cognitive impairment in Multiple Sclerosis MedDRA version: 9.1 Level: LLT Classification code 10028245 Term: Multiple sclerosis
Conditions
Interventions
Trade Name: Exelon transdermales Pflaster
Product Name: Exelon
Product Code: ENA713
Pharmaceutical Form: Transdermal patch
INN or Proposed INN: Rivastigmin
CAS Number: 123441-03-2
Current Sponsor code
Sponsors
Novartis Pharma GmbH
Eligibility
Sex/Gender
All
Inclusion 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 (Appendix 4) 4) MS-subtype: CIS, RRMS, SPMS; 6) Stable and well tolerated therapy with interferon beta-1b (Extavia®) for at least 60 days immediately prior to baseline. This period does not apply to patients swithed directly from Betaferon. 7) Cognitive Impairment defined as FST score of =3.0 and/or MUSIC score of =19 at screening 8) Verbal memory impairment defined as a score =0.5 standard deviations (SD) below age- and sex-based normative data on the RAVLT score at screening 9) Sufficient education to read, write and communicate comprehensibly Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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. Patient with advanced disease serious enough to, under the judgment of the physician-investigator, place the patient at a special risk situation. 3. Women o who are pregnant or breast feeding (pregnancy defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/ml)) o who are menstruating and capable of becoming pregnant* and not practicing a medically approved method of contraception 4. With a physical or sensory disability that can subjectively prevent the patient from completing all study requirements 5. Patients without contractual capability. 6. 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). 7. Patients suffering an acute relapse of MS in the previous 30 days (treated or not with intravenous or oral glucocorticoid regimens) prior to baseline. 8. Patients on any other treatment for MS than described in inclusion criteria 9. With a history or current problem of drug-addiction and/or alcohol abuse. 10. Current or historical laboratory evidence of vitamin B1 and/or vitamin B12 deficit 11. 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) 12. Any of the following hepatic conditions: • total or conjugated bilirubin greater than 2 times the upper limit of the normal range, unless in context of Gilbert’s syndrome • AST (=SGOT), ALT (=SGPT) greater than 3 times the upper limit of the normal range 13. With any of the following abnormal laboratory values at screening: • serum creatinine >2 ULN or a history of hemodialysis • white blood cell (WBC) count <3,500/mm³ (<3.5 x 109 / L) • Serum electrolyte, BUN and Thyroidea stimulating hormone (TSH) concentrations outside the range as specified also in Appendix 2. 14. With a history of severe or moderate-severe cranioencephalic trauma. 15. Study personnel or first degree relatives of investigator(s) must not be included in the study 16. 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. 17. Patients with any of the following diseases serious or unstable: gastrointestinal disease; clinically significant urinary obstruction under clinical judgement; acute, severe or unstable asthmatic conditions [for instance, severe chronic obstructive pulmonary disease (COPD)]; current and known diagnosis of severe or unstable cardiovascular disease; current and known diagnosis of bradycardia (? 40 bpm), sinus syndrome or conductivity disorders (atrial sinus blockage, 2nd or 3rd degree atrioventricular block). 18. With a history in the past year or a current diagnosis of cerebrovascular disease (for instance, stroke, transient ischemic events, aneurysms). 19. Severe depressive symptoms indicated by a score of more than = 14 on the MADRS at screening 20. Patients who have performed a cognitive testing with Brief rep
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate that rivastigmine patch (target patch size 10 cm²) has superior efficacy compared to placebo on a change from baseline of the total recall score of the selective reminding test (SRT) of the Brief Repeatable Battery of Neuropsychological Tests (BRB-N) in cognitive impaired MS patients after 16 weeks of treatment.;Secondary Objective: ? effect on different cognitive domains ? effect on fatigue in MS-patients treated with rivastigmine patch versus Placebo, the Modified Fatigue Impact Scale (mFIS) will be used after 16 weeks of treatment ? effect on depression in MS-patients ? effect on the course of disease in MS- patients, the multiple sclerosis functional composite (MSFC) will be used after 16 weeks of treatment ? effect on quality of life in MS-patients treated with rivastigmine patch versus Placebo, the QOL subscale of the PRIMuS will be used after 16 weeks of treatment ? safety and tolerability in MS patients up to 68 weeks of treatment ? the longterm effect on all primary and secondary objectives listed above, the BRB-N, PRIMuS, CGI, mFIS, MADRS and MSFC will be used after 32 and 68 weeks of treatment ? longitudinal measurement of screening instruments, the Faces Symbol Test (FST) will be used and compared with BRB after 16, 32 and 68 weeks of treatment;Primary end point(s): The primary endpoint is the change in score of total recall on the SRT (baseline to week 16). The SRT is a widely used measure of verbal learning and memory that is part of the Brief Repeatable Battery of Neuropsychological Test in MS (BRB-N). | — |
Countries
Germany
Outcome results
None listed