A study in which patients suffering from amyotrophic lateral sclerosis (ALS) may be assigned randomly to receive either the treatment or placebo to look at how safe the product is, whether it has an effect and is easy to take.

Conditions: Amyotrophic lateral sclerosis
MedDRA version: 16.0Level: PTClassification code 10002026Term: Amyotrophic lateral sclerosisSystem Organ Class: 10029205 - Nervous system disorders
Therapeutic area: Body processes [G] - Immune system processes [G12]

Registration Number: EUCTR2012-004987-23-DE

Lead Sponsor: Cytokinetics Inc

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 700

Inclusion Criteria

1. Able to comprehend and willing to sign an informed consent form (ICF)
2. Male or female 18 years or older
3. A diagnosis of familial or sporadic ALS (defined as meeting the possible, laboratory probable, probable, or definite criteria for a diagnosis of ALS according to the World Federation of Neurology EI 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, and in the opinion of the Investigator, is expected to do so for the duration of the study
8. A caregive (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 reporduction potential and to have female partners use an additional effective means of contraception (e.g. diaphragm plus spermicide, or oral contraceptives) or the male patients 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 dats 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 700
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Any use of non-invasive positive pressure ventilation (NIPPV, e.g. CPAP or BiPAP) for any protion 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 anticipates 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 the study participation
5. Serum chloride < 100 mmol/L
6. Neurological impairment due to a condition other than ALS, including a history of TIA within the past year
7. Presence at screening of any medically significant cardiac, pulmonary, 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, including, but not limited to:
a. Poorly controlled hypertension
b. NYHA Class II or greater congestive heart failure
c. Clinically significant ECG abnormalities
d. Chronic obstructive pulmonary disease or asthma requiring frequent use of bronchodilator medications
e. History of sleep apnea requiring CPAP or oxygen supplementation
f. GI disorder that might impair absorption of study drug from the gastorintestinal tract
g. History of significant liver disease defined by bilirubin > 2 times the upper limit of normal (ULN) or alanine transferase (ALT) or aspartate aminotransferase (AST) > 3 times the ULN on repeat testing
h. Poorly controlled diabetes mellitus
i. History of vertigo within 3 months of study entry
j. History of syncope without an explainable or treated cause
k. History of untreated intracranial aneurysm or poorly controlled seizure disorder
l. Amputation of a limb
m. Cognitive impairment, related to ALS or otherwise, sufficient to impair the patient's ability to understand and/or comply with study procedures and giving informed consent
n. Cancer with metatstic potential (other than basal cell carcinoma, carcinoma in situ of cervix, or squamous cell carcinoma of the skin excised with clean margins) daignosed and treated within the last 2 years
o. Any other condition, impairment or social circumstance that, in the opinion of the Investigator, would render the patient not suitable to participate in the study.
p. Patient judged to be actively suicidal and a suicide risk by the Investigator.
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 trial

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the effect of CK-2017357 versus placebo on the ALSFRS-R total score when administered twice daily at each patients's maximum tolerated dose, up to a maximum of 500 mg daily.;Secondary Objective: Exploration of alternative methods to assess the effect of CK-2017357 versus placebo on the change from baseline in the ALSFRS-R score and to assess the effect of CK-2017357 versus placebo on certain measures of respitratory and skeletal muscle function.;Primary end point(s): The primary endpoint is the change from baseline to the average of the ALSFRS-R total score obtained at Visits 6 and 7 (i.e. after approximately 8 and 12 weeks of double-blind treatment);Timepoint(s) of evaluation of this end point: After 8-12 weeks of double-blind treatment

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. ALSFRS-R enpoints for secondary analyses<br>2. Respiratory function<br>- Maximum Voluntary Ventilation (MVV)<br>- Sniff Nasal Inspiratory Pressure (SNIP)<br>- Slow Vital Capacity (SVC)<br>3. Skeletal muscle function<br>- Handgrip strength and fatigability<br>-Maximum handgrip strenth<br>-Sub-maximum handgrip fatigue<br>-Muscle strength by hand-held dynamometry (HDD) as determined by the megascore of:<br>-Elbow flexion (bilateral)<br>- Wrist extension (bilateral)<br>- Knee extension (bilateral)<br>-Ankle dorsiflexion (bilateral)<br><br>;Timepoint(s) of evaluation of this end point: At visit 5, 6, 7, 8 and follow-up