Dose Titration Study to Test Safety and Effects of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)
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Purpose
A Phase II, double-blind, randomized, placebo-controlled ascending dose titration study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamic effects of multiple ascending doses of CK-2017357 to an individual patient maximum tolerated dose (MTD), using a within-patient twice daily (BID) dose-titration regimen in ALS patients on 50 mg riluzole once daily (QD).
| Condition | Intervention | Phase |
|---|---|---|
|
Amyotrophic Lateral Sclerosis |
Drug: CK-2017357 Drug: Placebo |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| 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) |
- Number of participants with adverse events [ Time Frame: approximately 29 days ] [ Designated as safety issue: Yes ]
- Change from baseline in score on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) [ Time Frame: 21 days ] [ Designated as safety issue: No ]
- Change from baseline in scores on tests of muscle fatigue (handgrip fatigue, muscle strength, and timed up and go test) [ Time Frame: 21 days ] [ Designated as safety issue: No ]
- Change from baseline in scores on tests of pulmonary function (Sniff Nasal Inspiratory Pressure [SNIP], Slow Vital Capacity [SVC] and Maximum Voluntary Ventilation [MVV]) [ Time Frame: 21 days ] [ Designated as safety issue: No ]
- Change from baseline in patient global assessment [ Time Frame: 21 days ] [ Designated as safety issue: No ]
- Change from baseline in investigator global assessment [ Time Frame: 21 days ] [ Designated as safety issue: No ]
- Evaluate the pharmacokinetics of CK-2017357 [ Time Frame: Day 1, Day 15, and Day 22 ] [ Designated as safety issue: No ]
- Evaluate the pharmacokinetics of riluzole in patients receiving CK-2017357 [ Time Frame: Day 1, Day 15, and Day 22 ] [ Designated as safety issue: No ]
| Enrollment: | 28 |
| Study Start Date: | November 2011 |
| Study Completion Date: | March 2012 |
| Primary Completion Date: | March 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Dose Titration of CK-2017357 (Group 1)
Dose titration of active drug as add-on therapy to riluzole
|
Drug: CK-2017357
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
|
|
Placebo Comparator: Matching Placebo (Group 2)
Placebo as add-on therapy to riluzole
|
Drug: Placebo
Matching placebo tablets BID for 21 days
|
Detailed Description:
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Able to comprehend and willing to sign an Informed Consent Form (ICF)
- Males or females 18 years of age or older
- A diagnosis of familial or sporadic ALS (defined as meeting the possible, laboratory-supported probable, probable, or definite criteria for a diagnosis of ALS according to the World Federation of Neurology El Escorial criteria)
- Maximum voluntary grip strength in at least one hand between 10 & 40 pounds (females) and 10 & 60 pounds (males)
- Able to swallow tablets with water
- Currently taking and tolerating a stable dose of 50 mg BID riluzole
- Willing and able to reduce daily dose of riluzole to 50mg QD for 5 weeks
- Not currently taking or willing and able to remain off theophylline-containing medications during study participation
- Patient has a caregiver who is capable of observing and reporting patient status
- Upright Slow Vital Capacity (SVC) >50% of predicted for age, height, and sex
- Able to perform pulmonary function tests
Exclusion Criteria:
- Life expectancy <3 months
- Receipt of investigational study drug within 30 days or 5 half-lives of the prior agent, whichever is greater, prior to dosing
- Any prior treatment with CK-2017357
- Any use of non-invasive positive pressure ventilation (NIPPV), such as Continuous Positive Airway Pressure (CPAP) or Bilevel Positive Airway Pressure (BiPAP)
Other protocol-defined inclusion/exclusion criteria may apply.
Contacts and Locations| 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 | |
| Washington University | |
| St. 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 |
More Information
No publications provided
| Responsible Party: | Cytokinetics |
| ClinicalTrials.gov Identifier: | NCT01486849 History of Changes |
| Other Study ID Numbers: | CY 4025 |
| Study First Received: | November 23, 2011 |
| Last Updated: | March 12, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Amyotrophic Lateral Sclerosis Sclerosis Motor Neuron Disease Spinal Cord Diseases Central Nervous System Diseases Nervous System Diseases |
Neurodegenerative Diseases TDP-43 Proteinopathies Neuromuscular Diseases Proteostasis Deficiencies Metabolic Diseases Pathologic Processes |
ClinicalTrials.gov processed this record on May 23, 2013