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

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

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.

Study Overview

• Status: Terminated
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Biological: PF-04603629; Biological: Placebo

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
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Pfizer Investigational Site
  • Florida
    • Miami, Florida, United States, 33169
      • Pfizer Investigational Site
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Pfizer Investigational Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 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.
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.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To characterize the pharmacokinetics of PF-04603629 in serum after administration of escalating, multiple, subcutaneously injected doses of PF-04603629 to subjects with T2DM.	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).	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.	4 weeks per dose group

Secondary Outcome Measures

Outcome Measure	Time Frame
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.	4 weeks per dose group

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): September 1, 2008
• Study Completion (Actual): September 1, 2008

Study Registration Dates

• First Submitted: March 10, 2008
• First Submitted That Met QC Criteria: March 10, 2008
• First Posted (Estimate): March 17, 2008

Study Record Updates

• Last Update Posted (Estimate): July 31, 2009
• Last Update Submitted That Met QC Criteria: July 30, 2009
• Last Verified: November 1, 2008

More Information

Terms related to this study

• Keywords: Long-acting GLP-1 Diabetes
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: B0571002