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NEUROLOGY 1996;47:242S-250S
© 1996 American Academy of Neurology

A confirmatory dose-ranging study of riluzole in ALS

L. Lacomblez, MD, G. Bensimon, MD, PhD, P. N. Leigh, PhD, FRCP, P. Guillet, MD, L. Powe, MD, S. Durrleman, MD, J. C. Delumeau, MD, PhD and V. Meininger, MD, PhD

The ALS/Riluzole Study Group-II*.
*See the Appendix at the end of the article for study organization and other particpants.
From the Departments of Pharmacology (Drs. Lacomblez and Bensimon), and Neurology (Dr. Meininger), Hopital de la Pitie-Salpetriere, Paris; Rhone-Poulenc Rorer (Drs. Guillet, Powe, Durrleman, and Delumeau), Antony, France and Collegeville, USA; and the Department of Neurology (Professor Leigh), Institute of Psychiatry, de Crespigny Park, London, UK.
Address correspondence and reprint requests to Dr. L. Lacomblez, Department of Pharmacology, Hopital de la Pitie-Salpetriere, 47 blvd de l'Hopital, 75651 Paris Cedex 13, France.

Abstract.

ALS is a progressive motor neuron disease with no effective treatment.The anti-excitotoxic drug riluzole (100 mg/day) has been shown to decrease mortality and muscular deterioration in ALS patients. To confirm and extend the therapeutic effect of riluzole, we performed a double-blind, placebo-controlled, multicenter, international, dose-ranging (50, 100, 200 mg/day), stratified study in 959 ALS outpatients treated for up to 18 months. Primary efficacy criterion was survival and the effect of treatment was analyzed before (Wilcoxon and log rank tests) and after adjustment on prognostic factors (Cox model). Secondary efficacy criterion was disease progression assessed through change in functional measures. Tracheostomy-free survival rates were: 50.4% (placebo), 55.3% (50 mg riluzole) (p = 0.23, Wilcoxon test; p = 0.25, log-rank test), 56.8% (100 mg riluzole) (p = 0.05, Wilcoxon test; p = 0.076, log-rank test), and 57.8% (200 mg riluzole) (p = 0.061, Wilcoxon test; p = 0.075, log-rank test). At the end of the 18-month study, there was a significant dose-related decrease in risk of death or tracheostomy (p = 0.04). Adjustment for baseline prognostic factors showed a 35% decreased risk of death with the 100-mg dose compared with placebo (p = 0.002). No significant treatment effects were detected for the functional assessments. The most frequent dose-related adverse events included nausea, asthenia, and elevated liver enzyme levels. This study confirms the therapeutic effect of riluzole in a large representative ALS sample, over an 18-month period. Riluzole is well tolerated and decreases the risk of death or tracheostomy in ALS patients.

NEUROLOGY 1996;47(Suppl 4): S242-S250






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