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

Placebo komparator: Treatment Arm 1 (Stage 1A)

Biologisk: Placebo

Single subcutaneous injection of placebo

Biologisk: Placebo

Multiple weekly subcutaneous injections of placebo for 3 weeks

Andre navn:

• CVX-096

Eksperimentell: Treatment Arm 2 (Stage 1A)

Biologisk: PF-04856883

Single subcutaneous injection of PF-04856883

Andre navn:

• CVX-096

Biologisk: PF-04856883

Multiple weekly subcutaneous injections of PF-04856883 for 3 weeks

Andre navn:

• CVX-096

Eksperimentell: Treatment Arm 3 (Stage 1A)

Biologisk: PF-04856883

Single subcutaneous injection of PF-04856883

Andre navn:

• CVX-096

Biologisk: PF-04856883

Multiple weekly subcutaneous injections of PF-04856883 for 3 weeks

Andre navn:

• CVX-096

Eksperimentell: Treatment Arm 4 (Stage 1A)

Biologisk: PF-04856883

Single subcutaneous injection of PF-04856883

Andre navn:

• CVX-096

Biologisk: PF-04856883

Multiple weekly subcutaneous injections of PF-04856883 for 3 weeks

Andre navn:

• CVX-096

Placebo komparator: Treatment Arm 5 (Stage 1B)

Biologisk: Placebo

Single subcutaneous injection of placebo

Biologisk: Placebo

Multiple weekly subcutaneous injections of placebo for 3 weeks

Andre navn:

• CVX-096

Eksperimentell: Treatment Arm 6 (Stage 1B)

Biologisk: PF-04856883

Single subcutaneous injection of PF-04856883

Andre navn:

• CVX-096

Biologisk: PF-04856883

Multiple weekly subcutaneous injections of PF-04856883 for 3 weeks

Andre navn:

• CVX-096

Eksperimentell: Treatment Arm 7 (Stage 1B)

Biologisk: PF-04856883

Single subcutaneous injection of PF-04856883

Andre navn:

• CVX-096

Biologisk: PF-04856883

Multiple weekly subcutaneous injections of PF-04856883 for 3 weeks

Andre navn:

• CVX-096

Eksperimentell: Treatment Arm 8 (Stage 1B)

Biologisk: PF-04856883

Single subcutaneous injection of PF-04856883

Andre navn:

• CVX-096

Biologisk: PF-04856883

Multiple weekly subcutaneous injections of PF-04856883 for 3 weeks

Andre navn:

• CVX-096

Placebo komparator: Treatment Arm 9 (Stage 2)

Biologisk: Placebo

Single subcutaneous injection of placebo

Biologisk: Placebo

Multiple weekly subcutaneous injections of placebo for 3 weeks

Andre navn:

• CVX-096

Eksperimentell: Treatment Arm 10 (Stage 2)

Biologisk: PF-04856883

Single subcutaneous injection of PF-04856883

Andre navn:

• CVX-096

Biologisk: PF-04856883

Multiple weekly subcutaneous injections of PF-04856883 for 3 weeks

Andre navn:

• CVX-096

Eksperimentell: Treatment Arm 11 (Stage 2)

Biologisk: PF-04856883

Single subcutaneous injection of PF-04856883

Andre navn:

• CVX-096

Biologisk: PF-04856883

Multiple weekly subcutaneous injections of PF-04856883 for 3 weeks

Andre navn:

• CVX-096

Eksperimentell: Treatment Arm 12 (Stage 2)

Biologisk: PF-04856883

Single subcutaneous injection of PF-04856883

Andre navn:

• CVX-096

Biologisk: PF-04856883

Multiple weekly subcutaneous injections of PF-04856883 for 3 weeks

Andre navn:

• CVX-096

Eksperimentell: Treatment Arm 13 (Stage 2)

Biologisk: PF-04856883

Single subcutaneous injection of PF-04856883

Andre navn:

• CVX-096

Biologisk: PF-04856883

Multiple weekly subcutaneous injections of PF-04856883 for 3 weeks

Andre navn:

• CVX-096

Number of Participants With Treatment-Emergent Adverse Events (AEs) or 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 (Day 50) that were absent before treatment or that worsened relative to pretreatment state.

Number of Participants With Clinically Significant Physical Examination Findings

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.

Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiograms (ECG)

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.

Number of Participants With Vital Sign Abnormalities

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.

Number of Participants With Clinically Significant Abnormalities in Laboratory Measurements

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).

Maximum Observed Plasma Concentration (Cmax) of PF-04856883: Stage 1

Maximum Observed Plasma Concentration (Cmax) of PF-04856883: Stage 2

Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04856883: Stage 1

Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04856883: Stage 2

Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞]) of PF-04856883: Stage 1

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 Concentration Time Curve From Time Zero to Time Tau (AUCtau) of PF-04856883: Stage 2

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

Apparent Clearance (CL/F) of PF-04856883: Stage 1

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.

Apparent Clearance (CL/F) of PF-04856883: Stage 2

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.

Apparent Volume of Distribution (Vz/F) of PF-04856883: Stage 1

Apparent Volume of Distribution (Vz/F) of PF-04856883: Stage 2

Terminal Elimination Half- Life (t1/2) of PF-04856883: Stage 1

Terminal Elimination Half-life (t1/2) of PF-04856883: Stage 2

Change From Baseline in Post-prandial Glucose Area Under the Curve (AUC) After Mixed Meal Tolerance Test (MMTT) at Day 3 and 8: Stage 1

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 Glucose Area Under the Curve (AUC) After Mixed Meal Tolerance Test (MMTT) at Day 3, 15, 24, 29 and 50: Stage 2

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 Insulin Area Under the Curve (AUC) After Mixed Meal Tolerance Test (MMTT) at Day 3 and 8: Stage 1

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 Insulin Area Under the Curve (AUC) After Mixed Meal Tolerance Test (MMTT) at Day 3, 15, 24, 29 and 50: Stage 2

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 C-Peptide Area Under the Curve (AUC) After Mixed Meal Tolerance Test (MMTT) at Day 3 and 8: Stage 1

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 C-Peptide Area Under the Curve (AUC) After Mixed Meal Tolerance Test (MMTT) at Day 3, 15, 24, 29 and 50: Stage 2

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 Fasting Plasma Glucose (FPG) at Day 2, 4, 6, 15, 22 and 29: Stage 1

Change From Baseline in Fasting Plasma Glucose (FPG) at Day 2, 4, 6, 8, 22, 23, 25, 27, 30, 36 and 43: Stage 2

Change From Baseline in 24 Hours Glucose Normalized Area Under the Curve (NAUC) Profile at Day 30: Stage 2

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.

Percent Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Day 29 and 50: Stage 2

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.

Change From Baseline in Fructosamine Levels at Day 8, 15 and 29: Stage 1

Change From Baseline in Fructosamine Levels at Day 8, 15, 22, 29 and 50: Stage 2

Change From Baseline in 1, 5 Anhydroglucitol at Day 8, 15 and 29: Stage 1

Change From Baseline in 1, 5 Anhydroglucitol at Day 8, 15, 22, 29 and 50: Stage 2

Number of Participants With Anti-Drug Antibodies (ADA): Stage 1

Number of Participant With Anti-Drug Antibodies (ADA): Stage 2