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

Alzheimer's Disease Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01614886
• Other study ID #: CENA713D1303
• Status: Completed
• Phase: Phase 3
• First received: June 6, 2012
• Last updated: June 3, 2015
• Start date: July 2012
• Est. completion date: May 2014

Study information

• Verified date: June 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Pharmaceuticals and Medical Devices Agency (PMDA)
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 216
• Est. completion date: May 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years to 85 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

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.
• 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.

Locations

Country	Name	City	State
Japan	Novartis Investigative Site	Akita-city	Akita
Japan	Novartis Investigative Site	Anjo-city	Aichi
Japan	Novartis Investigative Site	Azumino-city	Nagano
Japan	Novartis Investigative Site	Bunkyo-ku	Tokyo
Japan	Novartis Investigative Site	Chiba-city	Chiba
Japan	Novartis Investigative Site	Fujioka-city	Gumma
Japan	Novartis Investigative Site	Fukuoka-city	Fukuoka
Japan	Novartis Investigative Site	Hachioji-city	Tokyo
Japan	Novartis Investigative Site	Hiroshima-city	Hiroshima
Japan	Novartis Investigative Site	Kamakura-city	Kanagawa
Japan	Novartis Investigative Site	Kanzaki-gun	Saga
Japan	Novartis Investigative Site	Kasama-city	Ibaraki
Japan	Novartis Investigative Site	Kasukabe-city	Saitama
Japan	Novartis Investigative Site	Kawaguchi-city	Saitama
Japan	Novartis Investigative Site	Kawasaki-city	Kanagawa
Japan	Novartis Investigative Site	Kawasaki-city	Kanagawa
Japan	Novartis Investigative Site	Kitamorokata-gun	Miyazaki
Japan	Novartis Investigative Site	Kochi-city	Kochi
Japan	Novartis Investigative Site	Kochi-city	Kochi
Japan	Novartis Investigative Site	Koshi-city	Kumamoto
Japan	Novartis Investigative Site	Koshigaya-city	Saitama
Japan	Novartis Investigative Site	Koto-ku	Tokyo
Japan	Novartis Investigative Site	Kumamoto City	Kumamoto
Japan	Novartis Investigative Site	Kumamoto-city	Kumamoto
Japan	Novartis Investigative Site	Kurashiki-city	Okayama
Japan	Novartis Investigative Site	Kyoto-city	Kyoto
Japan	Novartis Investigative Site	Kyoto-city	Kyoto
Japan	Novartis Investigative Site	Kyoto-city	Kyoto
Japan	Novartis Investigative Site	Matsumoto-city	Nagano
Japan	Novartis Investigative Site	Miyoshi-city	Hiroshima
Japan	Novartis Investigative Site	Musashino-city	Tokyo
Japan	Novartis Investigative Site	Nagaoka-city	Niigata
Japan	Novartis Investigative Site	Obu-city	Aichi
Japan	Novartis Investigative Site	Okayama-city	Okayama
Japan	Novartis Investigative Site	Ota-ku	Tokyo
Japan	Novartis Investigative Site	Sagamihara-city	Kanagawa
Japan	Novartis Investigative Site	Saitama-city	Saitama
Japan	Novartis Investigative Site	Sakai-city	Osaka
Japan	Novartis Investigative Site	Sendai-city	Miyagi
Japan	Novartis Investigative Site	Seto-city	Aichi
Japan	Novartis Investigative Site	Shimonoseki-city	Yamaguchi
Japan	Novartis Investigative Site	Shizuoka-city	Shizuoka
Japan	Novartis Investigative Site	Shizuoka-city	Shizuoka
Japan	Novartis Investigative Site	Suita-city	Osaka
Japan	Novartis Investigative Site	Suita-city	Osaka
Japan	Novartis Investigative Site	Tachikawa-city	Tokyo
Japan	Novartis Investigative Site	Tokushima-city	Tokushima
Japan	Novartis Investigative Site	Toon-city	Ehime
Japan	Novartis Investigative Site	Toyoake-city	Aichi
Japan	Novartis Investigative Site	Yokohama	Kanagawa

Sponsors (2)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals	Ono Pharmaceutical Co. Ltd

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Patients With Adverse Events Leading to Study Drug Discontinuation	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.	Up to 24 weeks	Yes
Secondary	Change From Baseline in the Alzheimer's Disease Assessment Scale - Japan Cognitive Subscale (ADAS-J Cog)	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.	Baseline, 8,16, and 24 weeks	No
Secondary	Change From Baseline in Mini-Mental State Examination (MMSE)	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.	Baseline and 24 weeks	No
Secondary	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	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, 8, 12,16, 20 and 24 weeks	No
Secondary	The Percentage of Treatment Retention.	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	Up to 24 weeks	No