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

This study has been completed.
Sponsor:
Information provided by:
Teva GTC
ClinicalTrials.gov Identifier:
NCT00358293
First received: July 27, 2006
Last updated: January 20, 2009
Last verified: April 2007
  Purpose

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.


Condition Intervention Phase
Muscle Spasticity
Drug: Tizanidine (sublingual or oral)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
Primary Purpose: Treatment
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 Spasticity in MS Patients

Resource links provided by NLM:


Further study details as provided by Teva GTC:

Primary Outcome Measures:
  • 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:
  • Secondary clinical efficacy - objective measure of sleep (actigraphy measures)

Estimated Enrollment: 20
Study Start Date: December 2006
Study Completion Date: February 2007
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.

  Eligibility

Ages Eligible for Study:   20 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00358293

Locations
Israel
Tel Aviv Sourasky Medical Center- Neurology Department
Tel Aviv, Israel
Sponsors and Collaborators
Teva GTC
Investigators
Principal Investigator: Arnon Karni, MD Department of Neurology, Tel Aviv Sourasky Medical Center
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00358293     History of Changes
Other Study ID Numbers: Protocol C2/5/TZ-MS-05
Study First Received: July 27, 2006
Last Updated: January 20, 2009
Health Authority: Israel: Ministry of Health

Keywords provided by Teva GTC:
Multiple Sclerosis
Spasticity
Sublingual Tizanidine
Ashworth Scores
Spasticity in Multiple Sclerosis Patients

Additional relevant MeSH terms:
Multiple Sclerosis
Muscle Spasticity
Autoimmune Diseases
Autoimmune Diseases of the Nervous System
Demyelinating Autoimmune Diseases, CNS
Demyelinating Diseases
Immune System Diseases
Muscle Hypertonia
Muscular Diseases
Musculoskeletal Diseases
Nervous System Diseases
Neurologic Manifestations
Neuromuscular Manifestations
Signs and Symptoms
Tizanidine
Adrenergic Agents
Adrenergic Agonists
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Analgesics
Anticonvulsants
Autonomic Agents
Central Nervous System Agents
Molecular Mechanisms of Pharmacological Action
Muscle Relaxants, Central
Neuromuscular Agents
Neurotransmitter Agents
Parasympatholytics
Peripheral Nervous System Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on November 24, 2014