Clinical trial NCT01819922: Effect Of Single-Dose PF-05175157 On Metabolic And Cardiopulmonary Parameters
Official title: A Phase 1 Randomized, Double-blind, Placebo-controlled, Two-way Crossover Study To Assess The Effect Of Pf-05175157 As A Single Oral Dose On Metabolic And Cardiopulmonary Parameters During Steady State And Graded Exercise In Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Cardiopulmonary exercise testing
metabolic parameters
Diabetes Mellitus Type 2
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2013-03-28
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: This study is designed to assess the effect of one single dose of PF-05175157 on metabolic and cardiopulmonary parameters before, during and after treadmill exercise in healthy volunteers.


Eligibility criteria: Inclusion Criteria:

* Healthy male and/or female subjects of non child bearing potential only, between the ages of 18 and 40 years, inclusive (Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12 lead ECG and clinical laboratory tests).
* Body Mass Index (BMI) of 18 to 28 kg/m2; and a total body weight \>50 kg (110 lbs).
* Subjects with maximum effort studies (peak RER \>1.05) and normal exercise capacity as defined by peak VO2 ≥80% and ≤120% of predicted and no evidence of inducible ischemia or significant arrhythmia at the time of peak aerobic capacity testing 3 (±1) days prior to initiation of the study.

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).
* History of smoking in the past 5 years or history or evidence of habitual use of other (non smoked) tobacco or nicotine-containing products within 3 months of Screening or positive cotinine test at Screening or Day -3 (±1).
* Dry eye symptoms

Primary outcomes:
measure: Systolic Function: Global Longitudinal Left Ventricular (LV) Strain: 20 Minutes Pre-dose
timeFrame: 20 minutes pre-dose
measure: Systolic Function: Global Longitudinal Left Ventricular (LV) Strain: 1 Hour 30 Minutes Post-dose
timeFrame: 1 hour 30 minutes post-dose
measure: Systolic Function: Global Longitudinal Left Ventricular (LV) Strain: 2 Hours 5 Minutes Post-dose
timeFrame: 2 hours 5 minutes post-dose
measure: Cardiopulmonary Exercise Test: Oxygen Uptake Efficiency Slope (OUES): 1 Hour 40 Minute Post-dose
timeFrame: 1 hour 40 minutes post-dose
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to 5-10 days after last dose of study drug (up to 25 days)
measure: Number of Participants With Clinically Significant Laboratory Abnormalities
timeFrame: Baseline up-to 3 hours post-dose
measure: Number of Participants With Categorical Post-dose Cardiovascular Monitoring Data
timeFrame: Baseline up-to 3 hours post-dose
measure: Number of Participants With Categorical Post-dose Cardiovascular Monitoring Data: Electrocardiogram (ECG) Parameters
timeFrame: Baseline up-to 3 hour post-dose
measure: Cardiopulmonary Exercise Test: Peak Volume of Oxygen (VO2)
timeFrame: 1 hour 40 minutes post-dose
measure: Cardiopulmonary Exercise Test: Respiratory Exchange Ratio (RER)
timeFrame: 1 hour 40 minutes post-dose
measure: Cardiopulmonary Exercise Test: Minute Ventilation and Carbon Dioxide Production (VE/VCO2 Slope)
timeFrame: 1 hour 40 minutes post-dose
measure: Cardiopulmonary Exercise Test: Volume of Oxygen (VO2) at Anaerobic Threshold (AT)
timeFrame: 1 hour 40 minutes post-dose
measure: Cardiopulmonary Exercise Test: Oxygen (O2) Pulse
timeFrame: 1 hour 40 minutes post-dose
measure: Cardiopulmonary Exercise Test: Oxygen (O2) Kinetics
timeFrame: 1 hour 40 minutes post-dose
measure: Cardiopulmonary Exercise Test: Aerobic Efficiency
timeFrame: 1 hour 40 minutes post-dose
measure: Cardiopulmonary Exercise Test: Physical Work Capacity at a Heart Rate of 130 Beats Per Minute (PWC 130)
timeFrame: 1 hour 40 minutes post-dose
measure: Cardiac Structure: Left Ventricular Volume
timeFrame: 20 minutes pre-dose, 1 hour 30 minutes and 2 hours 5 minutes post-dose
measure: Change From Baseline in the Left Ventricular Volume
timeFrame: 1 hour 30 minutes and 2 hours 5 minutes post-dose
measure: Cardiac Structure: Left Ventricular Wall Thickness
timeFrame: 20 minutes pre-dose, 1 hour 30 minutes and 2 hours 5 minutes post-dose
measure: Cardiac Structure: Left Ventricular Geometry
timeFrame: 20 minutes pre-dose, 1 hour 30 minutes and 2 hours 5 minutes post-dose
measure: Cardiac Structure: Right Ventricular Dimension
timeFrame: 20 minutes pre-dose, 1 hour 30 minutes and 2 hours 5 minutes post-dose
measure: Change From Baseline in Right Ventricular Dimension
timeFrame: 1 hour 30 minutes and 2 hours 5 minutes post-dose
measure: Cardiac Structure: Atrial Volume
timeFrame: 20 minutes pre-dose, 1 hour 30 minutes and 2 hours 5 minutes post-dose
measure: Change From Baseline in Atrial Volumes
timeFrame: 1 hour 30 minutes and 2 hours 5 minutes post-dose
measure: Systolic Function: Ejection Fraction
timeFrame: 20 minutes pre-dose, 1 hour 30 minutes and 2 hours 5 minutes post-dose
measure: Change From Baseline in Ejection Fraction
timeFrame: 1 hour 30 minutes and 2 hours 5 minutes post-dose
measure: Systolic Function: Peak Contractile Velocity
timeFrame: 20 minutes pre-dose, 1 hour 30 minutes and 2 hours 5 minutes post-dose
measure: Change From Baseline in Peak Contractile Velocity
timeFrame: 1 hour 30 minutes and 2 hours 5 minutes post-dose
measure: Systolic Function: Rotation/Torsion
timeFrame: 20 minutes pre-dose, 1 hour 30 minutes and 2 hours 5 minutes post-dose
measure: Systolic Function: Global Strain Rate
timeFrame: 20 minutes pre-dose, 1 hour 30 minutes and 2 hours 5 minutes
measure: Change From Baseline in Systolic Global Strain Rate
timeFrame: 1 hour 30 minutes and 2 hours 5 minutes post-dose
measure: Trans-mitral Doppler: Ratio
timeFrame: 20 minutes pre-dose, 1 hour 30 minutes and 2 hours 5 minutes
measure: Change From Baseline in Trans-mitral Doppler Ratio
timeFrame: 1 hour 30 minutes and 2 hours 5 minutes post-dose
measure: Trans-mitral Doppler: Time
timeFrame: 20 minutes pre-dose, 1 hour 30 minutes and 2 hours 5 minutes post-dose
measure: Change From Baseline in Trans-mitral Doppler Time
timeFrame: 1 hour 30 minutes and 2 hours 5 minutes post-dose
measure: Early and Late Peak Tissue Velocity
timeFrame: 20 minutes pre-dose, 1 hour 30 minutes and 2 hours 5 minutes post-dose
measure: Change From Baseline in Early and Late Peak Velocity
timeFrame: 1 hour 30 minutes and 2 hours 5 minutes post-dose
measure: Diastolic Strain Rate
timeFrame: 20 minutes pre-dose, 1 hour 30 minutes and 2 hours 5 minutes post-dose
measure: Peak Diastolic Untwisting Rate
timeFrame: 20 minutes pre-dose, 1 hour 30 minutes and 2 hours 5 minutes post-dose
measure: Plasma Metabolomic Profiles Before and Immediately Following Steady State and Incremental Exercise
timeFrame: 1 hour pre-dose, 1 hour 20 minutes and 2 hours 10 minutes post-dose
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: