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

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

A Phase 1, Double-blind, Placebo-controlled, Randomized, Parallel Group Study To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Pf-04856883 In Adult Female Subjects With Type 2 Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01301456
• Other study ID #: B1111002
• Status: Completed
• Phase: Phase 1
• First received: February 9, 2011
• Last updated: July 28, 2017
• Start date: March 2011
• Est. completion date: April 2012

Study information

• Verified date: July 2017
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: April 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• History of Type 2 diabetes and currently being treated with high dose metformin

• BMI between 22.0 and 40.0 kg/m2

• HbA1c between 7.0-10.0%

• Fasting C-peptide >1.21 ng/mL

Exclusion Criteria:

• History of clinically significant chronic conditions other than Type 2 diabetes not well controlled by either diet or medications

• Treatment with anti-diabetic therapies other than metformin

• History of allergic or anaphylactic reaction to any therapeutic or diagnostic monoclonal antibody

• Males or women of childbearing potential

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Endocrine System Diseases
• Glucose Metabolism Disorders
• Metabolic Diseases

Intervention

Biological:
• Placebo
Single subcutaneous injection of placebo
• PF-04856883
Single subcutaneous injection of PF-04856883
• PF-04856883
Single subcutaneous injection of PF-04856883
• PF-04856883
Single subcutaneous injection of PF-04856883
• Placebo
Single subcutaneous injection of placebo
• PF-04856883
Single subcutaneous injection of PF-04856883
• PF-04856883
Single subcutaneous injection of PF-04856883
• PF-04856883
Single subcutaneous injection of PF-04856883
• Placebo
Multiple weekly subcutaneous injections of placebo for 3 weeks
• PF-04856883
Multiple weekly subcutaneous injections of PF-04856883 for 3 weeks
• PF-04856883
Multiple weekly subcutaneous injections of PF-04856883 for 3 weeks
• PF-04856883
Multiple weekly subcutaneous injections of PF-04856883 for 3 weeks
• PF-04856883
Multiple weekly subcutaneous injections of PF-04856883 for 3 weeks

Locations

Country	Name	City	State
United States	Atlanta Center for Medical Research	Atlanta	Georgia
United States	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	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

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Stage 1: Baseline up to Day 29; Stage 2: Baseline up to Day 50
Primary	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.	Stage 1: Baseline up to Day 29; Stage 2: Baseline up to Day 50
Primary	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.	Stage 1: Baseline up to Day 29; Stage 2: Baseline up to Day 50
Primary	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.	Stage 1: Baseline up to Day 29; Stage 2 : Baseline up to Day 50
Primary	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).	Stage 1: Baseline up to Day 29; Stage 2: Baseline up to Day 50
Secondary	Maximum Observed Plasma Concentration (Cmax) of PF-04856883: Stage 1		predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 1
Secondary	Maximum Observed Plasma Concentration (Cmax) of PF-04856883: Stage 2		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
Secondary	Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04856883: Stage 1		predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 1
Secondary	Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04856883: Stage 2		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
Secondary	Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - 8]) of PF-04856883: Stage 1	AUC (0 - 8) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8).	predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 1
Secondary	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.	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
Secondary	Apparent Clearance (CL/F) of PF-04856883: Stage 1	It was calculated by dividing dose with AUC (0 - 8) where AUC (0 - 8) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). Outcome measure was planned to be analyzed in Stage 1 only.	predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 1
Secondary	Apparent Clearance (CL/F) of PF-04856883: Stage 2	It was calculated by dividing dose with AUC (0 - 8) where AUC (0 - 8) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). Outcome measure was planned to be analyzed in Stage 2 only. Data was not estimable if values were below the limit of quantification.	predose (0 hour), 1, 2, 6, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 22
Secondary	Apparent Volume of Distribution (Vz/F) of PF-04856883: Stage 1		predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 1
Secondary	Apparent Volume of Distribution (Vz/F) of PF-04856883: Stage 2		predose (0 hour), 1, 2, 6, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 22
Secondary	Terminal Elimination Half- Life (t1/2) of PF-04856883: Stage 1		predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 1
Secondary	Terminal Elimination Half-life (t1/2) of PF-04856883: Stage 2		predose (0 hour), 1, 2, 6, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 22
Secondary	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	Baseline, Day 3 and 8
Secondary	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.	Baseline, Day 3, 15, 24, 29 and 50
Secondary	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.	Baseline, Day 3 and 8
Secondary	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.	Baseline, Day 3, 15, 24, 29 and 50
Secondary	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.	Baseline, Day 3 and 8
Secondary	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.	Baseline, Day 3, 15, 24, 29 and 50
Secondary	Change From Baseline in Fasting Plasma Glucose (FPG) at Day 2, 4, 6, 15, 22 and 29: Stage 1		Baseline, Day 2, 4, 6, 15, 22 and 29
Secondary	Change From Baseline in Fasting Plasma Glucose (FPG) at Day 2, 4, 6, 8, 22, 23, 25, 27, 30, 36 and 43: Stage 2		Baseline, Day 2, 4, 6, 8, 22, 23, 25, 27, 30, 36 and 43
Secondary	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.	Baseline, Day 30
Secondary	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.	Baseline, Day 29 and 50
Secondary	Change From Baseline in Fructosamine Levels at Day 8, 15 and 29: Stage 1		Baseline, Day 8, 15 and 29
Secondary	Change From Baseline in Fructosamine Levels at Day 8, 15, 22, 29 and 50: Stage 2		Baseline, Day 8, 15, 22, 29 and 50
Secondary	Change From Baseline in 1, 5 Anhydroglucitol at Day 8, 15 and 29: Stage 1		Baseline, Day 8, 15 and 29
Secondary	Change From Baseline in 1, 5 Anhydroglucitol at Day 8, 15, 22, 29 and 50: Stage 2		Baseline, Day 8, 15, 22, 29 and 50
Secondary	Number of Participants With Anti-Drug Antibodies (ADA): Stage 1		Day 1 and 29
Secondary	Number of Participant With Anti-Drug Antibodies (ADA): Stage 2		Day 1, 29 and 50

External Links

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