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Trial record 2 of 6 for:    CK-2127107

A Study to Assess the Effect of CK-2127107 on Physical Function in Subjects With Chronic Obstructive Pulmonary Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02662582
Recruitment Status : Completed
First Posted : January 25, 2016
Results First Posted : February 5, 2021
Last Update Posted : March 24, 2021
Sponsor:
Collaborator:
Cytokinetics
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Chronic Obstructive Pulmonary Disease (COPD)
Interventions Drug: Reldesemtiv
Drug: Placebo
Enrollment 46
Recruitment Details  
Pre-assignment Details Participants with a clinical diagnosis of moderate to severe chronic obstructive pulmonary disease (COPD) between 40 to 75 years of age inclusive and met all of the inclusion and none of the exclusion criteria were enrolled in this study.
Arm/Group Title CK-2127107 1000 mg, Then Placebo Placebo, Then CK-212710 1000 mg
Hide Arm/Group Description Participants received CK-2127107 500 mg, orally, twice daily for 2 weeks in treatment period 1 followed by matching placebo orally, twice daily for 2 weeks in treatment period 2. A washout period of 2 weeks was maintained between the two treatment periods. Participants received matching placebo orally, twice daily for 2 weeks in treatment period 1 followed by CK-2127107 500 mg orally, twice daily for 2 weeks in treatment period 2. A washout period of 2 weeks was maintained between the two treatment periods.
Period Title: Treatment Period 1 (14 Days)
Started 23 23
Completed 18 19
Not Completed 5 4
Reason Not Completed
Adverse Event             3             2
Miscellaneous             0             1
Protocol Deviation             1             0
Withdrawal by Subject             1             1
Period Title: Washout Period (14 Days)
Started 18 19
Completed 18 19
Not Completed 0 0
Period Title: Treatment Period 2 (14 Days)
Started 18 19
Completed 18 19
Not Completed 0 0
Arm/Group Title CK-2127107 1000mg, Then Placebo Placebo, Then CK-2127107 1000mg Total
Hide Arm/Group Description Participants received CK-2127107 500 mg, orally, twice daily for 2 weeks in treatment period 1 followed by matching placebo orally, twice daily for 2 weeks in treatment period 2. A washout period of 2 weeks will be maintained between the two treatment periods. Participants received matching placebo orally, twice daily for 2 weeks in treatment period 1 followed by CK-2127107 500 mg, orally, twice daily for 2 weeks in treatment period 2. A washout period of 2 weeks will be maintained between the two treatment periods. Total of all reporting groups
Overall Number of Baseline Participants 23 23 46
Hide Baseline Analysis Population Description
The safety analysis set (SAF) consisted of all randomized participants who took ≥ 1 dose of study medication.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 23 participants 23 participants 46 participants
62.8  (7.9) 63.1  (8.3) 63  (8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants 23 participants 46 participants
Female
13
  56.5%
12
  52.2%
25
  54.3%
Male
10
  43.5%
11
  47.8%
21
  45.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants 23 participants 46 participants
Hispanic or Latino
0
   0.0%
1
   4.3%
1
   2.2%
Not Hispanic or Latino
23
 100.0%
22
  95.7%
45
  97.8%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants 23 participants 46 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
5
  21.7%
8
  34.8%
13
  28.3%
White
18
  78.3%
14
  60.9%
32
  69.6%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
1
   4.3%
1
   2.2%
Constant work rate (CWR) Endurance Time   [1] 
Mean (Standard Deviation)
Unit of measure:  Seconds
Number Analyzed 23 participants 23 participants 46 participants
334.5  (80.0) 346.4  (89.1) 340.4  (84.0)
[1]
Measure Description: The CWR defines how long it takes until the participant reaches symptom limitations while simultaneously being monitored and is called "CWR time to intolerance," which determines the "CWR endurance time".
1.Primary Outcome
Title Change From Period Baseline at Week 2 in Constant Work Rate (CWR) Endurance Time Relative to Placebo
Hide Description The CWR defines how long it takes until the participant reaches symptom limitations while simultaneously being monitored and is called "CWR time to intolerance," which determined the "CWR endurance time". Positive change indicates an improvement from baseline (i.e., a favorable outcome).
Time Frame Baseline and week 2 of each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) consisted of all participants who were randomized and received ≥ 1 dose of study drug and had ≥ 1 baseline measurement and 1 post baseline measurement within a period. FAS population with available data at each specified time point.
Arm/Group Title Placebo CK-2127107
Hide Arm/Group Description:
Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.
Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Overall Number of Participants Analyzed 32 35
Least Squares Mean (Standard Error)
Unit of Measure: seconds
-1.4  (22.2) -13.4  (21.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Least square means (LSMeans), LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.734
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value -12.0
Confidence Interval (2-Sided) 90%
-71.2 to 47.2
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Period Baseline at Week 2 in Oxygen Uptake (VO2)
Hide Description VO2 was defined as volume of O2 extracted from inspired air in a given period of time. VO2 was reported at isotime and peak exercise during CWR test.
Time Frame Baseline and week 2 of each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population with available data at each specified time point.
Arm/Group Title Placebo CK-2127107
Hide Arm/Group Description:
Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.
Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Overall Number of Participants Analyzed 32 35
Least Squares Mean (Standard Error)
Unit of Measure: Liter per minute (L/min)
Peak -0.0054  (0.0193) -0.0273  (0.0182)
Isotime -0.0006  (0.0155) -0.0330  (0.0147)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Peak: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.438
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean Difference
Estimated Value -0.0219
Confidence Interval (2-Sided) 90%
-0.0694 to 0.0256
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Isotime: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.114
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean Difference
Estimated Value -0.0325
Confidence Interval (2-Sided) 90%
-0.0663 to 0.0014
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Period Baseline at Week 2 in Ventilation (VE)
Hide Description VE was defined as volume of gas exhaled from the lungs in 1 minute, also called 'ventilation' or 'minute ventilation. VE was reported at isotime and peak exercise during CWR test.
Time Frame Baseline and week 2 of each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population with available data at each specified time point.
Arm/Group Title Placebo CK-2127107
Hide Arm/Group Description:
Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.
Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Overall Number of Participants Analyzed 32 35
Least Squares Mean (Standard Error)
Unit of Measure: L/min
Peak -0.17  (1.04) 0.58  (0.98)
Isotime 0.04  (0.84) 0.34  (0.80)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Peak: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.612
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value 0.75
Confidence Interval (2-Sided) 90%
-1.75 to 3.24
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Isotime: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.789
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value 0.29
Confidence Interval (2-Sided) 90%
-1.55 to 2.14
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Period Baseline at Week 2 in Ventilatory Equivalent for Carbon Dioxide (VE/VCO2)
Hide Description VE/VCO2 was a ratio of VE to VCO2. It is a dimensionless quantity. This ratio indicates how many liters of air exhaled were breathed to eliminate 1 liter of CO2. VE/VCO2 was reported at isotime and peak exercise during CWR test.
Time Frame Baseline and week 2 of each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population with available data at each specified time point.
Arm/Group Title Placebo CK-2127107
Hide Arm/Group Description:
Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.
Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Overall Number of Participants Analyzed 32 35
Least Squares Mean (Standard Error)
Unit of Measure: ratio
Peak 0.05  (0.37) 0.77  (0.36)
Isotime 0.05  (0.37) 0.97  (0.35)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Peak: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.225
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value 0.72
Confidence Interval (2-Sided) 90%
-0.26 to 1.70
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Isotime: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.064
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value 0.92
Confidence Interval 90%
0.11 to 1.174
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Period Baseline at Week 2 in Inspiratory Capacity (IC) Change From Peak to Rest
Hide Description IC was defined as the volume of air that can be inspired after a normal expiration; it is the sum of the tidal volume (VT) and the IRV.
Time Frame Baseline and week 2 of each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population with available data each specified time point.
Arm/Group Title Placebo CK-2127107
Hide Arm/Group Description:
Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.
Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Overall Number of Participants Analyzed 32 35
Least Squares Mean (Standard Error)
Unit of Measure: Liters
-0.008  (0.051) 0.044  (0.048)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.447
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value 0.052
Confidence Interval (2-Sided) 90%
-0.063 to 0.167
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Period Baseline at Week 2 in Perceived Exertion for Dyspnea and Leg Discomfort (BORG CR10)
Hide Description The Borg Scale (Borg CR10) is a simple 10-item method of rating perceived exertion and collects information on perceived exertion in an individual's rating of exercise intensity. Participants were asked to use this scale to rate the intensity of their breathing and leg discomfort before, during, and after exercise. Scores range from 0 (Complete Rest) to 10 (Extremely Hard (almost maximal)). BORG CR10 was reported at isotime and peak exercise during CWR test.
Time Frame Baseline and week 2 of each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population with available data at each specified time point.
Arm/Group Title Placebo CK-2127107
Hide Arm/Group Description:
Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.
Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Overall Number of Participants Analyzed 32 35
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Borg (Dyspnea) at Peak Number Analyzed 32 participants 35 participants
0.5  (0.4) -0.3  (0.3)
Borg (Dyspnea) at isotime Number Analyzed 32 participants 35 participants
0.4  (0.4) -0.1  (0.3)
Borg (Leg Effort) at Peak Number Analyzed 32 participants 35 participants
-0.1  (0.3) -0.3  (0.3)
Borg (Leg Effort) at isotime Number Analyzed 31 participants 35 participants
0.1  (0.3) -0.2  (0.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Borg (Dyspnea) at Peak: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.099
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value -0.8
Confidence Interval (2-Sided) 90%
-1.7 to 0.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Borg (Dyspnea) at isotime: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.255
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value -0.5
Confidence Interval (2-Sided) 90%
-1.3 to 0.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Borg (Leg Effort) at Peak: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.651
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value -0.2
Confidence Interval (2-Sided) 90%
-1.1 to 0.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Borg (Leg Effort) at isotime: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.591
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value -0.3
Confidence Interval (2-Sided) 90%
-1.0 to 0.5
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Period Baseline at Week 2 in Respiratory Exchange Ratio (RER)
Hide Description The respiratory exchange ratio is equal to the VCO2 / VO2 [RER = VCO2 (L/min) / VO2 (L/min)]. RER was reported at isotime and peak exercise during CWR test.
Time Frame Baseline and week 2 of each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population with available data at each specified time point.
Arm/Group Title Placebo CK-2127107
Hide Arm/Group Description:
Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.
Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Overall Number of Participants Analyzed 32 35
Least Squares Mean (Standard Error)
Unit of Measure: ratio
Peak -0.0036  (0.0125) 0.0250  (0.0119)
Isotime -0.0042  (0.0102) 0.0143  (0.0097)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Peak: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.040
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value 0.0286
Confidence Interval (2-Sided) 90%
0.0061 to 0.0511
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Isotime: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.155
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean differencce
Estimated Value 0.0185
Confidence Interval (2-Sided) 90%
-0.0031 to 0.0401
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From Period Baseline at Week 2 in Carbon Dioxide Output (VCO2)
Hide Description VCO2 was defined as volume of CO2 exhaled from the body per unit of time; also called the rate of elimination of CO2. VCO2 was reported at isotime and peak exercise during CWR test.
Time Frame Baseline and week 2 of each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population with available data at each specified time point.
Arm/Group Title Placebo CK-2127107
Hide Arm/Group Description:
Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.
Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Overall Number of Participants Analyzed 32 35
Least Squares Mean (Standard Error)
Unit of Measure: L/min
Peak -0.0129  (0.0231) -0.0119  (0.0219)
Isotime -0.0115  (0.0188) -0.0232  (0.0179)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Peak: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.972
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value 0.0010
Confidence Interval (2-Sided) 90%
-0.0459 to 0.0479
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Isotime: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.578
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value -0.0118
Confidence Interval (2-Sided) 90%
-0.0471 to 0.0236
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change From Period Baseline at Week 2 in End-tidal PCO2 (PETCO2)
Hide Description PETCO2 was defined as partial pressure of carbon dioxide in the expired gas at the end of an exhalation. This represents the mean partial pressure of carbon dioxide in the pulmonary alveoli. PETCO2 was reported at isotime and peak exercise during CWR test.
Time Frame Baseline and week 2 of each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population with available data at each specified time point.
Arm/Group Title Placebo CK-2127107
Hide Arm/Group Description:
Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.
Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Overall Number of Participants Analyzed 32 35
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
Peak -0.12  (0.34) -0.77  (0.33)
Isotime -0.07  (0.33) -0.64  (0.31)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Peak: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.235
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value -0.65
Confidence Interval (2-Sided) 90%
-1.55 to 0.26
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Isotime: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.215
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean differencce
Estimated Value -0.57
Confidence Interval (2-Sided) 90%
-1.33 to 0.19
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change From Period Baseline at Week 2 in End-tidal PO2 (PETO2)
Hide Description PETO2 was defined as Partial pressure of oxygen in the expired gas at the end of an exhalation. This represents the mean partial pressure of oxygen in the pulmonary alveoli. PETO2 was reported at isotime and peak exercise during CWR test.
Time Frame Baseline and week 2 of each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population with available data at each specified time point.
Arm/Group Title Placebo CK-2127107
Hide Arm/Group Description:
Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.
Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Overall Number of Participants Analyzed 32 35
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
Peak 0.38  (042) 1.08  (0.40)
Isotime 0.30  (0.40) 0.75  (0.38)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Peak: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.280
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value 0.70
Confidence Interval (2-Sided) 90%
-0.38 to 1.77
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Isotime: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.424
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value 0.46
Confidence Interval (2-Sided) 90%
-0.49 to 1.40
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Change From Period Baseline at Week 2 in Tidal Volume (VT)
Hide Description VT was defined as tidal volume is the volume of gas exhaled in each respiratory cycle. Tidal volume is typically measured as an average value over several respiratory cycles, and is expressed in liters. VT was reported at isotime and peak exercise during CWR test.
Time Frame Baseline and week 2 of each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population with available data at each specified time point.
Arm/Group Title Placebo CK-2127107
Hide Arm/Group Description:
Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.
Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Overall Number of Participants Analyzed 32 35
Least Squares Mean (Standard Error)
Unit of Measure: Liters
Peak -0.0689  (0.0216) -0.0299  (0.0204)
Isotime -0.0582  (0.0289) -0.0093  (0.0273)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Peak: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.187
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value 0.0390
Confidence Interval (2-Sided) 90%
-0.0099 to 0.0879
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Isotime: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.213
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value 0.0488
Confidence Interval (2-Sided) 90%
-0.0163 to 0.1140
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Change From Period Baseline at Week 2 in Breathing Frequency (Bf)
Hide Description Bf was defined as the number of breaths (i.e., an entire inspiratory and expiratory respiratory cycle) per minute. Bf was reported at isotime and peak exercise during CWR test.
Time Frame Baseline and week 2 of each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population with available data at each specified time point.
Arm/Group Title Placebo CK-2127107
Hide Arm/Group Description:
Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.
Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Overall Number of Participants Analyzed 32 34
Least Squares Mean (Standard Error)
Unit of Measure: Breaths/min
Peak 1.6  (0.6) 1.2  (0.6)
Isotime 1.4  (0.7) 0.7  (0.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Peak: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.640
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value -0.4
Confidence Interval 90%
-2.1 to 1.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Isotime: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.487
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value -0.7
Confidence Interval (2-Sided) 90%
-2.5 to 1.1
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Change From Period Baseline at Week 2 in Inspiratory Capacity (IC)
Hide Description IC was defined as the volume of air that can be inspired after a normal expiration; it is the sum of the VT and the IRV. IC was reported at isotime and peak exercise during CWR test.
Time Frame Baseline and week 2 of each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population with available data at each specified time point.
Arm/Group Title Placebo CK-2127107
Hide Arm/Group Description:
Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.
Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Overall Number of Participants Analyzed 32 35
Least Squares Mean (Standard Error)
Unit of Measure: Liters
Peak -0.047  (0.048) 0.048  (0.046)
Isotime -0.09  (0.045) 0.042  (0.043)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Peak: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.100
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value 0.095
Confidence Interval (2-Sided) 90%
0.000 to 0.189
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Isotime: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value 0.133
Confidence Interval (2-Sided) 90%
0.053 to 0.213
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Change From Period Baseline to Week 2 in Inspiratory Reserve Volume (IRV)
Hide Description The Inspiratory reserve volume was equal to VT - IC measured in liters [IRV (L) = VT (L) - IC (L)]. IRV was reported at isotime and peak exercise during CWR test.
Time Frame Baseline and week 2 of each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population with available data at each specified time point.
Arm/Group Title Placebo CK-2127107
Hide Arm/Group Description:
Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.
Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Overall Number of Participants Analyzed 32 35
Least Squares Mean (Standard Error)
Unit of Measure: Liters
Peak 0.026  (0.049) 0.077  (0.047)
Isotime -0.042  (0.050) 0.052  (0.048)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Peak: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.408
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value 0.051
Confidence Interval (2-Sided) 90%
-0.052 to 0.154
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Isotime: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.058
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value 0.094
Confidence Interval (2-Sided) 90%
0.013 to 0.174
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Change From Period Baseline at Week 2 in Ventilatory Reserve (VE/MVV)
Hide Description VE/MVV provides the rate of expired ventilation to the capacity. VE/MVV was reported at isotime and peak exercise during CWR test.
Time Frame Baseline and week 2 of each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population with available data at each specified time point.
Arm/Group Title Placebo CK-2127107
Hide Arm/Group Description:
Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.
Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Overall Number of Participants Analyzed 32 34
Least Squares Mean (Standard Error)
Unit of Measure: percentage of expired ventilation
Peak 2.19  (2.18) 3.62  (2.10)
Isotime 2.67  (2.34) 3.52  (2.26)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Peak: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.648
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value 1.44
Confidence Interval (2-Sided) 90%
-3.85 to 6.73
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Isotime: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.775
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value 0.85
Confidence Interval (2-Sided) 90%
-4.12 to 5.82
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Change From Period Baseline at Week 2 in Heart Rate (HR)
Hide Description HR was reported at isotime and peak exercise during CWR test.
Time Frame Baseline and week 2 of each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population with available data at each specified time point.
Arm/Group Title Placebo CK-2127107
Hide Arm/Group Description:
Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.
Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Overall Number of Participants Analyzed 32 35
Least Squares Mean (Standard Error)
Unit of Measure: Beats/min
Peak -1.6  (1.5) -0.5  (1.5)
Isotime -1.5  (1.7) 0.7  (1.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Peak: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.544
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value 1.1
Confidence Interval (2-Sided) 90%
-1.9 to 4.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Isotime: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.216
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value 2.1
Confidence Interval (2-Sided) 90%
-0.7 to 5.0
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Change From Period Baseline at Week 2 in Systolic Blood Pressure (SBP)
Hide Description SBP was reported at isotime and peak exercise during CWR test.
Time Frame Baseline and week 2 of each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population with available data each specified time point.
Arm/Group Title Placebo CK-2127107
Hide Arm/Group Description:
Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.
Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Overall Number of Participants Analyzed 32 35
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
Peak 3.0  (3.5) -4.5  (3.3)
Istotime 0.2  (4.2) 0.4  (4.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Peak: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.171
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value -7.4
Confidence Interval (2-Sided) 90%
-16.5 to 1.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Isotime: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.976
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value 0.2
Confidence Interval (2-Sided) 90%
-10.3 to 10.7
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Change From Period Baseline at Week 2 in Diastolic Blood Pressure (DBP)
Hide Description DBP was reported at isotime and peak exercise during CWR test.
Time Frame Baseline and week 2 of each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population with available data at each specified time point.
Arm/Group Title Placebo CK-2127107
Hide Arm/Group Description:
Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.
Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Overall Number of Participants Analyzed 32 35
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
Peak 0.3  (2.1) -0.3  (2.0)
Isotime -1.0  (2.0) -2.0  (1.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Peak: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.844
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value -0.6
Confidence Interval (2-Sided) 90%
-6.1 to 4.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Isotime: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.751
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value -0.9
Confidence Interval (2-Sided) 90%
-5.8 to 4.0
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Change From Period Baseline at Week 2 in Arterial Oxygen Saturation From Pulse Oximetry (SpO2)
Hide Description SPO2 was defined as the noninvasive estimation of arterial hemoglobin (Hb) oxygen saturation, using a device that utilizes the combined principles of spectrophotometry and pulse plethysmography. SPO2 was reported at isotime and peak exercise during CWR test.
Time Frame Baseline and week 2 of each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population with available data at each specified time point.
Arm/Group Title Placebo CK-2127107
Hide Arm/Group Description:
Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.
Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Overall Number of Participants Analyzed 31 34
Least Squares Mean (Standard Error)
Unit of Measure: percentage of oxygen saturation
Peak -0.4  (0.3) -0.2  (0.2)
Isotime -0.3  (0.3) 0.0  (0.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Peak: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.590
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value 0.2
Confidence Interval (2-Sided) 90%
-0.5 to 0.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Isotime: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.399
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value 0.3
Confidence Interval (2-Sided) 90%
-0.3 to 0.9
Estimation Comments [Not Specified]
20.Secondary Outcome
Title Change From Period Baseline at Week 2 in Forced Vital Capacity (FVC)
Hide Description Change From Period Baseline in FVC was reported.
Time Frame Baseline and week 2 of each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population with available data at each specified time point.
Arm/Group Title Placebo CK-2127107
Hide Arm/Group Description:
Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.
Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Overall Number of Participants Analyzed 33 34
Least Squares Mean (Standard Error)
Unit of Measure: Liters
0.00  (0.05) -0.10  (0.04)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.151
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value -0.09
Confidence Interval (2-Sided) 90%
-0.20 to 0.01
Estimation Comments [Not Specified]
21.Secondary Outcome
Title Change From Period Baseline at Week 2 in Forced Expiratory Volume 1 (FEV1)
Hide Description Change From Period Baseline in FEV1 was reported.
Time Frame Baseline and week 2 of each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population with available data at each specified time point.
Arm/Group Title Placebo CK-2127107
Hide Arm/Group Description:
Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.
Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Overall Number of Participants Analyzed 33 34
Least Squares Mean (Standard Error)
Unit of Measure: Liters
-0.030  (0.028) -0.037  (0.027)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.857
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value -0.007
Confidence Interval (2-Sided) 90%
-0.070 to 0.056
Estimation Comments [Not Specified]
22.Secondary Outcome
Title Change From Period Baseline at Week 2 in FVC/FEV1 Ratio
Hide Description Change From Period Baseline in FVC/FEV1 Ratio was reported.
Time Frame Baseline and week 2 of each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population with available data at each specified time point.
Arm/Group Title Placebo CK-2127107
Hide Arm/Group Description:
Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.
Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Overall Number of Participants Analyzed 33 34
Least Squares Mean (Standard Error)
Unit of Measure: ratio
-1.10  (0.71) 0.47  (0.69)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.110
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value 1.56
Confidence Interval (2-Sided) 90%
-0.05 to 3.17
Estimation Comments [Not Specified]
23.Secondary Outcome
Title Change From Period Baseline at Week 2 in Activation of Accessory Respiratory Muscles
Hide Description Activation of accessory respiratory muscles was assessed by electromyogram. Data was reported at peak and isotime.
Time Frame Baseline and week 2 of each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population with available data at each specified time point.
Arm/Group Title Placebo CK-2127107
Hide Arm/Group Description:
Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.
Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Overall Number of Participants Analyzed 31 32
Least Squares Mean (Standard Error)
Unit of Measure: percentage of activation
Peak 4.84  (4.76) 6.91  (4.65)
Isotime 1.04  (4.39) 3.98  (4.30)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Peak: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.766
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value 2.07
Confidence Interval (2-Sided) 90%
-9.57 to 13.71
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, CK-2127107
Comments Isotime: LSMeans, LSMean difference of CK-2127107 minus placebo, and 90% confidence intervals are based on a mixed effect model with treatment and period as fixed effects, subject as a random effect, and a compound symmetry covariance structure.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.642
Comments Statistical comparison was performed at a 2-sided 0.10 significance level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMean difference
Estimated Value 2.94
Confidence Interval (2-Sided) 90%
-7.66 to 13.54
Estimation Comments [Not Specified]
24.Secondary Outcome
Title Number of Participants With Treatment Emergent Adverse Events
Hide Description TEAEs were defined as any AE that started or worsened in severity after the first dose of study drug up to 14 days after the last dose of study drug. An AE was defined as any untoward medical occurrence in a participant administered a study drug or who had undergone study procedures and did not necessarily have a causal relationship with this treatment. An AE could therefore be any unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An abnormality identified during a medical test (e.g., laboratory parameter, vital sign, ECG data, physical examination) an AE only if the abnormality meets 1 of the following criteria: Induces clinical signs or symptoms, Requires active intervention, Requires interruption or discontinuation of study drug, The abnormality or test value is clinically significant in the opinion of the inves
Time Frame From first dose of study drug up to 14 days after last dose of study drug (8 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
SAF population
Arm/Group Title Placebo CK-2127107
Hide Arm/Group Description:
Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.
Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Overall Number of Participants Analyzed 41 42
Measure Type: Number
Unit of Measure: Participants
15 21
25.Secondary Outcome
Title Plasma Concentration of CK-2127107 at Day 1 Predose, Day 14 Lowest Concentration (Ctrough), and Day 14 Concentration Predose 6 Hours (C6h)
Hide Description Plasma concentration of CK-2127107 was reported.
Time Frame Day 1 predose, day 14 Ctrough, day 14 C6h
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Hide Analysis Population Description
The pharmacokinetic analysis set (PKAS) consisted of the administered population for which ≥ 1 quantifiable plasma trough concentration or concentration at 6 hours was available for CK-2127107, or its metabolite CK-2127106.
Arm/Group Title CK-2127107
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Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Overall Number of Participants Analyzed 33
Mean (Standard Deviation)
Unit of Measure: Nanogram per milliliter (ng/mL)
Day 1 predose Number Analyzed 17 participants
0  (0)
Day 14 Ctrough Number Analyzed 32 participants
2620  (2100)
Day 14 C6h Number Analyzed 33 participants
3290  (2000)
26.Secondary Outcome
Title Plasma Concentration of CK-2127106 (Metabolite of CK-2127107) at Day 1 Predose, Day 14 Ctrough, Day 14 C6h
Hide Description Plasma concentration of CK-2127106 (metabolite of CK-2127107) was reported.
Time Frame Day 1 predose, day 14 Ctrough, day 14 C6h
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Hide Analysis Population Description
PKAS population
Arm/Group Title CK-2127107
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Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Overall Number of Participants Analyzed 33
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 1 predose Number Analyzed 17 participants
0  (0)
Day 14 Ctrough Number Analyzed 32 participants
1760  (1710)
Day 14 C6h Number Analyzed 33 participants
1770  (1620)
Time Frame From first dose of study drug up to 14 days after last dose of study drug (8 weeks)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo CK-2127107
Hide Arm/Group Description Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2. Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
All-Cause Mortality
Placebo CK-2127107
Affected / at Risk (%) Affected / at Risk (%)
Total   0/41 (0.00%)      0/42 (0.00%)    
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Placebo CK-2127107
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/41 (2.44%)      2/42 (4.76%)    
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Renal cell carcinoma  1  0/41 (0.00%)  0 1/42 (2.38%)  1
Nervous system disorders     
IIIrd nerve paralysis  1  0/41 (0.00%)  0 1/42 (2.38%)  1
Renal and urinary disorders     
Haematuria  1  1/41 (2.44%)  1 0/42 (0.00%)  0
1
Term from vocabulary, MedDRA 17.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo CK-2127107
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/41 (2.44%)      3/42 (7.14%)    
Nervous system disorders     
Dizziness  1  1/41 (2.44%)  1 3/42 (7.14%)  3
1
Term from vocabulary, MedDRA 17.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site's manuscript prior to publication for review and comment as specified in the Investigator Agreement.
Results Point of Contact
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Name/Title: Clinical Trial Disclosure
Organization: Astellas Pharma Global Development, Inc.
Phone: 800-888-7704
EMail: astellas.resultsdisclosure@astellas.com
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Responsible Party: Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
ClinicalTrials.gov Identifier: NCT02662582    
Other Study ID Numbers: 3318-CL-3002
First Submitted: January 20, 2016
First Posted: January 25, 2016
Results First Submitted: January 16, 2021
Results First Posted: February 5, 2021
Last Update Posted: March 24, 2021