Phase 2 trial of sustained-release fampridine in chronic spinal cord injury

Study design: Double- blind, randomized, placebo- controlled, parallel- group clinical trial. Objective: Assess safety and efficacy of sustained- release fampridine in subjects with chronic spinal cord injury. Setting: A total of 11 academic rehabilitation research centers in the United States. Methods: A total of 91 subjects with motor-incomplete spinal cord injury ( SCI), randomized to three arms: fampridine, sustained release, 25 mg b. i. d. ( GroupI), 40 mg b. i. d. ( GroupII), and placebo ( Group III) for 8 weeks. Outcome measures: Patient diary questionnaire, Ashworth score, American Spinal Cord Injury Association International Standards, International Index of Erectile Function, bladder and bowel management questionnaires, and Clinician and Subject Global Impressions ( Clinician Global Impression of change, Subject Global Impression ( SGI)). Safety was evaluated from adverse events, physical examinations, vital signs, electrocardiograms, and laboratory tests. Results: In total, 78% of the subjects completed the study. More ( 13/ 30) discontinued from GroupII than GroupI ( 4/ 30) and GroupIII ( 3/ 31). The most frequent adverse events across groups were hypertonia, generalized spasm, insomnia, dizziness, asthenia, pain, constipation, and headache. One subject in GroupII experienced a seizure. SGI changed significantly in favor of GroupI ( P = 0.02). Subgroupanalys is of subjects with baseline Ashworth scores 41 showed signi. cant improvement in spasticity in Group I versus III ( P 0.02). Conclusions: Group I showed signi. cant improvement in SGI, and potential benefit on spasticity. The drug was well tolerated. Group II showed more adverse events and discontinuations.