Clinical trial NCT01469065: A 2-week Trial Of PF-04991532 In Patients With Type 2 Diabetes
Official title: A 2-week, Phase 1, Placebo-Controlled, Parallel Group Trial To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Multiple Oral Doses Of PF-04991532 Given As Monotherapy To Adult Patients With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus, Type 2
Keywords: inpatient
diabetes
phase 1
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2011-11-10
Enrollment: 82
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: This will be a 2-week oral dose study of PF 04991532, performed in patients with type 2 diabetes. Safety, pharmacokinetics (how the drug is distributed in the body), and pharmacodynamics (how the drug works in the body) will be studied. Patients may be asked to wash off their diabetes medication for 4-6 prior to study drug administration, and they will remain in the clinical research unit for a total of 20 days for baseline tests, 2 weeks of dosing, and some follow up tests.


Eligibility criteria: Inclusion Criteria:

* Patients with type 2 diabetes mellitus who are taking either no medication for the treatment of diabetes (diet/exercise therapy only), or who are taking only a single oral anti-diabetic drug (OAD) that can be temporarily discontinued for approximately 8-10 weeks. For those taking a single OAD, treatment should be stable, where this is defined as no change in the treatment, including dose, over the past 3 months prior to Screening. OAD medications that are acceptable to be discontinued include: a sulfonylurea (SU), a meglitinide, a biguanide (eg, metformin), a dipeptidyl peptidase 4 inhibitor (DPP-4i), or an alpha glucosidase inhibitor.
* Body Mass Index (BMI) of 18.5 to 45.0 kg/m2; and a total body weight \>50 kg (110 lbs).
* HbA1c \>/=7% and \</=10% if the patient is on diet/exercise therapy only and does not require any OAD discontinuation. HbA1c \>/=6.5% and \</=9% if the patient requires to be washed off an OAD.

Exclusion Criteria:

* Evidence or history of diabetic complications with significant end organ damage.
* History of stroke or transient ischemic attack.
* History of myocardial infarction.
* 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.
* One or more episodes of hypoglycemia within the last 3 months, or two or more episodes of hypoglycemia within the last 6 months.
* A positive urine drug screen.
* Use of tobacco or nicotine-containing products in excess of the equivalent of 10 cigarettes per day.
* Blood pressure \>/=160 mm Hg (systolic) or \>/=100 mm Hg (diastolic), following at least 5 minutes of rest.
* Pregnant or nursing females; females of childbearing potential.

Primary outcomes:
measure: Change From Baseline (Day -1) in Mean Daily Glucose at Day 14
timeFrame: Baseline: hours -46, -44, -42, -40, -38, -36, -33, -and -30 on Day -1 (Day 1 morning dose was hour 0); Day 14: 2, 4, 6, 8, 10, 12, 15, and 18 hours after Day 14 morning dose
Secondary outcomes:
measure: Area Under the Curve From Time Zero to 24 Hours Postdose (AUC24) of PF-04991532
timeFrame: 0 (before morning dose), 0.5, 1, 2, 3, 4, 6, 10, 10.5, 11, 12, 13, 15, 18, and 24 hours after morning dose on Day 1 and Day 14
measure: Area Under the Curve From Time Zero to 10 Hours Postdose (AUC10) of PF-04991532
timeFrame: 0 (before morning dose), 0.5, 1, 2, 3, 4, 6, and 10 hours after morning dose on Day 1 and Day 14
measure: Maximum Observed Plasma Concentration of PF-04991532 After Morning Dose Administration (Cmax(AM))
timeFrame: 0 (before morning dose), 0.5, 1, 2, 3, 4, 6, and 10 hours after morning
measure: Maximum Observed Plasma Concentration of PF-04991532 After Evening Dose Administration (Cmax(PM))
timeFrame: 10 (before evening dose), 10.5, 11, 12, 13, 15, 18, and 24 hours after morning dose on Day 1 and Day 14
measure: Minimum Observed Plasma Trough Concentration (Cmin) of PF-04991532
timeFrame: Day 14
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04991532 After Morning Dose Administration (Tmax(AM))
timeFrame: 0 (predose), 0.5, 1, 2, 3, 4, 6, and 10 hours after morning dose on Day 1 and Day 14
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04991532 After Evening Dose Administration (Tmax(PM))
timeFrame: 10 (before evening dose), 10.5, 11, 12, 13, 15, 18, and 24 hours after morning dose on Day 1 and Day 14
measure: Apparent Oral Clearance (CL/F) of PF-04991532
timeFrame: Day 1 and Day 14: 0 (before morning dose), 0.5, 1, 2, 3, 4, 6, 10 (before evening dose), 10.5, 11, 12, 13, 15, 18 and 24 hours after morning dose
measure: Observed Accumulation Ratio of Area Under the Curve From Time Zero to 10 Hours Postdose of PF-04991532 (Rac)
timeFrame: 0 (before morning dose), 0.5, 1, 2, 3, 4, 6, and 10 hours after morning dose on Day 1 and Day 14
measure: Observed Accumulation Ratio of Maximum Observed Plasma Concentration of PF-04991532 After Morning Dose Administration (Rac, Cmax(AM))
timeFrame: 0 (before morning dose), 0.5, 1, 2, 3, 4, 6, and 10 hours after morning dose on Day 1 and Day 14
measure: Dose Normalized Area Under the Curve From Time Zero to 24 Hours Postdose (AUC24(dn)) of PF-04991532
timeFrame: 0 (before morning dose), 0.5, 1, 2, 3, 4, 6, 10, 10.5, 11, 12, 13, 15, 18, and 24 hours after morning dose on Day 1 and Day 14
measure: Dose Normalized Maximum Plasma Concentration After Morning Dose Administration (Cmax(AM)(dn)) of PF-04991532
timeFrame: 0 (before morning dose), 0.5, 1, 2, 3, 4, 6, and 10 hours after morning dose on Day 1 and Day 14
measure: Change From Baseline (Day -2) in Mean Daily Glucose at Day 13
timeFrame: Baseline: hours -72, -70, -68, -66, -62, -60, -57, and -54 on Day -2 (Day 1 morning dose was hour 0); Day 13: 0 (before morning dose), 2, 4, 6, 10, 12, 15 and 18 hours after Day 13 morning dose
measure: Change From Baseline in Area Under the Curve of Glucose From Time 2 to 6 Hours Post Morning Dose (Glucose AUC(2-6)) Following Mixed Meal Tolerance Test (MMTT) at Day 14
timeFrame: Baseline: hours -46, -45.75, -45.5, -45, -44.5, -44, -43, -and -42 on Day -1 (Day 1 morning dose was hour 0); Day 14: 2, 2.25, 2.5, 3, 3.5, 4, 5, and 6 hours after Day 14 morning dose
measure: Change From Baseline in Fasting Plasma Glucose (FPG)
timeFrame: Baseline: hour -48 on Day -1, hour -24 on Day 0, and hour 0 (before morning dose) on Day 1; hour 0 (before morning dose of each day) on Days 1, 2, 3, 6, and 10; and 24 hours after Day 14 morning dose on Day 15
measure: Change From Baseline in Area Under the Curve of Insulin From Time 2 to 6 Hours Post Morning Dose (Insulin AUC(2-6)) Following Mixed Meal Tolerance Test (MMTT) at Day 14
timeFrame: Baseline: hours -46, -45.75, -45.5, -45, -44.5, -44, -43, -and -42 on Day -1 (Day 1 morning dose was hour 0); Day 14: 2, 2.25, 2.5, 3, 3.5, 4, 5, and 6 hours after Day 14 morning dose
measure: Change From Baseline in Area Under the Curve of C-peptide From Time 2 to 6 Hours Post Morning Dose (C-peptide AUC(2-6)) Following Mixed Meal Tolerance Test (MMTT) at Day 14
timeFrame: Baseline: hours -46, -45.75, -45.5, -45, -44.5, -44, -43, -and -42 on Day -1 (Day 1 morning dose was hour 0); Day 14: 2, 2.25, 2.5, 3, 3.5, 4, 5, and 6 hours after Day 14 morning dose
measure: Change From Baseline in Fasting Lipid Parameters at Day 14 and 16
timeFrame: Baseline: hour -48 on Day -1, hour -24 on Day 0, and hour 0 on Day 1 for TG and Hour 0 (before morning dose) on Day 1 for TC, HDL, and LDL; 48 hours after morning dose on Day 16 for TG and Hour 0 (before morning dose) on Day14 for TC, HDL, and LDL
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: Pfizer Investigational Site
state: California
city: Miami
country: United States
facility: Pfizer Investigational Site
state: Florida
city: Hachioji-shi
country: Japan
facility: Pfizer Investigational Site
state: Tokyo
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: