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Trial record 1 of 1 for:    NCT01044537
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A Trial To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Single Doses Of PF-04937319 In Subjects With Type 2 Diabetes Mellitus

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ClinicalTrials.gov Identifier: NCT01044537
Recruitment Status : Completed
First Posted : January 8, 2010
Results First Posted : March 10, 2017
Last Update Posted : March 10, 2017
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE January 7, 2010
First Posted Date  ICMJE January 8, 2010
Results First Submitted Date  ICMJE January 20, 2017
Results First Posted Date  ICMJE March 10, 2017
Last Update Posted Date March 10, 2017
Study Start Date  ICMJE February 2010
Actual Primary Completion Date May 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 20, 2017)
  • Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [ Time Frame: Day 1 up to 10 days after last dose of study medication (up to 11 days) ]
    An AE was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study medication and up to 10 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [ Time Frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose ]
    Area under the plasma concentration-time curve from zero to the last measured concentration (AUClast).
  • Maximum Observed Plasma Concentration (Cmax) [ Time Frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose ]
  • Apparent Oral Clearance (CL/F) [ Time Frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose ]
    Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
  • Apparent Volume of Distribution (Vz/F) [ Time Frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose ]
    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
  • Plasma Decay Half-Life (t1/2) [ Time Frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose ]
    Plasma decay half-life (t1/2) is the time measured for the plasma concentration to decrease by one half.
  • Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) [ Time Frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose ]
    AUCinf is the area under the plasma concentration versus time curve from time zero to extrapolated infinite time.
Original Primary Outcome Measures  ICMJE
 (submitted: January 7, 2010)
  • Safety and tolerability of PF-04937319 will be assessed by physical examinations, adverse event monitoring, 12 lead ECGs, continuous cardiac monitoring, vital sign, and safety laboratory measurements. [ Time Frame: ~4 months ]
  • The single dose PK of PF 04937319 will be described by estimating parameters of AUCinf, AUClast, AUC24, Cmax, Tmax, CL/F, Vz/F and half life (t1/2), as the data permit. [ Time Frame: ~4 months ]
Change History Complete list of historical versions of study NCT01044537 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 20, 2017)
  • 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 [ Time Frame: -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 ]
    Ratio of area under the plasma C-peptide concentration-time curve from time 2 to 6 hrs (in terms of nanogram*deciliter*hour [ng*dL*hour]) to area under the plasma glucose concentration-time curve from time 2 to 6 hrs (in terms of milligram*milliliter*hour [mg*mL*hour]) was calculated. Linear trapezoidal method was used to compute AUC. The change in ratio from baseline (Day -1) was calculated at Day 1.
  • 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 [ Time Frame: -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 ]
    Percent change from baseline in post-prandial area under the plasma glucose concentration-time curve as determined by standardized MMTT. Linear trapezoidal method was used to compute AUC. Baseline value was the AUC (2-6) calculated on Day -1.
  • 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 [ Time Frame: -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 ]
    Percent change from baseline in post-prandial area under the plasma insulin concentration-time curve as determined by standardized MMTT. Linear trapezoidal method was used to compute AUC. Baseline value was the AUC (2-6) calculated on Day -1.
  • 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 [ Time Frame: -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 ]
    Percent change from baseline in post-prandial area under the plasma C-peptide concentration-time curve as determined by standardized MMTT. Linear trapezoidal method was used to compute AUC. Baseline value was the AUC (2-6) calculated on Day -1.
  • Change From Baseline in Ratio of Insulin Delta C30 to Glucose Delta C30 After a Mixed Meal Tolerance Test (MMTT) on Day 1 [ Time Frame: -46, -45.5 hrs pre-dose on Day -1; 2, 2.5 hrs post-dose on Day 1 ]
    Ratio of insulin delta C30 (in terms of milliunits*deciliter [mU*dL]) to glucose delta C30 (in terms of milligram*liter [mg*liter]) was calculated. The change in ratio from baseline (Day -1) was calculated at Day 1.
  • Change From Baseline in Ratio of C-peptide Delta C30 to Glucose Delta C30 After a Mixed Meal Tolerance Test (MMTT) [ Time Frame: -46, -45.5 hrs pre-dose on Day -1; 2, 2.5 hrs post-dose on Day 1 ]
    Ratio of C-peptide Delta C30 (in terms of nanogram*deciliter [ng*dL]) to glucose delta C30 (in terms of milligram*milliliter [mg*mL]) was calculated. The change in ratio from baseline (Day -1) was calculated at Day 1.
  • 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 [ Time Frame: -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 ]
    Ratio of area under the plasma insulin concentration-time curve from time 2 to 6 hrs (in terms of milliunit*deciliter*hour [mU*dL*hour]) to area under the plasma glucose concentration-time curve from time 2 to 6 hrs (in terms of milligram*liter*hour [mg*liter*hour]) was calculated. Linear trapezoidal method was used to compute AUC. The change in ratio from baseline (Day -1) was calculated at Day 1.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 7, 2010)
Secondary PD endpoints will include glucose, insulin, and C peptide in response to an MMTT. [ Time Frame: ~4 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Other
Condition  ICMJE Type 2 Diabetes Mellitus
Intervention  ICMJE
  • Drug: Placebo
    Placebo to match PF-04937319 will be provided.
  • Drug: PF-04937319
    The initial planned dosing schedule is: 10, 30, 100, 200, and 400 mg, with one cohort to be determined. Doses shown may be adjusted upwards or downwards and may be adjusted to include intermediate doses. All doses will be administered as a single oral dose as a powder-in-capsule (PIC) formulation. PF-04937319 will be supplied as 10 mg and 80 mg (and potentially 1 mg) PIC.
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    In each ascending-dose cohort, approximately 6 subjects will receive active treatment and 3 will receive placebo.
    Intervention: Drug: Placebo
  • Experimental: PF-04937319
    In each ascending-dose cohort, approximately 6 subjects will receive active treatment and 3 will receive placebo. There will be approximately 6 dosing levels of PF-04937319
    Intervention: Drug: PF-04937319
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 7, 2010)
50
Original Estimated Enrollment  ICMJE
 (submitted: January 7, 2010)
54
Actual Study Completion Date  ICMJE May 2010
Actual Primary Completion Date May 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01044537
Other Study ID Numbers  ICMJE B1621001
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date January 2017

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