Clinical trial NCT01129258: Multiple Dose Study of PF-04991532 in Patients With Type 2 Diabetes
Official title: A Phase 1 Placebo-Controlled Trial to Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Multiple Escalating Oral Doses of PF-04991532 in Adult Patients With Type 2 Diabetes Mellitus (T2DM)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Keywords: phase 1
safety and tolerability
pharmacokinetics
PK
pharmacodynamics
PD
type 2 diabetes mellitus
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2010-05-24
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief summary: The purpose of this study is to characterize the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of PF-04991532 following multiple (14 days) escalating oral doses in patient wtih type 2 diabetes.

Detailed description: Safety/Tolerability, PK, and PD

Eligibility criteria: 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. Subjects treated with a sulfonylurea (SU) or a dipeptidyl peptidase-4 inhibitor (DPP-4i) in combination with metformin may be eligible if washed off the SU or DPP-4i to metformin only for a minimum of 4 weeks before dosing. Subjects being switched over from an SU and metformin or a DPP-4i and metformin to metformin only will still need to meet the fasting glucose requirements on Day -2 as defined in the protocol.
* Body Mass Index (BMI) of 18.5 to 45.0 kg/m2; and a total body weight \>50 kg (110 lbs).
* Fasting C-peptide \>0.8 ng/mL.
* HbA1c \>/=7% and \>/=10%. If the patient requires to be washed off an SU or DPP-4i, the HbA1c limits will be \>/=6.5% and \</=9%.

Exclusion Criteria:

* Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease. Subjects 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.
* Evidence or history of diabetic complications with significant end-organ damage.
* Any condition possibly affecting drug absorption (eg, gastrectomy).
* History of stroke, 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.
* Any history or clinical evidence of congestive heart failure, NYHA Classes II-IV.
* Current history of angina/unstable angina.
* ECG findings suggestive of asymptomatic myocardial ischemia or QTc \>470 msec at screening.
* 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) glucose, \</=90 or \>/=270 mg/dL, confirmed by a single repeat if deemed necessary.
* A positive urine drug screen.
* Use of tobacco or nicotine-containing products in excess of the equivalent of 10 cigarettes per day.
* History of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for males (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor) within 6 months of screening.
* Certain concomitant medications are excluded, as defined in the protocol.
* Screening supine blood pressure \>/=160 mm Hg (systolic) or \>/=100 mm Hg (diastolic).
* Certain laboratory values (for example, triglyceride and liver function test results).
* Pregnant or nursing females; females of childbearing potential.

Primary outcomes:
measure: Safety Endpoints: Safety and tolerability of PF-04991532 will be assessed by physical examinations, adverse event monitoring, 12-lead ECGs, vital sign, and clinical safety laboratory measurements.
timeFrame: 5 months
measure: Single-Dose PK Endpoints for PF-04991352: Cmax, Tmax, and AUC(0-tau).
timeFrame: 5 months
measure: Multiple-Dose PK Endpoints for PF-04991532: Cmax(ss), Tmax(ss), AUC(0-tau,ss), AUC(0-last), half-life, Cmin(ss), Cav(ss), Ae%, CL/F, Vz/F, CLrenal; accumulation ratios AUC(0-tau,ss)/AUC(0-tau,sd) and Cmax(ss)/Cmax(sd), as the data permit.
timeFrame: 5 months
measure: PD Endpoint: glucose excursion (change from Day -1 baseline) in response to a liquid meal test (MMTT) on Days 1 and 14.
timeFrame: 5 months
Secondary outcomes:
measure: Insulin and C-peptide (changes from Day -1 baseline) during an MMTT on Days 1 and 14.
timeFrame: 5 months
measure: Mean daily glucose (change from Day -1 baseline) on Days 1 and 14.
timeFrame: 5 months
measure: Fasting plasma glucose (change from Day -1 baseline) on Days 1, 3, 6, 10, and 14.
timeFrame: 5 months
measure: Lipids (change from Day -1 baseline), including: TG, TC, HDL-cholesterol, LDL-cholesterol, FFA, beta-OHB, and ACAC, at times specified in the SOA.
timeFrame: 5 months
measure: Lactate (change from Day -1 baseline), at times specified in the SOA.
timeFrame: 5 months
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: Pfizer Investigational Site
state: California
city: Fountain Valley
country: United States
facility: Pfizer Investigational Site
state: California
city: Miami
country: United States
facility: Pfizer Investigational Site
state: Florida
city: San Antonio
country: United States
facility: Pfizer Investigational Site
state: Texas
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: