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
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Pfizer
- Enrollment
- 12
- Locations
- 1
- Primary Endpoint
- Systolic Function: Global Longitudinal Left Ventricular (LV) Strain: 20 Minutes Pre-dose
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Basic Science
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 40 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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
Arms & Interventions
PF-05175157
Intervention: PF-05175157 (Drug)
Placebo
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Systolic Function: Global Longitudinal Left Ventricular (LV) Strain: 20 Minutes Pre-dose
Time Frame: 20 minutes pre-dose
Global longitudinal left ventricular strain was defined as the percent change in left ventricular longitudinal dimension in comparison to its original dimension. Global longitudinal LV strain was assessed by echocardiography using speckled tracking analysis.
Systolic Function: Global Longitudinal Left Ventricular (LV) Strain: 1 Hour 30 Minutes Post-dose
Time Frame: 1 hour 30 minutes post-dose
Global longitudinal left ventricular strain was defined as the percent change in left ventricular longitudinal dimension in comparison to its original dimension. Global longitudinal LV strain was assessed by echocardiography using speckled tracking analysis.
Systolic Function: Global Longitudinal Left Ventricular (LV) Strain: 2 Hours 5 Minutes Post-dose
Time Frame: 2 hours 5 minutes post-dose
Global longitudinal left ventricular strain was defined as the percent change in left ventricular longitudinal dimension in comparison to its original dimension. Global longitudinal LV strain was assessed by echocardiography using speckled tracking analysis.
Cardiopulmonary Exercise Test: Oxygen Uptake Efficiency Slope (OUES): 1 Hour 40 Minute Post-dose
Time Frame: 1 hour 40 minutes post-dose
OUES was defined as an index of cardiopulmonary functional reserve that was based upon a submaximal exercise effort. OUES relates oxygen uptake to total ventilation during exercise.
Secondary Outcomes
- Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)(Baseline up to 5-10 days after last dose of study drug (up to 25 days))
- Number of Participants With Clinically Significant Laboratory Abnormalities(Baseline up-to 3 hours post-dose)
- Number of Participants With Categorical Post-dose Cardiovascular Monitoring Data(Baseline up-to 3 hours post-dose)
- Cardiopulmonary Exercise Test: Physical Work Capacity at a Heart Rate of 130 Beats Per Minute (PWC 130)(1 hour 40 minutes post-dose)
- Cardiac Structure: Left Ventricular Volume(20 minutes pre-dose, 1 hour 30 minutes and 2 hours 5 minutes post-dose)
- Change From Baseline in the Left Ventricular Volume(1 hour 30 minutes and 2 hours 5 minutes post-dose)
- Number of Participants With Categorical Post-dose Cardiovascular Monitoring Data: Electrocardiogram (ECG) Parameters(Baseline up-to 3 hour post-dose)
- Cardiopulmonary Exercise Test: Minute Ventilation and Carbon Dioxide Production (VE/VCO2 Slope)(1 hour 40 minutes post-dose)
- Cardiopulmonary Exercise Test: Volume of Oxygen (VO2) at Anaerobic Threshold (AT)(1 hour 40 minutes post-dose)
- Cardiopulmonary Exercise Test: Oxygen (O2) Pulse(1 hour 40 minutes post-dose)
- Cardiopulmonary Exercise Test: Oxygen (O2) Kinetics(1 hour 40 minutes post-dose)
- Cardiopulmonary Exercise Test: Aerobic Efficiency(1 hour 40 minutes post-dose)
- Cardiopulmonary Exercise Test: Peak Volume of Oxygen (VO2)(1 hour 40 minutes post-dose)
- Cardiopulmonary Exercise Test: Respiratory Exchange Ratio (RER)(1 hour 40 minutes post-dose)
- Change From Baseline in Trans-mitral Doppler Ratio(1 hour 30 minutes and 2 hours 5 minutes post-dose)
- Trans-mitral Doppler: Time(20 minutes pre-dose, 1 hour 30 minutes and 2 hours 5 minutes post-dose)
- Change From Baseline in Trans-mitral Doppler Time(1 hour 30 minutes and 2 hours 5 minutes post-dose)
- Early and Late Peak Tissue Velocity(20 minutes pre-dose, 1 hour 30 minutes and 2 hours 5 minutes post-dose)
- Change From Baseline in Early and Late Peak Velocity(1 hour 30 minutes and 2 hours 5 minutes post-dose)
- Diastolic Strain Rate(20 minutes pre-dose, 1 hour 30 minutes and 2 hours 5 minutes post-dose)
- Peak Diastolic Untwisting Rate(20 minutes pre-dose, 1 hour 30 minutes and 2 hours 5 minutes post-dose)
- Plasma Metabolomic Profiles Before and Immediately Following Steady State and Incremental Exercise(1 hour pre-dose, 1 hour 20 minutes and 2 hours 10 minutes post-dose)
- Cardiac Structure: Left Ventricular Wall Thickness(20 minutes pre-dose, 1 hour 30 minutes and 2 hours 5 minutes post-dose)
- Cardiac Structure: Left Ventricular Geometry(20 minutes pre-dose, 1 hour 30 minutes and 2 hours 5 minutes post-dose)
- Cardiac Structure: Right Ventricular Dimension(20 minutes pre-dose, 1 hour 30 minutes and 2 hours 5 minutes post-dose)
- Change From Baseline in Right Ventricular Dimension(1 hour 30 minutes and 2 hours 5 minutes post-dose)
- Cardiac Structure: Atrial Volume(20 minutes pre-dose, 1 hour 30 minutes and 2 hours 5 minutes post-dose)
- Change From Baseline in Atrial Volumes(1 hour 30 minutes and 2 hours 5 minutes post-dose)
- Systolic Function: Ejection Fraction(20 minutes pre-dose, 1 hour 30 minutes and 2 hours 5 minutes post-dose)
- Change From Baseline in Ejection Fraction(1 hour 30 minutes and 2 hours 5 minutes post-dose)
- Systolic Function: Peak Contractile Velocity(20 minutes pre-dose, 1 hour 30 minutes and 2 hours 5 minutes post-dose)
- Change From Baseline in Peak Contractile Velocity(1 hour 30 minutes and 2 hours 5 minutes post-dose)
- Systolic Function: Rotation/Torsion(20 minutes pre-dose, 1 hour 30 minutes and 2 hours 5 minutes post-dose)
- Systolic Function: Global Strain Rate(20 minutes pre-dose, 1 hour 30 minutes and 2 hours 5 minutes)
- Change From Baseline in Systolic Global Strain Rate(1 hour 30 minutes and 2 hours 5 minutes post-dose)
- Trans-mitral Doppler: Ratio(20 minutes pre-dose, 1 hour 30 minutes and 2 hours 5 minutes)