Single-Dose And Multiple-Dose Safety And Tolerability Study Of PF-04856883 In Type 2 Diabetic Adult Females

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 (Day 50) that were absent before treatment or that worsened relative to pretreatment state.

Physical examination included examination of general appearance, head, ears, eyes (including fundoscopy), nose, mouth, throat, neck (including thyroid), skin, breast (optional), cardiac, respiratory, gastrointestinal, musculoskeletal and neurological systems.

ECG parameters included pulse rate (PR) interval, QRS interval, corrected QT interval using Bazett's formula (QTcB) and corrected QT interval using Fridericia's formula (QTcF). ECG criteria of clinically significant concern were 1) PR interval: greater than equal to (>=) 25 percent (%) increase when baseline greater than (>)200 milliseconds (msec); or increase >=50% when baseline less than or equal to (<=200) msec; 2) QRS interval: >=25% increase when baseline >100 msec; >=50% increase when baseline <= 100 msec; 3) QTCF interval: QTc interval using Fridericia's formula (QTcF interval) and Bazett's formula (QTcB interval): absolute value 450 - <480 msec, 480 - <500 msec >=500; absolute change 30 - <60, >=60 msec. The number of participants with potentially clinically significant ECG findings at any visit were reported. IFB = increase from baseline.

Criteria for vital signs abnormalities: sitting/supine systolic pulse rate less than (<) 40 beats per minute (bpm) or greater than (>) 120 bpm, standing/supine systolic pulse < 40 bpm or > 140 bpm, systolic blood pressure of >=30 millimeters of mercury (mmHg) change from baseline and systolic blood pressure <90 mmHg, diastolic blood pressure >=20 mmHg change from baseline and diastolic blood pressure <50 mm Hg.

Following parameters were analyzed for laboratory examination: Hematology: hemoglobin, hematocrit, red blood cell (RBC) <0.8*lower limit of the reference range (LLRR); leukocytes <0.6*LLRR or >1.5*ULRR; platelet count <0.5*LLRR or >1.75*upper limit of the reference range (ULRR); total neutrophils (absolute [abs]), lymphocytes (abs) <0.8*LLRR or >1.2*ULRR; eosinophils (abs), basophils (abs), monocytes (abs) >1.2*ULRR; chemistry (total bilirubin, direct bilirubin, indirect bilirubin >1.5*ULRR; aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase >3*ULRR, albumin, total protein <0.8*LLRR or >1.2*ULRR; blood urea nitrogen (BUN), creatinine >1.3*ULRR; glucose (fasting) <0.6*LLRR or >1.5*ULRR; uric acid >1.2* ULRR; sodium <0.95*LLRR or >1.05*ULRR; potassium, chloride, bicarbonate, calcium <0.9*LLRR or >1.1*ULRR. Urinalysis: Urine white blood cell (WBC), Urine RBC =>20/ high-power field (HPF).

AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).

Area under the serum concentration-time curve from time 0 to tau (AUCtau), where tau was the dosing interval of 168 hours.

It was calculated by dividing dose with AUC (0 - ∞) where AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). Outcome measure was planned to be analyzed in Stage 1 only.

It was calculated by dividing dose with AUC (0 - ∞) where AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). Outcome measure was planned to be analyzed in Stage 2 only. Data was not estimable if values were below the limit of quantification.

Change from baseline in post-prandial area under the plasma glucose concentration time curve as determined by standardized MMTT. Linear trapezoidal method was used to compute AUC

Change from baseline in post-prandial area under the plasma glucose concentration time curve as determined by standardized MMTT. Linear trapezoidal method was used to compute AUC.

Change from baseline in post-prandial plasma insulin AUC under the plasma insulin concentration versus time curve as determined by standardized MMTT. Linear trapezoidal method was used to compute AUC.

Change from baseline in post-prandial plasma insulin AUC under the plasma insulin concentration versus time curve as determined by standardized MMTT. Linear trapezoidal method was used to compute AUC.

Change from baseline in post-prandial area under the plasma C-peptide concentration time curve as determined by standardized MMTT. Linear trapezoidal method was used to compute AUC.

Change from baseline in post-prandial area under the plasma C-peptide concentration time curve as determined by standardized MMTT. Linear trapezoidal method was used to compute AUC.

A normalized area under the curve (NAUC) were computed by dividing the AUC by the amount of time between the last time point captured and the first time point captured.

HbA1c is a measure of the glycosylated hemoglobin. Change (measured as percent): HbA1c at observation minus HbA1c at baseline. Outcome measure was planned to analyzed only for Stage 2.