Study of Safety, Tolerability & Efficacy of CK-2017357 in Amyotrophic Lateral Sclerosis (ALS)
Condition: Amyotrophic Lateral Sclerosis
MeSH terms: Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis
Intervention: CK-2017357; Placebo tablets; Riluzole
Intervention description: CK-2017357 125 mg tablets twice daily; Tablets; Tablets
Intervention MeSH terms: Riluzole
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 711.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this research study is to evaluate the safety and effectiveness of CK-2017357
      when taken with or without riluzole (also called Rilutek®) in patients with Amyotrophic
      Lateral Sclerosis (ALS).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Able to comprehend and willing to sign an Informed Consent Form (ICF)

          2. Male or female 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. Upright Slow Vital Capacity (SVC) >50 % of predicted for age, height and sex

          5. At least 4 of the 12 ALSFRS-R questions must be scored 2 or 3

          6. Diminished but measurable maximum voluntary grip strength in at least one hand; i.e.,
             between 10 and 50 pounds (females) and 10 and 70 pounds (males)

          7. Able to swallow tablets without crushing

          8. A caregiver (if one is needed) who can and will observe and report the patient's
             status

          9. Pre-study clinical laboratory findings within normal range or, if outside of the
             normal range, deemed not clinically significant by the Investigator

         10. Male patients must agree for the duration of the study and 10 weeks after the end of
             the study to use a condom during sexual intercourse with female partners who are of
             reproductive potential and to have female partners use an additional effective means
             of contraception (e.g., diaphragm plus spermicide, or oral contraceptives) or the male
             patient must agree to abstain from sexual intercourse during and for 10 weeks after
             the end of the study

         11. Female patients must be post-menopausal (≥ 1 year) or sterilized, or, if of
             childbearing potential, not be breastfeeding, have a negative pregnancy test, have no
             intention to become pregnant during the course of the study, and use contraceptive
             drugs or devices as detailed in item 10 for the duration of the study and for 10 weeks
             after the end of the study

         12. Patients must be either on a stable dose of riluzole 50 mg twice daily for at least 30
             days prior to screening or have not taken riluzole for at least 30 days prior to
             screening and are willing not to begin riluzole use during the conduct of this study.

        Exclusion Criteria:

          1. Any use of non-invasive positive pressure ventilation (NIPPV, e.g. continuous positive
             airway pressure [CPAP] or bilevel positive airway pressure [BiPAP]) for any portion of
             the day, or mechanical ventilation via tracheostomy, or on any form of oxygen
             supplementation

          2. Patients with a diaphragm pacing system (DPS) at study entry or who anticipate DPS
             placement during the course of the study

          3. Body Mass Index (BMI) of 19.0 kg/m2 or lower

          4. Unwilling to discontinue tizanidine and theophylline-containing medications during
             study participation

          5. Serum chloride < 100 mmol/L

          6. Neurological impairment due to a condition other than ALS, including history of
             transient ischemic attack (TIA) within the past year

          7. Presence at screening of any medically significant cardiac, pulmonary,
             gastrointestinal (GI), musculoskeletal, or psychiatric illness that might interfere
             with the patient's ability to comply with study procedures or that might confound the
             interpretation of clinical safety or efficacy data

          8. Has taken any investigational study drug within 30 days or 5 half-lives of the prior
             agent, whichever is greater, prior to dosing

          9. Previously received CK-2017357 in any previous clinical trial