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A 2-week Trial Of PF-04991532 In Patients With Type 2 Diabetes

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ClinicalTrials.gov Identifier: NCT01469065
Recruitment Status : Completed
First Posted : November 10, 2011
Results First Posted : August 29, 2013
Last Update Posted : October 30, 2013
Sponsor:
Information provided by (Responsible Party):

October 25, 2011
November 10, 2011
June 12, 2013
August 29, 2013
October 30, 2013
December 2011
May 2012   (Final data collection date for primary outcome measure)
Change From Baseline (Day -1) in Mean Daily Glucose at Day 14 [ Time Frame: 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 ]
Mean daily glucose (MDG) was calculated based on the mean of 8 glucose measurements at pre-specified time points throughout the day on Day -1 and Day 14.
  • Safety and tolerability data (number of subjects wtih adverse events, and changes from baseline in standard safety laboratory tests, pulse rate, blood pressure, and ECG measurements over 14 days) [ Time Frame: 2 weeks ]
  • Glucose response (Day 14 versus Day -1 baseline) for mean daily glucose (MDG; average of 8 timepoints throughout the day) [ Time Frame: 2 weeks ]
Complete list of historical versions of study NCT01469065 on ClinicalTrials.gov Archive Site
  • Area Under the Curve From Time Zero to 24 Hours Postdose (AUC24) of PF-04991532 [ Time Frame: 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 ]
    Area under the plasma concentration versus time curve (AUC) from time zero to 24 hours post morning dose
  • Area Under the Curve From Time Zero to 10 Hours Postdose (AUC10) of PF-04991532 [ Time Frame: 0 (before morning dose), 0.5, 1, 2, 3, 4, 6, and 10 hours after morning dose on Day 1 and Day 14 ]
    Area under the plasma concentration versus time curve (AUC) from time zero to 10 hours post morning dose.
  • Maximum Observed Plasma Concentration of PF-04991532 After Morning Dose Administration (Cmax(AM)) [ Time Frame: 0 (before morning dose), 0.5, 1, 2, 3, 4, 6, and 10 hours after morning ]
  • Maximum Observed Plasma Concentration of PF-04991532 After Evening Dose Administration (Cmax(PM)) [ Time Frame: 10 (before evening dose), 10.5, 11, 12, 13, 15, 18, and 24 hours after morning dose on Day 1 and Day 14 ]
  • Minimum Observed Plasma Trough Concentration (Cmin) of PF-04991532 [ Time Frame: Day 14 ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04991532 After Morning Dose Administration (Tmax(AM)) [ Time Frame: 0 (predose), 0.5, 1, 2, 3, 4, 6, and 10 hours after morning dose on Day 1 and Day 14 ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04991532 After Evening Dose Administration (Tmax(PM)) [ Time Frame: 10 (before evening dose), 10.5, 11, 12, 13, 15, 18, and 24 hours after morning dose on Day 1 and Day 14 ]
    Time was computed as post morning dose.
  • Apparent Oral Clearance (CL/F) of PF-04991532 [ Time Frame: 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 ]
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
  • Observed Accumulation Ratio of Area Under the Curve From Time Zero to 10 Hours Postdose of PF-04991532 (Rac) [ Time Frame: 0 (before morning dose), 0.5, 1, 2, 3, 4, 6, and 10 hours after morning dose on Day 1 and Day 14 ]
    Area under the curve from time zero to 10 hours postdose of PF-04991532 (AUC10) of Day 14 divided by AUC10 of Day 1
  • Observed Accumulation Ratio of Maximum Observed Plasma Concentration of PF-04991532 After Morning Dose Administration (Rac, Cmax(AM)) [ Time Frame: 0 (before morning dose), 0.5, 1, 2, 3, 4, 6, and 10 hours after morning dose on Day 1 and Day 14 ]
    Maximum observed plasma concentration of PF-04991532 after morning dose administration (Cmax(AM)) of Day 14 divided by Cmax(AM) of Day 1
  • Dose Normalized Area Under the Curve From Time Zero to 24 Hours Postdose (AUC24(dn)) of PF-04991532 [ Time Frame: 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 ]
    Area under the curve from time zero to 24 Hours Postdose (AUC24) divided by total daily dose
  • Dose Normalized Maximum Plasma Concentration After Morning Dose Administration (Cmax(AM)(dn)) of PF-04991532 [ Time Frame: 0 (before morning dose), 0.5, 1, 2, 3, 4, 6, and 10 hours after morning dose on Day 1 and Day 14 ]
    Maximum Observed Plasma Concentration of PF-04991532 after Morning Dose Administration (Cmax(AM)) divided by dose
  • Change From Baseline (Day -2) in Mean Daily Glucose at Day 13 [ Time Frame: 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 ]
    Mean daily glucose (MDG) was calculated based on the mean of 8 glucose measurements at pre-specified time points throughout the day.
  • 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 [ Time Frame: 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 ]
    Area under the curve of glucose from time 2 to 6 hours post morning dose (Glucose AUC(2-6)) was calculated based on 8 glucose measurements at prespecified time points using the linear trapezoidal method. Nominal times were used in the calculation. Liquid meal was administered 2 hours post morning dose of PF-04991532 for mixed meal tolerance test (MMTT).
  • Change From Baseline in Fasting Plasma Glucose (FPG) [ Time Frame: 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 ]
    The average of the Day -1 (hour -48), Day 0 (hour -24) and Day 1 pre-dose (hour 0) measurements was the baseline for fasting plasma glucose (FPG) analyses.
  • 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 [ Time Frame: 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 ]
    Area Under the Curve of Insulin from Time 2 to 6 Hours Post Morning Dose (Insulin AUC(2-6)) was calculated based on 8 insulin measurements at prespecified time points using the linear trapezoidal method. Nominal times were used in the calculation. Liquid meal was administered 2 hours post morning dose of PF-04991532 for mixed meal tolerance test (MMTT).
  • 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 [ Time Frame: 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 ]
    Area Under the Curve of C-peptide from Time 2 to 6 Hours Post Morning Dose (C-peptide AUC(2-6)) was calculated based on 8 C-peptide measurements at prespecified timepoints using the linear trapezoidal method. Nominal times were used in the calculation. Liquid meal was administered 2 hours post morning dose of PF-04991532 for mixed meal tolerance test (MMTT).
  • Change From Baseline in Fasting Lipid Parameters at Day 14 and 16 [ Time Frame: 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 ]
    Baseline for fasting triglycerides (TG) was defined as the average of the Day -1 (hour -48), Day 0 (hour -24), and Day 1 pre-dose (hour 0) measurements. Baseline for fasting total cholesterol (TC), cholesterol (high-density lipoprotein (HDL)), and cholesterol (low-density lipoprotein (LDL)) was defined as the Day 1 pre-dose (hour 0) measurement.
  • Profile of pharmacokinetics; timeframe: 0, 0.5, 1, 2, 3, 4, 6, 10, 10.5, 11, 12, 13, 15, and 18 hours (post dosing Days 1 and 14), and 24, 36, and 48 hours (post dosing Day 14). Parameters: Cmax, area under the curve over 24 hours (AUC24), Tmax [ Time Frame: 2 weeks ]
  • Glucose response (Day 13 versus Day -2 baseline) for mean daily glucose (MDG; average of 8 timepoints throughout the day) [ Time Frame: 2 weeks ]
  • Glucose response (Day 14 versus Day -1 baseline) for a mixed meal tolerance test (MMTT) glucose area under the curve (AUC) [ Time Frame: 2 weeks ]
  • Glucose response (Days 1, 3, 6, 10, and 14 versus baseline) for fasting plasma glucose (FPG) [ Time Frame: 2 weeks ]
  • Insulin and C-peptide responses (Day 14 versus baseline) during a mixed meal tolerance test (MMTT) [ Time Frame: 2 weeks ]
  • Standard lipid panel characterization (post-treatment Days vs. baseline) [ Time Frame: 2 weeks ]
Not Provided
Not Provided
 
A 2-week Trial Of PF-04991532 In Patients With Type 2 Diabetes
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
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.
Not Provided
Interventional
Phase 1
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Diabetes Mellitus, Type 2
  • Drug: PF-04991532
    Oral administration of PF-04991532; 25 mg given twice a day (BID) for 14 days
  • Drug: PF-04991532
    Oral administration of PF-04991532; 75 mg given twice a day (BID) for 14 days
  • Drug: PF-04991532
    Oral administration of PF-04991532; 150 mg given twice a day (BID) for 14 days
  • Drug: PF-0499132
    Oral administration of PF-04991532; 300 mg given twice a day (BID) for 14 days
  • Drug: Placebo
    Oral administration of PF-04991532 Matching Placebo; given twice a day (BID) for 14 days
  • Experimental: PF-04991532
    PF-04991532 experimental study medication
    Interventions:
    • Drug: PF-04991532
    • Drug: PF-04991532
    • Drug: PF-04991532
    • Drug: PF-0499132
  • Placebo Comparator: Placebo
    PF-04991532 Matching Placebo
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
82
May 2012
May 2012   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
18 Years to 70 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Japan,   United States
 
 
NCT01469065
B2611005
No
Not Provided
Not Provided
Pfizer
Pfizer
Not Provided
Study Director: Pfizer CT.gov Call Center Pfizer
Pfizer
September 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP