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

NCT02662582 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 3318-CL-3002
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study was to assess the effect of CK-2127107 relative to placebo on cycle ergometer exercise tolerance, assessed as change from period baseline in constant work rate (CWR) endurance time, utilizing a breath-by-breath metabolic measurement system with integrated electrocardiogram (ECG). The time to intolerance was assessed by a stopwatch and verified from electronic recordings of the cycle ergometer. This study assessed cardiopulmonary and neuromuscular effects of CK-2127107 relative to placebo; the effect of CK-2127107 on resting spirometry relative to placebo; the safety and tolerability of CK-2127107 as well as the pharmacokinetics of CK-2127107.

Conditions

Chronic Obstructive Pulmonary Disease (COPD)

Keywords

Chronic Obstructive Pulmonary Disease; CK-2127107; COPD

Outcome Measures

Primary Outcomes (1)

• Change From Period Baseline at Week 2 in Constant Work Rate (CWR) Endurance Time Relative to Placebo

  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).

  Baseline and week 2 of each treatment period

Secondary Outcomes (25)

• Change From Period Baseline at Week 2 in Oxygen Uptake (VO2)

  Baseline and week 2 of each treatment period

• Change From Period Baseline at Week 2 in Ventilation (VE)

  Baseline and week 2 of each treatment period

• Change From Period Baseline at Week 2 in Ventilatory Equivalent for Carbon Dioxide (VE/VCO2)

  Baseline and week 2 of each treatment period

• Change From Period Baseline at Week 2 in Inspiratory Capacity (IC) Change From Peak to Rest

  Baseline and week 2 of each treatment period

• Change From Period Baseline at Week 2 in Perceived Exertion for Dyspnea and Leg Discomfort (BORG CR10)

  Baseline and week 2 of each treatment period

Study Arms (2)

CK-2127107 1000 mg, then placebo

EXPERIMENTAL

Participants received CK-2127107 500 milligram (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.

Drug: Reldesemtiv; Drug: Placebo

Placebo, then CK-212710 1000 mg

EXPERIMENTAL

Participants received matching placebo orally, twice daily for 2 weeks in treatment period 1 followed by CK-2127107 500 mg in treatment period 2. A washout period of 2 weeks was maintained between the two treatment periods.

Drug: Reldesemtiv; Drug: Placebo

Interventions

Reldesemtiv DRUG

Oral tablet

Also known as: CK-2127107

CK-2127107 1000 mg, then placebo; Placebo, then CK-212710 1000 mg

Placebo DRUG

Oral tablet

CK-2127107 1000 mg, then placebo; Placebo, then CK-212710 1000 mg

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject has a body mass index (BMI) of 18-35 kg/m2 inclusive.
• Subject must have all of the following:
• Clinical diagnosis of moderate to severe COPD, with a postbronchodilator FEV1/FVC ratio \< 70% and 30% ≤ FEV1 \< 65% predicted at screening. The predicted values for normal spirometry will be those recommended by the American Thoracic Society (ATS) / European Respiratory Society (ERS) \[Miller et al, 2005\].
• General stable health with no change in medication (including non-COPD agents and dietary aids/food supplements) within 2 weeks prior to screening, no systemic corticosteroid administration (topical or inhaled corticosteroids are allowed) within 6 weeks prior to screening, no exacerbations or hospitalization within 6 weeks prior to screening.
• Current or ex-smokers with a smoking history of at least 10 pack years.
• Grade of 2 or 3 on the Modified Medical Research Council (mMRC) Dyspnea Scale at screening:
• Grade 2: walks slower than people of the same age on the level because of breathlessness or has to stop for breath when walking at own pace on the level.
• Grade 3: stops for breath after walking about 100 meters or after a few minutes on the level.
• Subject is able to complete technically acceptable respiratory muscle strength tests, spirometry, physical performance test and exercise tests.
• Female subject must either:
• Be of non-child bearing potential: Postmenopausal (defined as at least 1 year without any menses) prior to screening, or documented surgically sterile.
• Or, if of childbearing potential: Agree not to try to become pregnant during the study and for 28 days after the last dose, and have a negative serum pregnancy test at screening, and, if heterosexually active, agree to consistently use 2 forms of highly-effective birth control (at least 1 of which must be a barrier method) starting at screening, throughout the study, and for 28 days after the last dose.
• Female subject must agree not to breastfeed starting at screening and throughout the study and for 28 days after the last dose.
• Female subject must not donate ova starting at screening, throughout the study and for 28 days after the last dose.
• Male subject and their female spouse/partners who are of childbearing potential must be using highly effective form of contraception consisting of 2 forms of birth control (at least 1 of which must be a barrier method) starting at screening, and continuing throughout the study and for 90 days after the last dose.

You may not qualify if:

• Subject has previously enrolled in a clinical study of CK-2127107.
• Subject has any clinically significant abnormality following the investigator's review of the physical examination, ECG and protocol-defined clinical laboratory tests at screening. A significant abnormality is defined as an abnormality which, in the opinion of the investigator, may (i) put the subject at risk because of participation in the study, (ii) influence the results of the study or (iii) cause concern regarding the subject's ability to participate in the study.
• Subject has any of the liver function tests (LFTs; i.e., aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], alkaline phosphatase \[ALP\], γ-glutamyl transferase \[GGT\] and/or total bilirubin \[TBL\]) above 1.5 times the upper limit of normal (ULN) at screening. These assessments may be repeated once at the investigator's discretion (within the screening window).
• Subject has an estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73 m2 by the Cockcroft-Gault equation at screening.
• Subject has a serious cardiovascular disease, including a current New York Heart Association (NYHA) class III or IV congestive heart failure or clinically significant valvular disease, history of cardiac arrest, uncontrolled angina or arrhythmia, untreated serious conduction disorder (e.g., third-degree heart block), or acute myocardial ischemic condition suspected on the ECG at screening (e.g., ST-segment elevation, ST-segment depressions \> 2 mm).
• Subject has had a myocardial infarction or other acute coronary syndrome, major heart surgery (i.e., valve replacement or bypass surgery), stroke, deep vein thrombosis or pulmonary embolus in the 6 months prior to screening.
• Subject has known active tuberculosis.
• Subject has undergone thoracotomy with pulmonary resection (except for sub-lobar resection).
• Subject has resting pulse \< 40 bpm or \> 100 bpm; resting systolic blood pressure \> 160 mm Hg or \< 90 mm Hg; resting diastolic blood pressure \> 100 mm Hg at screening. These assessments may be repeated once at the investigator's discretion (within the screening window).
• Subject desaturates to SpO2 \< 85% for at least 1 minute on screening IET.
• Subject has a limitation of exercise performance as a result of factors other than fatigue or exertional dyspnea/shortness of breath (considered to be due to COPD), such as arthritis in the leg, angina pectoris, heart failure, claudication or morbid obesity.
• Subject has a CWR cycle ergometry endurance time less than 4 or greater than 8 minutes after WR adjustment procedures.
• Subject has used the following drugs within 14 days prior to day -1:
• Strong cytochrome P450 (CYP)3A4 inhibitor (e.g., itraconazole, clarithromycin).
• Strong CYP3A4 inducer (e.g., barbiturates, rifampin).

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead
• Cytokinetics: collaborator

Study Sites (2)

Site US10001

Torrance, California, 90502, United States

Location

Site US10003

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Links

• Link to results on the Astellas Clinical Study Results website.

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

reldesemtiv

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Clinical Trial Disclosure
• Organization: Astellas Pharma Global Development, Inc.

astellas.resultsdisclosure@astellas.com

800-888-7704

Study Officials

• Senior Medical Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2016
• First Posted: January 25, 2016
• Study Start: June 30, 2016
• Primary Completion: June 8, 2018
• Study Completion: June 8, 2018
• Last Updated: November 14, 2024
• Results First Posted: February 5, 2021

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)