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A 6-Week Study Of PF-05175157 In Type 2 Diabetes Mellitus

This study has been terminated.
(The study was terminated prematurely on 16 May 2014 due to a safety concern.)
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01792635
First received: December 20, 2012
Last updated: December 22, 2016
Last verified: December 2016
  Purpose
This study is designed to assess the safety, tolerability and pharmacodynamics of 6 weeks of oral doses of PF-05175157 provided as monotherapy in subjects with type 2 diabetes mellitus.

Condition Intervention Phase
Diabetes Mellitus, Type 2 Drug: PF-05175157 Drug: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: A 6-week Phase 2a Randomized, Double-blind, Placebo-controlled, Parallel Group Study To Assess Safety, Tolerability And Pharmacodynamics Of Oral Pf-05175157 As Monotherapy In Subjects With Type 2 Diabetes Mellitus

Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Glucose Infusion Rates (GIR) in Part A [ Time Frame: 1 day ]
    GIR obtained averaging respectively the last 30 minutes of glucose infusion at steady state on Step 1 (ie 150 to 180 min) and Step 2 (ie 330 to 360 min) insulin infusion. Whole-body insulin sensitivity was assessed with the euglycemic hyperinsulinemic clamp procedure; the use of 2 stepped insulin infusions and labeled glucose allowed the differentiation between hepatic and peripheral insulin sensitivity. Assessment of whole body insulin sensitivity was performed during the steady states of the low insulin infusion rate (ie, Step 1) and during the steady state of the high insulin infusion rate (ie, Step 2). These indices were called GIR1 and GIR2, respectively.

  • Endogenous Gucose Production (EGP) in Part A [ Time Frame: 1 day ]
    EGP measured by means of euglycemic hyperinsulinemic clamp preceding insulin infusion (EGP0), on Step 1 insulin infusion (EGP1) and on Step 2 insulin infusion (EGP2). Whole-body insulin sensitivity was assessed with the euglycemic hyperinsulinemic clamp procedure; the use of 2 stepped insulin infusions and labeled glucose allowed the differentiation between hepatic and peripheral insulin sensitivity. EGP was measured under basal conditions; then during the low dose insulin infusion EGP was partially suppressed (hepatic insulin sensitivity), while during the high dose insulin infusion, EGP was almost completely suppressed and peripheral glucose uptake was maximally stimulated (peripheral insulin sensitivity).

  • [6,6-2H2] Plasma Glucose Enrichment (PGE) in Part A [ Time Frame: 1 day ]
    [6,6-2H2] PGE was the molar fraction of labeled glucose measured in plasma. Whole-body insulin sensitivity was assessed with the euglycemic hyperinsulinemic clamp procedure; the use of 2 stepped insulin infusions and labeled glucose allowed the differentiation between hepatic and peripheral insulin sensitivity.

  • Rate of Appearance of Glucose (Ra) in Part A [ Time Frame: 1 day ]
    Rate of appearance of glucose (Ra) in fasting state and during insulin infusions (Step 1 and Step 2).

  • Whole-body Glucose Uptake in Part A [ Time Frame: 1 day ]
    Whole-body glucose uptake (Rate of glucose disappearance, Rd) during the Step 2 Clamp

  • Whole-body Glucose Uptake in Part B in Placebo Group [ Time Frame: 6 weeks ]
    Whole-body glucose uptake (Rate of glucose disappearance, Rd) during the Step 2 Clamp

  • Whole-body Glucose Uptake in Part B in PF-05175157 200 mg BID Group [ Time Frame: 6 weeks ]
    Whole-body glucose uptake (Rate of glucose disappearance, Rd) during the Step 2 Clamp

  • Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs), or Discontinuation Due to Adverse Events (AEs) in Part B [ Time Frame: Baseline to follow-up (up to approximately 10 to 14 days after the last study drug administration) ]
    An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. 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.

  • Number of Participants With Laboratory Test Abnormalities in Part B [ Time Frame: Screening up to follow-up (up to approximately 10 to 14 days after the last study drug administration) ]
    Number of participants with laboratory test abnormalities without regard to baseline abnormality. The following laboratory parameters were analyzed: hematology (hemoglobin, hematocrit, red blood cell [RBC] count, platelet count, white blood cell [WBC] count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (blood urea nitrogen [BUN], creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase [AST], alanine aminotransferase [ALT], total bilirubin, alkaline phosphatase, uric acid, albumin, total protein, and creatine phosphokinase); urinalysis (pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, and microscopy); others (follicle stimulating hormone [FSH], urine drug screen, lipid profile and very-low-density lipoproteins [VLDL], hemoglobin A1c [HbA1c], C-peptide, thyroid-stimulating hormone [TSH], Hepatitis B and C, human immunodeficiency virus [HIV], triglycerides, urine creatinine).

  • Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria in Part B [ Time Frame: Screening up to follow-up (up to approximately 10 to 14 days after the last study drug administration) ]
    Criteria for potentially clinical important (PCI) change in vital signs included: sitting systolic blood pressure (SBP) of less than (<) 90 millimeters of mercury (mm Hg) or change in sitting SBP of greater or equal to (>=)30 mm Hg, sitting diastolic blood pressure (DBP) of <50 mm Hg or change in sitting DBP of >=20 mm Hg, sitting pulse rate of <40 or greater than (>) 120 beats per minute (bpm).

  • Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarisation Criteria in Part B [ Time Frame: Screening up to follow-up (up to approximately 10 to 14 days after the last study drug administration) ]
    Criteria for PCI changes in ECG (12-lead) were defined as: the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization (PR interval) >=300 milliseconds (msec) and increase of >=25% from baseline when baseline >200 msec or increase of >=50% when baseline less than or equal to (<=) 200 msec; the time from the beginning of the electrocardiogram Q wave to the end of the S wave corresponding to ventricular depolarization (QRS interval) >=140 msec and increase of >=50% from baseline; the time corresponding to the beginning of depolarization to repolarization of the ventricles (QT), corrected for heart rate (QTc) using the Fridericia formula (QTcF) of 450 to < 480 msec and >=480 msec, or an increase from baseline of 30 to <60 msec or >=60 msec.


Secondary Outcome Measures:
  • GIR in Part B in Placebo Group [ Time Frame: 6 weeks ]
    Glucose Infusion Rate rates obtained averaging respectively the last 30 minutes of glucose infusion at steady state on Step 1 (ie 150 to 180 min) and Step 2 (ie 330 to 360 min) insulin infusion.

  • GIR in Part B in PF-05175157 200 mg BID Group [ Time Frame: 6 weeks ]
    Glucose Infusion Rate rates obtained averaging respectively the last 30 minutes of glucose infusion at steady state on Step 1 (ie 150 to 180 min) and Step 2 (ie 330 to 360 min) insulin infusion.

  • EGP in Part B in Placebo Group [ Time Frame: 6 weeks ]
    EGP measured by means of euglycemic hyperinsulinemic clamp preceding insulin infusion (EGP0), on Step 1 insulin infusion (EGP1) and on Step 2 insulin infusion (EGP2)

  • EGP in Part B in PF-05175157 200 mg BID Group [ Time Frame: 6 weeks ]
    EGP measured by means of euglycemic hyperinsulinemic clamp preceding insulin infusion (EGP0), on Step 1 insulin infusion (EGP1) and on Step 2 insulin infusion (EGP2)

  • Ra in Part B in Placebo Group [ Time Frame: 6 weeks ]
    Ra in fasting state and during insulin infusions (Step 1 and Step 2).

  • Ra in Part B in PF-05175157 200 mg BID Group [ Time Frame: 6 weeks ]
    Ra in fasting state and during insulin infusions (Step 1 and Step 2).


Enrollment: 19
Study Start Date: December 2012
Study Completion Date: May 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Part A (Pilot Study)
Experimental: Monotherapy (Part B) Drug: PF-05175157
PF-05175157 will be administered at 200 mg twice a day for 43 days.
Drug: Placebo
Placebo tablets matched to PF-05175157 will be administered twice a day for 43 days.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects who have been diagnosed with type 2 diabetes mellitus by a medical professional according to the American Diabetes Association guidelines.
  • Hemoglobin A1c of ≥7 and ≤10.0% in subjects who are metformin-naive or have not taken metformin for 2 months or Hemoglobin A1c of ≥6.5 and ≤9.5% in subjects who are metformin-naïve and are taking SU or DPP-IVi which is washed off or taking metformin and are willing to discontinue metformin in a 8-week washout period.

Exclusion Criteria:

  • Evidence or history of clinically significant hematological, renal, endocrine (other than T2DM and hypothyroidism), gastrointestinal, cardiovascular, pulmonary, hepatic, psychiatric or neurologic disease.
  • A waist circumference which makes fitting imto the bore of the MR scanner impossible.

Subjects with history of dry eye, known ocular or systemic disease that affect the sclera or cornea.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01792635

Locations
United States, California
Profil Institute for Clinical Research, Inc.
Chula Vista, California, United States, 91911
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01792635     History of Changes
Other Study ID Numbers: B1731003
Study First Received: December 20, 2012
Results First Received: January 11, 2016
Last Updated: December 22, 2016

Keywords provided by Pfizer:
Type 2 Diabetes Mellitus
Pharmacodynamics
Safety & Tolerability

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on July 21, 2017