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Completed

NCT Number: NCT01469065

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

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.

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Key information

Conditions

Diabetes Mellitus, Type 2 Diabetes Mellitus Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Pfizer Investigational Site, Hachioji-shi, Tokyo, Japan

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

PF-04991532

Drug

Oral administration of PF-04991532; 25 mg given twice a day (BID) for 14 days

PF-0499132

Drug

Oral administration of PF-04991532; 300 mg given twice a day (BID) for 14 days

Placebo

Drug

Oral administration of PF-04991532 Matching Placebo; given twice a day (BID) for 14 days

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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

  2. 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.

  3. 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

  4. 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

  5. Minimum Observed Plasma Trough Concentration (Cmin) of PF-04991532

    Time frame: Day 14

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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.

  14. 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).

  15. 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.

  16. 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).

  17. 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).

  18. 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.

Sponsors and collaborators

Lead sponsor

Pfizer

Industry

Registry information

Official study 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

Important dates

Study start
2011
Primary completion
2012
Study completion
2012
First posted
Nov 10, 2011
Registry last updated
Oct 30, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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