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

This study has been terminated.
(Study was stopped as the sponsor is no longer funding this project)
Sponsor:
Information provided by:
Teva GTC
ClinicalTrials.gov Identifier:
NCT00464958
First received: April 22, 2007
Last updated: February 17, 2009
Last verified: January 2009
  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 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Teva GTC:

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
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

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
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: NCT00464958

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

Additional Information:
No publications provided

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

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

Additional relevant MeSH terms:
Multiple Sclerosis
Muscle Spasticity
Sclerosis
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
Pathologic Processes
Tizanidine
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anticonvulsants
Muscle Relaxants, Central
Neuromuscular Agents
Parasympatholytics
Autonomic Agents
Adrenergic alpha-2 Receptor Agonists

ClinicalTrials.gov processed this record on August 20, 2014