Rivastigmine in Multiple Sclerosis Patients With Cognitive Impairment
Condition: Multiple Sclerosis; Cognitive Impairment
MeSH terms: Multiple Sclerosis; Sclerosis; Cognitive Dysfunction
Intervention: Rivastigmine transdermal patch; Placebo
Intervention description: Transdermalapplication of one 5 cm² patch, followed by an increase to the target dose of 10 cm² patch size. All patches are round, beige in color.; Transdermal application of one 5 cm² patch, followed by an increase to the target dose of 10 cm² patch size. Matching the size, shape and color of rivastigmine patches.
Intervention MeSH terms: Rivastigmine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 86.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Multiple Sclerosis; Cognition; Rivastigmine; Patch

Summary:

      This study evaluated the efficacy and safety of 10 cm² rivastigmine patch vs. placebo in
      cognitively impaired Multiple Sclerosis (MS) patients. Primary objective was the assessment
      of cognition by the Selective Reminding Test (SRT) -a subtest of the brief repeatable battery
      (BRB) - after titration of 4 weeks and maintenance of 12 weeks. This double-blind period was
      followed by a 52-week open-label treatment phase to assess long-term safety of rivastigmine
      patch in these patients.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Written informed consent to participate in the trial

          2. Males and females between 18 and 55 years of age;

          3. Definite diagnosis of multiple sclerosis as defined by 2005 revised McDonald criteria

          4. MS-subtype: Clinical isolated syndrome (CIS), Relapsing Remitting Multiple Sclerosis
             (RRMS), Secondary progressive Multiple Sclerosis (SPMS);

          5. Cognitive Impairment

          6. Sufficient education to read, write and communicate comprehensibly

        Exclusion Criteria:

          1. Use of other investigational drugs at the time of enrollment, or within 30 days or 5
             half-lives of enrollment, whichever is longer

          2. Women who are pregnant or breast feeding or who are menstruating and capable of
             becoming pregnant and not practicing a medically approved method of contraception

          3. With a physical or sensory disability that can subjectively prevent the patient from
             completing all study requirements

          4. Patients suffering any other type of concomitant psychiatric and/or neurological
             disorder other than MS which is known to affect cognition (e.g. severe depressive
             symptoms, cerebrovascular diseases, epilepsy).

          5. Patients suffering an acute relapse of MS in the previous 30 days (treated or not with
             intravenous or oral glucocorticoid regimens) prior to baseline.

          6. With a history or current problem of drug-addiction and/or alcohol abuse.

          7. Known or 'new' diagnosis of diabetes mellitus (if screening blood glucose is
             suspicious for diabetes [≥126 mg/dL or ≥7 mmol/L if fasting and ≥200 mg/dL or 11.1
             mmol/L if random testing] a patient should be further evaluated for diabetes mellitus)

          8. With a history of severe or moderate-severe cranioencephalic trauma.

          9. History or presence of any intolerance or contraindication for the application of
             rivastigmine (or for drugs with similar chemical structures) as listed in the current
             Investigator's Brochure and/or SPC, i.e. severe liver insufficiency, pancreatitis,
             gastric ulcer, convulsions.

         10. With a history in the past year or a current diagnosis of cerebrovascular disease (for
             instance, stroke, transient ischemic events, aneurysms).

         11. Severe depressive symptoms indicated by a score of more than ≥ 14 on the MADRS at
             screening

         12. History of malignancy of any organ system, treated or untreated, within the past 5
             years whether or not there is evidence of local recurrence or metastases, with the
             exception of localized basal cell carcinoma of the skin

        Other protocol-defined inclusion/exclusion criteria may apply