Multiple Dose Study Of PF-04937319 In Patients With Type 2 Diabetes

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

A Phase 1 Placebo-Controlled Trial To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Multiple Escalating Oral Doses Of PF-04937319 In Adult Patients With Type 2 Diabetes Mellitus (T2DM)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01272804
• Other study ID #: B1621003
• Status: Completed
• Phase: Phase 1
• First received: January 6, 2011
• Last updated: January 25, 2012
• Start date: February 2011
• Est. completion date: July 2011

Study information

• Verified date: January 2012
• 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 (PK), and pharmacodynamics (PD) of PF-04937319 following multiple (14 days) escalating oral doses in patients with type 2 diabetes.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Patients with type 2 diabetes mellitus who are taking metformin only.

• Treatment should be stable, where this is defined as no change in the treatment, including dose, over the past 2 months. Regimens may include once daily and twice daily dosing only.

• Male and/or female patients (females will be women of non childbearing potential)

• Body Mass Index (BMI) of 18.5 to 45.0 kg/m2; and a total body weight >50 kg (110 lbs).

• HbA1c between 7.0% and 10.0%.

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). Patients who have chronic conditions other than T2DM (for example, hypercholesterolemia or hypertension) but are controlled by either diet or stable (for the last 2 months) doses of medications may be included as well (for example, a subject with hypercholesterolemia on appropriate treatment is eligible).

• Evidence or history of diabetic complications with significant end organ damage, eg, proliferative retinopathy and/or macular edema, creatinine clearance less than 60 mL/min

• Any condition possibly affecting drug absorption (eg, gastrectomy)

• History of stroke or transient ischemic attack or myocardial infarction within the past 6 months

• History of coronary artery bypass graft or stent implantation.

• Clinically significant peripheral vascular disease (eg, manifested by claudication).

• Any history or clinical evidence of congestive heart failure, NYHA Classes II to IV.

• One or more self reported significant/severe/requiring treatment episodes of hypoglycemia within the last 3 months, or two or more self reported significant/severe/requiring treatment episodes of hypoglycaemia within the last 6 months.

• Current history of angina/unstable angina.

• Milk or soy allergy

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• NIDDM

Intervention

Drug:
• PF-04937319
Subjects will be dosed with PF-04937319 for 14 days. The doses planned are 10, 30, 100 and 300 mg QD. All doses will be administered as tablets (10 and 100 mg strengths). In each Cohort, 9 patients will receive PF 04937319 and 3 will receive placebo. An additional cohort of 12 patients (9 active, 3 placebo) may be performed to explore a QD or BID dose. The dose for this additional cohort could be a dose already studied or a new dose that is within the exposure stopping criteria.
• Placebo
Placebo to match PF-04937319 will be provided. Subjects will be dosed for 14 days. In each cohort 9 subjects will receive PF-04937319 and 3 will receive placebo.

Locations

Country	Name	City	State
United States	Pfizer Investigational Site	Cincinnati	Ohio
United States	Pfizer Investigational Site	Miami	Florida
United States	Pfizer Investigational Site	South Miami	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety Endpoints: Safety and tolerability of PF 04937319 will be assessed by physical examinations, adverse event and hypoglycemia monitoring, 12 lead ECGs, vital sign, and clinical safety laboratory measurements.		5 months	Yes
Primary	Single Dose PK endpoints: Cmax, Tmax, and AUC(0-Tau)		5 months	No
Primary	Day 6 PK Endpoints: Cmax, Tmax, and AUC(0-8)		5 months	No
Primary	Multiple Dose PK Endpoints: Cmax(ss), Tmax(ss), AUC(0-Tau,ss), AUC(0-8), AUC(0-last), half life, Cmin(ss), Cav(ss), Ae%, CL/F, Vz/F; accumulation ratios AUC(0-Tau,ss)/AUC(0-Tau,sd) and Cmax(ss)/Cmax(sd), as the data permit.		5 months	No
Primary	PD Endpoint: glucose excursion (change from Day -1 baseline) in response to a liquid meal test (MMTT) on Days 1 and 14.		5 months	No
Secondary	Insulin and C peptide (changes from Day -1 baseline) during an MMTT on Days 1 and 14.		5 months	No
Secondary	Average daily glucose (change from Day -1 baseline) on Days 1, 6, and 14.		5 months	No
Secondary	Fasting plasma glucose (change from Day 1 pre dose baseline) on Days 1 through 15.		5 months	No
Secondary	Lipids (change from baseline), including: TG, TC, HDL cholesterol, and LDL cholesterol, at times specified in the SOA.		5 months	Yes
Secondary	Lactate (change from baseline), at times specified in the SOA.		5 months	Yes

External Links

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