title: A phase II trial of talampanel in subjects with amyotrophic lateral sclerosis.
abstract: Our objective was to determine if chronic treatment with the non-competitive AMPA antagonist talampanel is efficacious and safe in subjects with ALS. A double-blind, placebo-controlled, multicenter, randomized clinical trial of nine months treatment duration was conducted in 59 subjects with ALS, with 40 subjects receiving talampanel 50 mg p.o. t.i.d, and 19 subjects receiving placebo. Primary outcome measure was rate of decline in isometric arm strength (as measured by change in arm strength megaslope of the Tufts Quantitative Neuromuscular Exam (TQNE)). Other efficacy endpoints included rate of decline in respiratory function, isometric leg strength, bulbar function, fine motor function, the ALS Functional Rating Scale (ALSFRS), and survival. Secondary safety outcome measures were frequency of adverse events, neurological status, plasma concentration of talampanel, vital signs, routine laboratory tests, and electrocardiograms. Decline in muscle strength was 15% less in talampanel treated subjects, and decline in ALSFRS was 30% slower in talampanel treated subjects. Talampanel was safe in subjects with ALS. Mortality rates (8% talampanel, 5% placebo) and drug discontinuation rates (25% talampanel, 16% placebo) were similar in active treatment and placebo groups. Dizziness and somnolence occurred significantly more often in talampanel treated subjects. Although no efficacy measure reached statistical significance, there was a repeated trend toward slower decline in ALSFRS and isometric muscle strength in talampanel treated subjects. Talampanel was well tolerated in subjects with ALS. Although certain adverse events occurred more frequently in the active treatment group, the rate of subject drop-out after nine months did not exceed that seen in other trials. These findings provide strong support for a phase III trial to determine the efficacy of talampanel in subjects with ALS.
authors: Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors: Robert M
authors: RM
authors: Pascuzzi
authors: Jeremy
authors: J
authors: Shefner
authors: Amy S
authors: AS
authors: Chappell
authors: John S
authors: JS
authors: Bjerke
authors: Roy
authors: R
authors: Tamura
authors: Vinay
authors: V
authors: Chaudhry
authors: Lora
authors: L
authors: Clawson
authors: Lisa
authors: L
authors: Haas
authors: Jeffrey D
authors: JD
authors: Rothstein
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D001569:Benzodiazepines / Q000097:blood / Q000627:therapeutic use*; D004185:Disability Evaluation; D004311:Double-Blind Method; D004562:Electrocardiography / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000097:blood / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D053580:Muscle Strength / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000503:physiopathology; D009460:Neurologic Examination; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018691:Excitatory Amino Acid Antagonists; D001569:Benzodiazepines; C085266:talampanel