Clinical trial NCT01378676: A Study to Evaluate the Effects of Multiple Doses of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)
Official title: A Phase II, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Effects of Multiple Doses of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Amyotrophic Lateral Sclerosis
Lead sponsor: Cytokinetics
Sponsor class: INDUSTRY
First posted: 2011-06-22
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study will generate data on safety, tolerability and pharmacokinetics after multiple daily doses of CK-2017357 in patients with ALS. Patients will be randomized into one of four different treatment groups, receiving daily oral doses of either placebo, 125 mg, 250 mg, or 375 mg of CK-2017357 for 14 days.

Detailed description: In Part A, approximately 24 patients will be randomized to one of four different treatment groups. After a 7-day washout of riluzole, patients in each treatment group will receive daily oral doses of placebo, 125 mg, 250 mg, or 375 mg of CK-2017357 for 14 days. Patients will take daily doses of CK-2017357 or placebo (Day 1 through Day 14) and will return to the study site on Day 2, Day 8 and Day 15. All patients will return for a follow-up visit 7 days (± 2 days) after their last dose.

In Part B, approximately additional 24 patients will be randomized to one of four different treatment groups as in Part A. Patients in Part B will be required to decrease their riluzole dose to 50 mg once a day (QD) for 7 days prior to randomization. After this 7 day period, patients will take riluzole at 50 mg QD concurrently with their morning dose of blinded study drug.

Eligibility criteria: Key Inclusion Criteria:

1. Able to comprehend and willing to sign an Informed Consent Form (ICF)
2. Males or females 18 years of age or older
3. 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)
4. Maximum voluntary grip strength in at least one hand between 10 \& 40 pounds (females) and 10 \& 60 pounds (males)
5. Upright Slow Vital Capacity (SVC) \>50% of predicted for age, height, and sex
6. Able to swallow tablets with water
7. Willing and able to remain off riluzole for 4 weeks (Part A only)
8. Currently taking and tolerating a stable dose of 50 mg BID riluzole (Part B only)
9. Willing and able to reduce daily dose of riluzole to 50 mg for 4 weeks (Part B only)
10. Willing and able to refrain from caffeine-containing products during study participation
11. Willing and able to remain off warfarin and theophylline-containing medications during study participation
12. Has a caregiver who is capable of observing and reporting patient status, and also assisting in the proper use of nocturnal oximetry equipment
13. Able to perform pulmonary function tests

Key Exclusion Criteria:

1. Life expectancy \<3 months
2. Participation in any trial in which receipt of investigational study drug occurred within 30 days or 5 half-lives of the prior agent, whichever is greater, prior to dosing
3. Any prior treatment with CK-2017357
4. Use of non-invasive positive pressure ventilation (NIPPV) for any part of the day or night

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: 21 days
Secondary outcomes:
measure: Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R)
timeFrame: 21 days
measure: Measurement of Grip Strength and Handgrip Fatigue
timeFrame: 21 days
measure: Measurement of muscle strength
timeFrame: 21 days
measure: Measurement of Slow Vital Capacity (SVC)
timeFrame: 21 days
measure: Measurement of Sniff Nasal Inspiratory Pressure (SNIP)
timeFrame: 21 days
measure: Measurement of Maximum Voluntary Ventilation (MVV)
timeFrame: 21 days
measure: Patient global assessment
timeFrame: 15 days
measure: Investigator global assessment
timeFrame: 15 days
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: Jacksonville
country: United States
facility: Mayo Florida
state: Florida
city: Kansas City
country: United States
facility: University of Kansas
state: Kansas
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical Center
state: New York
city: Charlotte
country: United States
facility: Carolinas Neuromuscular ALS-MND Center
state: North Carolina
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Drexel University College of Medicine
state: Pennsylvania
Study officials:
affiliation: State University of New York - Upstate Medical University
name: Jeremy Shefner, MD, PhD
role: STUDY_CHAIR
References:
citation: Shefner JM, Watson ML, Meng L, Wolff AA; Neals/Cytokinetics STUDY Team. A study to evaluate safety and tolerability of repeated doses of tirasemtiv in patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2013 Dec;14(7-8):574-81. doi: 10.3109/21678421.2013.822517. Epub 2013 Aug 19.