Trial Outcomes & Findings for NextStep:Study to Evaluate Safety,Efficacy & Tolerability of Rivastigmine Patch in Mild to Moderate Alzheimer's Patients. (NCT NCT02703636)
NCT ID: NCT02703636
Last Updated: 2019-09-12
Results Overview
Evaluation of 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 MMSE in mild to moderate Alzheimer's disease (AD) patients who failed to benefit from other cholinesterase inhibitors (ChEIs) The MMSE is a screening test for cognitive dysfunction. The test consists of five sections (orientation, registration, attention-calculation, recall, and language); the total score can range from 0 to 30, with a higher score indicating better function. A positive change score indicates improvement from baseline. Abbreviated Scale title: Mini Mental State Evaluation Minimum Score: 0 Maximum score: 30 Higher score indicated better cognitive function
COMPLETED
PHASE4
118 participants
baseline, weeks 8 and 24
2019-09-12
Participant Flow
The full analysis set (FAS) included all patients who received at least one dose of study treatment and had at least a baseline and any post-baseline assessment on treatment.
In total, 147 patients were screened for the study. 129 completed screening and 18 discontinued from screening. 118 patients were enrolled and the remaining 11 patients discontinued at baseline. All 118 enrolled patients received study treatment. 102 completed the study and 16 discontinued
Participant milestones
| Measure |
Rivastigmine Patch
Alzheimer's disease patient who is applicable to 1 step titration method (initial loading dose is a rivastigmine patch 9.0 mg/day and was up-titrated after 4 weeks to reach the maintenance dose of 18 mg/day). Rivastigmine patch is a marketed drug, therefore the dose, dose regimen and titration scheme are in accordance with product label.
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|---|---|
|
Overall Study
STARTED
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118
|
|
Overall Study
COMPLETED
|
102
|
|
Overall Study
NOT COMPLETED
|
16
|
Reasons for withdrawal
| Measure |
Rivastigmine Patch
Alzheimer's disease patient who is applicable to 1 step titration method (initial loading dose is a rivastigmine patch 9.0 mg/day and was up-titrated after 4 weeks to reach the maintenance dose of 18 mg/day). Rivastigmine patch is a marketed drug, therefore the dose, dose regimen and titration scheme are in accordance with product label.
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|---|---|
|
Overall Study
Adverse Event
|
14
|
|
Overall Study
Study stopped by sponsor
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
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Baseline Characteristics
NextStep:Study to Evaluate Safety,Efficacy & Tolerability of Rivastigmine Patch in Mild to Moderate Alzheimer's Patients.
Baseline characteristics by cohort
| Measure |
Rivastigmine Patch
n=118 Participants
Alzheimer's disease patient who is applicable to 1 step titration method (initial loading dose is a rivastigmine patch 9.0 mg/day and was up-titrated after 4 weeks to reach the maintenance dose of 18 mg/day). Rivastigmine patch is a marketed drug, therefore the dose, dose regimen and titration scheme are in accordance with product label.
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|---|---|
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Age, Continuous
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76.4 years
STANDARD_DEVIATION 6.43 • n=5 Participants
|
|
Sex: Female, Male
Female
|
71 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
47 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
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117 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: baseline, weeks 8 and 24Population: The full analysis set (FAS) included all patients who received at least one dose of study treatment and had at least a baseline and any post-baseline assessment on treatment
Evaluation of 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 MMSE in mild to moderate Alzheimer's disease (AD) patients who failed to benefit from other cholinesterase inhibitors (ChEIs) The MMSE is a screening test for cognitive dysfunction. The test consists of five sections (orientation, registration, attention-calculation, recall, and language); the total score can range from 0 to 30, with a higher score indicating better function. A positive change score indicates improvement from baseline. Abbreviated Scale title: Mini Mental State Evaluation Minimum Score: 0 Maximum score: 30 Higher score indicated better cognitive function
Outcome measures
| Measure |
Rivastigmine Patch
n=118 Participants
Alzheimer's disease patient who is applicable to 1 step titration method (initial loading dose is a rivastigmine patch 9.0 mg/day and was up-titrated after 4 weeks to reach the maintenance dose of 18 mg/day). Rivastigmine patch is a marketed drug, therefore the dose, dose regimen and titration scheme are in accordance with product label.
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|---|---|
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MMSE Total Score: Change From Baseline to Week 8 and Week 24 (Full Analysis Set)
baseline
|
17.33 scores on a scale
Standard Deviation 3.80
|
|
MMSE Total Score: Change From Baseline to Week 8 and Week 24 (Full Analysis Set)
change at week 8
|
0.29 scores on a scale
Standard Deviation 2.17
|
|
MMSE Total Score: Change From Baseline to Week 8 and Week 24 (Full Analysis Set)
change at week 24
|
-0.36 scores on a scale
Standard Deviation 2.64
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SECONDARY outcome
Timeframe: baseline, weeks 8 and 24Population: Per Protocol Set (PPS): The per protocol set includes all patients in the FAS who had only 1 step titration without any major deviations from the protocol procedures
Evaluation of the safety, tolerability of rivastigmine patch with 1-step titration for up to 24 weeks. Per Protocol, The MMSE is a brief, practical screening test for cognitive dysfunction. The MMSE consists of 2 parts: language (time orientation, registration and attention) and performance (recall, response to written/verbal commands, writing ability and reproduction of complex polygons), and the total possible score is 30. Lower score indicates more severe impairment. It is the most common and simple cognitive scale for Alzheimer's disease. Unabbreviated Scale : MMSE - Mini Mental State Evaluation: Minimum values - 0 Maximum value - 30 Higher Value means a better outcome Positive change score from baseline indicates improvement in cognitive function
Outcome measures
| Measure |
Rivastigmine Patch
n=118 Participants
Alzheimer's disease patient who is applicable to 1 step titration method (initial loading dose is a rivastigmine patch 9.0 mg/day and was up-titrated after 4 weeks to reach the maintenance dose of 18 mg/day). Rivastigmine patch is a marketed drug, therefore the dose, dose regimen and titration scheme are in accordance with product label.
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|---|---|
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MMSE Total Score: Change From Baseline to Week 8 and Week 24
week 24
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-0.32 scores on a scale
Standard Deviation 2.63
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|
MMSE Total Score: Change From Baseline to Week 8 and Week 24
baseline
|
17.24 scores on a scale
Standard Deviation 3.84
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|
MMSE Total Score: Change From Baseline to Week 8 and Week 24
week 8
|
0.33 scores on a scale
Standard Deviation 2.19
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SECONDARY outcome
Timeframe: baseline and week 8Population: FAS
Evaluation of the efficacy of rivastigmine patch with 1-step titration measured as the MMSE score at week 8 for patients who had 1-step titration MMSE total score: change from baseline to Week 8 and Week 24 for patients who had 1-step titration Unabbreviated Scale : MMSE - Mini Mental State Evaluation: Minimum values - 0 Maximum value - 30 Higher Value means a better outcome Positive change score from baseline indicates better outcome
Outcome measures
| Measure |
Rivastigmine Patch
n=114 Participants
Alzheimer's disease patient who is applicable to 1 step titration method (initial loading dose is a rivastigmine patch 9.0 mg/day and was up-titrated after 4 weeks to reach the maintenance dose of 18 mg/day). Rivastigmine patch is a marketed drug, therefore the dose, dose regimen and titration scheme are in accordance with product label.
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|---|---|
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Change From Baseline to Week 8 in Mini-Mental State Examination (MMSE) Total Score
week 8
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0.31 scores on a scale
Standard Deviation 2.18
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Change From Baseline to Week 8 in Mini-Mental State Examination (MMSE) Total Score
baseline
|
17.25 scores on a scale
Standard Deviation 3.82
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SECONDARY outcome
Timeframe: baseline, week 8, week 24Population: FAS The number of participants analysed per row differs from overall number of participants because this is based on available data and patient continuation/discontinuation during that respective study period.
Evaluation of the efficacy of rivastigmine patch with 1-step titration measured as the Neuropsychiatric Inventory - 10 Item (NPI-10) score at week 8 and week 24. Per protocol, Neuropsychiatric The NPI-10 total score is a sum of the 10 items, where the score for a domain is defined as the product of frequency (range: 1-4) and severity (range: 1-3). Each domain has a maximum score of 12 and all domains are equally weighted for the total score (thus the range for the total score is 0 to 120). A higher score indicates more severe impairment. Neuropsychiatry Inventory - 10 Minimum Score = 0 Maximum Score = 120 Higher Score indicates worse outcome
Outcome measures
| Measure |
Rivastigmine Patch
n=118 Participants
Alzheimer's disease patient who is applicable to 1 step titration method (initial loading dose is a rivastigmine patch 9.0 mg/day and was up-titrated after 4 weeks to reach the maintenance dose of 18 mg/day). Rivastigmine patch is a marketed drug, therefore the dose, dose regimen and titration scheme are in accordance with product label.
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|---|---|
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Change in Neuropsychiatric Inventory - 10 Item (NPI-10) Score From Baseline to Week 8 and Week 24
week 24
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-0.89 scores on a scale
Standard Deviation 11.10
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Change in Neuropsychiatric Inventory - 10 Item (NPI-10) Score From Baseline to Week 8 and Week 24
baseline
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11.43 scores on a scale
Standard Deviation 11.15
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Change in Neuropsychiatric Inventory - 10 Item (NPI-10) Score From Baseline to Week 8 and Week 24
week 8
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-1.81 scores on a scale
Standard Deviation 8.81
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SECONDARY outcome
Timeframe: baseline and week 24Population: FAS The number of participants analysed per row differs from overall number of participants because this is based on available data and patient continuation/discontinuation during that respective study period.
Evaluation of the efficacy of rivastigmine patch with 1-step titration measured as QOL-AD score at week 24. Unabbreviated Scale Name: Quality of Life - Alzheimer's Disease Minimum Score = 13 Maximum Score = 52 Higher value indicates a better outcome QOL-AD is a 13-item questionnaire to assess the quality of life of Alzheimer's patients from the perspectives of patients and their caregivers. It covers several aspects, for example, the perception of health status, mood, functional capacity, personal relationships and leisure, financial situation, and life as a whole. Each item is quantified using a Likert scale with score one classified as poor, and score four as excellent where total scores range from 13 to 52. A lower score indicates more severe impairment.
Outcome measures
| Measure |
Rivastigmine Patch
n=118 Participants
Alzheimer's disease patient who is applicable to 1 step titration method (initial loading dose is a rivastigmine patch 9.0 mg/day and was up-titrated after 4 weeks to reach the maintenance dose of 18 mg/day). Rivastigmine patch is a marketed drug, therefore the dose, dose regimen and titration scheme are in accordance with product label.
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|---|---|
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Change in QOL-AD Score From Baseline to Week 24
baseline - Patient's assessment
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34.37 scores on a scale
Standard Deviation 5.78
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Change in QOL-AD Score From Baseline to Week 24
week 24 - Patient's assessment
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-0.34 scores on a scale
Standard Deviation 5.32
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Change in QOL-AD Score From Baseline to Week 24
baseline - Caregiver's assessment
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28.75 scores on a scale
Standard Deviation 5.74
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Change in QOL-AD Score From Baseline to Week 24
week 24 - Caregiver's assessment
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-0.16 scores on a scale
Standard Deviation 5.42
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SECONDARY outcome
Timeframe: baseline and week 24Population: FAS
Evaluation of the efficacy of rivastigmine patch with 1-step titration measured as the The Japanese-Clinical Global Impression of Change (J-CGIC) score at baseline and week 24 J-CGIC is a 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 At week 24, 103 patients had available data Total score is in the 0 to 56 range. Higher score means more severe impairment. Unabbreviated scale title: Japanese -Cinical Global Impression of Change Minimum Score - 1 Maximum Score - 7
Outcome measures
| Measure |
Rivastigmine Patch
n=103 Participants
Alzheimer's disease patient who is applicable to 1 step titration method (initial loading dose is a rivastigmine patch 9.0 mg/day and was up-titrated after 4 weeks to reach the maintenance dose of 18 mg/day). Rivastigmine patch is a marketed drug, therefore the dose, dose regimen and titration scheme are in accordance with product label.
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|---|---|
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Change in J-CGIC Score From Baseline and at Week 24
Patients without worsening, total
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91 Participants
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Change in J-CGIC Score From Baseline and at Week 24
Patients with improvement
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48 Participants
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|
Change in J-CGIC Score From Baseline and at Week 24
Patients with worsening, total
|
12 Participants
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|
Change in J-CGIC Score From Baseline and at Week 24
Markedly improved
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3 Participants
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Change in J-CGIC Score From Baseline and at Week 24
Improved
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6 Participants
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|
Change in J-CGIC Score From Baseline and at Week 24
Slightly improved
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39 Participants
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|
Change in J-CGIC Score From Baseline and at Week 24
No change
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43 Participants
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|
Change in J-CGIC Score From Baseline and at Week 24
Slightly aggravated
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11 Participants
|
|
Change in J-CGIC Score From Baseline and at Week 24
Aggravated
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1 Participants
|
|
Change in J-CGIC Score From Baseline and at Week 24
Markedly aggravated
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0 Participants
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Change in J-CGIC Score From Baseline and at Week 24
Unassessable
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0 Participants
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SECONDARY outcome
Timeframe: baseline, weeks 4, 8, 16, 24Population: FAS The number of participants analysed per row (modified crichton scale) differs from overall number of participants because this is based on available data and patient continuation/discontinuation during that respective study period.
Evaluation of the efficacy of rivastigmine patch with 1-step titration measured as Modified Crichton Scale score week 4, week 8, week 16, and week 24. Modified Crichton Scale that assess basic activation of daily living, communication functions, and quality of life The following 7 items will be evaluated by caregiver. Total score is in the 0 to 56 range. Higher score means more severe impairment. Unabbreviated Scale Title: Modified Crichton scale Minimum score = 0 Maximum Score = 56 Higher score indicates worse outcome
Outcome measures
| Measure |
Rivastigmine Patch
n=118 Participants
Alzheimer's disease patient who is applicable to 1 step titration method (initial loading dose is a rivastigmine patch 9.0 mg/day and was up-titrated after 4 weeks to reach the maintenance dose of 18 mg/day). Rivastigmine patch is a marketed drug, therefore the dose, dose regimen and titration scheme are in accordance with product label.
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|---|---|
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Change in as Modified Crichton Scale Score From Baseline to Week 4, 8, 16 and 24
baseline
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18.38 scores on a scale
Standard Deviation 9.41
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Change in as Modified Crichton Scale Score From Baseline to Week 4, 8, 16 and 24
week 4
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-0.41 scores on a scale
Standard Deviation 5.44
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Change in as Modified Crichton Scale Score From Baseline to Week 4, 8, 16 and 24
week 8
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-0.55 scores on a scale
Standard Deviation 6.58
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Change in as Modified Crichton Scale Score From Baseline to Week 4, 8, 16 and 24
week 16
|
1.04 scores on a scale
Standard Deviation 6.94
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Change in as Modified Crichton Scale Score From Baseline to Week 4, 8, 16 and 24
week 24
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2.23 scores on a scale
Standard Deviation 6.69
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SECONDARY outcome
Timeframe: Up to week 24Population: FAS
Evaluation of the formulation usability of rivastigmine patch for up to 24 weeks as measured by the formulation usability questionnaire answered by caregiver. The Formulation usability preference questionnaire had been used to compare the previous oral AD drugs versus the patch The caregiver selects one of the following answers (1. Very easy to use, 2. Easy to use, 3. No change, 4. Not easy to use, 5. Not easy to use at all, 6. Unknown). This questionnaire data is used to assess if the usability of rivastigmine patch was preferred by the majority (\> 50%) of AD patient caregivers or not. Unabbreviated Questionnaire title: Formulation Usability questionnaire Minimum Score = 1 Maximum Score = 6 A higher score indicates its not easy to use and worse outcome.
Outcome measures
| Measure |
Rivastigmine Patch
n=117 Participants
Alzheimer's disease patient who is applicable to 1 step titration method (initial loading dose is a rivastigmine patch 9.0 mg/day and was up-titrated after 4 weeks to reach the maintenance dose of 18 mg/day). Rivastigmine patch is a marketed drug, therefore the dose, dose regimen and titration scheme are in accordance with product label.
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|---|---|
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Formulation Usability Questionnaire Form Score up to Week 24
Easy to use
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26 Participants
|
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Formulation Usability Questionnaire Form Score up to Week 24
Very easy to use
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38 Participants
|
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Formulation Usability Questionnaire Form Score up to Week 24
No change
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12 Participants
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|
Formulation Usability Questionnaire Form Score up to Week 24
Not easy to use
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36 Participants
|
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Formulation Usability Questionnaire Form Score up to Week 24
Not easy to use at all
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5 Participants
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Adverse Events
Exelon/Rivastigmine Patch
Serious adverse events
| Measure |
Exelon/Rivastigmine Patch
n=118 participants at risk
Alzheimer's disease patient who is applicable to 1 step titration method (initial loading dose is a rivastigmine patch 9.0 mg/day and was up-titrated after 4 weeks to reach the maintenance dose of 18 mg/day). Rivastigmine patch is a marketed drug, therefore the dose, dose regimen and titration scheme are in accordance with product label.
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|---|---|
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Gastrointestinal disorders
Ileus
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0.85%
1/118 • up to week 24
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Gastrointestinal disorders
Pancreatitis acute
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0.85%
1/118 • up to week 24
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|
Infections and infestations
Herpes zoster
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0.85%
1/118 • up to week 24
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|
Infections and infestations
Pneumonia
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0.85%
1/118 • up to week 24
|
|
Metabolism and nutrition disorders
Dehydration
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0.85%
1/118 • up to week 24
|
|
Metabolism and nutrition disorders
Hypoglycaemia
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0.85%
1/118 • up to week 24
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
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0.85%
1/118 • up to week 24
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.85%
1/118 • up to week 24
|
Other adverse events
| Measure |
Exelon/Rivastigmine Patch
n=118 participants at risk
Alzheimer's disease patient who is applicable to 1 step titration method (initial loading dose is a rivastigmine patch 9.0 mg/day and was up-titrated after 4 weeks to reach the maintenance dose of 18 mg/day). Rivastigmine patch is a marketed drug, therefore the dose, dose regimen and titration scheme are in accordance with product label.
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|---|---|
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General disorders
Application site erythema
|
7.6%
9/118 • up to week 24
|
|
General disorders
Application site pruritus
|
8.5%
10/118 • up to week 24
|
|
Infections and infestations
Nasopharyngitis
|
10.2%
12/118 • up to week 24
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
15.3%
18/118 • up to week 24
|
|
Skin and subcutaneous tissue disorders
Erythema
|
8.5%
10/118 • up to week 24
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
8.5%
10/118 • up to week 24
|
|
Skin and subcutaneous tissue disorders
Rash
|
5.1%
6/118 • up to week 24
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER