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

This study has been completed.
Sponsor:
Collaborator:
Ono Pharmaceutical Co. Ltd
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01614886
First received: June 6, 2012
Last updated: June 3, 2015
Last verified: June 2015
  Purpose

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


Condition Intervention Phase
Alzheimer's Disease
Drug: Active Comparator
Drug: ENA713
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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)

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Percentage of Patients With Adverse Events Leading to Study Drug Discontinuation [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: Yes ]
    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:
  • Change From Baseline in the Alzheimer's Disease Assessment Scale - Japan Cognitive Subscale (ADAS-J Cog) [ Time Frame: Baseline, 8,16, and 24 weeks ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Mini-Mental State Examination (MMSE) [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • The Percentage of Treatment Retention. [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: No ]
    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


Enrollment: 216
Study Start Date: July 2012
Study Completion Date: May 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   50 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT01614886

  Show 50 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Ono Pharmaceutical Co. Ltd
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01614886     History of Changes
Other Study ID Numbers: CENA713D1303
Study First Received: June 6, 2012
Results First Received: April 16, 2015
Last Updated: June 3, 2015
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency (PMDA)

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

Additional relevant MeSH terms:
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Dementia
Mental Disorders
Nervous System Diseases
Neurodegenerative Diseases
Tauopathies
Rivastigmine
Central Nervous System Agents
Cholinergic Agents
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Neuroprotective Agents
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 28, 2015