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

Sponsor:	Teva R&D Initiative
Information provided by:	Teva R&D Initiative
ClinicalTrials.gov Identifier:	NCT00464958

Purpose

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	Intervention	Phase
Spasticity Multiple Sclerosis	Drug: sublingual tizanidine 12 mg	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
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

Resource links provided by NLM:

MedlinePlus related topics: Multiple Sclerosis

Drug Information available for: Tizanidine Tizanidine hydrochloride

U.S. FDA Resources

Further study details as provided by Teva R&D Initiative:

Primary Outcome Measures:

Clinical Efficacy- reduction in next-day spasticity (Ashworth scores) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Safety- No increase in next-day somnolence/fatigue, measured via Epworth Sleepiness Scale (ESS) and Fatigue Severity Scale (FSS) questionnaires [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]

Enrollment:	10
Study Start Date:	January 2008
Study Completion Date:	December 2008
Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Sublingual tizanidine: Experimental 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

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.

Eligibility

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

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00464958

Locations

Israel
Tel Aviv Sourasky Medical Center
Tel Aviv, Israel, 64239

Sponsors and Collaborators

Teva R&D Initiative

Investigators

Principal Investigator:

Arnon Karni, MD

Tel-Aviv Sourasky Medical Center

More Information

Additional Information:

ClinicalTrials.gov Identifier: NCT00358293 This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	Protocol C2/5/TZ:MS-05 EXT
Study First Received:	April 22, 2007
Last Updated:	February 17, 2009
ClinicalTrials.gov Identifier:	NCT00464958 History of Changes
Health Authority:	Israel: Ministry of Health

Keywords provided by Teva R&D Initiative:

Fatigue
Spasticity
Sublingual Tizanidine
Epworth Sleepiness Scale
Fatigue Severity Scale

Additional relevant MeSH terms:

Parasympatholytics
Neurotransmitter Agents
Adrenergic Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Neuromuscular Agents
Adrenergic Agonists
Signs and Symptoms
Multiple Sclerosis
Pathologic Processes
Musculoskeletal Diseases
Sensory System Agents
Muscle Hypertonia
Muscle Relaxants, Central
Therapeutic Uses

Tizanidine
Analgesics
Autoimmune Diseases of the Nervous System
Neuromuscular Manifestations
Autoimmune Diseases
Adrenergic alpha-Agonists
Immune System Diseases
Demyelinating Diseases
Nervous System Diseases
Sclerosis
Pharmacologic Actions
Muscle Spasticity
Muscular Diseases
Autonomic Agents
Demyelinating Autoimmune Diseases, CNS

ClinicalTrials.gov processed this record on November 05, 2009