Clinical trial NCT01044537: A Trial To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Single Doses Of PF-04937319 In Subjects With Type 2 Diabetes Mellitus
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 2 Diabetes Mellitus
Keywords: phase 1
safety and tolerability
PK
PD
type 2 diabetes mellitus
T2DM
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2010-01-08
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief 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).

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
timeFrame: Day 1 up to 10 days after last dose of study medication (up to 11 days)
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
timeFrame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose
measure: Apparent Oral Clearance (CL/F)
timeFrame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose
measure: Apparent Volume of Distribution (Vz/F)
timeFrame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose
measure: Plasma Decay Half-Life (t1/2)
timeFrame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf)
timeFrame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose
Secondary outcomes:
measure: Change From Baseline in Ratio of C-peptide Area Under Curve (C-peptide AUC) to Glucose Area Under Curve (Glucose AUC) After a Mixed Meal Tolerance Test (MMTT) on Day 1
timeFrame: -46, -45.75, -45.5, -45, -44.5, -44, -43, -42 hours pre-dose on Day -1; 2, 2.25, 2.5, 3, 3.5, 4, 5, 6 hours post-dose on Day 1
measure: Percent Change From Baseline in Post-Prandial Glucose Area Under the Curve From Time 2 to 6 Hours (AUC [2-6]) After a Mixed Meal Tolerance Test (MMTT) on Day 1
timeFrame: -46, -45.75, -45.5, -45, -44.5, -44, -43, -42 hrs pre-dose on Day -1; 2, 2.25, 2.5, 3, 3.5, 4, 5, 6 hrs post-dose on Day 1
measure: Percent Change From Baseline in Post-Prandial Insulin Area Under the Curve From Time 2 to 6 Hours (AUC [2-6]) After a Mixed Meal Tolerance Test (MMTT) on Day 1
timeFrame: -46, -45.75, -45.5, -45, -44.5, -44, -43, -42 hrs pre-dose on Day -1; 2, 2.25, 2.5, 3, 3.5, 4, 5, 6 hrs post-dose on Day 1
measure: Percent Change From Baseline in Post-Prandial C-peptide Area Under the Curve From Time 2 to 6 Hours (AUC [2-6]) After a Mixed Meal Tolerance Test (MMTT) on Day 1
timeFrame: -46, -45.75, -45.5, -45, -44.5, -44, -43, -42 hrs pre-dose on Day -1; 2, 2.25, 2.5, 3, 3.5, 4, 5, 6 hrs post-dose on Day 1
measure: Change From Baseline in Ratio of Insulin Delta C30 to Glucose Delta C30 After a Mixed Meal Tolerance Test (MMTT) on Day 1
timeFrame: -46, -45.5 hrs pre-dose on Day -1; 2, 2.5 hrs post-dose on Day 1
measure: Change From Baseline in Ratio of C-peptide Delta C30 to Glucose Delta C30 After a Mixed Meal Tolerance Test (MMTT)
timeFrame: -46, -45.5 hrs pre-dose on Day -1; 2, 2.5 hrs post-dose on Day 1
measure: Change From Baseline in Ratio of Insulin Area Under Curve (Insulin AUC) to Glucose Area Under Curve (Glucose AUC) After a Mixed Meal Tolerance Test (MMTT) on Day 1
timeFrame: -46, -45.75, -45.5, -45, -44.5, -44, -43, -42 hrs pre-dose on Day -1; 2, 2.25, 2.5, 3, 3.5, 4, 5, 6 hrs post-dose on Day 1
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Dedicated Phase 1
state: Arizona
city: Cypress
country: United States
facility: West Coast Clinical Trials, LLC
state: California
city: Miami
country: United States
facility: Elite Research Institute
state: Florida
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: