One Year Extension Study To Protocol C2/5/TZ:MS-05

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00464958
Recruitment Status : Terminated (Study was stopped as the sponsor is no longer funding this project)
First Posted : April 24, 2007
Last Update Posted : February 19, 2009
Information provided by:
Teva GTC

Brief Summary:
Open label, one year extension study to evaluate the clinical efficacy and safety of 12 mg sublingual tizanidine administered once nightly in MS patients who successfully completed Phase I/II protocol C2/5/TZ:MS-05 at the Tel Aviv Sourasky Medical Center, Department of Neurology, Dr. Arnon Karni, PI.

Condition or disease Intervention/treatment Phase
Spasticity Multiple Sclerosis Drug: sublingual tizanidine 12 mg Phase 1 Phase 2

Detailed Description:

The previous study, Protocol C2/5/TZ-MS-05, using 12 mg sublingual tizanidine, confirmed that administration of once nightly sublingual tizanidine before sleep results in a statistically and clinically significant reduction in next-day spasticity, as compared to placebo. The clinical effect following 12 mg sublingual tizanidine was larger (4-5 units on the Ashworth scale) and more sustained (up to 18-20 hours post-dose) than was seen for 8 mg tizanidine (earlier study, Protocol C2/5/TZ:MS-03z). This study also reconfirmed that the increased improvement in next-day reduction of spasticity following overnight sublingual tizanidine dosing is not accompanied by a concomitant increase in next-day somnolence.

This study, a 12 month open label extension, will allow those patients who successfully completed Protocol C2/5/TZ-MS-05 and who found tizanidine to be beneficial, to continue treatment under close medical supervision. The study will provide long-term (12 months) clinical efficacy and safety data re: the use of once daily sublingual tizanidine, administered at night, just before bedtime.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Long Term Clinical Efficacy and Safety of Novel Sublingual Tizanidine HCl (12 mg) for the Treatment of Spasticity in Patients With Multiple Sclerosis - Open Label Extension Study
Study Start Date : January 2008
Primary Completion Date : December 2008
Study Completion Date : December 2008

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Sublingual tizanidine
Once nightly dosing of 12 mg sublingual tizanidine tablet
Drug: sublingual tizanidine 12 mg
Single sublingual tizanidine 12 mg tablet, to be administered once nightly, via sublingual administration for 12 months

Primary Outcome Measures :
  1. Clinical Efficacy- reduction in next-day spasticity (Ashworth scores) [ Time Frame: 12 months ]
  2. Safety- No increase in next-day somnolence/fatigue, measured via Epworth Sleepiness Scale (ESS) and Fatigue Severity Scale (FSS) questionnaires [ Time Frame: 12 months ]

Secondary Outcome Measures :
  1. Additional Safety Measures: Clinical Laboratories (hematology and clinical chemistry, with special emphasis on liver function tests); Blood pressure monitoring (standard vital signs: BP and pulse at every monthly visit, + 24 hour Holter ambulatory Blood [ Time Frame: 12 months ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Ages Eligible for Study:   20 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Successful completion of previous protocol, Study C2/5/TZ:MS-05
  • Have a definitive diagnosis of Multiple Sclerosis
  • Patients may be allowed to take other anti-spasticity medication during the study (other than Baclofen pump)as per their individual daily dosing regimen, with the following qualification: (1) No dose after 18:00 on any study day (2) No dose at all on a clinic evaluation day
  • Females must agree to use a medically accepted form of birth control, be surgically sterile, or be two years post-menopausal. Oral contraception in NOT acceptable as it is contraindicated for tizanidine use.
  • Patients must meet criteria for stable 24 hour BP values based on the screening ABPM monitorings (with and without tizanidine challenge) as determined by the study's BP consultant

Exclusion Criteria:

  • Use of CYP1A2 inhibitors [e.g. ciprofloxacin or fluvoxamine as well as zileuton, other fluroquinolones (norfloxacin), antiarrythmics (amiodarone, mexiletine, propafenone), cimetidine, famotidine, oral contraceptives, acyclovir, and ticlopidine] from baseline and for the duration of the study
  • Taking medications from baseline and for the duration of the study that would potentially interfere with the actions of the study medication or outcome variables as determined by the PI
  • 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
  • Significant abnormalities in screening laboratory parameters as described below:
  • ALT > 2xULN
  • AST > 2xULN
  • Creatinine > 2.0 mg/dL
  • Bilirubin > 2xULN
  • WBC < 2,300/mm3
  • Platelets < 80,000/mm3
  • History of allergy to tizanidine or any inactive component (including lactose intolerance) of the sublingual tizanidine tablet
  • History of substance abuse within past 12 months
  • Patients who are non-cooperative or unwilling to sign consent form

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00464958

Tel Aviv Sourasky Medical Center
Tel Aviv, Israel, 64239
Sponsors and Collaborators
Teva GTC
Principal Investigator: Arnon Karni, MD Tel-Aviv Sourasky Medical Center

Additional Information: Identifier: NCT00464958     History of Changes
Other Study ID Numbers: Protocol C2/5/TZ:MS-05 EXT
First Posted: April 24, 2007    Key Record Dates
Last Update Posted: February 19, 2009
Last Verified: January 2009

Keywords provided by Teva GTC:
Sublingual Tizanidine
Epworth Sleepiness Scale
Fatigue Severity Scale

Additional relevant MeSH terms:
Multiple Sclerosis
Muscle Spasticity
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Muscular Diseases
Musculoskeletal Diseases
Muscle Hypertonia
Neuromuscular Manifestations
Neurologic Manifestations
Signs and Symptoms
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Muscle Relaxants, Central
Neuromuscular Agents
Autonomic Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists