Alzheimer's DiseasePhase 3NCT01614886
Randomized, Double-blind Study to Evaluate the Tolerability of 2 Different Titration Methods of Rivastigmine Patch in AD Patients (MMSE 10-20)
A Phase 3 study testing Active Comparator and ENA713 in people with Alzheimer's Disease, run by Novartis Pharmaceuticals at 50 sites in Japan.
Trial summary
To evaluate the tolerability, safety and efficacy of 3-step titration versus 1-step titration of Rivastigmine patch in the Japanese population. Read more about this study
- Who is it for?
- Ages 50 to 85 years
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- Active Comparator and ENA713
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 216 participants
- Where
- 50 sitesJapan
- Study dates
- Jul 2012to May 2014
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
50 sites in 1 country.
50 sites in 1 country
Japan50 sites
Novartis Investigative Site
Akita, Akita, 010-0874
Novartis Investigative Site
Anjo, Aichi-ken, 446-8510
Novartis Investigative Site
Azumino, Nagano, 399-8204
Novartis Investigative Site
Bunkyo-ku, Tokyo, 113-8603
Novartis Investigative Site
Chiba, Chiba, 260-8712
Novartis Investigative Site
Fujioka, Gunma, 375-0017
Novartis Investigative Site
Fukuoka, Fukuoka, 814-0180
Novartis Investigative Site
Hachiōji, Tokyo, 193-0998
Novartis Investigative Site
Hiroshima, Hiroshima, 734-8530
Novartis Investigative Site
Kamakura, Kanagawa, 247-8533
Novartis Investigative Site
Kanzaki-gun, Saga-ken, 842-0192
Novartis Investigative Site
Kasama, Ibaraki, 309-1793
Novartis Investigative Site
Kasukabe, Saitama, 344-0036
Novartis Investigative Site
Kawaguchi, Saitama, 333-0832
Novartis Investigative Site
Kawasaki, Kanagawa, 212-0016
Novartis Investigative Site
Kawasaki, Kanagawa, 216-8511
Novartis Investigative Site
Kitamorokata-gun, Miyazaki, 889-1911
Novartis Investigative Site
Kochi, Kochi, 780-0842
Novartis Investigative Site
Kochi, Kochi, 780-8037
Novartis Investigative Site
Kōshi, Kumamoto, 861-1116
Novartis Investigative Site
Koshigaya, Saitama, 343-0032
Novartis Investigative Site
Koto-ku, Tokyo, 136-0075
Novartis Investigative Site
Kumamoto, Kumamoto, 860-8556
Novartis Investigative Site
Kumamoto, Kumamoto, 861-8002
Novartis Investigative Site
Kurashiki, Okayama-ken, 710-0826
Novartis Investigative Site
Kyoto, Kyoto, 600-8558
Novartis Investigative Site
Kyoto, Kyoto, 607-8411
Novartis Investigative Site
Kyoto, Kyoto, 616-8255
Novartis Investigative Site
Matsumoto, Nagano, 399-8701
Novartis Investigative Site
Miyoshi, Hiroshima, 728-0013
Novartis Investigative Site
Musashino, Tokyo, 180-8610
Novartis Investigative Site
Nagaoka, Niigata, 940-2302
Novartis Investigative Site
Ōbu, Aichi-ken, 474-8511
Novartis Investigative Site
Okayama, Okayama-ken, 700-8607
Novartis Investigative Site
Ōta-ku, Tokyo, 143-0016
Novartis Investigative Site
Sagamihara, Kanagawa, 252-5188
Novartis Investigative Site
Saitama, Saitama, 338-0003
Novartis Investigative Site
Sakai, Osaka, 590-0018
Novartis Investigative Site
Sendai, Miyagi, 982-8523
Novartis Investigative Site
Seto, Aichi-ken, 489-8642
Novartis Investigative Site
Shimonoseki, Yamaguchi, 752-8510
Novartis Investigative Site
Shizuoka, Shizuoka, 420-8688
Novartis Investigative Site
Shizuoka, Shizuoka, 424-8636
Novartis Investigative Site
Suita, Osaka, 565-0871
Novartis Investigative Site
Suita, Osaka, 565-0874
Novartis Investigative Site
Tachikawa, Tokyo, 190-8531
Novartis Investigative Site
Tokushima, Tokushima, 770-8503
Novartis Investigative Site
Tōon, Ehime, 791-0295
Novartis Investigative Site
Toyoake, Aichi-ken, 470-1168
Novartis Investigative Site
Yokohama, Kanagawa, 241-0811
About this study
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)
To evaluate the tolerability, safety and efficacy of 3-step titration versus 1-step titration of Rivastigmine patch in the Japanese population.
- Conditions
- Alzheimer's Disease
- Being tested
- Active Comparator, ENA713
- Keywords
- Rivastigmine, Alzheimer's disease, Transdermal patch
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active ComparatorDrug
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.
ENA713Drug
-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.
| Study group | Role | What they receive |
|---|---|---|
| 1 step | Experimental | Not described Receives: Drug: Active Comparator |
| 3 step | Active comparator | Not described Receives: Drug: ENA713 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 24 weeks
Secondary outcomes (4)
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.
Measured: Baseline, 8,16, and 24 weeks
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.
Measured: Baseline and 24 weeks
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.
Measured: 4, 8, 12,16, 20 and 24 weeks
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
Measured: Up to 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2012 (estimated)
- Study startJul 2012
- Primary completionMay 2014
- Study completionMay 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 216 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Ono Pharmaceutical Co., Ltd.
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01614886
- Sponsor's protocol ID
- CENA713D1303
- Status last verified
- Jun 2015
- First submitted
- 6 Jun 2012
- Last updated
- 1 Aug 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01614886
- Acronym / sponsor ID
- CENA713D1303
- Conditions
- Alzheimer's Disease
- Keywords
- Rivastigmine, Alzheimer's disease, Transdermal patch
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 216 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Collaborators
- Ono Pharmaceutical Co., Ltd.
- Study start
- Jul 2012
- Primary completion
- May 2014 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 8 Jun 2012 (estimated)
- Results
- Posted 12 May 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate the tolerability, safety and efficacy of 3-step titration versus 1-step titration of Rivastigmine patch in the Japanese population.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 step | Experimental | Drug: Active Comparator |
| 3 step | Active comparator | Drug: ENA713 |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Active Comparator1-step titration group begin treatment with a rivastigmine patch 9 mg/day for 4 weeks, followed by a dose increase to 18 mg/day. | Drug | 1 step |
| 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. | Drug | 3 step |
Primary outcome
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.
4 secondary outcomes
Change From Baseline in the Alzheimer's Disease Assessment Scale - Japan Cognitive Subscale (ADAS-J Cog)
Time frame: Baseline, 8,16, and 24 weeks
Change From Baseline in Mini-Mental State Examination (MMSE)
Time frame: Baseline and 24 weeks
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 Percentage of Treatment Retention.
Time frame: Up to 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
50 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Active Comparator and ENA713 in people with Alzheimer's Disease, run by Novartis Pharmaceuticals at 50 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 50 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 May 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Patients With Adverse Events Leading to Study Drug Discontinuation (time frame: Up to 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2016.