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

Condition(s) targeted: Spasticity; Fatigue

Intervention: Sublingual Tizanidine 12 mg tablet (Drug)

Phase: Phase 1/Phase 2

Status: Not yet recruiting

Sponsored by: Teva R&D Initiative

Official(s) and/or principal investigator(s):
Arnon Karni, MD, Principal Investigator, Affiliation: Tel-Aviv Sourasky Medical Center

Overall contact:
Arnon Karni, MD, Phone: 011 972 3 697 3495, Email: arnonk@tasmc.health.gov.il

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.

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

Primary outcome:

Clinical Efficacy- reduction in next-day spasticity (Ashworth scores)

Safety- No increase in next-day somnolence/fatigue, measured via Epworth Sleepiness Scale (ESS) and Fatigue Severity Scale (FSS) questionnaires

Secondary outcome: 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

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.

Minimum age: 20 Years. Maximum age: 65 Years. Gender(s): Both.

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

Arnon Karni, MD, Phone: 011 972 3 697 3495, Email: arnonk@tasmc.health.gov.il

Tel Aviv Sourasky Medical Center, Tel Aviv 64239, Israel

ClinicalTrials.gov Identifier: NCT00358293

Starting date: May 2007
Ending date: May 2008
Last updated: April 25, 2007