To examine the clinical efficacy and safety of ultra-high dose (50mg, im, twice a week) methylcobalamin in retarding the progression of symptoms in amyotrophic lateral sclerosis (ALS) patients, we enroll ALS patients diagnosed by Updated Awaji Criteria within 12 months after the clinical onset. First they are followed for 12 weeks with Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) scores, and only those who exhibit drops of 1-2 points are allowed to enter into the test period. A total of 128 patients are randomized and the half having placebo. They are blindly evaluated for drops of ALSFRS-R in 16 weeks, as the primary outcome. After this, all subjects receive methylcobalamin.
Inclusion Criteria:
Treatment and OLE Phase:
- ALS patients within 12 months after clinical onset at the entry
- Diagnosed based on updated Awaji criteria: definite, probably or laboratory
supported probable
- Decline of ALSFRSR being 1 or 2 during observation period of 12 weeks
- Japanese Clinical Severity Scale 1 or 2
- Those who can visit the participating medical centers
Tsunagi Phase:
- The subjects for the Tsunagi phase are patients with ALS who are continuing the
administration of this drug at the time of approval, and have obtained consent for
the transition to the Tsunagi phase.
Exclusion Criteria:
Treatment and OLE Phase:
- Those who have tracheostomy
- Those who had NIPPV
- %FVC<60%
- Those who have Chronic Obstructive Pulmonary Disease (COPD)
- Those who have symptoms and signs of B12 deficiency
- Those who had edaravone less than 4 weeks prior to entry
- Those who changed the schedule and dosing of riluzole
- Those who have dementia
- Those who have the possibility of pregnancy
- Those who have serious respiratory or cardiac diseases
- Those who have malignancies
- Those who participated other clinical trials within 12 weeks
- Those who have allergies to B12 and related compounds
Tsunagi Phase:
Not applicable.