Multiple Dose Escalation Trial Of PF-04603629 Given To Subjects With Type 2 Diabetes Mellitus

• ClinicalTrials.gov Identifier: NCT00637338
• Recruitment Status: Terminated
• First Posted: March 17, 2008
• Last Update Posted: July 31, 2009
• Sponsor: Pfizer
• Information provided by: Pfizer

Tracking Information

• First Submitted Date: March 10, 2008
• First Posted Date: March 17, 2008
• Last Update Posted Date: July 31, 2009
• Study Start Date: April 2008
• Actual Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 23, 2008)

• To characterize the pharmacokinetics of PF-04603629 in serum after administration of escalating, multiple, subcutaneously injected doses of PF-04603629 to subjects with T2DM. [ Time Frame: 4 weeks per dose group ]
• To evaluate the effects of multiple, escalating, subcutaneously injected doses of PF-04603629, on the pharmacodynamic responses of glucose, insulin, C-peptide and glucagon during a mixed meal tolerance test (MMTT). [ Time Frame: 4 weeks per dose group ]
• To describe the safety and tolerability of escalating, multiple, subcutaneously injected doses of PF-04603629 administered to subjects with T2DM. [ Time Frame: 4 weeks per dose group ]

Original Primary Outcome Measures (submitted: March 10, 2008)

• To describe the safety and tolerability of escalating, multiple, subcutaneously injected doses of PF-04603629 administered to subjects with T2DM. [ Time Frame: 4 weeks per dose group ]
• To characterize the pharmacokinetics of PF-04603629 in serum after administration of escalating, multiple, subcutaneously injected doses of PF-04603629 to subjects with T2DM. [ Time Frame: 4 weeks per dose group ]
• To evaluate the effects of multiple, escalating, subcutaneously injected doses of PF-04603629, on the pharmacodynamic responses of glucose, insulin, C-peptide and glucagon during a mixed meal tolerance test (MMTT). [ Time Frame: 4 weeks per dose group ]

• Current Secondary Outcome Measures (submitted: March 10, 2008): To evaluate the effect of multiple, escalating, subcutaneously injected doses of PF-04603926 on additional exploratory efficacy biomarkers related to this drug's target in subjects with T2DM. [ Time Frame: 4 weeks per dose group ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Multiple Dose Escalation Trial Of PF-04603629 Given To Subjects With Type 2 Diabetes Mellitus
• Official Title: A Phase 1, Randomized, Placebo-Controlled, Sequential Parallel Group, Multiple Dose Escalation Trial To Evaluate The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of 4, Once-Weekly Subcutaneous Doses Of PF-04603629 To Subjects With Type 2 Diabetes Mellitus
• Brief Summary: PF-04603629 is being investigated for the treatment of Type 2 diabetes mellitus (T2DM). Specifically, PF-04603629 is a protein that is a combination of exendin-4 (a glucagon-like peptide-1 (GLP-1) mimetic currently marketed as Byetta®) fused to human transferrin (a naturally occuring protein) in order to increase the concentration of exendin-4 in the blood. The purpose of this study is to characterize the safety, tolerability, pharmacokinetics, and pharmacodynamics of PF-04603629 following multiple escalating subcutaneous doses in adult subjects with T2DM.
• Detailed Description: B0571002 was terminated August 19 2008 due to the decision to discontinue development of PF-04603629 after observing (in both B0571001 and B0571002) a trend for a reversible increase in heart rate within the normal range, which occurred at efficacious doses. Thus, the compound was primarily terminated due to safety concerns, although there was no immediate safety risk to any subject in the study.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Diabetes Mellitus, Type 2

Intervention

• Biological: PF-04603629
  Subjects will be given either PF-04603629 or Placebo in a blinded fashion. Subjects will receive 4 weekly injections of PF-04603629 or Placebo.
• Biological: Placebo
  Subjects will be given either PF-04603629 or Placebo in a blinded fashion during the study. Subjects will receive 4 weekly injections of PF-04603629 or Placebo.

Study Arms

• Experimental: PF-04603629
  The dose range initially planned is 3 mg up to 70 mg, although the specific doses administered may be modified based on emerging study data.
  Intervention: Biological: PF-04603629
• Placebo Comparator: Placebo
  Intervention: Biological: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: November 3, 2008): 42
• Original Estimated Enrollment (submitted: March 10, 2008): 100
• Actual Study Completion Date: September 2008
• Actual Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients with type 2 diabetes mellitus who are not taking any treatment or are taking metformin (with no change in the treatment, including dose, over the past 2 months). Subjects previously treated with a sulfonylurea in combination with metformin may be eligible if switched over to metformin only for a minimum of 4 weeks before dosing.
• Male and/or female subjects (females will be women of non-childbearing potential) between the ages of 18 and 70 years, inclusive.
• Body Mass Index (BMI) of approximately 22 to 40 kg/m2
• Fasting C-peptide test result must be >0.4 nmol/L.
• HbA1c ≥7% and ≤11%. If the subject requires to be washed off a sulfonylurea, the HbA1c limits will be ≥7% and ≤9.5%.

Exclusion Criteria:

• Screening fasting blood glucose, ≤60 or ≥270 mg/dL. One repeat screening fasting blood glucose will be allowed.
• Previous treatment with an approved or investigational GLP-1 mimetic.
• Have a known allergy to yeast, yeast-derived or yeast containing products.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00637338
• Other Study ID Numbers: B0571002
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer, Inc.
• Study Sponsor: Pfizer
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: November 2008