Rivastigmine in Multiple Sclerosis Patients With Cognitive Impairment

NCT00881205 | Terminated Phase 4 Results

• 1 other identifier: CENA713DDE18
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 49

Brief 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.

Conditions

Multiple Sclerosis; Cognitive Impairment

Keywords

Multiple Sclerosis; Cognition; Rivastigmine; Patch

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to Week 16 in Total Recall on the Selective Reminding Test (SRT) in the Intent to Treat (ITT) Population

  The Selective Reminding Test(SRT) is a test to assess verbal learning and memory. During the administration of the SRT only the examiner and the patient should be in the testing room. A list of twelve words is read aloud by the examiner at a rate of one word per two seconds. The patient is asked to recall all twelve words. Only the words that are missed on the preceding trial are given in the consecutive trial. The total score represents a sum score of 6 trials, therefore the range is from 0-72. The lower the value the worse the outcome.

  After 16 weeks of treatment

Study Arms (2)

Rivastigmine

EXPERIMENTAL

Rivastigmine patch arm with the application of one 5 cm² patch, followed by an increase to the target dose of 10 cm² patch size.

Drug: Rivastigmine transdermal patch

Placebo

PLACEBO COMPARATOR

Placebo patch arm with the application of one 5 cm² patch, followed by an increase to the target dose of 10 cm² patch size.

Drug: Placebo

Interventions

Rivastigmine transdermal patch DRUG

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.

Rivastigmine

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent to participate in the trial
• Males and females between 18 and 55 years of age;
• Definite diagnosis of multiple sclerosis as defined by 2005 revised McDonald criteria
• MS-subtype: Clinical isolated syndrome (CIS), Relapsing Remitting Multiple Sclerosis (RRMS), Secondary progressive Multiple Sclerosis (SPMS);
• Cognitive Impairment
• Sufficient education to read, write and communicate comprehensibly

You may not qualify if:

• Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer
• 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
• With a physical or sensory disability that can subjectively prevent the patient from completing all study requirements
• 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).
• Patients suffering an acute relapse of MS in the previous 30 days (treated or not with intravenous or oral glucocorticoid regimens) prior to baseline.
• With a history or current problem of drug-addiction and/or alcohol abuse.
• 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)
• With a history of severe or moderate-severe cranioencephalic trauma.
• 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.
• With a history in the past year or a current diagnosis of cerebrovascular disease (for instance, stroke, transient ischemic events, aneurysms).
• Severe depressive symptoms indicated by a score of more than ≥ 14 on the MADRS at screening
• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (49)

Novartis Investigative Site

Aachen, 52062, Germany

Location

Novartis Investigative Site

Aalen, 73430, Germany

Location

Novartis Investigative Site

Abensberg, 93326, Germany

Location

Novartis Investigative Site

Achim, 28832, Germany

Location

Novartis Investigative Site

Alzenau in Unterfranken, 63755, Germany

Location

Novartis Investigative Site

Aschaffenburg, 63739, Germany

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Novartis Investigative Site

Bad Mergentheim, 97980, Germany

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Novartis Investigative Site

Bayreuth, 95445, Germany

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Novartis Investigative Site

Berlin, 10178, Germany

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Novartis Investigative SIte

Berlin, 10713, Germany

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Novartis Investigative Site

Berlin, 12103, Germany

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Novartis Investigative Site

Berlin, 13347, Germany

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Novartis Investigative Site

Bochum, 44892, Germany

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Novartis Investigative Site

Böblingen, 71034, Germany

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Novartis Investigative Site

Cologne, 51109, Germany

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Novartis Investigative Site

Düsseldorf, 40211, Germany

Location

Novartis Investigative Site

Eisenach, 99817, Germany

Location

Novartis Investigative Site

Ellwangen, 73479, Germany

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Novartis Investigative Site

Erbach im Odenwald, 64711, Germany

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Novartis Investigative Site

Erlangen, 91054, Germany

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Novartis Investigative Site

Essen, 45122, Germany

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Novartis Investigative Site

Essen, 45138, Germany

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Novartis Investigative Site

Giessen, 35385, Germany

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Novartis Investigative Site

Göttingen, 37075, Germany

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Novartis Investigative Site

Hamburg, 20354, Germany

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Novartis Investigative Site

Hamburg, 22083, Germany

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Novartis Investigational Site

Hamburg, 22179, Germany

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Novartis Investigative Site

Hanover, 30623, Germany

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Novartis Investigative Site

Itzehoe, 25524, Germany

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Novartis Investigative Site

Kaltenkirchen, 24568, Germany

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Novartis Investigative Site

Krefeld, 47798, Germany

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Novartis Investigative Site

Lappersdorf, 93138, Germany

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Novartis Investigative Site

Leipzig, 04103, Germany

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Novartis Investigative Site

Leipzig, 04157, Germany

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Novartis Investigative Site

Ludwigshafen, 67059, Germany

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Novartis Investigative Site

Lüneburg, 21335, Germany

Location

Novartis Investigative Site

Neu-Ulm, 89231, Germany

Location

Novartis Investigative Site

Neuburg am Inn, 86633, Germany

Location

Novartis Investigative Site

Oldenburg, 26122, Germany

Location

Novartis Investigative Site

Osnabrück, 49078, Germany

Location

Novartis Investigative Site

Rostock, 18147, Germany

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Novartis Investigative Site

Stade, 21682, Germany

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Novartis Investigative Site

Stuttgart, 70182, Germany

Location

Novartis Investigative Site

Stuttgart, 70191, Germany

Location

Novartis Investigative Site

Ulm, 89073, Germany

Location

Novartis Investigative Site

Unterhaching, 82008, Germany

Location

Novartis Investigative Site

Viernheim, 69518, Germany

Location

Novartis Investigative Site

Wiesbaden, 65183, Germany

Location

Novartis Investigative Site

Wolfratshausen, 82515, Germany

Location

MeSH Terms

Conditions

Multiple Sclerosis; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Limitations and Caveats

This study was terminated early due to low recruitment numbers. This study did not have the anticipated 80% power.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2009
• First Posted: April 15, 2009
• Study Start: April 1, 2009
• Primary Completion: January 1, 2011
• Study Completion: January 1, 2011
• Last Updated: March 12, 2012
• Results First Posted: February 24, 2012

Record last verified: 2012-03

Locations

DE (49)