation 30.5 |
| PF-06291874 15 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | Total Cholesterol-Day 14 Mean Percent Change | -5.6 percentage of change | Standard Deviation 14.1 |
| PF-06291874 15 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | HDL Cholesterol -Day 14 Mean Percent Change | -6.5 percentage of change | Standard Deviation 9.9 |
| PF-06291874 15 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | LDL Cholesterol -Day 14 Mean Percent Change | -6.4 percentage of change | Standard Deviation 16.7 |
| PF-06291874 50 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | LDL Cholesterol -Day 14 Mean Percent Change | 2.0 percentage of change | Standard Deviation 17.9 |
| PF-06291874 50 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | HDL Cholesterol -Day 14 Mean Percent Change | -4.0 percentage of change | Standard Deviation 9.7 |
| PF-06291874 50 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | ApoB100 -Day 14 Mean Percent Change | 1.4 percentage of change | Standard Deviation 10.8 |
| PF-06291874 50 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | Total Cholesterol-Day 14 Mean Percent Change | 1.7 percentage of change | Standard Deviation 11.8 |
| PF-06291874 50 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | Triglycerides -Day 14 Mean Percent Change | 11.6 percentage of change | Standard Deviation 33.9 |
| PF-06291874 100 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | ApoB100 -Day 28 Mean Percent Change | 2.7 percentage of change | Standard Deviation 10 |
| PF-06291874 100 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | Total Cholesterol-Day 14 Mean Percent Change | 0.0 percentage of change | Standard Deviation 9.9 |
| PF-06291874 100 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | Total Cholesterol-Day28 Mean Percent Change | 4.3 percentage of change | Standard Deviation 13.3 |
| PF-06291874 100 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | LDL Cholesterol -Day 14 Mean Percent Change | -0.4 percentage of change | Standard Deviation 12.2 |
| PF-06291874 100 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | LDL Cholesterol -Day28 Mean Percent Change | 4.7 percentage of change | Standard Deviation 14 |
| PF-06291874 100 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | HDL Cholesterol -Day 14 Mean Percent Change | -1.5 percentage of change | Standard Deviation 8.4 |
| PF-06291874 100 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | HDL Cholesterol -Day28 Mean Percent Change | 0.2 percentage of change | Standard Deviation 10.7 |
| PF-06291874 100 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | Triglycerides -Day 14 Mean Percent Change | -0.2 percentage of change | Standard Deviation 23.9 |
| PF-06291874 100 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | Triglycerides -Day28 Mean Percent Change | 6.4 percentage of change | Standard Deviation 19.6 |
| PF-06291874 100 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | ApoB100 -Day 14 Mean Percent Change | -0.2 percentage of change | Standard Deviation 10.3 |
| PF-06291874 150 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | HDL Cholesterol -Day 14 Mean Percent Change | 2.6 percentage of change | Standard Deviation 12.7 |
| PF-06291874 150 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | Total Cholesterol-Day 14 Mean Percent Change | 9.7 percentage of change | Standard Deviation 10.3 |
| PF-06291874 150 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | ApoB100 -Day 14 Mean Percent Change | 9.0 percentage of change | Standard Deviation 11 |
| PF-06291874 150 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | LDL Cholesterol -Day 14 Mean Percent Change | 12.0 percentage of change | Standard Deviation 18.3 |
| PF-06291874 150 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part A | Triglycerides -Day 14 Mean Percent Change | 18.3 percentage of change | Standard Deviation 19.9 |
Secondary
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
Population: All subjects administered PF-06291874 or placebo were included in PD analysis. Placebo subjects within each cohort in Part A or B were pooled into a single placebo group for the inpatient portion of the study. Data collected from placebo subjects during the outpatient portion of study (Day 28) were also pooled separately for Parts A and B.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part B | HDL Cholesterol -Day 14 Mean Percent Change | -4.7 Percentage of change | Standard Deviation 12.9 |
| Placebo | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part B | LDL Cholesterol -Day28 Mean Percent Change | 15.7 Percentage of change | Standard Deviation 28.8 |
| Placebo | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part B | LDL Cholesterol -Day 14 Mean Percent Change | -5.5 Percentage of change | Standard Deviation 15.6 |
| Placebo | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part B | HDL Cholesterol -Day28 Mean Percent Change | 7.8 Percentage of change | Standard Deviation 13.6 |
| Placebo | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part B | Triglycerides -Day 14 Mean Percent Change | -18.6 Percentage of change | Standard Deviation 15.7 |
| Placebo | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part B | ApoB100 -Day 14 Mean Percent Change | -3.5 Percentage of change | Standard Deviation 12.4 |
| Placebo | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part B | Total Cholesterol-Day28 Mean Percent Change | 8.4 Percentage of change | Standard Deviation 25.3 |
| Placebo | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part B | Triglycerides -Day28 Mean Percent Change | 4.3 Percentage of change | Standard Deviation 60.9 |
| Placebo | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part B | ApoB100 -Day 28 Mean Percent Change | 12.7 Percentage of change | Standard Deviation 21.2 |
| Placebo | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part B | Total Cholesterol-Day 14 Mean Percent Change | -4.0 Percentage of change | Standard Deviation 12.6 |
| PF-06291874 5 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part B | LDL Cholesterol -Day 14 Mean Percent Change | 1.50 Percentage of change | Standard Deviation 21.5 |
| PF-06291874 5 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part B | Triglycerides -Day 14 Mean Percent Change | -6.0 Percentage of change | Standard Deviation 17.5 |
| PF-06291874 5 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part B | ApoB100 -Day 14 Mean Percent Change | -4.1 Percentage of change | Standard Deviation 10.3 |
| PF-06291874 5 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part B | Total Cholesterol-Day 14 Mean Percent Change | -0.6 Percentage of change | Standard Deviation 11.9 |
| PF-06291874 5 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part B | HDL Cholesterol -Day 14 Mean Percent Change | -5.8 Percentage of change | Standard Deviation 12.2 |
| PF-06291874 15 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part B | ApoB100 -Day 28 Mean Percent Change | -1.1 Percentage of change | Standard Deviation 4.5 |
| PF-06291874 15 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part B | Total Cholesterol-Day 14 Mean Percent Change | -4.7 Percentage of change | Standard Deviation 8.4 |
| PF-06291874 15 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part B | Total Cholesterol-Day28 Mean Percent Change | -1.5 Percentage of change | Standard Deviation 7.7 |
| PF-06291874 15 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part B | LDL Cholesterol -Day 14 Mean Percent Change | -7.5 Percentage of change | Standard Deviation 14.2 |
| PF-06291874 15 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part B | LDL Cholesterol -Day28 Mean Percent Change | -0.7 Percentage of change | Standard Deviation 10 |
| PF-06291874 15 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part B | HDL Cholesterol -Day 14 Mean Percent Change | -2.9 Percentage of change | Standard Deviation 10.6 |
| PF-06291874 15 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part B | HDL Cholesterol -Day28 Mean Percent Change | 1.7 Percentage of change | Standard Deviation 11.2 |
| PF-06291874 15 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part B | Triglycerides -Day 14 Mean Percent Change | -8.4 Percentage of change | Standard Deviation 20.5 |
| PF-06291874 15 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part B | Triglycerides -Day28 Mean Percent Change | -1.9 Percentage of change | Standard Deviation 23.7 |
| PF-06291874 15 mg | Percent Change From Baseline in Lipid Parameters (mg/dL) by Treatment Group on Days 14 and 28 - Part B | ApoB100 -Day 14 Mean Percent Change | -5.6 Percentage of change | Standard Deviation 10.7 |
Secondary
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.
Population: All subjects administered PF-06291874 or placebo were included in PD analysis. Placebo subjects within each cohort in Part A or B were pooled into a single placebo group for the inpatient portion of the study. Data collected from placebo subjects during the outpatient portion of study (Day 28) were also pooled separately for Parts A and B.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Changes From Baseline of AUC0-4 for Glucagon Following MMTT on Day 14 - Part A | 1.38 Percentage of change | Standard Deviation 20.396 |
| PF-06291874 5 mg | Percent Changes From Baseline of AUC0-4 for Glucagon Following MMTT on Day 14 - Part A | 12.17 Percentage of change | Standard Deviation 11.91 |
| PF-06291874 15 mg | Percent Changes From Baseline of AUC0-4 for Glucagon Following MMTT on Day 14 - Part A | 50.45 Percentage of change | Standard Deviation 37.048 |
| PF-06291874 50 mg | Percent Changes From Baseline of AUC0-4 for Glucagon Following MMTT on Day 14 - Part A | 46.90 Percentage of change | Standard Deviation 30.179 |
| PF-06291874 100 mg | Percent Changes From Baseline of AUC0-4 for Glucagon Following MMTT on Day 14 - Part A | 142.62 Percentage of change | Standard Deviation 113.394 |
| PF-06291874 150 mg | Percent Changes From Baseline of AUC0-4 for Glucagon Following MMTT on Day 14 - Part A | 214.32 Percentage of change | Standard Deviation 118.612 |
Secondary
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.
Population: All subjects administered PF-06291874 or placebo were included in PD analysis. Placebo subjects within each cohort in Part A or B were pooled into a single placebo group for the inpatient portion of the study. Data collected from placebo subjects during the outpatient portion of study (Day 28) were also pooled separately for Parts A and B.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Changes From Baseline of AUC0-4 for Glucagon Following MMTT on Day 14 - Part B | 33.19 Percentage of change | Standard Deviation 23.47 |
| PF-06291874 5 mg | Percent Changes From Baseline of AUC0-4 for Glucagon Following MMTT on Day 14 - Part B | 50.35 Percentage of change | Standard Deviation 24.33 |
| PF-06291874 15 mg | Percent Changes From Baseline of AUC0-4 for Glucagon Following MMTT on Day 14 - Part B | 7.23 Percentage of change | Standard Deviation 22.59 |
Secondary
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.
Population: All subjects administered PF-06291874 or placebo were included in PD analysis. Placebo subjects within each cohort in Part A or B were pooled into a single placebo group for the inpatient portion of the study. Data collected from placebo subjects during the outpatient portion of study (Day 28) were also pooled separately for Parts A and B.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Changes From Baseline of AUC0-4 for Glucagon Following MMTT on Day 28 | 23.04 Percentage of change | Standard Deviation 52.52 |
| PF-06291874 5 mg | Percent Changes From Baseline of AUC0-4 for Glucagon Following MMTT on Day 28 | 125.15 Percentage of change | Standard Deviation 120.82 |
| PF-06291874 15 mg | Percent Changes From Baseline of AUC0-4 for Glucagon Following MMTT on Day 28 | -1.19 Percentage of change | Standard Deviation 29.18 |
| PF-06291874 50 mg | Percent Changes From Baseline of AUC0-4 for Glucagon Following MMTT on Day 28 | 36.49 Percentage of change | Standard Deviation 45.17 |