Trial Outcomes & Findings for A Study to Assess the Effect of CK-2127107 on Physical Function in Subjects With Chronic Obstructive Pulmonary Disease (NCT NCT02662582)

NCT ID: NCT02662582

Last Updated: 2024-11-14

Results Overview

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).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 46 participants
• Primary outcome timeframe: Baseline and week 2 of each treatment period
• Results posted on: 2024-11-14

Participant Flow

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.

Participant milestones

Measure	CK-2127107 1000 mg, Then Placebo 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.	Placebo, Then CK-212710 1000 mg 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.
Treatment Period 1 (14 Days) STARTED	23	23
Treatment Period 1 (14 Days) COMPLETED	18	19
Treatment Period 1 (14 Days) NOT COMPLETED	5	4
Washout Period (14 Days) STARTED	18	19
Washout Period (14 Days) COMPLETED	18	19
Washout Period (14 Days) NOT COMPLETED	0	0
Treatment Period 2 (14 Days) STARTED	18	19
Treatment Period 2 (14 Days) COMPLETED	18	19
Treatment Period 2 (14 Days) NOT COMPLETED	0	0

Reasons for withdrawal

Measure	CK-2127107 1000 mg, Then Placebo 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.	Placebo, Then CK-212710 1000 mg 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.
Treatment Period 1 (14 Days) Adverse Event	3	2
Treatment Period 1 (14 Days) Miscellaneous	0	1
Treatment Period 1 (14 Days) Protocol Deviation	1	0
Treatment Period 1 (14 Days) Withdrawal by Subject	1	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	CK-2127107 1000mg, Then Placebo n=23 Participants 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.	Placebo, Then CK-2127107 1000mg n=23 Participants 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 n=46 Participants Total of all reporting groups
Age, Continuous	62.8 Years STANDARD_DEVIATION 7.9 • n=5 Participants	63.1 Years STANDARD_DEVIATION 8.3 • n=7 Participants	63 Years STANDARD_DEVIATION 8 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	12 Participants n=7 Participants	25 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	11 Participants n=7 Participants	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	23 Participants n=5 Participants	22 Participants n=7 Participants	45 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	8 Participants n=7 Participants	13 Participants n=5 Participants
Race (NIH/OMB) White	18 Participants n=5 Participants	14 Participants n=7 Participants	32 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Constant work rate (CWR) Endurance Time	334.5 Seconds STANDARD_DEVIATION 80.0 • n=5 Participants	346.4 Seconds STANDARD_DEVIATION 89.1 • n=7 Participants	340.4 Seconds STANDARD_DEVIATION 84.0 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and week 2 of each treatment period

Population: 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.

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).

Outcome measures

Measure	Placebo n=32 Participants Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.	CK-2127107 n=35 Participants Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Change From Period Baseline at Week 2 in Constant Work Rate (CWR) Endurance Time Relative to Placebo	-1.4 seconds Standard Error 22.2	-13.4 seconds Standard Error 21.2

SECONDARY outcome

Timeframe: Baseline and week 2 of each treatment period

Population: FAS population with available data at each specified time point.

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.

Outcome measures

Measure	Placebo n=32 Participants Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.	CK-2127107 n=35 Participants Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Change From Period Baseline at Week 2 in Oxygen Uptake (VO2) Peak	-0.0054 Liter per minute (L/min) Standard Error 0.0193	-0.0273 Liter per minute (L/min) Standard Error 0.0182
Change From Period Baseline at Week 2 in Oxygen Uptake (VO2) Isotime	-0.0006 Liter per minute (L/min) Standard Error 0.0155	-0.0330 Liter per minute (L/min) Standard Error 0.0147

SECONDARY outcome

Timeframe: Baseline and week 2 of each treatment period

Population: FAS population with available data at each specified time point.

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.

Outcome measures

Measure	Placebo n=32 Participants Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.	CK-2127107 n=35 Participants Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Change From Period Baseline at Week 2 in Ventilation (VE) Peak	-0.17 L/min Standard Error 1.04	0.58 L/min Standard Error 0.98
Change From Period Baseline at Week 2 in Ventilation (VE) Isotime	0.04 L/min Standard Error 0.84	0.34 L/min Standard Error 0.80

SECONDARY outcome

Timeframe: Baseline and week 2 of each treatment period

Population: FAS population with available data at each specified time point.

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.

Outcome measures

Measure	Placebo n=32 Participants Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.	CK-2127107 n=35 Participants Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Change From Period Baseline at Week 2 in Ventilatory Equivalent for Carbon Dioxide (VE/VCO2) Peak	0.05 ratio Standard Error 0.37	0.77 ratio Standard Error 0.36
Change From Period Baseline at Week 2 in Ventilatory Equivalent for Carbon Dioxide (VE/VCO2) Isotime	0.05 ratio Standard Error 0.37	0.97 ratio Standard Error 0.35

SECONDARY outcome

Timeframe: Baseline and week 2 of each treatment period

Population: FAS population with available data each specified time point.

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.

Outcome measures

Measure	Placebo n=32 Participants Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.	CK-2127107 n=35 Participants Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Change From Period Baseline at Week 2 in Inspiratory Capacity (IC) Change From Peak to Rest	-0.008 Liters Standard Error 0.051	0.044 Liters Standard Error 0.048

SECONDARY outcome

Timeframe: Baseline and week 2 of each treatment period

Population: FAS population with available data at each specified time point.

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.

Outcome measures

Measure	Placebo n=32 Participants Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.	CK-2127107 n=35 Participants Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Change From Period Baseline at Week 2 in Perceived Exertion for Dyspnea and Leg Discomfort (BORG CR10) Borg (Dyspnea) at Peak	0.5 units on a scale Standard Error 0.4	-0.3 units on a scale Standard Error 0.3
Change From Period Baseline at Week 2 in Perceived Exertion for Dyspnea and Leg Discomfort (BORG CR10) Borg (Dyspnea) at isotime	0.4 units on a scale Standard Error 0.4	-0.1 units on a scale Standard Error 0.3
Change From Period Baseline at Week 2 in Perceived Exertion for Dyspnea and Leg Discomfort (BORG CR10) Borg (Leg Effort) at Peak	-0.1 units on a scale Standard Error 0.3	-0.3 units on a scale Standard Error 0.3
Change From Period Baseline at Week 2 in Perceived Exertion for Dyspnea and Leg Discomfort (BORG CR10) Borg (Leg Effort) at isotime	0.1 units on a scale Standard Error 0.3	-0.2 units on a scale Standard Error 0.3

SECONDARY outcome

Timeframe: Baseline and week 2 of each treatment period

Population: FAS population with available data at each specified time point.

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.

Outcome measures

Measure	Placebo n=32 Participants Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.	CK-2127107 n=35 Participants Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Change From Period Baseline at Week 2 in Respiratory Exchange Ratio (RER) Peak	-0.0036 ratio Standard Error 0.0125	0.0250 ratio Standard Error 0.0119
Change From Period Baseline at Week 2 in Respiratory Exchange Ratio (RER) Isotime	-0.0042 ratio Standard Error 0.0102	0.0143 ratio Standard Error 0.0097

SECONDARY outcome

Timeframe: Baseline and week 2 of each treatment period

Population: FAS population with available data at each specified time point.

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.

Outcome measures

Measure	Placebo n=32 Participants Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.	CK-2127107 n=35 Participants Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Change From Period Baseline at Week 2 in Carbon Dioxide Output (VCO2) Peak	-0.0129 L/min Standard Error 0.0231	-0.0119 L/min Standard Error 0.0219
Change From Period Baseline at Week 2 in Carbon Dioxide Output (VCO2) Isotime	-0.0115 L/min Standard Error 0.0188	-0.0232 L/min Standard Error 0.0179

SECONDARY outcome

Timeframe: Baseline and week 2 of each treatment period

Population: FAS population with available data at each specified time point.

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.

Outcome measures

Measure	Placebo n=32 Participants Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.	CK-2127107 n=35 Participants Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Change From Period Baseline at Week 2 in End-tidal PCO2 (PETCO2) Peak	-0.12 mmHg Standard Error 0.34	-0.77 mmHg Standard Error 0.33
Change From Period Baseline at Week 2 in End-tidal PCO2 (PETCO2) Isotime	-0.07 mmHg Standard Error 0.33	-0.64 mmHg Standard Error 0.31

SECONDARY outcome

Timeframe: Baseline and week 2 of each treatment period

Population: FAS population with available data at each specified time point.

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.

Outcome measures

Measure	Placebo n=32 Participants Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.	CK-2127107 n=35 Participants Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Change From Period Baseline at Week 2 in End-tidal PO2 (PETO2) Peak	0.38 mmHg Standard Error 042	1.08 mmHg Standard Error 0.40
Change From Period Baseline at Week 2 in End-tidal PO2 (PETO2) Isotime	0.30 mmHg Standard Error 0.40	0.75 mmHg Standard Error 0.38

SECONDARY outcome

Timeframe: Baseline and week 2 of each treatment period

Population: FAS population with available data at each specified time point.

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.

Outcome measures

Measure	Placebo n=32 Participants Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.	CK-2127107 n=35 Participants Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Change From Period Baseline at Week 2 in Tidal Volume (VT) Peak	-0.0689 Liters Standard Error 0.0216	-0.0299 Liters Standard Error 0.0204
Change From Period Baseline at Week 2 in Tidal Volume (VT) Isotime	-0.0582 Liters Standard Error 0.0289	-0.0093 Liters Standard Error 0.0273

SECONDARY outcome

Timeframe: Baseline and week 2 of each treatment period

Population: FAS population with available data at each specified time point.

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.

Outcome measures

Measure	Placebo n=32 Participants Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.	CK-2127107 n=34 Participants Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Change From Period Baseline at Week 2 in Breathing Frequency (Bf) Peak	1.6 Breaths/min Standard Error 0.6	1.2 Breaths/min Standard Error 0.6
Change From Period Baseline at Week 2 in Breathing Frequency (Bf) Isotime	1.4 Breaths/min Standard Error 0.7	0.7 Breaths/min Standard Error 0.7

SECONDARY outcome

Timeframe: Baseline and week 2 of each treatment period

Population: FAS population with available data at each specified time point.

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.

Outcome measures

Measure	Placebo n=32 Participants Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.	CK-2127107 n=35 Participants Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Change From Period Baseline at Week 2 in Inspiratory Capacity (IC) Peak	-0.047 Liters Standard Error 0.048	0.048 Liters Standard Error 0.046
Change From Period Baseline at Week 2 in Inspiratory Capacity (IC) Isotime	-0.09 Liters Standard Error 0.045	0.042 Liters Standard Error 0.043

SECONDARY outcome

Timeframe: Baseline and week 2 of each treatment period

Population: FAS population with available data at each specified time point.

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.

Outcome measures

Measure	Placebo n=32 Participants Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.	CK-2127107 n=35 Participants Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Change From Period Baseline to Week 2 in Inspiratory Reserve Volume (IRV) Peak	0.026 Liters Standard Error 0.049	0.077 Liters Standard Error 0.047
Change From Period Baseline to Week 2 in Inspiratory Reserve Volume (IRV) Isotime	-0.042 Liters Standard Error 0.050	0.052 Liters Standard Error 0.048

SECONDARY outcome

Timeframe: Baseline and week 2 of each treatment period

Population: FAS population with available data at each specified time point.

VE/MVV provides the rate of expired ventilation to the capacity. VE/MVV was reported at isotime and peak exercise during CWR test.

Outcome measures

Measure	Placebo n=32 Participants Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.	CK-2127107 n=34 Participants Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Change From Period Baseline at Week 2 in Ventilatory Reserve (VE/MVV) Peak	2.19 percentage of expired ventilation Standard Error 2.18	3.62 percentage of expired ventilation Standard Error 2.10
Change From Period Baseline at Week 2 in Ventilatory Reserve (VE/MVV) Isotime	2.67 percentage of expired ventilation Standard Error 2.34	3.52 percentage of expired ventilation Standard Error 2.26

SECONDARY outcome

Timeframe: Baseline and week 2 of each treatment period

Population: FAS population with available data at each specified time point.

HR was reported at isotime and peak exercise during CWR test.

Outcome measures

Measure	Placebo n=32 Participants Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.	CK-2127107 n=35 Participants Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Change From Period Baseline at Week 2 in Heart Rate (HR) Peak	-1.6 Beats/min Standard Error 1.5	-0.5 Beats/min Standard Error 1.5
Change From Period Baseline at Week 2 in Heart Rate (HR) Isotime	-1.5 Beats/min Standard Error 1.7	0.7 Beats/min Standard Error 1.6

SECONDARY outcome

Timeframe: Baseline and week 2 of each treatment period

Population: FAS population with available data each specified time point.

SBP was reported at isotime and peak exercise during CWR test.

Outcome measures

Measure	Placebo n=32 Participants Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.	CK-2127107 n=35 Participants Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Change From Period Baseline at Week 2 in Systolic Blood Pressure (SBP) Peak	3.0 mmHg Standard Error 3.5	-4.5 mmHg Standard Error 3.3
Change From Period Baseline at Week 2 in Systolic Blood Pressure (SBP) Istotime	0.2 mmHg Standard Error 4.2	0.4 mmHg Standard Error 4.0

SECONDARY outcome

Timeframe: Baseline and week 2 of each treatment period

Population: FAS population with available data at each specified time point.

DBP was reported at isotime and peak exercise during CWR test.

Outcome measures

Measure	Placebo n=32 Participants Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.	CK-2127107 n=35 Participants Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Change From Period Baseline at Week 2 in Diastolic Blood Pressure (DBP) Peak	0.3 mmHg Standard Error 2.1	-0.3 mmHg Standard Error 2.0
Change From Period Baseline at Week 2 in Diastolic Blood Pressure (DBP) Isotime	-1.0 mmHg Standard Error 2.0	-2.0 mmHg Standard Error 1.9

SECONDARY outcome

Timeframe: Baseline and week 2 of each treatment period

Population: FAS population with available data at each specified time point.

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.

Outcome measures

Measure	Placebo n=31 Participants Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.	CK-2127107 n=34 Participants Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Change From Period Baseline at Week 2 in Arterial Oxygen Saturation From Pulse Oximetry (SpO2) Peak	-0.4 percentage of oxygen saturation Standard Error 0.3	-0.2 percentage of oxygen saturation Standard Error 0.2
Change From Period Baseline at Week 2 in Arterial Oxygen Saturation From Pulse Oximetry (SpO2) Isotime	-0.3 percentage of oxygen saturation Standard Error 0.3	0.0 percentage of oxygen saturation Standard Error 0.2

SECONDARY outcome

Timeframe: Baseline and week 2 of each treatment period

Population: FAS population with available data at each specified time point.

Change From Period Baseline in FVC was reported.

Outcome measures

Measure	Placebo n=33 Participants Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.	CK-2127107 n=34 Participants Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Change From Period Baseline at Week 2 in Forced Vital Capacity (FVC)	0.00 Liters Standard Error 0.05	-0.10 Liters Standard Error 0.04

SECONDARY outcome

Timeframe: Baseline and week 2 of each treatment period

Population: FAS population with available data at each specified time point.

Change From Period Baseline in FEV1 was reported.

Outcome measures

Measure	Placebo n=33 Participants Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.	CK-2127107 n=34 Participants Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Change From Period Baseline at Week 2 in Forced Expiratory Volume 1 (FEV1)	-0.030 Liters Standard Error 0.028	-0.037 Liters Standard Error 0.027

SECONDARY outcome

Timeframe: Baseline and week 2 of each treatment period

Population: FAS population with available data at each specified time point.

Change From Period Baseline in FVC/FEV1 Ratio was reported.

Outcome measures

Measure	Placebo n=33 Participants Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.	CK-2127107 n=34 Participants Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Change From Period Baseline at Week 2 in FVC/FEV1 Ratio	-1.10 ratio Standard Error 0.71	0.47 ratio Standard Error 0.69

SECONDARY outcome

Timeframe: Baseline and week 2 of each treatment period

Population: FAS population with available data at each specified time point.

Activation of accessory respiratory muscles was assessed by electromyogram. Data was reported at peak and isotime.

Outcome measures

Measure	Placebo n=31 Participants Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.	CK-2127107 n=32 Participants Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Change From Period Baseline at Week 2 in Activation of Accessory Respiratory Muscles Peak	4.84 percentage of activation Standard Error 4.76	6.91 percentage of activation Standard Error 4.65
Change From Period Baseline at Week 2 in Activation of Accessory Respiratory Muscles Isotime	1.04 percentage of activation Standard Error 4.39	3.98 percentage of activation Standard Error 4.30

SECONDARY outcome

Timeframe: From first dose of study drug up to 14 days after last dose of study drug (8 weeks)

Population: SAF population

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

Outcome measures

Measure	Placebo n=41 Participants Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.	CK-2127107 n=42 Participants Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Number of Participants With Treatment Emergent Adverse Events	15 Participants	21 Participants

SECONDARY outcome

Timeframe: Day 1 predose, day 14 Ctrough, day 14 C6h

Population: 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.

Plasma concentration of CK-2127107 was reported.

Outcome measures

Measure	Placebo n=33 Participants Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.	CK-2127107 Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Plasma Concentration of CK-2127107 at Day 1 Predose, Day 14 Lowest Concentration (Ctrough), and Day 14 Concentration Predose 6 Hours (C6h) Day 1 predose	0 Nanogram per milliliter (ng/mL) Standard Deviation 0	—
Plasma Concentration of CK-2127107 at Day 1 Predose, Day 14 Lowest Concentration (Ctrough), and Day 14 Concentration Predose 6 Hours (C6h) Day 14 Ctrough	2620 Nanogram per milliliter (ng/mL) Standard Deviation 2100	—
Plasma Concentration of CK-2127107 at Day 1 Predose, Day 14 Lowest Concentration (Ctrough), and Day 14 Concentration Predose 6 Hours (C6h) Day 14 C6h	3290 Nanogram per milliliter (ng/mL) Standard Deviation 2000	—

SECONDARY outcome

Timeframe: Day 1 predose, day 14 Ctrough, day 14 C6h

Population: PKAS population

Plasma concentration of CK-2127106 (metabolite of CK-2127107) was reported.

Outcome measures

Measure	Placebo n=33 Participants Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.	CK-2127107 Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Plasma Concentration of CK-2127106 (Metabolite of CK-2127107) at Day 1 Predose, Day 14 Ctrough, Day 14 C6h Day 1 predose	0 ng/mL Standard Deviation 0	—
Plasma Concentration of CK-2127106 (Metabolite of CK-2127107) at Day 1 Predose, Day 14 Ctrough, Day 14 C6h Day 14 Ctrough	1760 ng/mL Standard Deviation 1710	—
Plasma Concentration of CK-2127106 (Metabolite of CK-2127107) at Day 1 Predose, Day 14 Ctrough, Day 14 C6h Day 14 C6h	1770 ng/mL Standard Deviation 1620	—

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

CK-2127107

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=41 participants at risk Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.	CK-2127107 n=42 participants at risk Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.00% 0/41 • From first dose of study drug up to 14 days after last dose of study drug (8 weeks)	2.4% 1/42 • Number of events 1 • From first dose of study drug up to 14 days after last dose of study drug (8 weeks)
Nervous system disorders IIIrd nerve paralysis	0.00% 0/41 • From first dose of study drug up to 14 days after last dose of study drug (8 weeks)	2.4% 1/42 • Number of events 1 • From first dose of study drug up to 14 days after last dose of study drug (8 weeks)
Renal and urinary disorders Haematuria	2.4% 1/41 • Number of events 1 • From first dose of study drug up to 14 days after last dose of study drug (8 weeks)	0.00% 0/42 • From first dose of study drug up to 14 days after last dose of study drug (8 weeks)

Other adverse events

Measure	Placebo n=41 participants at risk Participants received matching placebo orally, twice daily for 2 weeks in treatment periods 1 and 2.	CK-2127107 n=42 participants at risk Participants received CK-2127107 500 mg orally twice daily for 2 weeks in treatment periods 1 and 2.
Nervous system disorders Dizziness	2.4% 1/41 • Number of events 1 • From first dose of study drug up to 14 days after last dose of study drug (8 weeks)	7.1% 3/42 • Number of events 3 • From first dose of study drug up to 14 days after last dose of study drug (8 weeks)

Additional Information

Clinical Trial Disclosure

Astellas Pharma Global Development, Inc.

Phone: 800-888-7704

Email: astellas.resultsdisclosure@astellas.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER