Randomized, Double-blind Study to Evaluate the Tolerability of 2 Different Titration Methods of Rivastigmine Patch in AD Patients (MMSE 10-20)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01614886
Recruitment Status : Completed
First Posted : June 8, 2012
Results First Posted : May 12, 2015
Last Update Posted : August 1, 2016
Ono Pharmaceutical Co. Ltd
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
To evaluate the tolerability, safety and efficacy of 3-step titration versus 1-step titration of Rivastigmine patch in the Japanese population.

Condition or disease Intervention/treatment Phase
Alzheimer's Disease Drug: Active Comparator Drug: ENA713 Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 216 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 24-week, Multicenter, Parallel-group, Randomized,Double-blind Study to Evaluate the Tolerability, Safety and Efficacy of 2 Different Titration Methods of Rivastigmine Patch (ENA713D/ONO-2540) in Patients With Mild to Moderate Alzheimer's Disease (MMSE 10-20)
Study Start Date : July 2012
Actual Primary Completion Date : May 2014
Actual Study Completion Date : May 2014

Arm Intervention/treatment
Experimental: 1 step Drug: Active Comparator
1-step titration group begin treatment with a rivastigmine patch 9 mg/day for 4 weeks, followed by a dose increase to 18 mg/day.

Active Comparator: 3 step Drug: ENA713
-3-step titration group will begin treatment with a rivastigmine patch 4.5 mg/day for 4 weeks, followed by a further dose increase of 4.5 mg/day at 4-week intervals up to the maintenance dose of 18 mg/day.

Primary Outcome Measures :
  1. Percentage of Patients With Adverse Events Leading to Study Drug Discontinuation [ Time Frame: Up to 24 weeks ]
    The primary variable of this study is the percentage of patients having an AE leading to study drug discontinuation during the 24-week double-blind treatment period.

Secondary Outcome Measures :
  1. Change From Baseline in the Alzheimer's Disease Assessment Scale - Japan Cognitive Subscale (ADAS-J Cog) [ Time Frame: Baseline, 8,16, and 24 weeks ]
    The Alzheimer's Disease Assessment Scale - Japan cognitive subscale (ADAS-J cog) was used to measure change in cognitive function. The ADAS-J cog score ranges from 0-70, with higher total scores indicating more impairment. A negative change score indicates improvement from baseline.

  2. Change From Baseline in Mini-Mental State Examination (MMSE) [ Time Frame: Baseline and 24 weeks ]
    The MMSE was used to measure severity of Alzheimer's disease. The test consists of 2 parts: language (time orientation, registration and attention) and performance (recall, response to written/verbal commands, sriting ability and reproduction of complex polygons); the total score can range from 0 to 30, with a higher score indicating better function. A positive change score indicates improvement from baseline.

  3. Number of Participants With Improvement in Japanese Clinical Global Impression of Change (J-CGIC). Patients With "Improvement": a Total of 1. Markedly Improved, 2. Improved, and 3. Slightly [ Time Frame: 4, 8, 12,16, 20 and 24 weeks ]
    The J-CGIC is simple 7 grade investigator's impression scale (1. Markedly improved, 2. Improved, 3. Slightly improved, 4. No change, 5. Slightly aggravated, 6. Aggravated, 7. Markedly aggravated) and a patient is defined to have improvement if J-CGIC tool the values 1, 2, or 3.

  4. The Percentage of Treatment Retention. [ Time Frame: Up to 24 weeks ]
    Treatment retention rate at effective dose is defined as the proportion of patients who met all the followings - 1) completed the study, 2) received rivastigmine patch 18 mg/day throughout the last 8 weeks 3) received 18 mg/day for ≥75% of the days during the last 8 weeks

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Ages Eligible for Study:   50 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • A diagnosis of dementia of the Alzheimer's type according to the DSM-IV criteria
  • A clinical diagnosis of probable AD according to NINCDS/ADRDA criteria
  • An MMSE score of ≥ 10 and ≤ 20 at baseline

Exclusion Criteria:

  • Any medical or neurological conditions other than AD that could explain the patient's dementia
  • A current diagnosis of probable or possible vascular dementia
  • A score of > 5 on the Modified Hachinski Ischemic Scale (MHIS)
  • A current DSM-IV Axis 1 diagnosis that may interfere with the evaluation of the patient's response to study medication.
  • Treated with donepezil or galantamine within last 4 weeks before the efficacy assessment at baseline.
  • an advanced severe progressive or unstable disease of any type that may interfere with efficacy and safety assessments or put the patient's at special risk
  • Other protocol-defined inclusion/exclusion criteria may apply.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01614886

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Sponsors and Collaborators
Novartis Pharmaceuticals
Ono Pharmaceutical Co. Ltd
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Responsible Party: Novartis Pharmaceuticals Identifier: NCT01614886     History of Changes
Other Study ID Numbers: CENA713D1303
First Posted: June 8, 2012    Key Record Dates
Results First Posted: May 12, 2015
Last Update Posted: August 1, 2016
Last Verified: June 2015

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Rivastigmine, Alzheimer's disease, Transdermal patch

Additional relevant MeSH terms:
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Neuroprotective Agents
Protective Agents