Clinical trial NCT02703636: NextStep:Study to Evaluate Safety,Efficacy & Tolerability of Rivastigmine Patch in Mild to Moderate Alzheimer's Patients.
Official title: A 24-week, Open-label, Multicenter Study to Evaluate the Efficacy, Safety and Tolerability of Rivastigmine Patch With 1-step Titration in Patients With Mild to Moderate Alzheimer's Disease (MMSE 10 - 23) Switched Directly From Holinesterase Inhibitors (Donepezil, Galantamine)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Mild to Moderate Alzheimer's Disease
Keywords: Alzheimer's disease
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-03-09
Enrollment: 118
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To evaluate the efficacy of rivastigmine patch with 1-step titration on cognitive function measured as change from baseline to week 24 in the total score of Mini-Mental State Examination (MMSE) in mild to moderate Alzheimer's disease (AD) patients who failed to benefit from other cholinesterase inhibitors (ChEIs).


Eligibility criteria: Inclusion Criteria:

1. Outpatient status at baseline.
2. Males, and females not of child-bearing potential (surgically sterile, or one year or more from last menses).
3. A diagnosis of dementia of the Alzheimer's type according to the DSM-IV criteria.
4. A clinical diagnosis of probable AD according to National Institute of Neurological and Communicative Disorders and Stroke - Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria.
5. Brain scan (magnetic resonance imaging \[MRI\], or computed tomography \[CT\]) were met diagnosis criteria conducted within 3 years prior to baseline.
6. Positron emission tomography (PET) or single photon emission computed tomography (SPECT) was met diagnosis criteria conducted within 3 years prior to baseline visit, as long as in the past a brain scan (MRI or CT) also was met.
7. MMSE score of ≥ 10 and ≤ 23 at screening and baseline.
8. Patients are currently on the oral monotherapy (donepezil, 5 mg), or galantamine (16-24 mg) for 4 weeks prior to baseline visit.
9. Patients who failed to receive enough treatment benefit from the previous treatment can be defined if the patients meet at least one of following conditions at screening and baseline (multiple choices allowed)
10. Patients who declined ≥ 2 points of MMSE despite of treatment of other oral Cholinesterase (ChE) inhibitors within initial 3-month and continued to show insufficient treatment effect until at baseline.
11. During 6 months prior to screening visit, patients who declined ≥2 points of MMSE with other oral ChE inhibitors and continued to show insufficient treatment effect until at baseline.
12. Patients who show marked worsening of BPSD, or ADL (can be defined by 1 state progression of FAST) judged by a physician despite of treatment of other oral ChE inhibitors in initial 3-month or last 6-month with other oral ChE inhibitors
13. Patients having difficulties being treated orally with ChEIs (donepezil or galantamine) by physician's judgement.
14. Poor compliance or adverse event except GI symptoms
15. Patients with swallowing difficulties.

Exclusion Criteria:

1. Any medical or neurological condition other than AD that could explain the patient's dementia (e.g., abnormal thyroid function tests, vitamin B12 or folate deficiency, posttraumatic conditions, syphilis, head injury, Huntington's disease, Parkinson's disease, subdural hematoma, normal pressure hydrocephalus, brain tumor) at baseline
2. Any other DSM-IV Axis 1 diagnosis that may interfere with the evaluation of the patient's response to study medication, including other primary neurodegenerative dementia, schizophrenia, or bipolar disorder
3. An advanced, severe, progressive, or unstable disease of any type that may interfere with efficacy and safety assessments or put the patient at special risk
4. Current diagnosis of an active skin lesion/disorder
5. Patients with a history of hypersensitivity to any ingredients of rivastigmine or carbamate derivatives
6. Each patient will be required to have a primary caregiver willing to accept responsibility for supervising treatment, assessing the patient's condition throughout the study, and for providing input into efficacy assessments.

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: MMSE Total Score: Change From Baseline to Week 8 and Week 24 (Full Analysis Set)
timeFrame: baseline, weeks 8 and 24
Secondary outcomes:
measure: MMSE Total Score: Change From Baseline to Week 8 and Week 24
timeFrame: baseline, weeks 8 and 24
measure: Change From Baseline to Week 8 in Mini-Mental State Examination (MMSE) Total Score
timeFrame: baseline and week 8
measure: Change in Neuropsychiatric Inventory - 10 Item (NPI-10) Score From Baseline to Week 8 and Week 24
timeFrame: baseline, week 8, week 24
measure: Change in QOL-AD Score From Baseline to Week 24
timeFrame: baseline and week 24
measure: Change in J-CGIC Score From Baseline and at Week 24
timeFrame: baseline and week 24
measure: Change in as Modified Crichton Scale Score From Baseline to Week 4, 8, 16 and 24
timeFrame: baseline, weeks 4, 8, 16, 24
measure: Formulation Usability Questionnaire Form Score up to Week 24
timeFrame: Up to week 24
Other outcomes:
Locations:
city: Fukuoka city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Fukuoka city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Aizuwakamatsu
country: Japan
facility: Novartis Investigative Site
state: Fukushima
city: Tsukuba-city
country: Japan
facility: Novartis Investigative Site
state: Ibaraki
city: Kita-gun
country: Japan
facility: Novartis Investigative Site
state: Kagawa
city: Sagamihara-city
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Kochi-city
country: Japan
facility: Novartis Investigative Site
state: Kochi
city: Sanjo-city
country: Japan
facility: Novartis Investigative Site
state: Niigata
city: Kurashiki-city
country: Japan
facility: Novartis Investigative Site
state: Okayama
city: Osaka-city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Suita city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Kasukabe-city
country: Japan
facility: Novartis Investigative Site
state: Saitama
city: Koshigaya-city
country: Japan
facility: Novartis Investigative Site
state: Saitama
city: Fuji city
country: Japan
facility: Novartis Investigative Site
state: Shizuoka
city: Bunkyo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Hachioji-city
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Suginami Ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Okayama
country: Japan
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: