Clinical Trial: Study of Nighttime Dosing of Sublingual Tizanidine (12 mg) in Multiple Sclerosis (MS) Patients With Significant Spasticity

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Double-Blind, Randomized, Crossover Study to Evaluate the Clinical Efficacy and Safety of Oral Tizanidine HCl (12 mg) Versus Novel Sublingual Tizanidine HCl (12 mg) for the Treatment of

Brief Summary: Nightly administration of 8 mg of a unique sublingual (under the tongue) formulation of tizanidine, a known anti-spasticity medication, has been shown in a previous study to improve next-day spasticity, about 12 hours following dosing in 20 multiple sclerosis (MS) patients. This improvement was statistically significant when compared to oral tizanidine dosing. The current study is being undertaken to see if increasing the dose to 12 mg once nightly will result in an even greater improvement, with a longer effect, i.e., next day improvement in spasticity both in the morning as well as in the late afternoon.

Detailed Summary:

Sublingual tizanidine, a novel test formulation of the known effective antispasticity agent, has been shown to have a unique pharmacokinetic profile [(i.e., nearly twice the bioavailability/AUC), but with little or no increase in peak plasma levels (Cmax) as compared to oral tizanidine (Zanaflex)]. When administered nightly to 20 MS patients, at a dose of 8 mg, it was shown to improve next-day spasticity (statistically significant improvement in Ashworth scores) about 12 hours post-dosing), improvement in nighttime (first quartile) sleep efficiency (as demonstrated by actigraphic measurement), and no increase in daytime somnolence.

Current study is being undertaken to evaluate if increased dosing (12 mg once nightly) of sublingual tizanidine (vs. oral) will show a concomitant increase in clinical effect, i.e., longer improvement, with next-day spasticity score improvement both in AM (as previously) as well as at PM (late afternoon) evaluation, with no increase in daytime somnolence.


Sponsor: Teva GTC

Current Primary Outcome:

  • Clinical efficacy - improvement in next-day spasticity (Ashworth scores)
  • Safety - no increase in next-day somnolence (measured objectively using PVT psychomotor vigilance task monitoring) and subjectively, using Epworth Sleepiness Scale (ESS) and Fatigue Severity Scale (FSS) questionnaires


Original Primary Outcome:

  • Clinical Efficacy-Improvement in Next-Day Spasticity (Ashworth scores)
  • Safety- No increase in Next-Day Somnolence (measured objectively using PVT Psychomotor Vigilance Task Monitoring) and subjectively, using Epworth Sleepiness Scale (ESS) and Fatigue Severity Scale (FSS) questionnaires


Current Secondary Outcome: Secondary clinical efficacy - objective measure of sleep (actigraphy measures)

Original Secondary Outcome: Secondary Clinical Efficacy- Objective Measure of Sleep (Actigraphy Measures)

Information By: Teva GTC

Dates:
Date Received: July 27, 2006
Date Started: December 2006
Date Completion:
Last Updated: January 20, 2009
Last Verified: April 2007