Clinical trial NCT00637338: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Diabetes Mellitus, Type 2
Keywords: Long-acting GLP-1 Diabetes
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2008-03-17
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: To characterize the pharmacokinetics of PF-04603629 in serum after administration of escalating, multiple, subcutaneously injected doses of PF-04603629 to subjects with T2DM.
timeFrame: 4 weeks per dose group
measure: 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).
timeFrame: 4 weeks per dose group
measure: To describe the safety and tolerability of escalating, multiple, subcutaneously injected doses of PF-04603629 administered to subjects with T2DM.
timeFrame: 4 weeks per dose group
Secondary outcomes:
measure: 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.
timeFrame: 4 weeks per dose group
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Pfizer Investigational Site
state: Arizona
city: Miami
country: United States
facility: Pfizer Investigational Site
state: Florida
city: Wichita
country: United States
facility: Pfizer Investigational Site
state: Kansas
city: Portland
country: United States
facility: Pfizer Investigational Site
state: Oregon
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: