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

NCT00358293 | Completed Phase 1

• 1 other identifier: Protocol C2/5/TZ-MS-05
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Muscle Spasticity

Keywords

Multiple Sclerosis; Spasticity; Sublingual Tizanidine; Ashworth Scores; Spasticity in Multiple Sclerosis Patients

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

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

Interventions

Tizanidine (sublingual or oral) DRUG

Eligibility Criteria

• Age: 20 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Teva GTC: lead

Study Sites (1)

Tel Aviv Sourasky Medical Center- Neurology Department

Tel Aviv, Israel

Location

MeSH Terms

Conditions

Muscle Spasticity; Multiple Sclerosis

Interventions

tizanidine; Administration, Sublingual

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Administration, Oral; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Arnon Karni, MD

  Department of Neurology, Tel Aviv Sourasky Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: July 27, 2006
• First Posted: July 31, 2006
• Study Start: December 1, 2006
• Study Completion: February 1, 2007
• Last Updated: January 21, 2009

Record last verified: 2007-04

Locations

IL (1)