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

Multiple Sclerosis Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00464958
• Other study ID #: Protocol C2/5/TZ:MS-05 EXT
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: April 22, 2007
• Last updated: February 17, 2009
• Start date: January 2008
• Est. completion date: December 2008

Study information

• Verified date: January 2009
• Source: Teva GTC
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: December 2008
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 65 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Muscle Spasticity
• Sclerosis
• Spasticity

Intervention

Drug:
• sublingual tizanidine 12 mg
Single sublingual tizanidine 12 mg tablet, to be administered once nightly, via sublingual administration for 12 months

Locations

Country	Name	City	State
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv

Sponsors (1)

Lead Sponsor	Collaborator
Teva GTC

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical Efficacy- reduction in next-day spasticity (Ashworth scores)		12 months	No
Primary	Safety- No increase in next-day somnolence/fatigue, measured via Epworth Sleepiness Scale (ESS) and Fatigue Severity Scale (FSS) questionnaires		12 months	Yes
Secondary	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		12 months	Yes

External Links

•   ClinicalTrials.gov Identifier: NCT00358293