The primary objective of this study is to evaluate the safety and tolerability of PF-04856883 (CVX-096) in adult female subjects with Type 2 diabetes mellitus on high dose of metformin.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
84
Single subcutaneous injection of placebo
Single subcutaneous injection of PF-04856883
Single subcutaneous injection of PF-04856883
Profil Institute for Clinical Research, Inc.
Chula Vista, California, United States
Elite Research Institute
Miami, Florida, United States
Comprehensive Phase One (A Division of Comprehensive NeuroScience, Inc.)
Miramar, Florida, United States
Atlanta Center for Medical Research
Atlanta, Georgia, United States
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.
Time frame: Stage 1: Baseline up to Day 29; Stage 2: Baseline up to Day 50
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.
Time frame: Stage 1: Baseline up to Day 29; Stage 2: Baseline up to Day 50
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.
Time frame: Stage 1: Baseline up to Day 29; Stage 2: Baseline up to Day 50
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Single subcutaneous injection of PF-04856883
Single subcutaneous injection of placebo
Single subcutaneous injection of PF-04856883
Single subcutaneous injection of PF-04856883
Single subcutaneous injection of PF-04856883
Multiple weekly subcutaneous injections of placebo for 3 weeks
Multiple weekly subcutaneous injections of PF-04856883 for 3 weeks
Multiple weekly subcutaneous injections of PF-04856883 for 3 weeks
Multiple weekly subcutaneous injections of PF-04856883 for 3 weeks
Multiple weekly subcutaneous injections of PF-04856883 for 3 weeks
ICON Clinical Pharmacology, LLC
Omaha, Nebraska, United States
CRI Worldwide, LLC
Philadelphia, Pennsylvania, United States
Healthcare Discoveries LLC d/b/a ICON Development Solutions
San Antonio, Texas, United States
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.
Time frame: Stage 1: Baseline up to Day 29; Stage 2 : Baseline up to Day 50
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).
Time frame: Stage 1: Baseline up to Day 29; Stage 2: Baseline up to Day 50
Maximum Observed Plasma Concentration (Cmax) of PF-04856883: Stage 1
Time frame: predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 1
Maximum Observed Plasma Concentration (Cmax) of PF-04856883: Stage 2
Time frame: predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336 hours postdose on Day 1; predose (0 hour), 1, 2, 6, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 22
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04856883: Stage 1
Time frame: predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 1
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04856883: Stage 2
Time frame: predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336 hours postdose on Day 1; predose (0 hour), 1, 2, 6, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 22
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 - ∞).
Time frame: predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 1
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.
Time frame: predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168 hours postdose Day 1; predose (0 hour), 1, 2, 6, 24, 48, 72, 120, 168 hours postdose Day 22
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.
Time frame: predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 1
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.
Time frame: predose (0 hour), 1, 2, 6, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 22
Apparent Volume of Distribution (Vz/F) of PF-04856883: Stage 1
Time frame: predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 1
Apparent Volume of Distribution (Vz/F) of PF-04856883: Stage 2
Time frame: predose (0 hour), 1, 2, 6, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 22
Terminal Elimination Half- Life (t1/2) of PF-04856883: Stage 1
Time frame: predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 1
Terminal Elimination Half-life (t1/2) of PF-04856883: Stage 2
Time frame: predose (0 hour), 1, 2, 6, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 22
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
Time frame: Baseline, Day 3 and 8
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.
Time frame: Baseline, Day 3, 15, 24, 29 and 50
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.
Time frame: Baseline, Day 3 and 8
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.
Time frame: Baseline, Day 3, 15, 24, 29 and 50
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.
Time frame: Baseline, Day 3 and 8
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.
Time frame: Baseline, Day 3, 15, 24, 29 and 50
Change From Baseline in Fasting Plasma Glucose (FPG) at Day 2, 4, 6, 15, 22 and 29: Stage 1
Time frame: Baseline, Day 2, 4, 6, 15, 22 and 29
Change From Baseline in Fasting Plasma Glucose (FPG) at Day 2, 4, 6, 8, 22, 23, 25, 27, 30, 36 and 43: Stage 2
Time frame: Baseline, Day 2, 4, 6, 8, 22, 23, 25, 27, 30, 36 and 43
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.
Time frame: Baseline, Day 30
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.
Time frame: Baseline, Day 29 and 50
Change From Baseline in Fructosamine Levels at Day 8, 15 and 29: Stage 1
Time frame: Baseline, Day 8, 15 and 29
Change From Baseline in Fructosamine Levels at Day 8, 15, 22, 29 and 50: Stage 2
Time frame: Baseline, Day 8, 15, 22, 29 and 50
Change From Baseline in 1, 5 Anhydroglucitol at Day 8, 15 and 29: Stage 1
Time frame: Baseline, Day 8, 15 and 29
Change From Baseline in 1, 5 Anhydroglucitol at Day 8, 15, 22, 29 and 50: Stage 2
Time frame: Baseline, Day 8, 15, 22, 29 and 50
Number of Participants With Anti-Drug Antibodies (ADA): Stage 1
Time frame: Day 1 and 29
Number of Participant With Anti-Drug Antibodies (ADA): Stage 2
Time frame: Day 1, 29 and 50