Dose Titration Study to Test Safety and Effects of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)
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|ClinicalTrials.gov Identifier: NCT01486849|
Recruitment Status : Completed
First Posted : December 7, 2011
Last Update Posted : May 3, 2019
|Condition or disease||Intervention/treatment||Phase|
|Amyotrophic Lateral Sclerosis||Drug: CK-2017357 Drug: Placebo Drug: Riluzole 50 MG||Phase 2|
Patients will be randomized to one of two dosing groups, active CK-2017357 or placebo, in a 3:1 ratio. Prior to study drug dosing, patients will be required to decrease their riluzole dose to 50 mg QD for 7 days; after this 7 day period patients will either receive placebo or start the titration on active CK-2017357 while continuing to take riluzole at 50 mg QD.
Potential patients will be screened to assess their eligibility to enter the study within 21 days prior to Day -7, when they will begin taking riluzole at the decreased dose of 50 mg QD. Patients will be randomized in a 3:1 ratio to CK-2017357 (Group 1) or placebo (Group 2). On Day 1, patients will begin taking a total daily dose of 250 mg (125 mg BID) of CK-2017357 or matching placebo tablets BID for 7 days. Then they will take a total daily dose of 375 mg (125 mg morning [AM] and 250 mg evening [PM]) of CK-2017357 or matching placebo tablets BID for 7 days, and finally, they will take a total daily dose of 500 mg (250 mg BID) of CK-2017357 or matching placebo tablets BID for 7 days. A final dose of 250 mg of CK-2017357 or placebo will be taken in the morning on Day 22 at the study site.
Dose-escalation of CK-2017357 or placebo may be stopped, or the dose reduced to a lower level, based on tolerability. All patients who return to a lower dose will stay on that dose for the remainder of the study.
Patients will remain on the decreased dose of riluzole until the follow-up visit approximately 7 days after Day 22.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||27 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Phase II, Multicenter, Double-Blind, Randomized, Placebo-Controlled Dose Titration Study to Evaluate the Safety, Tolerability and Pharmacodynamic Effects of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)|
|Study Start Date :||November 2011|
|Actual Primary Completion Date :||March 2012|
|Actual Study Completion Date :||March 2012|
Experimental: Dose Titration of CK-2017357 (Group 1)
Dose titration of active drug as add-on therapy to riluzole
Total daily oral dose of 250 mg (125 mg BID) of CK-2017357 for 7 days followed by total daily oral dose of 375 mg (125 mg AM and 250 mg PM) for 7 days followed by total daily oral dose of 500 mg (250 mg BID) of CK-2017357 for 7 days
Other Name: tirasemtiv
Drug: Riluzole 50 MG
Placebo Comparator: Matching Placebo (Group 2)
Placebo as add-on therapy to riluzole
Matching placebo tablets BID for 21 days
Drug: Riluzole 50 MG
- Number of participants with adverse events [ Time Frame: approximately 29 days ]
- Change from baseline in score on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) [ Time Frame: 22 days ]An instrument for evaluating the functional status of patients with ALS. Minimum score is 0 and maximum score is 40. The higher the score the more function is retained. This will be administered at Screening, Day -7, Day 1, Day 15 and Day 22.
- Change from baseline in scores on tests of maximum handgrip strength and handgrip fatigue [ Time Frame: 22 days ]Measured using the DynEx Electronic Hand Dynamometer. Patients asked to squeeze the device with the maximum possible force to establish the maximum voluntary contraction. Handgrip fatigue is then measured. Patient is asked to squeeze the device until they can no longer stay above 60% of target or 120 seconds. This will be measured at Screening, Day -7, Day 1, Day 15 and Day 22.
- Change from baseline in scores on tests of muscle strength [ Time Frame: 22 days ]Muscle strength is measured using Hand Held Dynamometry. A series of assessments are done on different muscle groups. This will be measured at Day -7, Day 1, and Day 22.
- Change from baseline in scores on tests of Timed Up and Go [ Time Frame: 22 days ]TUG is measured by timing how long it takes for a subject to stand up from a chair, walk 10 feet, turn around, walk back to the chair and sit down. This will be measured at Day -7, Day 1, and Day 22.
- Change from baseline in scores on tests of Sniff Nasal Inspiratory Pressure (SNIP) [ Time Frame: 22 days ]SNIP will be measured using the Micro Medical Respiratory Pressure Meter (MicroRPM) at Screening, Day -7, Day 1, Day 15 and Day 22.
- Change from baseline in scores on tests of Slow Vital Capacity (SVC) [ Time Frame: 22 days ]SVC will be measured using the ndd EasyOne Spirometer System at Screening, Day -7, Day 1, Day 15 and Day 22.
- Change from baseline in scores on tests of Maximum Voluntary Ventilation (MVV) [ Time Frame: 21 days ]MVV will be measured using the EasyOne Spirometer System at Screening, Day -7, Day 1, Day 15 and Day 22.
- Change from baseline in Patient Global Assessment [ Time Frame: 22 days ]Patients will be asked to assess whether they feel the same, better or worse as compared to how they felt at pre-dose on Day 1
- Change from baseline in Investigator Global Assessment [ Time Frame: 22 days ]Investigator will assess whether the patient appears the same, better or worse as compared to the patient's status at pre-dose on Day 1.
- Evaluate the pharmacokinetics of CK-2017357 [ Time Frame: Day 1, Day 15, and Day 22 ]Plasma levels of CK-2017357 will be measured at pre-dose, and at 2 and 4 hours post AM dose
- Evaluate the pharmacokinetics of riluzole in patients receiving CK-2017357 [ Time Frame: Day 1, Day 15, and Day 22 ]Plasma levels of riluzole will be measured at pre-dose and at 2 and 4 hours post AM dose
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01486849
|United States, California|
|University of California at San Francisco, Fresno Campus, Central California Neurological Institute|
|Fresno, California, United States, 93701|
|Coordinated Clinical Research|
|La Jolla, California, United States, 92037|
|University of California at Irvine, ALS and Neuromuscular Center|
|Orange, California, United States, 92868|
|United States, Connecticut|
|Hospital for Special Care|
|New Britain, Connecticut, United States, 06053|
|United States, Massachusetts|
|Massachusetts General Hospital, Neurology Clinical Trials Unit|
|Charlestown, Massachusetts, United States, 02129|
|United States, Missouri|
|Saint Louis, Missouri, United States, 63110|
|United States, New York|
|Cornell Faculty, Hospital for Special Surgery|
|New York, New York, United States, 10021|
|United States, North Carolina|
|Duke University School of Medicine, Division of Neurology|
|Durham, North Carolina, United States, 27710|
|United States, Ohio|
|Ohio State University, Department of Neurology|
|Columbus, Ohio, United States, 43210|
|United States, Oregon|
|Providence ALS Center|
|Portland, Oregon, United States, 97213|
|United States, Texas|
|University of Texas Health Science Center, Department of Neurology|
|San Antonio, Texas, United States, 78229|
|Study Chair:||Jeremy Shefner, MD, PhD||State University of New York - Upstate Medical University|