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

January 20, 2009 updated by: Teva GTC

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 Spasticity in MS Patients

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment

20

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Israel
      • Tel Aviv, Israel
        • Tel Aviv Sourasky Medical Center- Neurology Department

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male and female patients between the ages of 20-65
  • Definitive diagnosis of MS, with Expanded Disability Status Scale (EDSS) less than 6.5 at screening
  • Has significant spasticity (total Ashworth => 6) at screening
  • Can maintain sleep regimens of at least 5 hours nightly for study duration

  • May be allowed to take other anti-spasticity medication during study (including oral baclofen) as per individual dosing regimen, with the following qualifications:

    • No dose after 6pm on any study day
    • No dose at all on a clinic evaluation day (Visits 3, 4, 5)
  • Females must agree to use a medically accepted form of birth control, be surgically sterile, or be two years post-menopausal. Oral contraception is contraindicated with tizanidine use.

Exclusion Criteria:

  • Acute MS exacerbation requiring treatment with steroids within 30 days of screening
  • Initiation of discontinuation of interferon beta within 30 days of screening
  • Use of baclofen pump
  • Use of CYP1A2 inhibitors during study
  • Taking medications that would potentially interfere with the actions of the study medication or outcome variables, including: sedatives, stimulants, anti-hypertensives, tricyclic antidepressants, etc.
  • Previous diagnosis of a sleep disorder, distinct from MS, such as obstructive sleep apnea or narcolepsy
  • Score >18 on Beck Depression Inventory at screening
  • Changes in chronic oral medications within 2 weeks of baseline and during study
  • Significant abnormalities in screening lab parameters (ex: ALT, AST, bilirubin > 2 x upper limit of normal [ULN]; creatinine > 2 mg/dl; white blood cell [WBC] < 2,300; platelets < 80,000).
  • Previous history of dementia, unstable psychiatric disease, or current signs and symptoms of significant medical disorders such as severe, progressive, or uncontrolled renal, hepatic, hematological, endocrine, pulmonary, cardiac, neurological, or cerebral disease
  • History of allergy to tizanidine or any inactive component (including lactose intolerance) of test or reference formulation
  • History of substance abuse within the past 12 months
  • Within 30 days of baseline, worked a rotating or nighttime shift
  • Participation in another clinical trial within 30 days of baseline
  • Patients who are uncooperative or unwilling to sign consent form

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Teva GTC

Investigators

  • Principal Investigator: Arnon Karni, MD, Department of Neurology, Tel Aviv Sourasky Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2006

Study Completion (Actual)

February 1, 2007

Study Registration Dates

First Submitted

July 27, 2006

First Submitted That Met QC Criteria

July 27, 2006

First Posted (Estimate)

July 31, 2006

Study Record Updates

Last Update Posted (Estimate)

January 21, 2009

Last Update Submitted That Met QC Criteria

January 20, 2009

Last Verified

April 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Protocol C2/5/TZ-MS-05

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Muscle Spasticity

Clinical Trials on Tizanidine (sublingual or oral)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in United Kingdom

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe