A Trial To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Single Doses Of PF-04937319 In Subjects With Type 2 Diabetes Mellitus

Type 2 Diabetes Mellitus Clinical Trial

Official title:

A Phase 1 Placebo-Controlled Trial To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Single Escalating Oral Doses Of PF-04937319 In Adult Subjects With Type 2 Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01044537
• Other study ID #: B1621001
• Status: Completed
• Phase: Phase 1
• First received: January 7, 2010
• Last updated: June 7, 2010
• Start date: February 2010
• Est. completion date: May 2010

Study information

• Verified date: June 2010
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to characterize the safety, tolerability, pharmacokinetics, and pharmacodynamics of PF-04937319 following single escalating oral doses in adult subjects with Type 2 Diabetes Mellitus (T2DM).

Description:

The purpose of this phase 1 study is to characterize the safety, tolerability, pharmacokinetics, and pharmacodynamics of PF04937319 following single escalating oral doses in adult subjects with T2DM.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: May 2010
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Patients with type 2 diabetes mellitus who are taking stable doses of metformin only. Subjects treated with a sulfonylurea (SU) or a dipeptidyl peptidase-IV inhibitor (DPP-IVi) in combination with metformin may be eligible if washed off the SU or DPP-IVi 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 65 years, inclusive, with a body mass index (BMI) of 18.5 to 45.0 kg/m2 and C-peptide >0.8 ng/mL.

• Screening and Day -2 troponin I concentration </=0.05 ng/mL as measured by the Bayer Centaur Ultra assay.

• HbA1c >/=7% and </=11%. If the patient requires to be washed off an SU or DPP-IVi, the HbA1c limits will be >/=7% and </=9.5%.

Exclusion Criteria:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).

• Evidence or history of diabetic complications with significant end organ damage, eg, proliferative retinopathy and/or macular edema, creatinine clearance </=60 mL/min based on the Cockcroft-Gault equation, diabetic neuropathy complicated by neuropathic ulcers.

• History of stroke, transient ischemic attack, or myocardial infarction within the past 6 months. Additionally, history of coronary artery bypass graft or stent implantation, clinically significant peripheral vascular disease, or congestive heart failure (NYHA Classes II-IV). Furthermore, a current history of angina/unstable angina. Also, 12 lead electrocardiogram (ECG) demonstrating QTc >450 msec at screening, ECG findings suggestive of asymptomatic myocardial ischemia, or supine blood pressure >/=160 mm Hg (systolic) or </=100 mm Hg (diastolic).

• One or more self reported episodes of hypoglycemia within the last 3 months, or two or more self reported episodes of hypoglycemia within the last 6 months.

• Screening or Day -2 fasting (>/=8 hours) blood glucose, </=70 or >/=270 mg/dL, confirmed by a single repeat if deemed necessary.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator)

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Placebo
Placebo to match PF-04937319 will be provided.
• PF-04937319
The initial planned dosing schedule is: 10, 30, 100, 200, and 400 mg, with one cohort to be determined. Doses shown may be adjusted upwards or downwards and may be adjusted to include intermediate doses. All doses will be administered as a single oral dose as a powder-in-capsule (PIC) formulation. PF-04937319 will be supplied as 10 mg and 80 mg (and potentially 1 mg) PIC.

Locations

Country	Name	City	State
United States	Pfizer Investigational Site	Cypress	California
United States	Pfizer Investigational Site	Miami	Florida
United States	Pfizer Investigational Site	Phoenix	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability of PF-04937319 will be assessed by physical examinations, adverse event monitoring, 12 lead ECGs, continuous cardiac monitoring, vital sign, and safety laboratory measurements.		~4 months	Yes
Primary	The single dose pharmacokinetics (PK) of PF-04937319 will be described by estimating parameters of AUCinf, AUClast, AUC24, Cmax, Tmax, CL/F, Vz/F and half life (t1/2), as the data permit.		~4 months	No
Secondary	Secondary pharmacodynamic (PD) endpoints will include glucose, insulin, and C-peptide in response to a mixed meal tolerance test (MMTT).		~4 months	No

External Links

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