Diabetes Mellitus, Type 2
Conditions
Keywords
Phase 1 Type 2 diabetes CVX-096 diabetes mellitus, adult-onset diabetes mellitus, non-insulin dependent
Brief summary
The purpose of this study is to determine safety and tolerability of CVX-096 in adult, type 2 diabetic patients.
Interventions
BIOLOGICALCVX-096
Subcutaneous administration of CVX-096 with doses ranging from 0.1 mg up to a maximum of 36 mg
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Male and/or female patients (females will be women of non-childbearing potential) with an historical diagnosis of type 2 diabetes mellitus, who are currently being treated with metformin at a dose at or near maximum. * Hb A1c between 7-10%. * Fasting C-peptide \>0.4 nmol/L.
Exclusion criteria
* History of clinically significant chronic conditions other than T2DM not well controlled by either diet or medications. * Patients with pancreatitis or considered a high risk for pancreatitis. * History of contraindications to metformin therapy. * Previous treatment with an approved or investigational GLP 1 mimetic.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Stage 1: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-04856883 on Day 1 | pre-dose, 1, 6, 18, 24, 36, 48, 72, 96, 144, and 168 hours post-dose on Day 1 | AUClast was defined as area under the concentration-time curve from time zero to the time of last measured concentration and calculated by using linear up/log down trapezoidal method. |
| Stage 2: Maximum Observed Plasma Concentration (Cmax) of PF-04856883 on Day 22 | pre-dose, 1 and 6 hours post-dose on Day 22 | — |
| Stage 1: Maximum Observed Plasma Concentration (Cmax) of PF-04856883 on Day 8 | pre-dose, 1, 6, 18, 24, 36, 48, 72, 96, 144, and 168 hours post-dose on Day 8 | — |
| Maximum Observed Plasma Concentration (Cmax) of PF-04856883 on Day 1 | Cohort 1-9: pre-dose, 1, 6, 18, 24, 36, 48, 72, 96, 144, and 168 hours post-dose on Day 1; Cohort 10-12: pre-dose, 1 and 6 hours post-dose on Day 1 | — |
| Stage 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04856883 on Day 22 | pre-dose, 1 and 6 hours post-dose on Day 22 | — |
| Stage 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04856883 on Day 8 | pre-dose, 1, 6, 18, 24, 36, 48, 72, 96, 144, and 168 hours post-dose on Day 8 | — |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04856883 on Day 1 | Cohort 1-9: pre-dose, 1, 6, 18, 24, 36, 48, 72, 96, 144, and 168 hours post-dose on Day 1; Cohort 10-12: pre-dose, 1 and 6 hours post-dose on Day 1 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stage 1: Apparent Terminal Half-Life (t1/2) of PF-04856883 on Day 8 | pre-dose, 1, 6, 18, 24, 36, 48, 72, 96, 144, and 168 hours post-dose on Day 8 | Apparent terminal elimination half-life is the time measured for the plasma concentration of PF-04856883 to decrease by one-half of its initial concentration. |
| Stage 1: Apparent Terminal Elimination Half-Life (t1/2) of PF-04856883 on Day 1 | pre-dose, 1, 6, 18, 24, 36, 48, 72, 96, 144, and 168 hours post-dose on Day 1 | Apparent terminal elimination half-life is the time measured for the plasma concentration of PF-04856883 to decrease by one-half of its initial concentration. |
| Stage 2: Apparent Terminal Elimination Half-Life (t1/2) of PF-04856883 on Day 22 | pre-dose, 1 and 6 hours post-dose on Day 22 | Apparent terminal elimination half-life is the time measured for the plasma concentration of PF-04856883 to decrease by one-half of its initial concentration. |
| Stage 1: Mean Residence Time (MRT) of PF-04856883 on Day 1 | pre-dose, 1, 6, 18, 24, 36, 48, 72, 96, 144, and 168 hours post-dose Day 1 | MRT is defined as AUMC(0 - inf) divided by AUC(0 - inf), where AUMC(0 - inf) is the area under the first moment curve from time 0 extrapolated to infinite time, calculated using the linear/log trapezoidal method and AUC(0 - inf) is the area under the concentration-time curve extrapolated to infinity. |
| Stage 1: Apparent Oral Clearance (CL/F) of PF-04856883 on Day 1 | pre-dose, 1, 6, 18, 24, 36, 48, 72, 96, 144, and 168 hours post-dose Day 1 | Apparent oral clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. It was obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug apparent oral clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. |
| Stage 1: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC[0 - Inf]) of PF-04856883 on Day 1 | pre-dose, 1, 6, 18, 24, 36, 48, 72, 96, 144, and 168 hours post-dose Day 1 | AUC(0 - inf) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - inf). It was calculated as AUC (0-t) plus (last measurable concentration divided by apparent terminal elimination rate constant). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Significant Vital Signs | Cohort 1-8: Baseline up to Day 28; Cohort 9: Baseline up to Day 35; Cohort 10-12; Baseline up to Day 50 | Criteria for vital signs: pulse rate \<40 beats per minute (bpm), supine, sitting and erect pulse rate \<40 bpm, supine pulse rate \>120 bpm, sitting pulse rate \>120 bpm, and erect pulse rate \>120 bpm; systolic blood pressure: SBP \<90 millimeters of mercury (mmHg), change from baseline in SBP greater than or equal to (\>=) 30 mmHg; diastolic blood pressure: DBP \<50 mmHg, change from baseline in DBP \>=20 mmHg. |
| Number of Participants With Clinically Significant Laboratory Abnormalities | Cohort 1-8: Baseline up to Day 28; Cohort 9: Baseline up to Day 35; Cohort 10-12; Baseline up to Day 50 | Criteria for laboratory abnormalities: Hemoglobin (Hgb), hematocrit: less than (\<) 0.8\*lower limit of normal (LLN), platelet: \<75 or greater than (\>) 700\*10\^3/millimeter (mm)\^3\*upper limit of normal (ULN), leukocyte: \<2.5 or \>17.5\*10\^3/mm\^3\*ULN; total bilirubin 1.5\*ULN, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase: \>3.0\*ULN, total protein, albumin: \<0.8\*LLN or \>1.2\*ULN ;blood urea nitrogen, creatinine: \>1.3\*ULN, uric acid \>1.2\*ULN; sodium \<0.95\*LLN or \>1.05\*ULN, potassium, calcium: \<0.9\*LLN or \>1.1\*ULN, albumin, total protein \<0.8\*LLN or \>1.2\*ULN; glucose \<0.6\*LLN or \>1.5\*ULN, creatine kinase \>2.0\*ULN; urine (red blood cell, white blood cell \>6/high power field). |
| Stage 1: Change From Baseline in 7-point Weighted Mean Glucose at Day 3 and Day 7 | Baseline, Day 3 and 7 | It was assessed by 7-point glucose measurements via the glucose oxidase method. |
| Stage 1: Change From Baseline in Post-Prandial Area Under the Curve (AUC) of Glucose at Day 3 and 7 | Baseline, Day 3 and 7 | Area under the glucose concentration-time curve from 0 minute (approximately 20 minutes prior to the meal) to 180 minutes post initiation of meal. |
| Stage 1: Number of Participants With Hypoglycemia | Day 1: 0 hour (pre-dose) up to 48 hours post dose | Blood glucose level was checked for hypoglycemia by glucometer. Criteria for hypoglycemia: blood glucose level \<60 mg/dL if accompanied by symptoms, blood glucose level \<=50 mg/dL regardless of symptoms. |
| Number of Participants With Clinically Significant Physical Examinations | Cohort 1-8: Baseline up to Day 28; Cohort 9: Baseline up to Day 35; Cohort 10-12; Baseline up to Day 50 | Full physical examination included examination of the skin, eyes, ears, throat, neck, and cardiac, respiratory, gastrointestinal and musculoskeletal systems. The examination assessed the participants for any clinically significant changes in physical status, as determined by the investigator. |
| Stage 1: Number of Participants With Clinically Significant Abnormal Rhythms | Cohort 1- 8: Day 1 up to Day 3; Cohort 9: Day 1 up to Day 10 | Criteria for abnormal rhythms: asymptomatic marked sinus bradycardia rate \<35 bpm; asymptomatic supraventricular couplets, atrial bigeminy lasting \>30 seconds; asymptomatic ventricular couplets, ventricular bigeminy lasting \>30 seconds; asymptomatic type I second degree (wenckebach) atrioventricular block of \>30 seconds duration; asymptomatic frequent premature ventricular complexes (=\>200/24 hours); asymptomatic frequent premature atrial complexes (=\>240/24 hours). |
| Stage 1: Number of Participants With Anti-Drug Antibodies | Day 0, 8, 14, 15, 21, 28 and 35 | — |
| Stage 2: Number of Participants With Anti-Drug Antibodies | Day 0, 29 and 50 | — |
| Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings | Cohort 1-8: Baseline up to Day 28; Cohort 9: Baseline up to Day 35; Cohort 10-12; Baseline up to Day 50 | Criteria for ECG findings: PR interval \>=300 millisecond (msec), \>=25 percent increase when baseline \>200 msec, and \>=50 percent increase when baseline less than or equal to (\<=) 200 msec; QRS interval \>=200 msec, \>=25 percent increase when baseline \>=100 msec, and \>=50 percent increase when baseline \<=100 msec; QT/QTc interval (corrected QT interval) \>=500 msec. |
| Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Cohort 1-8: Baseline up to Day 29; Cohort 9: Baseline up to Day 36; Cohort 10-12: Baseline up to Day 50 | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. |
Countries
United States
Participant flow
Pre-assignment details
Study consist of two stages: stage 1 and stage 2. Participants were enrolled and randomized for stage 1 and stage 2 separately.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: PF-04856883 0.1 Milligram (mg) Participants received single subcutaneous injection of PF-04856883 (CVX-096) 0.1 mg on Day 1. | 7 |
| Cohort 2: PF-04856883 0.3 mg Participants received single subcutaneous injection of PF-04856883 0.3 mg on Day 1. | 6 |
| Cohort 3: PF-04856883 1.0 mg Participants received single subcutaneous injection of PF-04856883 1.0 mg on Day 1. | 6 |
| Cohort 4: PF-04856883 3.0 mg Participants received single subcutaneous injection of PF-04856883 3.0 mg on Day 1. | 7 |
| Cohort 5: PF-04856883 6.0 mg Participants received single subcutaneous injection of PF-04856883 6.0 mg on Day 1. | 6 |
| Cohort 6: PF-04856883 12.0 mg Participants received single subcutaneous injection of PF-04856883 12.0 mg on Day 1. | 6 |
| Cohort 7: PF-04856883 24.0 mg Participants received single subcutaneous injection of PF-04856883 24.0 mg on Day 1. | 6 |
| Cohort 8: PF-04856883 36.0 mg Participants received single subcutaneous injection of PF-04856883 36.0 mg on Day 1. | 6 |
| Cohort 9: PF-04856883 18.0 mg Participants received subcutaneous injection of PF-04856883 18.0 mg on Day 1 and 8. | 6 |
| Cohort 9: Placebo Participants received placebo matched to PF-04856883 subcutaneous injection either single dose on Day 1 or two dose on Day 1 and 8 respectively. | 18 |
| Cohort 10: PF-04856883 15.0 mg Participants received subcutaneous injection of PF-04856883 15.0 mg on Day 1, 8, 15 and 22. | 9 |
| Cohort 11: PF-04856883 20.0 mg Participants received subcutaneous injection of PF-04856883 20.0 mg on Day 1, 8, 15 and 22. | 9 |
| Cohort 12: PF-04856883 25.0 mg Participants received subcutaneous injection of PF-04856883 25.0 mg on Day 1, 8, 15 and 22. | 13 |
| Cohort 10-12: Placebo Participants received placebo matched to PF-04856883 subcutaneous injection on Day 1, 8, 15 and 22. | 9 |
| Total | 114 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Stage 2 | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 3 | 0 |
| Stage 2 | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 1 |
Baseline characteristics
| Characteristic | Total | Cohort 2: PF-04856883 0.3 mg | Cohort 3: PF-04856883 1.0 mg | Cohort 4: PF-04856883 3.0 mg | Cohort 5: PF-04856883 6.0 mg | Cohort 6: PF-04856883 12.0 mg | Cohort 7: PF-04856883 24.0 mg | Cohort 8: PF-04856883 36.0 mg | Cohort 9: PF-04856883 18.0 mg | Cohort 9: Placebo | Cohort 10: PF-04856883 15.0 mg | Cohort 11: PF-04856883 20.0 mg | Cohort 12: PF-04856883 25.0 mg | Cohort 10-12: Placebo | Cohort 1: PF-04856883 0.1 Milligram (mg) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 13 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 5 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 101 Participants | 6 Participants | 6 Participants | 7 Participants | 6 Participants | 5 Participants | 5 Participants | 4 Participants | 5 Participants | 13 Participants | 8 Participants | 8 Participants | 13 Participants | 8 Participants | 7 Participants |
| Sex: Female, Male Female | 39 Participants | 3 Participants | 1 Participants | 5 Participants | 3 Participants | 2 Participants | 5 Participants | 6 Participants | 0 Participants | 3 Participants | 4 Participants | 4 Participants | 3 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 75 Participants | 3 Participants | 5 Participants | 2 Participants | 3 Participants | 4 Participants | 1 Participants | 0 Participants | 6 Participants | 15 Participants | 5 Participants | 5 Participants | 10 Participants | 9 Participants | 7 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 | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 7 | 2 / 6 | 5 / 6 | 1 / 7 | 2 / 6 | 4 / 6 | 5 / 6 | 6 / 6 | 3 / 6 | 4 / 18 | 5 / 9 | 7 / 9 | 8 / 13 | 4 / 9 |
| serious Total, serious adverse events | 0 / 7 | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 18 | 0 / 9 | 0 / 9 | 0 / 13 | 0 / 9 |
Outcome results
Primary
Maximum Observed Plasma Concentration (Cmax) of PF-04856883 on Day 1
Time frame: Cohort 1-9: pre-dose, 1, 6, 18, 24, 36, 48, 72, 96, 144, and 168 hours post-dose on Day 1; Cohort 10-12: pre-dose, 1 and 6 hours post-dose on Day 1
Population: PK analysis population included all randomized participants who received at least 1 dose of PF-04856883 and had PK data. Here, 'N' signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: PF-04856883 0.1 Milligram (mg) | Maximum Observed Plasma Concentration (Cmax) of PF-04856883 on Day 1 | 7.05 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 104.9 |
| Cohort 2: PF-04856883 0.3 mg | Maximum Observed Plasma Concentration (Cmax) of PF-04856883 on Day 1 | 29.0 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 126.3 |
| Cohort 3: PF-04856883 1.0 mg | Maximum Observed Plasma Concentration (Cmax) of PF-04856883 on Day 1 | 24.8 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 92.3 |
| Cohort 4: PF-04856883 3.0 mg | Maximum Observed Plasma Concentration (Cmax) of PF-04856883 on Day 1 | 149 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 63.2 |
| Cohort 5: PF-04856883 6.0 mg | Maximum Observed Plasma Concentration (Cmax) of PF-04856883 on Day 1 | 387 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 52.4 |
| Cohort 6: PF-04856883 12.0 mg | Maximum Observed Plasma Concentration (Cmax) of PF-04856883 on Day 1 | 900 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 36.2 |
| Cohort 7: PF-04856883 24.0 mg | Maximum Observed Plasma Concentration (Cmax) of PF-04856883 on Day 1 | 579 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 1314.6 |
| Cohort 8: PF-04856883 36.0 mg | Maximum Observed Plasma Concentration (Cmax) of PF-04856883 on Day 1 | 1299 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 104.3 |
| Cohort 9: PF-04856883 18.0 mg | Maximum Observed Plasma Concentration (Cmax) of PF-04856883 on Day 1 | 1082 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 50 |
| Cohort 10: PF-04856883 15.0 mg | Maximum Observed Plasma Concentration (Cmax) of PF-04856883 on Day 1 | 736 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 47.1 |
| Cohort 11: PF-04856883 20.0 mg | Maximum Observed Plasma Concentration (Cmax) of PF-04856883 on Day 1 | 1554 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 38.3 |
| Cohort 12: PF-04856883 25.0 mg | Maximum Observed Plasma Concentration (Cmax) of PF-04856883 on Day 1 | 958 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 63.1 |
Primary
Stage 1: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-04856883 on Day 1
AUClast was defined as area under the concentration-time curve from time zero to the time of last measured concentration and calculated by using linear up/log down trapezoidal method.
Time frame: pre-dose, 1, 6, 18, 24, 36, 48, 72, 96, 144, and 168 hours post-dose on Day 1
Population: Pharmacokinetic (PK) analysis population included all randomized participants who received at least 1 dose of PF-04856883 and had PK data. 'N'(Overall number of participants)=participants who were evaluable for this outcome measure. This outcome measure was not planned to be analyzed in multiple dosing cohort(Cohort 9),as pre-specified in protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: PF-04856883 0.1 Milligram (mg) | Stage 1: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-04856883 on Day 1 | 865 nanogram*hour per milliliter (ng*hr)/mL | Geometric Coefficient of Variation 625.3 |
| Cohort 2: PF-04856883 0.3 mg | Stage 1: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-04856883 on Day 1 | 4960 nanogram*hour per milliliter (ng*hr)/mL | Geometric Coefficient of Variation 462 |
| Cohort 3: PF-04856883 1.0 mg | Stage 1: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-04856883 on Day 1 | 7065 nanogram*hour per milliliter (ng*hr)/mL | Geometric Coefficient of Variation 192.1 |
| Cohort 4: PF-04856883 3.0 mg | Stage 1: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-04856883 on Day 1 | 32552 nanogram*hour per milliliter (ng*hr)/mL | Geometric Coefficient of Variation 127.7 |
| Cohort 5: PF-04856883 6.0 mg | Stage 1: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-04856883 on Day 1 | 105950 nanogram*hour per milliliter (ng*hr)/mL | Geometric Coefficient of Variation 53.4 |
| Cohort 6: PF-04856883 12.0 mg | Stage 1: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-04856883 on Day 1 | 304167 nanogram*hour per milliliter (ng*hr)/mL | Geometric Coefficient of Variation 25.9 |
| Cohort 7: PF-04856883 24.0 mg | Stage 1: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-04856883 on Day 1 | 120521 nanogram*hour per milliliter (ng*hr)/mL | Geometric Coefficient of Variation 5404.6 |
| Cohort 8: PF-04856883 36.0 mg | Stage 1: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-04856883 on Day 1 | 297503 nanogram*hour per milliliter (ng*hr)/mL | Geometric Coefficient of Variation 211.1 |
Primary
Stage 1: Maximum Observed Plasma Concentration (Cmax) of PF-04856883 on Day 8
Time frame: pre-dose, 1, 6, 18, 24, 36, 48, 72, 96, 144, and 168 hours post-dose on Day 8
Population: PK analysis population included all randomized participants who received at least 1 dose of PF-04856883 and had PK data. The outcome was not planned to be analyzed for single dosing cohorts (Cohort 1 to 8), since the dosing was done only on Day 1 in these cohorts.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: PF-04856883 0.1 Milligram (mg) | Stage 1: Maximum Observed Plasma Concentration (Cmax) of PF-04856883 on Day 8 | 1536 ng/mL | Geometric Coefficient of Variation 54.9 |
Primary
Stage 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04856883 on Day 8
Time frame: pre-dose, 1, 6, 18, 24, 36, 48, 72, 96, 144, and 168 hours post-dose on Day 8
Population: PK analysis population included all randomized participants who received at least 1 dose of PF-04856883 and had PK data. The outcome was not planned to be analyzed for single dosing cohorts (Cohort 1 to 8), since the dosing was done only on Day 1 in these cohorts.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: PF-04856883 0.1 Milligram (mg) | Stage 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04856883 on Day 8 | 72.0 hour |
Primary
Stage 2: Maximum Observed Plasma Concentration (Cmax) of PF-04856883 on Day 22
Time frame: pre-dose, 1 and 6 hours post-dose on Day 22
Population: PK analysis population included all randomized participants who received at least 1 dose of PF-04856883 and had PK data. Here, 'N' signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: PF-04856883 0.1 Milligram (mg) | Stage 2: Maximum Observed Plasma Concentration (Cmax) of PF-04856883 on Day 22 | 1767 ng/mL | Geometric Coefficient of Variation 37.6 |
| Cohort 2: PF-04856883 0.3 mg | Stage 2: Maximum Observed Plasma Concentration (Cmax) of PF-04856883 on Day 22 | 2193 ng/mL | Geometric Coefficient of Variation 36.9 |
| Cohort 3: PF-04856883 1.0 mg | Stage 2: Maximum Observed Plasma Concentration (Cmax) of PF-04856883 on Day 22 | 2253 ng/mL | Geometric Coefficient of Variation 31.9 |
Primary
Stage 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04856883 on Day 22
Time frame: pre-dose, 1 and 6 hours post-dose on Day 22
Population: PK analysis population included all randomized participants who received at least 1 dose of PF-04856883 and had PK data. Here, 'N' signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: PF-04856883 0.1 Milligram (mg) | Stage 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04856883 on Day 22 | 48.0 hour |
| Cohort 2: PF-04856883 0.3 mg | Stage 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04856883 on Day 22 | 46.9 hour |
| Cohort 3: PF-04856883 1.0 mg | Stage 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04856883 on Day 22 | 48.0 hour |
Primary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04856883 on Day 1
Time frame: Cohort 1-9: pre-dose, 1, 6, 18, 24, 36, 48, 72, 96, 144, and 168 hours post-dose on Day 1; Cohort 10-12: pre-dose, 1 and 6 hours post-dose on Day 1
Population: PK analysis population included all randomized participants who received at least 1 dose of PF-04856883 and had PK data. Here, 'N' signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: PF-04856883 0.1 Milligram (mg) | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04856883 on Day 1 | 156 hour |
| Cohort 2: PF-04856883 0.3 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04856883 on Day 1 | 72.1 hour |
| Cohort 3: PF-04856883 1.0 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04856883 on Day 1 | 168 hour |
| Cohort 4: PF-04856883 3.0 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04856883 on Day 1 | 72.0 hour |
| Cohort 5: PF-04856883 6.0 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04856883 on Day 1 | 144 hour |
| Cohort 6: PF-04856883 12.0 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04856883 on Day 1 | 120 hour |
| Cohort 7: PF-04856883 24.0 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04856883 on Day 1 | 108 hour |
| Cohort 8: PF-04856883 36.0 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04856883 on Day 1 | 96.0 hour |
| Cohort 9: PF-04856883 18.0 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04856883 on Day 1 | 84.0 hour |
| Cohort 10: PF-04856883 15.0 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04856883 on Day 1 | 168 hour |
| Cohort 11: PF-04856883 20.0 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04856883 on Day 1 | 168 hour |
| Cohort 12: PF-04856883 25.0 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04856883 on Day 1 | 168 hour |
Secondary
Stage 1: Apparent Oral Clearance (CL/F) of PF-04856883 on Day 1
Apparent oral clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. It was obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug apparent oral clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time frame: pre-dose, 1, 6, 18, 24, 36, 48, 72, 96, 144, and 168 hours post-dose Day 1
Population: PK analysis population included all randomized participants who received at least 1 dose of PF-04856883 and had PK data. Here, 'N' signifies those participants who were evaluable for this outcome measure. This outcome measure was not planned to be analyzed in multiple dosing cohort (Cohort 9), as pre specified in protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: PF-04856883 0.1 Milligram (mg) | Stage 1: Apparent Oral Clearance (CL/F) of PF-04856883 on Day 1 | NA Liter per hour (L/hr) | — |
| Cohort 2: PF-04856883 0.3 mg | Stage 1: Apparent Oral Clearance (CL/F) of PF-04856883 on Day 1 | 0.0176 Liter per hour (L/hr) | Geometric Coefficient of Variation 20.4 |
| Cohort 3: PF-04856883 1.0 mg | Stage 1: Apparent Oral Clearance (CL/F) of PF-04856883 on Day 1 | 0.0643 Liter per hour (L/hr) | Geometric Coefficient of Variation 27.4 |
| Cohort 4: PF-04856883 3.0 mg | Stage 1: Apparent Oral Clearance (CL/F) of PF-04856883 on Day 1 | 0.0562 Liter per hour (L/hr) | Geometric Coefficient of Variation 36.5 |
| Cohort 5: PF-04856883 6.0 mg | Stage 1: Apparent Oral Clearance (CL/F) of PF-04856883 on Day 1 | 0.0487 Liter per hour (L/hr) | Geometric Coefficient of Variation 53.5 |
| Cohort 6: PF-04856883 12.0 mg | Stage 1: Apparent Oral Clearance (CL/F) of PF-04856883 on Day 1 | 0.0354 Liter per hour (L/hr) | Geometric Coefficient of Variation 25.6 |
| Cohort 7: PF-04856883 24.0 mg | Stage 1: Apparent Oral Clearance (CL/F) of PF-04856883 on Day 1 | 0.0530 Liter per hour (L/hr) | Geometric Coefficient of Variation 47.5 |
| Cohort 8: PF-04856883 36.0 mg | Stage 1: Apparent Oral Clearance (CL/F) of PF-04856883 on Day 1 | 0.0527 Liter per hour (L/hr) | Geometric Coefficient of Variation 28.6 |
Secondary
Stage 1: Apparent Terminal Elimination Half-Life (t1/2) of PF-04856883 on Day 1
Apparent terminal elimination half-life is the time measured for the plasma concentration of PF-04856883 to decrease by one-half of its initial concentration.
Time frame: pre-dose, 1, 6, 18, 24, 36, 48, 72, 96, 144, and 168 hours post-dose on Day 1
Population: PK analysis population included all randomized participants who received at least 1 dose of PF-04856883 and had PK data. Here, 'N' signifies those participants who were evaluable for this outcome measure. This outcome measure was not planned to be analyzed in multiple dosing cohort (Cohort 9), as pre specified in protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: PF-04856883 0.1 Milligram (mg) | Stage 1: Apparent Terminal Elimination Half-Life (t1/2) of PF-04856883 on Day 1 | NA hour | — |
| Cohort 2: PF-04856883 0.3 mg | Stage 1: Apparent Terminal Elimination Half-Life (t1/2) of PF-04856883 on Day 1 | 188 hour | Standard Deviation 42.6 |
| Cohort 3: PF-04856883 1.0 mg | Stage 1: Apparent Terminal Elimination Half-Life (t1/2) of PF-04856883 on Day 1 | 151 hour | Standard Deviation 5.14 |
| Cohort 4: PF-04856883 3.0 mg | Stage 1: Apparent Terminal Elimination Half-Life (t1/2) of PF-04856883 on Day 1 | 186 hour | Standard Deviation 53.3 |
| Cohort 5: PF-04856883 6.0 mg | Stage 1: Apparent Terminal Elimination Half-Life (t1/2) of PF-04856883 on Day 1 | 144 hour | Standard Deviation 12 |
| Cohort 6: PF-04856883 12.0 mg | Stage 1: Apparent Terminal Elimination Half-Life (t1/2) of PF-04856883 on Day 1 | 163 hour | Standard Deviation 52 |
| Cohort 7: PF-04856883 24.0 mg | Stage 1: Apparent Terminal Elimination Half-Life (t1/2) of PF-04856883 on Day 1 | 156 hour | Standard Deviation 45.6 |
| Cohort 8: PF-04856883 36.0 mg | Stage 1: Apparent Terminal Elimination Half-Life (t1/2) of PF-04856883 on Day 1 | 159 hour | Standard Deviation 37.5 |
Secondary
Stage 1: Apparent Terminal Half-Life (t1/2) of PF-04856883 on Day 8
Apparent terminal elimination half-life is the time measured for the plasma concentration of PF-04856883 to decrease by one-half of its initial concentration.
Time frame: pre-dose, 1, 6, 18, 24, 36, 48, 72, 96, 144, and 168 hours post-dose on Day 8
Population: PK analysis population included all randomized participants who received at least 1 dose of PF-04856883 and had PK data. The outcome was not planned to be analyzed for single dosing cohorts (Cohort 1 to 8), since the dosing was done only on Day 1 in these cohorts.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: PF-04856883 0.1 Milligram (mg) | Stage 1: Apparent Terminal Half-Life (t1/2) of PF-04856883 on Day 8 | 156 hour | Standard Deviation 23.4 |
Secondary
Stage 1: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC[0 - Inf]) of PF-04856883 on Day 1
AUC(0 - inf) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - inf). It was calculated as AUC (0-t) plus (last measurable concentration divided by apparent terminal elimination rate constant).
Time frame: pre-dose, 1, 6, 18, 24, 36, 48, 72, 96, 144, and 168 hours post-dose Day 1
Population: PK analysis population included all randomized participants who received at least 1 dose of PF-04856883 and had PK data. Here, 'N' signifies those participants who were evaluable for this outcome measure. This outcome measure was not planned to be analyzed in multiple dosing cohort (Cohort 9), as pre specified in protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: PF-04856883 0.1 Milligram (mg) | Stage 1: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC[0 - Inf]) of PF-04856883 on Day 1 | NA L/hr | — |
| Cohort 2: PF-04856883 0.3 mg | Stage 1: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC[0 - Inf]) of PF-04856883 on Day 1 | 17013 L/hr | Geometric Coefficient of Variation 20.4 |
| Cohort 3: PF-04856883 1.0 mg | Stage 1: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC[0 - Inf]) of PF-04856883 on Day 1 | 15550 L/hr | Geometric Coefficient of Variation 27.4 |
| Cohort 4: PF-04856883 3.0 mg | Stage 1: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC[0 - Inf]) of PF-04856883 on Day 1 | 53420 L/hr | Geometric Coefficient of Variation 36.5 |
| Cohort 5: PF-04856883 6.0 mg | Stage 1: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC[0 - Inf]) of PF-04856883 on Day 1 | 123081 L/hr | Geometric Coefficient of Variation 53.5 |
| Cohort 6: PF-04856883 12.0 mg | Stage 1: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC[0 - Inf]) of PF-04856883 on Day 1 | 339062 L/hr | Geometric Coefficient of Variation 25.6 |
| Cohort 7: PF-04856883 24.0 mg | Stage 1: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC[0 - Inf]) of PF-04856883 on Day 1 | 452842 L/hr | Geometric Coefficient of Variation 47.5 |
| Cohort 8: PF-04856883 36.0 mg | Stage 1: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC[0 - Inf]) of PF-04856883 on Day 1 | 682543 L/hr | Geometric Coefficient of Variation 28.6 |
Secondary
Stage 1: Mean Residence Time (MRT) of PF-04856883 on Day 1
MRT is defined as AUMC(0 - inf) divided by AUC(0 - inf), where AUMC(0 - inf) is the area under the first moment curve from time 0 extrapolated to infinite time, calculated using the linear/log trapezoidal method and AUC(0 - inf) is the area under the concentration-time curve extrapolated to infinity.
Time frame: pre-dose, 1, 6, 18, 24, 36, 48, 72, 96, 144, and 168 hours post-dose Day 1
Population: PK analysis population included all randomized participants who received at least 1 dose of PF-04856883 and had PK data. Here, 'N' signifies those participants who were evaluable for this outcome measure. This outcome measure was not planned to be analyzed in multiple dosing cohort (Cohort 9), as pre specified in protocol.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Cohort 1: PF-04856883 0.1 Milligram (mg) | Stage 1: Mean Residence Time (MRT) of PF-04856883 on Day 1 | NA hour | — |
| Cohort 2: PF-04856883 0.3 mg | Stage 1: Mean Residence Time (MRT) of PF-04856883 on Day 1 | 310 hour | Full Range 69.4 |
| Cohort 3: PF-04856883 1.0 mg | Stage 1: Mean Residence Time (MRT) of PF-04856883 on Day 1 | 316 hour | Full Range 20.3 |
| Cohort 4: PF-04856883 3.0 mg | Stage 1: Mean Residence Time (MRT) of PF-04856883 on Day 1 | 350 hour | Full Range 70.5 |
| Cohort 5: PF-04856883 6.0 mg | Stage 1: Mean Residence Time (MRT) of PF-04856883 on Day 1 | 281 hour | Full Range 31.6 |
| Cohort 6: PF-04856883 12.0 mg | Stage 1: Mean Residence Time (MRT) of PF-04856883 on Day 1 | 319 hour | Full Range 77.8 |
| Cohort 7: PF-04856883 24.0 mg | Stage 1: Mean Residence Time (MRT) of PF-04856883 on Day 1 | 239 hour | Full Range 89.7 |
| Cohort 8: PF-04856883 36.0 mg | Stage 1: Mean Residence Time (MRT) of PF-04856883 on Day 1 | 312 hour | Full Range 70.7 |
Secondary
Stage 2: Apparent Terminal Elimination Half-Life (t1/2) of PF-04856883 on Day 22
Apparent terminal elimination half-life is the time measured for the plasma concentration of PF-04856883 to decrease by one-half of its initial concentration.
Time frame: pre-dose, 1 and 6 hours post-dose on Day 22
Population: PK analysis population included all randomized participants who received at least 1 dose of PF-04856883 and had PK data. Here, 'N' signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: PF-04856883 0.1 Milligram (mg) | Stage 2: Apparent Terminal Elimination Half-Life (t1/2) of PF-04856883 on Day 22 | 156 hour | Standard Deviation 32.7 |
| Cohort 2: PF-04856883 0.3 mg | Stage 2: Apparent Terminal Elimination Half-Life (t1/2) of PF-04856883 on Day 22 | 102 hour | Standard Deviation 44.9 |
| Cohort 3: PF-04856883 1.0 mg | Stage 2: Apparent Terminal Elimination Half-Life (t1/2) of PF-04856883 on Day 22 | 149 hour | Standard Deviation 29 |
Other Pre-specified
Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings
Criteria for ECG findings: PR interval \>=300 millisecond (msec), \>=25 percent increase when baseline \>200 msec, and \>=50 percent increase when baseline less than or equal to (\<=) 200 msec; QRS interval \>=200 msec, \>=25 percent increase when baseline \>=100 msec, and \>=50 percent increase when baseline \<=100 msec; QT/QTc interval (corrected QT interval) \>=500 msec.
Time frame: Cohort 1-8: Baseline up to Day 28; Cohort 9: Baseline up to Day 35; Cohort 10-12; Baseline up to Day 50
Population: Safety population included all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: PF-04856883 0.1 Milligram (mg) | Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings | 0 Participants |
| Cohort 2: PF-04856883 0.3 mg | Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings | 0 Participants |
| Cohort 3: PF-04856883 1.0 mg | Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings | 0 Participants |
| Cohort 4: PF-04856883 3.0 mg | Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings | 0 Participants |
| Cohort 5: PF-04856883 6.0 mg | Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings | 0 Participants |
| Cohort 6: PF-04856883 12.0 mg | Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings | 0 Participants |
| Cohort 7: PF-04856883 24.0 mg | Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings | 0 Participants |
| Cohort 8: PF-04856883 36.0 mg | Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings | 0 Participants |
| Cohort 9: PF-04856883 18.0 mg | Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings | 0 Participants |
| Cohort 10: PF-04856883 15.0 mg | Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings | 0 Participants |
| Cohort 11: PF-04856883 20.0 mg | Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings | 0 Participants |
| Cohort 12: PF-04856883 25.0 mg | Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings | 0 Participants |
| Cohort 12: PF-04856883 25.0 mg | Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings | 0 Participants |
| Cohort 10-12: Placebo | Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings | 0 Participants |
| Cohort 10-12: Placebo | Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings | 0 Participants |
Other Pre-specified
Number of Participants With Clinically Significant Laboratory Abnormalities
Criteria for laboratory abnormalities: Hemoglobin (Hgb), hematocrit: less than (\<) 0.8\*lower limit of normal (LLN), platelet: \<75 or greater than (\>) 700\*10\^3/millimeter (mm)\^3\*upper limit of normal (ULN), leukocyte: \<2.5 or \>17.5\*10\^3/mm\^3\*ULN; total bilirubin 1.5\*ULN, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase: \>3.0\*ULN, total protein, albumin: \<0.8\*LLN or \>1.2\*ULN ;blood urea nitrogen, creatinine: \>1.3\*ULN, uric acid \>1.2\*ULN; sodium \<0.95\*LLN or \>1.05\*ULN, potassium, calcium: \<0.9\*LLN or \>1.1\*ULN, albumin, total protein \<0.8\*LLN or \>1.2\*ULN; glucose \<0.6\*LLN or \>1.5\*ULN, creatine kinase \>2.0\*ULN; urine (red blood cell, white blood cell \>6/high power field).
Time frame: Cohort 1-8: Baseline up to Day 28; Cohort 9: Baseline up to Day 35; Cohort 10-12; Baseline up to Day 50
Population: Safety population included all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: PF-04856883 0.1 Milligram (mg) | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Cohort 2: PF-04856883 0.3 mg | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Cohort 3: PF-04856883 1.0 mg | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Cohort 4: PF-04856883 3.0 mg | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Cohort 5: PF-04856883 6.0 mg | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Cohort 6: PF-04856883 12.0 mg | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Cohort 7: PF-04856883 24.0 mg | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Cohort 8: PF-04856883 36.0 mg | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Cohort 9: PF-04856883 18.0 mg | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Cohort 10: PF-04856883 15.0 mg | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Cohort 11: PF-04856883 20.0 mg | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Cohort 12: PF-04856883 25.0 mg | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Cohort 12: PF-04856883 25.0 mg | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Cohort 10-12: Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Cohort 10-12: Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
Other Pre-specified
Number of Participants With Clinically Significant Physical Examinations
Full physical examination included examination of the skin, eyes, ears, throat, neck, and cardiac, respiratory, gastrointestinal and musculoskeletal systems. The examination assessed the participants for any clinically significant changes in physical status, as determined by the investigator.
Time frame: Cohort 1-8: Baseline up to Day 28; Cohort 9: Baseline up to Day 35; Cohort 10-12; Baseline up to Day 50
Population: Safety population included all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: PF-04856883 0.1 Milligram (mg) | Number of Participants With Clinically Significant Physical Examinations | 0 Participants |
| Cohort 2: PF-04856883 0.3 mg | Number of Participants With Clinically Significant Physical Examinations | 0 Participants |
| Cohort 3: PF-04856883 1.0 mg | Number of Participants With Clinically Significant Physical Examinations | 0 Participants |
| Cohort 4: PF-04856883 3.0 mg | Number of Participants With Clinically Significant Physical Examinations | 0 Participants |
| Cohort 5: PF-04856883 6.0 mg | Number of Participants With Clinically Significant Physical Examinations | 0 Participants |
| Cohort 6: PF-04856883 12.0 mg | Number of Participants With Clinically Significant Physical Examinations | 0 Participants |
| Cohort 7: PF-04856883 24.0 mg | Number of Participants With Clinically Significant Physical Examinations | 0 Participants |
| Cohort 8: PF-04856883 36.0 mg | Number of Participants With Clinically Significant Physical Examinations | 0 Participants |
| Cohort 9: PF-04856883 18.0 mg | Number of Participants With Clinically Significant Physical Examinations | 0 Participants |
| Cohort 10: PF-04856883 15.0 mg | Number of Participants With Clinically Significant Physical Examinations | 0 Participants |
| Cohort 11: PF-04856883 20.0 mg | Number of Participants With Clinically Significant Physical Examinations | 0 Participants |
| Cohort 12: PF-04856883 25.0 mg | Number of Participants With Clinically Significant Physical Examinations | 0 Participants |
| Cohort 12: PF-04856883 25.0 mg | Number of Participants With Clinically Significant Physical Examinations | 0 Participants |
| Cohort 10-12: Placebo | Number of Participants With Clinically Significant Physical Examinations | 0 Participants |
| Cohort 10-12: Placebo | Number of Participants With Clinically Significant Physical Examinations | 0 Participants |
Other Pre-specified
Number of Participants With Clinically Significant Vital Signs
Criteria for vital signs: pulse rate \<40 beats per minute (bpm), supine, sitting and erect pulse rate \<40 bpm, supine pulse rate \>120 bpm, sitting pulse rate \>120 bpm, and erect pulse rate \>120 bpm; systolic blood pressure: SBP \<90 millimeters of mercury (mmHg), change from baseline in SBP greater than or equal to (\>=) 30 mmHg; diastolic blood pressure: DBP \<50 mmHg, change from baseline in DBP \>=20 mmHg.
Time frame: Cohort 1-8: Baseline up to Day 28; Cohort 9: Baseline up to Day 35; Cohort 10-12; Baseline up to Day 50
Population: Safety population included all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: PF-04856883 0.1 Milligram (mg) | Number of Participants With Clinically Significant Vital Signs | 0 Participants |
| Cohort 2: PF-04856883 0.3 mg | Number of Participants With Clinically Significant Vital Signs | 0 Participants |
| Cohort 3: PF-04856883 1.0 mg | Number of Participants With Clinically Significant Vital Signs | 0 Participants |
| Cohort 4: PF-04856883 3.0 mg | Number of Participants With Clinically Significant Vital Signs | 0 Participants |
| Cohort 5: PF-04856883 6.0 mg | Number of Participants With Clinically Significant Vital Signs | 0 Participants |
| Cohort 6: PF-04856883 12.0 mg | Number of Participants With Clinically Significant Vital Signs | 0 Participants |
| Cohort 7: PF-04856883 24.0 mg | Number of Participants With Clinically Significant Vital Signs | 0 Participants |
| Cohort 8: PF-04856883 36.0 mg | Number of Participants With Clinically Significant Vital Signs | 0 Participants |
| Cohort 9: PF-04856883 18.0 mg | Number of Participants With Clinically Significant Vital Signs | 0 Participants |
| Cohort 10: PF-04856883 15.0 mg | Number of Participants With Clinically Significant Vital Signs | 0 Participants |
| Cohort 11: PF-04856883 20.0 mg | Number of Participants With Clinically Significant Vital Signs | 0 Participants |
| Cohort 12: PF-04856883 25.0 mg | Number of Participants With Clinically Significant Vital Signs | 0 Participants |
| Cohort 12: PF-04856883 25.0 mg | Number of Participants With Clinically Significant Vital Signs | 0 Participants |
| Cohort 10-12: Placebo | Number of Participants With Clinically Significant Vital Signs | 0 Participants |
| Cohort 10-12: Placebo | Number of Participants With Clinically Significant Vital Signs | 0 Participants |
Other Pre-specified
Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Time frame: Cohort 1-8: Baseline up to Day 29; Cohort 9: Baseline up to Day 36; Cohort 10-12: Baseline up to Day 50
Population: Safety population included all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: PF-04856883 0.1 Milligram (mg) | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 2 Participants |
| Cohort 1: PF-04856883 0.1 Milligram (mg) | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Cohort 2: PF-04856883 0.3 mg | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 2 Participants |
| Cohort 2: PF-04856883 0.3 mg | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Cohort 3: PF-04856883 1.0 mg | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 5 Participants |
| Cohort 3: PF-04856883 1.0 mg | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Cohort 4: PF-04856883 3.0 mg | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 1 Participants |
| Cohort 4: PF-04856883 3.0 mg | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Cohort 5: PF-04856883 6.0 mg | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Cohort 5: PF-04856883 6.0 mg | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 2 Participants |
| Cohort 6: PF-04856883 12.0 mg | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Cohort 6: PF-04856883 12.0 mg | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 4 Participants |
| Cohort 7: PF-04856883 24.0 mg | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 5 Participants |
| Cohort 7: PF-04856883 24.0 mg | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Cohort 8: PF-04856883 36.0 mg | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 6 Participants |
| Cohort 8: PF-04856883 36.0 mg | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Cohort 9: PF-04856883 18.0 mg | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Cohort 9: PF-04856883 18.0 mg | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 3 Participants |
| Cohort 10: PF-04856883 15.0 mg | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Cohort 10: PF-04856883 15.0 mg | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 4 Participants |
| Cohort 11: PF-04856883 20.0 mg | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Cohort 11: PF-04856883 20.0 mg | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 5 Participants |
| Cohort 12: PF-04856883 25.0 mg | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Cohort 12: PF-04856883 25.0 mg | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 7 Participants |
| Cohort 12: PF-04856883 25.0 mg | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 8 Participants |
| Cohort 12: PF-04856883 25.0 mg | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Cohort 10-12: Placebo | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Cohort 10-12: Placebo | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 4 Participants |
Other Pre-specified
Stage 1: Change From Baseline in 7-point Weighted Mean Glucose at Day 3 and Day 7
It was assessed by 7-point glucose measurements via the glucose oxidase method.
Time frame: Baseline, Day 3 and 7
Population: Pharmacodynamic analysis population included all randomized participants who had received at least 1 dose of study medication and had PD data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: PF-04856883 0.1 Milligram (mg) | Stage 1: Change From Baseline in 7-point Weighted Mean Glucose at Day 3 and Day 7 | Change at Day 3 | 3.27 milligram per deciliter(mg/dL) | Standard Deviation 24.1 |
| Cohort 1: PF-04856883 0.1 Milligram (mg) | Stage 1: Change From Baseline in 7-point Weighted Mean Glucose at Day 3 and Day 7 | Change at Day 7 | -15.6 milligram per deciliter(mg/dL) | Standard Deviation 23 |
| Cohort 2: PF-04856883 0.3 mg | Stage 1: Change From Baseline in 7-point Weighted Mean Glucose at Day 3 and Day 7 | Change at Day 3 | -0.0252 milligram per deciliter(mg/dL) | Standard Deviation 16.3 |
| Cohort 2: PF-04856883 0.3 mg | Stage 1: Change From Baseline in 7-point Weighted Mean Glucose at Day 3 and Day 7 | Change at Day 7 | 7.44 milligram per deciliter(mg/dL) | Standard Deviation 42.1 |
| Cohort 3: PF-04856883 1.0 mg | Stage 1: Change From Baseline in 7-point Weighted Mean Glucose at Day 3 and Day 7 | Change at Day 3 | -17.9 milligram per deciliter(mg/dL) | Standard Deviation 21.7 |
| Cohort 3: PF-04856883 1.0 mg | Stage 1: Change From Baseline in 7-point Weighted Mean Glucose at Day 3 and Day 7 | Change at Day 7 | -28.7 milligram per deciliter(mg/dL) | Standard Deviation 26.9 |
| Cohort 4: PF-04856883 3.0 mg | Stage 1: Change From Baseline in 7-point Weighted Mean Glucose at Day 3 and Day 7 | Change at Day 3 | 1.04 milligram per deciliter(mg/dL) | Standard Deviation 18.2 |
| Cohort 4: PF-04856883 3.0 mg | Stage 1: Change From Baseline in 7-point Weighted Mean Glucose at Day 3 and Day 7 | Change at Day 7 | -8.45 milligram per deciliter(mg/dL) | Standard Deviation 33.6 |
| Cohort 5: PF-04856883 6.0 mg | Stage 1: Change From Baseline in 7-point Weighted Mean Glucose at Day 3 and Day 7 | Change at Day 3 | 20.2 milligram per deciliter(mg/dL) | Standard Deviation 18.4 |
| Cohort 5: PF-04856883 6.0 mg | Stage 1: Change From Baseline in 7-point Weighted Mean Glucose at Day 3 and Day 7 | Change at Day 7 | 7.05 milligram per deciliter(mg/dL) | Standard Deviation 53.2 |
| Cohort 6: PF-04856883 12.0 mg | Stage 1: Change From Baseline in 7-point Weighted Mean Glucose at Day 3 and Day 7 | Change at Day 7 | -20.5 milligram per deciliter(mg/dL) | Standard Deviation 10.2 |
| Cohort 6: PF-04856883 12.0 mg | Stage 1: Change From Baseline in 7-point Weighted Mean Glucose at Day 3 and Day 7 | Change at Day 3 | -15.7 milligram per deciliter(mg/dL) | Standard Deviation 12.4 |
| Cohort 7: PF-04856883 24.0 mg | Stage 1: Change From Baseline in 7-point Weighted Mean Glucose at Day 3 and Day 7 | Change at Day 7 | -33.9 milligram per deciliter(mg/dL) | Standard Deviation 42.1 |
| Cohort 7: PF-04856883 24.0 mg | Stage 1: Change From Baseline in 7-point Weighted Mean Glucose at Day 3 and Day 7 | Change at Day 3 | -31.7 milligram per deciliter(mg/dL) | Standard Deviation 30.5 |
| Cohort 8: PF-04856883 36.0 mg | Stage 1: Change From Baseline in 7-point Weighted Mean Glucose at Day 3 and Day 7 | Change at Day 3 | -26.4 milligram per deciliter(mg/dL) | Standard Deviation 22.9 |
| Cohort 8: PF-04856883 36.0 mg | Stage 1: Change From Baseline in 7-point Weighted Mean Glucose at Day 3 and Day 7 | Change at Day 7 | -24.4 milligram per deciliter(mg/dL) | Standard Deviation 29.4 |
| Cohort 9: PF-04856883 18.0 mg | Stage 1: Change From Baseline in 7-point Weighted Mean Glucose at Day 3 and Day 7 | Change at Day 3 | -23.9 milligram per deciliter(mg/dL) | Standard Deviation 10.6 |
| Cohort 9: PF-04856883 18.0 mg | Stage 1: Change From Baseline in 7-point Weighted Mean Glucose at Day 3 and Day 7 | Change at Day 7 | -12.8 milligram per deciliter(mg/dL) | Standard Deviation 29.8 |
| Cohort 10: PF-04856883 15.0 mg | Stage 1: Change From Baseline in 7-point Weighted Mean Glucose at Day 3 and Day 7 | Change at Day 3 | 0.506 milligram per deciliter(mg/dL) | Standard Deviation 25 |
| Cohort 10: PF-04856883 15.0 mg | Stage 1: Change From Baseline in 7-point Weighted Mean Glucose at Day 3 and Day 7 | Change at Day 7 | -5.22 milligram per deciliter(mg/dL) | Standard Deviation 25.9 |
| Cohort 11: PF-04856883 20.0 mg | Stage 1: Change From Baseline in 7-point Weighted Mean Glucose at Day 3 and Day 7 | Change at Day 3 | -16.6 milligram per deciliter(mg/dL) | Standard Deviation 12 |
| Cohort 11: PF-04856883 20.0 mg | Stage 1: Change From Baseline in 7-point Weighted Mean Glucose at Day 3 and Day 7 | Change at Day 7 | -23.0 milligram per deciliter(mg/dL) | Standard Deviation 11 |
Other Pre-specified
Stage 1: Change From Baseline in Post-Prandial Area Under the Curve (AUC) of Glucose at Day 3 and 7
Area under the glucose concentration-time curve from 0 minute (approximately 20 minutes prior to the meal) to 180 minutes post initiation of meal.
Time frame: Baseline, Day 3 and 7
Population: Pharmacodynamic analysis population included all randomized participants who had received at least 1 dose of study medication and had PD data. Here, number analyzed signifies those participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: PF-04856883 0.1 Milligram (mg) | Stage 1: Change From Baseline in Post-Prandial Area Under the Curve (AUC) of Glucose at Day 3 and 7 | Change at Day 3 | 1.44 milligram*hour per deciliter (mg*hr)/dL | Standard Deviation 102 |
| Cohort 1: PF-04856883 0.1 Milligram (mg) | Stage 1: Change From Baseline in Post-Prandial Area Under the Curve (AUC) of Glucose at Day 3 and 7 | Change at Day 7 | -38.8 milligram*hour per deciliter (mg*hr)/dL | Standard Deviation 95.5 |
| Cohort 2: PF-04856883 0.3 mg | Stage 1: Change From Baseline in Post-Prandial Area Under the Curve (AUC) of Glucose at Day 3 and 7 | Change at Day 7 | 29.3 milligram*hour per deciliter (mg*hr)/dL | Standard Deviation 161 |
| Cohort 2: PF-04856883 0.3 mg | Stage 1: Change From Baseline in Post-Prandial Area Under the Curve (AUC) of Glucose at Day 3 and 7 | Change at Day 3 | 44.9 milligram*hour per deciliter (mg*hr)/dL | Standard Deviation 76.8 |
| Cohort 3: PF-04856883 1.0 mg | Stage 1: Change From Baseline in Post-Prandial Area Under the Curve (AUC) of Glucose at Day 3 and 7 | Change at Day 7 | -147 milligram*hour per deciliter (mg*hr)/dL | Standard Deviation 93.4 |
| Cohort 3: PF-04856883 1.0 mg | Stage 1: Change From Baseline in Post-Prandial Area Under the Curve (AUC) of Glucose at Day 3 and 7 | Change at Day 3 | -92.3 milligram*hour per deciliter (mg*hr)/dL | Standard Deviation 78.2 |
| Cohort 4: PF-04856883 3.0 mg | Stage 1: Change From Baseline in Post-Prandial Area Under the Curve (AUC) of Glucose at Day 3 and 7 | Change at Day 3 | -54.0 milligram*hour per deciliter (mg*hr)/dL | Standard Deviation 60 |
| Cohort 4: PF-04856883 3.0 mg | Stage 1: Change From Baseline in Post-Prandial Area Under the Curve (AUC) of Glucose at Day 3 and 7 | Change at Day 7 | -23.0 milligram*hour per deciliter (mg*hr)/dL | Standard Deviation 125 |
| Cohort 5: PF-04856883 6.0 mg | Stage 1: Change From Baseline in Post-Prandial Area Under the Curve (AUC) of Glucose at Day 3 and 7 | Change at Day 3 | 46.7 milligram*hour per deciliter (mg*hr)/dL | Standard Deviation 70.9 |
| Cohort 5: PF-04856883 6.0 mg | Stage 1: Change From Baseline in Post-Prandial Area Under the Curve (AUC) of Glucose at Day 3 and 7 | Change at Day 7 | 65.1 milligram*hour per deciliter (mg*hr)/dL | Standard Deviation 85.1 |
| Cohort 6: PF-04856883 12.0 mg | Stage 1: Change From Baseline in Post-Prandial Area Under the Curve (AUC) of Glucose at Day 3 and 7 | Change at Day 7 | -39.6 milligram*hour per deciliter (mg*hr)/dL | Standard Deviation 52.6 |
| Cohort 6: PF-04856883 12.0 mg | Stage 1: Change From Baseline in Post-Prandial Area Under the Curve (AUC) of Glucose at Day 3 and 7 | Change at Day 3 | -74.5 milligram*hour per deciliter (mg*hr)/dL | Standard Deviation 59.7 |
| Cohort 7: PF-04856883 24.0 mg | Stage 1: Change From Baseline in Post-Prandial Area Under the Curve (AUC) of Glucose at Day 3 and 7 | Change at Day 3 | -140 milligram*hour per deciliter (mg*hr)/dL | Standard Deviation 124 |
| Cohort 7: PF-04856883 24.0 mg | Stage 1: Change From Baseline in Post-Prandial Area Under the Curve (AUC) of Glucose at Day 3 and 7 | Change at Day 7 | -108 milligram*hour per deciliter (mg*hr)/dL | Standard Deviation 139 |
| Cohort 8: PF-04856883 36.0 mg | Stage 1: Change From Baseline in Post-Prandial Area Under the Curve (AUC) of Glucose at Day 3 and 7 | Change at Day 3 | -80.1 milligram*hour per deciliter (mg*hr)/dL | Standard Deviation 70.6 |
| Cohort 8: PF-04856883 36.0 mg | Stage 1: Change From Baseline in Post-Prandial Area Under the Curve (AUC) of Glucose at Day 3 and 7 | Change at Day 7 | -38.4 milligram*hour per deciliter (mg*hr)/dL | Standard Deviation 66.7 |
| Cohort 9: PF-04856883 18.0 mg | Stage 1: Change From Baseline in Post-Prandial Area Under the Curve (AUC) of Glucose at Day 3 and 7 | Change at Day 7 | -119 milligram*hour per deciliter (mg*hr)/dL | Standard Deviation 81.7 |
| Cohort 10: PF-04856883 15.0 mg | Stage 1: Change From Baseline in Post-Prandial Area Under the Curve (AUC) of Glucose at Day 3 and 7 | Change at Day 3 | -10.6 milligram*hour per deciliter (mg*hr)/dL | Standard Deviation 95.3 |
| Cohort 10: PF-04856883 15.0 mg | Stage 1: Change From Baseline in Post-Prandial Area Under the Curve (AUC) of Glucose at Day 3 and 7 | Change at Day 7 | -9.04 milligram*hour per deciliter (mg*hr)/dL | Standard Deviation 119 |
| Cohort 11: PF-04856883 20.0 mg | Stage 1: Change From Baseline in Post-Prandial Area Under the Curve (AUC) of Glucose at Day 3 and 7 | Change at Day 7 | -46.1 milligram*hour per deciliter (mg*hr)/dL | Standard Deviation 6.98 |
Other Pre-specified
Stage 1: Number of Participants With Anti-Drug Antibodies
Time frame: Day 0, 8, 14, 15, 21, 28 and 35
Population: Safety population included all randomized participants who received at least 1 dose of study medication. Here, number analyzed signifies those participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: PF-04856883 0.1 Milligram (mg) | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 0 | 1 Participants |
| Cohort 1: PF-04856883 0.1 Milligram (mg) | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 14 | 0 Participants |
| Cohort 1: PF-04856883 0.1 Milligram (mg) | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 28 | 0 Participants |
| Cohort 1: PF-04856883 0.1 Milligram (mg) | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 8 | 0 Participants |
| Cohort 1: PF-04856883 0.1 Milligram (mg) | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 21 | 0 Participants |
| Cohort 2: PF-04856883 0.3 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 14 | 2 Participants |
| Cohort 2: PF-04856883 0.3 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 21 | 2 Participants |
| Cohort 2: PF-04856883 0.3 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 8 | 2 Participants |
| Cohort 2: PF-04856883 0.3 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 28 | 2 Participants |
| Cohort 2: PF-04856883 0.3 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 0 | 2 Participants |
| Cohort 3: PF-04856883 1.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 14 | 2 Participants |
| Cohort 3: PF-04856883 1.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 21 | 1 Participants |
| Cohort 3: PF-04856883 1.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 8 | 1 Participants |
| Cohort 3: PF-04856883 1.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 28 | 1 Participants |
| Cohort 3: PF-04856883 1.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 0 | 1 Participants |
| Cohort 4: PF-04856883 3.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 8 | 2 Participants |
| Cohort 4: PF-04856883 3.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 28 | 2 Participants |
| Cohort 4: PF-04856883 3.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 21 | 2 Participants |
| Cohort 4: PF-04856883 3.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 14 | 2 Participants |
| Cohort 4: PF-04856883 3.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 0 | 3 Participants |
| Cohort 5: PF-04856883 6.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 0 | 1 Participants |
| Cohort 5: PF-04856883 6.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 8 | 0 Participants |
| Cohort 5: PF-04856883 6.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 28 | 1 Participants |
| Cohort 5: PF-04856883 6.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 21 | 1 Participants |
| Cohort 5: PF-04856883 6.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 14 | 1 Participants |
| Cohort 6: PF-04856883 12.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 21 | 2 Participants |
| Cohort 6: PF-04856883 12.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 0 | 1 Participants |
| Cohort 6: PF-04856883 12.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 8 | 1 Participants |
| Cohort 6: PF-04856883 12.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 28 | 1 Participants |
| Cohort 6: PF-04856883 12.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 14 | 1 Participants |
| Cohort 7: PF-04856883 24.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 14 | 3 Participants |
| Cohort 7: PF-04856883 24.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 8 | 2 Participants |
| Cohort 7: PF-04856883 24.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 0 | 3 Participants |
| Cohort 7: PF-04856883 24.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 28 | 4 Participants |
| Cohort 7: PF-04856883 24.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 21 | 4 Participants |
| Cohort 8: PF-04856883 36.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 28 | 2 Participants |
| Cohort 8: PF-04856883 36.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 8 | 2 Participants |
| Cohort 8: PF-04856883 36.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 14 | 2 Participants |
| Cohort 8: PF-04856883 36.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 0 | 2 Participants |
| Cohort 8: PF-04856883 36.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 21 | 2 Participants |
| Cohort 9: PF-04856883 18.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 21 | 1 Participants |
| Cohort 9: PF-04856883 18.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 0 | 1 Participants |
| Cohort 9: PF-04856883 18.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 8 | 0 Participants |
| Cohort 9: PF-04856883 18.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 15 | 0 Participants |
| Cohort 9: PF-04856883 18.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 35 | 0 Participants |
| Cohort 10: PF-04856883 15.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 14 | 1 Participants |
| Cohort 10: PF-04856883 15.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 0 | 1 Participants |
| Cohort 10: PF-04856883 15.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 28 | 1 Participants |
| Cohort 10: PF-04856883 15.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 8 | 1 Participants |
| Cohort 10: PF-04856883 15.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 21 | 1 Participants |
| Cohort 11: PF-04856883 20.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 21 | 0 Participants |
| Cohort 11: PF-04856883 20.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 15 | 0 Participants |
| Cohort 11: PF-04856883 20.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 8 | 0 Participants |
| Cohort 11: PF-04856883 20.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 0 | 0 Participants |
| Cohort 11: PF-04856883 20.0 mg | Stage 1: Number of Participants With Anti-Drug Antibodies | Day 35 | 0 Participants |
Other Pre-specified
Stage 1: Number of Participants With Clinically Significant Abnormal Rhythms
Criteria for abnormal rhythms: asymptomatic marked sinus bradycardia rate \<35 bpm; asymptomatic supraventricular couplets, atrial bigeminy lasting \>30 seconds; asymptomatic ventricular couplets, ventricular bigeminy lasting \>30 seconds; asymptomatic type I second degree (wenckebach) atrioventricular block of \>30 seconds duration; asymptomatic frequent premature ventricular complexes (=\>200/24 hours); asymptomatic frequent premature atrial complexes (=\>240/24 hours).
Time frame: Cohort 1- 8: Day 1 up to Day 3; Cohort 9: Day 1 up to Day 10
Population: Safety population will consist of all randomized patients who received at least 1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: PF-04856883 0.1 Milligram (mg) | Stage 1: Number of Participants With Clinically Significant Abnormal Rhythms | 0 Participants |
| Cohort 2: PF-04856883 0.3 mg | Stage 1: Number of Participants With Clinically Significant Abnormal Rhythms | 0 Participants |
| Cohort 3: PF-04856883 1.0 mg | Stage 1: Number of Participants With Clinically Significant Abnormal Rhythms | 0 Participants |
| Cohort 4: PF-04856883 3.0 mg | Stage 1: Number of Participants With Clinically Significant Abnormal Rhythms | 0 Participants |
| Cohort 5: PF-04856883 6.0 mg | Stage 1: Number of Participants With Clinically Significant Abnormal Rhythms | 0 Participants |
| Cohort 6: PF-04856883 12.0 mg | Stage 1: Number of Participants With Clinically Significant Abnormal Rhythms | 0 Participants |
| Cohort 7: PF-04856883 24.0 mg | Stage 1: Number of Participants With Clinically Significant Abnormal Rhythms | 0 Participants |
| Cohort 8: PF-04856883 36.0 mg | Stage 1: Number of Participants With Clinically Significant Abnormal Rhythms | 0 Participants |
| Cohort 9: PF-04856883 18.0 mg | Stage 1: Number of Participants With Clinically Significant Abnormal Rhythms | 0 Participants |
| Cohort 10: PF-04856883 15.0 mg | Stage 1: Number of Participants With Clinically Significant Abnormal Rhythms | 0 Participants |
| Cohort 11: PF-04856883 20.0 mg | Stage 1: Number of Participants With Clinically Significant Abnormal Rhythms | 0 Participants |
Other Pre-specified
Stage 1: Number of Participants With Hypoglycemia
Blood glucose level was checked for hypoglycemia by glucometer. Criteria for hypoglycemia: blood glucose level \<60 mg/dL if accompanied by symptoms, blood glucose level \<=50 mg/dL regardless of symptoms.
Time frame: Day 1: 0 hour (pre-dose) up to 48 hours post dose
Population: Safety population included all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: PF-04856883 0.1 Milligram (mg) | Stage 1: Number of Participants With Hypoglycemia | 0 Participants |
| Cohort 2: PF-04856883 0.3 mg | Stage 1: Number of Participants With Hypoglycemia | 0 Participants |
| Cohort 3: PF-04856883 1.0 mg | Stage 1: Number of Participants With Hypoglycemia | 0 Participants |
| Cohort 4: PF-04856883 3.0 mg | Stage 1: Number of Participants With Hypoglycemia | 0 Participants |
| Cohort 5: PF-04856883 6.0 mg | Stage 1: Number of Participants With Hypoglycemia | 0 Participants |
| Cohort 6: PF-04856883 12.0 mg | Stage 1: Number of Participants With Hypoglycemia | 0 Participants |
| Cohort 7: PF-04856883 24.0 mg | Stage 1: Number of Participants With Hypoglycemia | 0 Participants |
| Cohort 8: PF-04856883 36.0 mg | Stage 1: Number of Participants With Hypoglycemia | 0 Participants |
| Cohort 9: PF-04856883 18.0 mg | Stage 1: Number of Participants With Hypoglycemia | 0 Participants |
| Cohort 10: PF-04856883 15.0 mg | Stage 1: Number of Participants With Hypoglycemia | 0 Participants |
| Cohort 11: PF-04856883 20.0 mg | Stage 1: Number of Participants With Hypoglycemia | 0 Participants |
Other Pre-specified
Stage 2: Number of Participants With Anti-Drug Antibodies
Time frame: Day 0, 29 and 50
Population: Safety population included all randomized participants who received at least 1 dose of study medication. Here, number analyzed signifies those participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: PF-04856883 0.1 Milligram (mg) | Stage 2: Number of Participants With Anti-Drug Antibodies | Day 0 (n= 9, 9, 13 ,9) | 1 Participants |
| Cohort 1: PF-04856883 0.1 Milligram (mg) | Stage 2: Number of Participants With Anti-Drug Antibodies | Day 50 (n= 9, 8, 8, 8) | 0 Participants |
| Cohort 1: PF-04856883 0.1 Milligram (mg) | Stage 2: Number of Participants With Anti-Drug Antibodies | Day 29 (n= 9, 8, 7, 8) | 0 Participants |
| Cohort 2: PF-04856883 0.3 mg | Stage 2: Number of Participants With Anti-Drug Antibodies | Day 0 (n= 9, 9, 13 ,9) | 1 Participants |
| Cohort 2: PF-04856883 0.3 mg | Stage 2: Number of Participants With Anti-Drug Antibodies | Day 50 (n= 9, 8, 8, 8) | 3 Participants |
| Cohort 2: PF-04856883 0.3 mg | Stage 2: Number of Participants With Anti-Drug Antibodies | Day 29 (n= 9, 8, 7, 8) | 1 Participants |
| Cohort 3: PF-04856883 1.0 mg | Stage 2: Number of Participants With Anti-Drug Antibodies | Day 29 (n= 9, 8, 7, 8) | 2 Participants |
| Cohort 3: PF-04856883 1.0 mg | Stage 2: Number of Participants With Anti-Drug Antibodies | Day 0 (n= 9, 9, 13 ,9) | 2 Participants |
| Cohort 3: PF-04856883 1.0 mg | Stage 2: Number of Participants With Anti-Drug Antibodies | Day 50 (n= 9, 8, 8, 8) | 3 Participants |
| Cohort 4: PF-04856883 3.0 mg | Stage 2: Number of Participants With Anti-Drug Antibodies | Day 0 (n= 9, 9, 13 ,9) | 0 Participants |
| Cohort 4: PF-04856883 3.0 mg | Stage 2: Number of Participants With Anti-Drug Antibodies | Day 50 (n= 9, 8, 8, 8) | 0 Participants |
| Cohort 4: PF-04856883 3.0 mg | Stage 2: Number of Participants With Anti-Drug Antibodies | Day 29 (n= 9, 8, 7, 8) | 0 Participants |