A prospective, multicenter phase I trial was undertaken by the North American Clinical Trials Network (NACTN) to investigate the pharmacokinetics and safety of, as well as obtain pilot data on, the effects of
riluzole on neurological outcome in acute
spinal cord injury (SCI). Thirty-six patients, with ASIA impairment grades A-C (28 cervical and 8 thoracic) were enrolled at 6 NACTN sites between April 2010 and June 2011. Patients received 50 mg of
riluzole PO/NG twice-daily, within 12 h 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 14-70% 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 (p=0.021). Patients with cervical
injuries treated with
riluzole had more-robust conversions of impairment grades to higher grades than the comparison group.