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History of Changes for Study: NCT02662582
A Study to Assess the Effect of CK-2127107 on Physical Function in Subjects With Chronic Obstructive Pulmonary Disease
Latest version (submitted February 26, 2021) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 January 20, 2016 None (earliest Version on record)
2 April 22, 2016 Study Status and Contacts/Locations
3 June 9, 2016 Study Status
4 June 17, 2016 Contacts/Locations and Study Status
5 August 29, 2016 Recruitment Status, Study Status and Contacts/Locations
6 January 12, 2017 Study Status and Contacts/Locations
7 February 23, 2017 Study Status
8 June 7, 2017 Study Status
9 September 5, 2017 Study Status
10 December 5, 2017 Study Status and Eligibility
11 April 30, 2018 Study Status and Contacts/Locations
12 May 29, 2018 Study Status
13 June 7, 2018 Recruitment Status, Study Status, Contacts/Locations and Study Design
14 June 20, 2018 Recruitment Status and Study Status
15 June 5, 2019 Arms and Interventions, Study Status, IPDSharing
16 May 26, 2020 Outcome Measures, Arms and Interventions, Oversight and Study Status
17 January 16, 2021 Outcome Measures, Study Status, More Information, Arms and Interventions, Study Description, Document Section, Adverse Events, Baseline Characteristics, Participant Flow and References
18 February 26, 2021 Study Status and Outcome Measures
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Study NCT02662582
Submitted Date:  January 20, 2016 (v1)

Open or close this module Study Identification
Unique Protocol ID: 3318-CL-3002
Brief Title: A Study to Assess the Effect of CK-2127107 on Physical Function in Subjects With Chronic Obstructive Pulmonary Disease
Official Title: A Phase 2a, Randomized, Double-blind, Placebo-controlled, Two Period, Crossover Study to Assess the Effect of CK-2127107 on Physical Function in Subjects With Chronic Obstructive Pulmonary Disease
Secondary IDs:
Open or close this module Study Status
Record Verification: January 2016
Overall Status: Not yet recruiting
Study Start: March 2016
Primary Completion: July 2017 [Anticipated]
Study Completion: July 2017 [Anticipated]
First Submitted: January 20, 2016
First Submitted that
Met QC Criteria:
January 20, 2016
First Posted: January 25, 2016 [Estimate]
Last Update Submitted that
Met QC Criteria:
January 20, 2016
Last Update Posted: January 25, 2016 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: Astellas Pharma Global Development, Inc.
Responsible Party: Sponsor
Collaborators: Cytokinetics
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: No
Open or close this module Study Description
Brief Summary:

The purpose of this study is 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 is assessed by a stopwatch and verified from electronic recordings of the cycle ergometer.

This study will also assess 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.

Detailed Description: Enrolled participants will be randomly assigned to 1 of 2 treatment sequences and will receive both CK-2127107 and matching placebo over 2 treatment periods.
Open or close this module Conditions
Conditions: Chronic Obstructive Pulmonary Disease (COPD)
Keywords: Chronic Obstructive Pulmonary Disease
COPD
CK-2127107
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Crossover Assignment
Number of Arms: 2
Masking: Double (Participant, Investigator)
Allocation: Randomized
Enrollment: 40 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: CK-2127107, then Placebo
Participants will first receive CK-2127107 for 14 days. After a washout period of 14 days, participants will then receive matching Placebo for 14 days.
Drug: CK-2127107
Oral
Drug: Placebo
Oral
Experimental: Placebo, then CK-212710
Participants will first receive Placebo for 14 days. After a washout period of 14 days, participants will then receive matching CK-2127107 for 14 days.
Drug: CK-2127107
Oral
Drug: Placebo
Oral
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Change from period baseline in Constant Work Rate (CWR) endurance time
[ Time Frame: Baseline and up to Day 14 of each treatment period ]

Secondary Outcome Measures:
1. Change from period baseline in oxygen uptake (VO2)
[ Time Frame: Baseline and up to Day 14 of each treatment period ]

2. Change from period baseline in ventilation (VE)
[ Time Frame: Baseline and up to Day 14 of each treatment period ]

3. Change from period baseline in ventilatory equivalent for carbon dioxide (VE/VCO2)
[ Time Frame: Baseline and up to Day 14 of each treatment period ]

4. Change from period baseline in inspiratory capacity (IC)
[ Time Frame: Baseline and up to Day 14 of each treatment period ]

5. Change from period baseline in fractions of expired O2 (FeO2 )
[ Time Frame: Baseline and up to Day 14 of each treatment period ]

6. Change from period baseline in fractions of expired CO2 (FeCO2)
[ Time Frame: Baseline and up to Day 14 of each treatment period ]

7. Change from period baseline in minute ventilation
[ Time Frame: Baseline and up to Day 14 of each treatment period ]

8. Change from period baseline in oxygen consumption (VO2)
[ Time Frame: Baseline and up to Day 14 of each treatment period ]

9. Change from period baseline in carbon dioxide production (VCO2)
[ Time Frame: Baseline and up to Day 14 of each treatment period ]

10. Change from period baseline respiratory exchange ratio (RER)
[ Time Frame: Baseline and up to Day 14 of each treatment period ]

11. Change from period baseline in perceived exertion for dyspnea and leg discomfort (Borg CR10) at isotime during CWR
[ Time Frame: Baseline and up to Day 14 of each treatment period ]

The Borg Scale (Borg CR10) is a simple 10-item method of rating perceived exertion (RPE) and collects information on perceived exertion in an individual's rating of exercise intensity. Subjects will be 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)).
12. Change from period baseline in activation of accessory respiratory muscles (by electromyogram) at isotime and peak exercise during CWR
[ Time Frame: Baseline and up to Day 14 of each treatment period ]

13. Change in resting spirometry
[ Time Frame: Baseline and up to Day 14 of each treatment period ]

Open or close this module Eligibility
Minimum Age: 40 Years
Maximum Age: 75 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • 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:
      1. 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.
      2. 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, muscle strength test, physical performance test and exercise tests.
  • Subject is willing to wear an accelerometer during waking hours in assigned periods during the study.
  • 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.
  • Male subject must not donate sperm starting at screening, throughout the study and for 90 days after the last dose.
  • Subject agrees not to participate in another interventional study from screening through the follow-up visit (FUV) of the study.

Exclusion Criteria:

  • 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).
  • Subject has hemoglobin (Hb) concentration below 10.0 g/dL at screening.
  • Subject has a cancer requiring treatment currently or in the past 3 years (except primary nonmelanoma skin cancer, carcinoma in situ or cancers that have an excellent prognosis such as early stage breast or prostate cancer).
  • Subject giving a history of asthma, allergic rhinitis or atopy shall be evaluated by the investigator to determine whether the subject's predominant diagnosis is COPD rather than asthma.
  • Subject has neurological conditions or neuromuscular diseases that are causing impaired muscle function or mobility.
  • Subject has a current diagnosis of schizophrenia, other psychotic disorders or bipolar disorder.
  • Subject in the active phase of pulmonary rehabilitation or had completed pulmonary rehabilitation or exercise training within the 13 weeks prior to screening.
  • Subject has severe and/or uncontrolled medical conditions that could interfere with the study (e.g., severe neurological deficit after stroke, developed diabetic peripheral neuropathy, respiratory diseases requiring daytime supplemental oxygen, infection, gastrointestinal disorder, uncontrolled pain or any other non-stable illness) as judged by the medical investigator.
  • Subject has a known history of positive test for hepatitis B surface antigen (HBsAg) or hepatitis C antibody or history of a positive test for human immunodeficiency virus (HIV) infection.
  • Subject has a history of alcoholism or drug/chemical substance abuse within 2 years prior to screening.
  • Subject has used any medications known to affect physical function or muscle mass including androgen supplements, anti-androgens (such as luteinizing hormone-releasing hormone [LHRH] agonists), anti-estrogen (tamoxifen, etc.), recombinant human growth hormone (rhGH), insulin, oral beta adrenergic agonists, megestrol acetate, dronabinol, metformin or other drugs which, in the opinion of the investigator, might influence physical function or muscle mass within 6 weeks prior to screening.
  • Subject has participated in any interventional clinical study or has been treated with any investigational drugs within 28 days or 5 half-lives whichever is longer, prior to the initiation of screening.
  • Subject has any other condition that in the opinion of the investigator precludes the subject's participation in the trial.
Open or close this module Contacts/Locations
Central Contact Person: Astellas Pharma Global Development
Telephone: 800-888-7704 Ext. 5473
Email: astellas.registration@astellas.com
Study Officials: Senior Medical Director
Study Director
Astellas Pharma Global Development, Inc.
Locations:
Open or close this module IPDSharing
Plan to Share IPD: Undecided
Open or close this module References
Citations:
Links:
Available IPD/Information:

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