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Phase 1 Completed N=12 Randomized Double-blind Basic Science

Effect Of Single-Dose PF-05175157 On Metabolic And Cardiopulmonary Parameters

Healthy
Source: ClinicalTrials.gov NCT01819922 ↗
Enrolled (actual)
12
Serious AEs
0.0%
Results posted
May 2016
Primary outcomePrimary: Systolic Function: Global Longitudinal Left Ventricular (LV) Strain: 20 Minutes Pre-dose — -19.779; -20.483 percent change

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.

Outcome Measures

OutcomeResultp-value
PRIMARY
Systolic Function: Global Longitudinal Left Ventricular (LV) Strain: 20 Minutes Pre-dose
-19.779; -20.483
PRIMARY
Systolic Function: Global Longitudinal Left Ventricular (LV) Strain: 1 Hour 30 Minutes Post-dose
-19.728; -20.183
PRIMARY
Systolic Function: Global Longitudinal Left Ventricular (LV) Strain: 2 Hours 5 Minutes Post-dose
-24.058; -24.587
PRIMARY
Cardiopulmonary Exercise Test: Oxygen Uptake Efficiency Slope (OUES): 1 Hour 40 Minute Post-dose
3192.500; 3165.833
SECONDARY
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
0; 2; 0; 0
SECONDARY
Number of Participants With Clinically Significant Laboratory Abnormalities
4; 6
SECONDARY
Number of Participants With Categorical Post-dose Cardiovascular Monitoring Data
0; 0; 0; 0; 0; 0
SECONDARY
Number of Participants With Categorical Post-dose Cardiovascular Monitoring Data: Electrocardiogram (ECG) Parameters
0; 0; 0; 0; 1; 0
SECONDARY
Cardiopulmonary Exercise Test: Peak Volume of Oxygen (VO2)
41.325; 42.092
SECONDARY
Cardiopulmonary Exercise Test: Respiratory Exchange Ratio (RER)
0.984; 1.013
SECONDARY
Cardiopulmonary Exercise Test: Minute Ventilation and Carbon Dioxide Production (VE/VCO2 Slope)
22.325; 21.375
SECONDARY
Cardiopulmonary Exercise Test: Volume of Oxygen (VO2) at Anaerobic Threshold (AT)
19.008; 18.633
SECONDARY
Cardiopulmonary Exercise Test: Oxygen (O2) Pulse
16.692; 16.850
SECONDARY
Cardiopulmonary Exercise Test: Oxygen (O2) Kinetics
SECONDARY
Cardiopulmonary Exercise Test: Aerobic Efficiency
10.358; 10.483
SECONDARY
Cardiopulmonary Exercise Test: Physical Work Capacity at a Heart Rate of 130 Beats Per Minute (PWC 130)
156.583; 156.667
SECONDARY
Cardiac Structure: Left Ventricular Volume
76.750; 76.333; 77.167; 77.333; 85.250; 85.000
SECONDARY
Change From Baseline in the Left Ventricular Volume
0.417; 1.000; 8.500; 8.667
SECONDARY
Cardiac Structure: Left Ventricular Wall Thickness
SECONDARY
Cardiac Structure: Left Ventricular Geometry
SECONDARY
Cardiac Structure: Right Ventricular Dimension
24.250; 23.704; 24.408; 23.975; 24.203; 23.642
SECONDARY
Change From Baseline in Right Ventricular Dimension
0.158; 0.271; -0.047; -0.062; -0.325; 0.350
SECONDARY
Cardiac Structure: Atrial Volume
47.000; 50.750; 47.000; 49.833; 42.917; 44.917
SECONDARY
Change From Baseline in Atrial Volumes
0.000; -0.917; -4.083; -5.833; 1.417; 1.333
SECONDARY
Systolic Function: Ejection Fraction
63.190; 63.058; 62.525; 62.633; 72.462; 72.949
SECONDARY
Change From Baseline in Ejection Fraction
-0.665; -0.426; 9.272; 9.891
SECONDARY
Systolic Function: Peak Contractile Velocity
7.625; 9.025; 7.758; 9.083; 12.875; 13.925
SECONDARY
Change From Baseline in Peak Contractile Velocity
0.133; 0.058; 5.250; 4.900
SECONDARY
Systolic Function: Rotation/Torsion
SECONDARY
Systolic Function: Global Strain Rate
-1.043; -1.124; -1.047; -1.078; -1.845; -1.916
SECONDARY
Change From Baseline in Systolic Global Strain Rate
-0.003; 0.047; -0.802; -0.792
SECONDARY
Trans-mitral Doppler: Ratio
186.894; 182.236; 184.050; 190.424; 134.205; 125.156
SECONDARY
Change From Baseline in Trans-mitral Doppler Ratio
-2.844; 8.188; -57.803; -61.330
SECONDARY
Trans-mitral Doppler: Time
168.333; 158.917; 166.417; 160.750; 179.091; 173.727
SECONDARY
Change From Baseline in Trans-mitral Doppler Time
-1.917; 1.833; 11.273; 14.273
SECONDARY
Early and Late Peak Tissue Velocity
9.892; 10.375; 10.017; 10.342; 11.600; 11.825
SECONDARY
Change From Baseline in Early and Late Peak Velocity
-0.300; 0.125; 1.713; 1.144; 0.125; -0.033
SECONDARY
Diastolic Strain Rate
SECONDARY
Peak Diastolic Untwisting Rate
SECONDARY
Plasma Metabolomic Profiles Before and Immediately Following Steady State and Incremental Exercise

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
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01819922). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

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