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

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ClinicalTrials.gov Identifier: NCT01301456
Recruitment Status : Completed
First Posted : February 23, 2011
Results First Posted : February 9, 2018
Last Update Posted : February 9, 2018
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief 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.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus Diabetes Mellitus, Type 2 Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Biological: Placebo Biological: PF-04856883 Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 84 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : March 2011
Primary Completion Date : December 2011
Study Completion Date : April 2012

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Placebo Comparator: Treatment Arm 1 (Stage 1A) Biological: Placebo
Single subcutaneous injection of placebo
Experimental: Treatment Arm 2 (Stage 1A) Biological: PF-04856883
Single subcutaneous injection of PF-04856883
Other Name: CVX-096
Experimental: Treatment Arm 3 (Stage 1A) Biological: PF-04856883
Single subcutaneous injection of PF-04856883
Other Name: CVX-096
Experimental: Treatment Arm 4 (Stage 1A) Biological: PF-04856883
Single subcutaneous injection of PF-04856883
Other Name: CVX-096
Placebo Comparator: Treatment Arm 5 (Stage 1B) Biological: Placebo
Single subcutaneous injection of placebo
Experimental: Treatment Arm 6 (Stage 1B) Biological: PF-04856883
Single subcutaneous injection of PF-04856883
Other Name: CVX-096
Experimental: Treatment Arm 7 (Stage 1B) Biological: PF-04856883
Single subcutaneous injection of PF-04856883
Other Name: CVX-096
Experimental: Treatment Arm 8 (Stage 1B) Biological: PF-04856883
Single subcutaneous injection of PF-04856883
Other Name: CVX-096
Placebo Comparator: Treatment Arm 9 (Stage 2) Biological: Placebo
Multiple weekly subcutaneous injections of placebo for 3 weeks
Other Name: CVX-096
Experimental: Treatment Arm 10 (Stage 2) Biological: PF-04856883
Multiple weekly subcutaneous injections of PF-04856883 for 3 weeks
Other Name: CVX-096
Experimental: Treatment Arm 11 (Stage 2) Biological: PF-04856883
Multiple weekly subcutaneous injections of PF-04856883 for 3 weeks
Other Name: CVX-096
Experimental: Treatment Arm 12 (Stage 2) Biological: PF-04856883
Multiple weekly subcutaneous injections of PF-04856883 for 3 weeks
Other Name: CVX-096
Experimental: Treatment Arm 13 (Stage 2) Biological: PF-04856883
Multiple weekly subcutaneous injections of PF-04856883 for 3 weeks
Other Name: CVX-096



Primary Outcome Measures :
  1. Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [ Time Frame: Stage 1: Baseline up to Day 29; Stage 2: 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 (Day 50) that were absent before treatment or that worsened relative to pretreatment state.

  2. Number of Participants With Clinically Significant Physical Examination Findings [ Time Frame: Stage 1: Baseline up to Day 29; Stage 2: Baseline up to Day 50 ]
    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.

  3. Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiograms (ECG) [ Time Frame: Stage 1: Baseline up to Day 29; Stage 2: Baseline up to Day 50 ]
    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.

  4. Number of Participants With Vital Sign Abnormalities [ Time Frame: Stage 1: Baseline up to Day 29; Stage 2 : Baseline up to Day 50 ]
    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.

  5. Number of Participants With Clinically Significant Abnormalities in Laboratory Measurements [ Time Frame: Stage 1: Baseline up to Day 29; Stage 2: Baseline up to Day 50 ]
    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).


Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞]) 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 ]
    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 - ∞).

  6. Area Under the Concentration Time Curve From Time Zero to Time Tau (AUCtau) of PF-04856883: Stage 2 [ 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 ]
    Area under the serum concentration-time curve from time 0 to tau (AUCtau), where tau was the dosing interval of 168 hours.

  7. Apparent Clearance (CL/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 ]
    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.

  8. Apparent Clearance (CL/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 ]
    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.

  9. 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 ]
  10. 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 ]
  11. 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 ]
  12. 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 ]
  13. 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 [ Time Frame: Baseline, Day 3 and 8 ]
    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

  14. 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 [ Time Frame: Baseline, Day 3, 15, 24, 29 and 50 ]
    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.

  15. Change From Baseline in Insulin Area Under the Curve (AUC) After Mixed Meal Tolerance Test (MMTT) at Day 3 and 8: Stage 1 [ Time Frame: Baseline, Day 3 and 8 ]
    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.

  16. 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 [ Time Frame: Baseline, Day 3, 15, 24, 29 and 50 ]
    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.

  17. Change From Baseline in C-Peptide Area Under the Curve (AUC) After Mixed Meal Tolerance Test (MMTT) at Day 3 and 8: Stage 1 [ Time Frame: Baseline, Day 3 and 8 ]
    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.

  18. 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 [ Time Frame: Baseline, Day 3, 15, 24, 29 and 50 ]
    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.

  19. 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 ]
  20. 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 ]
  21. Change From Baseline in 24 Hours Glucose Normalized Area Under the Curve (NAUC) Profile at Day 30: Stage 2 [ Time Frame: Baseline, Day 30 ]
    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.

  22. Percent Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Day 29 and 50: Stage 2 [ Time Frame: Baseline, Day 29 and 50 ]
    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.

  23. Change From Baseline in Fructosamine Levels at Day 8, 15 and 29: Stage 1 [ Time Frame: Baseline, Day 8, 15 and 29 ]
  24. 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 ]
  25. Change From Baseline in 1, 5 Anhydroglucitol at Day 8, 15 and 29: Stage 1 [ Time Frame: Baseline, Day 8, 15 and 29 ]
  26. 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 ]
  27. Number of Participants With Anti-Drug Antibodies (ADA): Stage 1 [ Time Frame: Day 1 and 29 ]
  28. Number of Participant With Anti-Drug Antibodies (ADA): Stage 2 [ Time Frame: Day 1, 29 and 50 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01301456


Locations
United States, California
Profil Institute for Clinical Research, Inc.
Chula Vista, California, United States, 91911
United States, Florida
Elite Research Institute
Miami, Florida, United States, 33169
Comprehensive Phase One (A Division of Comprehensive NeuroScience, Inc.)
Miramar, Florida, United States, 33025
United States, Georgia
Atlanta Center for Medical Research
Atlanta, Georgia, United States, 30308
United States, Nebraska
ICON Clinical Pharmacology, LLC
Omaha, Nebraska, United States, 68154
United States, Pennsylvania
CRI Worldwide, LLC
Philadelphia, Pennsylvania, United States, 19139
United States, Texas
Healthcare Discoveries LLC d/b/a ICON Development Solutions
San Antonio, Texas, United States, 78209
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01301456     History of Changes
Other Study ID Numbers: B1111002
First Posted: February 23, 2011    Key Record Dates
Results First Posted: February 9, 2018
Last Update Posted: February 9, 2018
Last Verified: July 2017

Keywords provided by Pfizer:
Phase 1
Type 2 Diabetes
CVX-096

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Metabolic Diseases
Glucose Metabolism Disorders
Endocrine System Diseases