A prospective, multicenter, phase I matched comparison group trial of safety, pharmacokinetics, and preliminary efficacy of rilzole in patients with traumatic spinal cord injury

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Study investigated the pharmacokinetics, safety, and effects of riluzole, a sodium-channel blocking medication, on neurological outcome in acute spinal cord injury (SCI). Thirty-six patients (28 cervical and 8 thoracic), enrolled at 6 North American Clinical Trials Network (NACTN) sites, received 50 milligrams of riluzole twice daily, within 12 hours of SCI, for 14 days. Peak and trough plasma concentrations were quantified on days 3 and 14. Peak plasma concentration (Cmax) and systemic exposure to riluzole varied significantly between patients. On the same-dose basis, Cmax did not reach levels comparable to those in patients with amyotrophic lateral sclerosis. Riluzole plasma levels were significantly higher on day 3 than on day 14, resulting from a lower clearance and a smaller volume of distribution on day 3. Rates of medical complications, adverse events, and progression of neurological status were evaluated by comparison with matched patients in the NACTN SCI Registry. Medical complications in riluzole-treated patients occurred with incidences similar to those in patients in the comparison group. Mild-to-moderate increase in liver enzyme and bilirubin levels were found in 14 to 70 percent of patients for different enzymes. Three patients had borderline severe elevations of enzymes. No patient had elevated bilirubin on day 14 of administration of riluzole. There were no serious adverse events related to riluzole and no deaths. The mean motor score of 24 cervical injury riluzole-treated patients gained 31.2 points from admission to 90 days, compared to 15.7 points for 26 registry patients, a 15.5-point difference. Patients with cervical injuries treated with riluzole had more-robust conversions of impairment grades to higher grades than the comparison group.

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