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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Biological: PF-04603629
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-04603629<br>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<br>* Subjects will be given either PF-04603629 or Placebo in a blinded fashion. Subjects will receive 4 weekly injections of PF-04603629 or Placebo.<br>|
| Placebo Comparator: Placebo<br> | Biological: Placebo<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Long-acting GLP-1 Diabetes