A Study to Evaluate the Effects of Multiple Doses of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)
- Conditions
- Amyotrophic Lateral Sclerosis
- Interventions
- Drug: Placebo (Part A)Drug: CK-2017357 (Part A)Drug: Placebo (Part B)Drug: CK-2017357 (Part B)
- Registration Number
- NCT01378676
- Lead Sponsor
- Cytokinetics
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 49
- 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)
- Upright Slow Vital Capacity (SVC) >50% of predicted for age, height, and sex
- Able to swallow tablets with water
- Willing and able to remain off riluzole for 4 weeks (Part A only)
- Currently taking and tolerating a stable dose of 50 mg BID riluzole (Part B only)
- Willing and able to reduce daily dose of riluzole to 50 mg for 4 weeks (Part B only)
- Willing and able to refrain from caffeine-containing products during study participation
- Willing and able to remain off warfarin and theophylline-containing medications during study participation
- Has a caregiver who is capable of observing and reporting patient status, and also assisting in the proper use of nocturnal oximetry equipment
- Able to perform pulmonary function tests
Key
- Life expectancy <3 months
- 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
- Any prior treatment with CK-2017357
- Use of non-invasive positive pressure ventilation (NIPPV) for any part of the day or night
Other protocol-defined inclusion/exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Active Drug High Dose (CK-2017357 375 mg) Riluzole 50 MG (Part B) - Active Drug Low Dose (CK-2017357 125 mg) CK-2017357 (Part B) - Active Drug Mid Dose (CK-2017357 250 mg) CK-2017357 (Part B) - Matching Placebo Placebo (Part A) - Active Drug Low Dose (CK-2017357 125 mg) Riluzole 50 MG (Part B) - Matching Placebo Placebo (Part B) - Active Drug Low Dose (CK-2017357 125 mg) Placebo (Part B) - Active Drug Low Dose (CK-2017357 125 mg) CK-2017357 (Part A) - Active Drug Mid Dose (CK-2017357 250 mg) CK-2017357 (Part A) - Active Drug High Dose (CK-2017357 375 mg) CK-2017357 (Part A) - Matching Placebo Riluzole 50 MG (Part B) - Active Drug Low Dose (CK-2017357 125 mg) Placebo (Part A) - Active Drug Mid Dose (CK-2017357 250 mg) Placebo (Part A) - Active Drug Mid Dose (CK-2017357 250 mg) Riluzole 50 MG (Part B) - Active Drug High Dose (CK-2017357 375 mg) CK-2017357 (Part B) - Active Drug Mid Dose (CK-2017357 250 mg) Placebo (Part B) -
- Primary Outcome Measures
Name Time Method Number of Participants with Adverse Events as a Measure of Safety and Tolerability 21 days Safety and tolerability of CK-2017357 after multiple oral doses to steady state in patients with ALS
- Secondary Outcome Measures
Name Time Method Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) 21 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.
Measurement of Grip Strength and Handgrip Fatigue 21 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.
Measurement of Maximum Voluntary Ventilation (MVV) 21 days MVV will be measured using the EasyOne Spirometer System at Screening, Day -7, Day 1, Day 2, Day 8, Day 15 and at the Follow-Up Visit
Patient global assessment 15 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
Investigator global assessment 15 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.
Measurement of Slow Vital Capacity (SVC) 21 days SVC will be measured using the ndd EasyOne Spirometer System at Screening, Day -7, Day 1, Day 2, Day 8, Day 15 and at the Follow-Up Visit
Measurement of muscle strength 21 days Muscle strength is measured using Hand Held Dynamometry. A series of assessments are done on different muscle groups.
Measurement of Sniff Nasal Inspiratory Pressure (SNIP) 21 days SNIP will be measured using the Micro Medical Respiratory Pressure Meter (MicroRPM) at Screening, Day -7, Day 1, Day 2, Day 8, Day 15 and at the Follow-Up Visit
Trial Locations
- Locations (9)
SUNY Upstate Medical Center
🇺🇸Syracuse, New York, United States
University of Kansas
🇺🇸Kansas City, Kansas, United States
Mayo Florida
🇺🇸Jacksonville, Florida, United States
California Pacific Medical Center
🇺🇸San Francisco, California, United States
Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Drexel University College of Medicine
🇺🇸Philadelphia, Pennsylvania, United States
Penn State Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Carolinas Neuromuscular ALS-MND Center
🇺🇸Charlotte, North Carolina, United States