Trial Outcomes & Findings for Randomized, Double-blind Study to Evaluate the Tolerability of 2 Different Titration Methods of Rivastigmine Patch in AD Patients (MMSE 10-20) (NCT NCT01614886)
NCT ID: NCT01614886
Last Updated: 2016-08-01
Results Overview
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.
COMPLETED
PHASE3
216 participants
Up to 24 weeks
2016-08-01
Participant Flow
Participant milestones
| Measure |
Rivastigmine Patch 1 Step
1-step titration group begins treatment with a rivastigmine patch 9 mg/day for 4 weeks, followed by a dose increase to 18 mg/day
|
Rivastigmine Patch 3 Step
3-step titration group begins 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.
|
|---|---|---|
|
Overall Study
STARTED
|
107
|
109
|
|
Overall Study
Safety Population (SAF)
|
107
|
108
|
|
Overall Study
Full Analysis Set (FAS)
|
104
|
105
|
|
Overall Study
COMPLETED
|
87
|
83
|
|
Overall Study
NOT COMPLETED
|
20
|
26
|
Reasons for withdrawal
| Measure |
Rivastigmine Patch 1 Step
1-step titration group begins treatment with a rivastigmine patch 9 mg/day for 4 weeks, followed by a dose increase to 18 mg/day
|
Rivastigmine Patch 3 Step
3-step titration group begins 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.
|
|---|---|---|
|
Overall Study
Adverse Event
|
15
|
20
|
|
Overall Study
Withdrawal by Subject
|
4
|
4
|
|
Overall Study
Death
|
1
|
0
|
|
Overall Study
Protocol deviation
|
0
|
2
|
Baseline Characteristics
Randomized, Double-blind Study to Evaluate the Tolerability of 2 Different Titration Methods of Rivastigmine Patch in AD Patients (MMSE 10-20)
Baseline characteristics by cohort
| Measure |
Rivastigmine Patch 1 Step
n=107 Participants
1-step titration group begins treatment with a rivastigmine patch 9 mg/day for 4 weeks, followed by a dose increase to 18 mg/day
|
Rivastigmine Patch 3 Step
n=109 Participants
3-step titration group begins 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.
|
Total
n=216 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
77.5 Years
STANDARD_DEVIATION 6.54 • n=5 Participants
|
77.6 Years
STANDARD_DEVIATION 5.89 • n=7 Participants
|
77.5 Years
STANDARD_DEVIATION 6.21 • n=5 Participants
|
|
Sex/Gender, Customized
Female
|
69 Participants
n=5 Participants
|
76 Participants
n=7 Participants
|
145 Participants
n=5 Participants
|
|
Sex/Gender, Customized
Male
|
38 Participants
n=5 Participants
|
32 Participants
n=7 Participants
|
70 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 24 weeksPopulation: Safety population (SAF) This population consisted of all randomized patients who received at least one dose of study medication and had at least one safety assessment after baseline.
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.
Outcome measures
| Measure |
Rivastigmine Patch 1 Step
n=107 Participants
1-step titration group begins treatment with a rivastigmine patch 9 mg/day for 4 weeks, followed by a dose increase to 18 mg/day
|
Rivastigmine Patch 3 Step
n=108 Participants
3-step titration group begins 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.
|
|---|---|---|
|
Percentage of Patients With Adverse Events Leading to Study Drug Discontinuation
|
15 Percentage of participants
|
18.5 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, 8,16, and 24 weeksPopulation: Full analysis set (FAS): includes all randomized patients who received at least one dose of study drug and had at least one pre- and post-baseline assessment for any of the efficacy variables. n is the number of patients with an assessment at baseline and the corresponding visit.
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.
Outcome measures
| Measure |
Rivastigmine Patch 1 Step
n=104 Participants
1-step titration group begins treatment with a rivastigmine patch 9 mg/day for 4 weeks, followed by a dose increase to 18 mg/day
|
Rivastigmine Patch 3 Step
n=105 Participants
3-step titration group begins 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.
|
|---|---|---|
|
Change From Baseline in the Alzheimer's Disease Assessment Scale - Japan Cognitive Subscale (ADAS-J Cog)
Week 16 (n=100, 100)
|
-1.6 Units on a scale
Standard Deviation 5.01
|
-1.2 Units on a scale
Standard Deviation 5.48
|
|
Change From Baseline in the Alzheimer's Disease Assessment Scale - Japan Cognitive Subscale (ADAS-J Cog)
Week 8 (n=99, 100)
|
-1.3 Units on a scale
Standard Deviation 3.94
|
-0.9 Units on a scale
Standard Deviation 4.49
|
|
Change From Baseline in the Alzheimer's Disease Assessment Scale - Japan Cognitive Subscale (ADAS-J Cog)
Week 24 (n=100, 100)
|
-1.6 Units on a scale
Standard Deviation 4.66
|
-1.8 Units on a scale
Standard Deviation 5.58
|
SECONDARY outcome
Timeframe: Baseline and 24 weeksPopulation: Full analysis set (FAS): The FAS includes all randomized patients who received at least one dose of study drug and had at least one pre- and post-baseline assessment for any of the efficacy variables. n is the number of patients with an assessment at baseline and the corresponding visit.
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.
Outcome measures
| Measure |
Rivastigmine Patch 1 Step
n=94 Participants
1-step titration group begins treatment with a rivastigmine patch 9 mg/day for 4 weeks, followed by a dose increase to 18 mg/day
|
Rivastigmine Patch 3 Step
n=88 Participants
3-step titration group begins 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.
|
|---|---|---|
|
Change From Baseline in Mini-Mental State Examination (MMSE)
|
0.6 Units on a scale
Standard Deviation 2.91
|
0.5 Units on a scale
Standard Deviation 3.15
|
SECONDARY outcome
Timeframe: 4, 8, 12,16, 20 and 24 weeksPopulation: Full analysis set (FAS): The FAS includes all randomized patients who received at least one dose of study drug and had at least one pre- and post-baseline assessment for any of the efficacy variables. n is the number of patients with an assessment at baseline and the corresponding visit.
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.
Outcome measures
| Measure |
Rivastigmine Patch 1 Step
n=104 Participants
1-step titration group begins treatment with a rivastigmine patch 9 mg/day for 4 weeks, followed by a dose increase to 18 mg/day
|
Rivastigmine Patch 3 Step
n=105 Participants
3-step titration group begins 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.
|
|---|---|---|
|
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
Week 16
|
35 Participants
|
31 Participants
|
|
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
Week 20
|
32 Participants
|
32 Participants
|
|
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
Week 24
|
39 Participants
|
38 Participants
|
|
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
Week 4
|
22 Participants
|
23 Participants
|
|
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
Week 8
|
35 Participants
|
26 Participants
|
|
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
Week 12
|
37 Participants
|
33 Participants
|
SECONDARY outcome
Timeframe: Up to 24 weeksPopulation: Safety population (SAF) This population consisted of all randomized patients who received at least one dose of study medication and had at least one safety assessment after baseline. Patients were analyzed according to the treatment group they were assigned to at randomization.
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
Outcome measures
| Measure |
Rivastigmine Patch 1 Step
n=107 Participants
1-step titration group begins treatment with a rivastigmine patch 9 mg/day for 4 weeks, followed by a dose increase to 18 mg/day
|
Rivastigmine Patch 3 Step
n=108 Participants
3-step titration group begins 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.
|
|---|---|---|
|
The Percentage of Treatment Retention.
|
71 Percentage of Participants
|
69.4 Percentage of Participants
|
Adverse Events
Rivastigmine Patch 1-step
Rivastigmine Patch 3-step
Serious adverse events
| Measure |
Rivastigmine Patch 1-step
n=107 participants at risk
Rivastigmine patch 1-step
|
Rivastigmine Patch 3-step
n=108 participants at risk
Rivastigmine patch 3-step
|
|---|---|---|
|
Cardiac disorders
Bradycardia
|
0.93%
1/107
|
0.00%
0/108
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/107
|
0.93%
1/108
|
|
Eye disorders
Retinal vein occlusion
|
0.93%
1/107
|
0.00%
0/108
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/107
|
0.93%
1/108
|
|
Gastrointestinal disorders
Large intestine polyp
|
0.93%
1/107
|
0.00%
0/108
|
|
General disorders
Death
|
0.93%
1/107
|
0.00%
0/108
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/107
|
0.93%
1/108
|
|
Infections and infestations
Urinary tract infection
|
0.93%
1/107
|
0.00%
0/108
|
|
Injury, poisoning and procedural complications
Cervical vertebral fracture
|
0.00%
0/107
|
0.93%
1/108
|
|
Injury, poisoning and procedural complications
Pelvic fracture
|
0.00%
0/107
|
0.93%
1/108
|
|
Injury, poisoning and procedural complications
Pneumothorax traumatic
|
0.93%
1/107
|
0.00%
0/108
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.00%
0/107
|
0.93%
1/108
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
0.93%
1/107
|
0.00%
0/108
|
|
Investigations
Liver function test abnormal
|
0.00%
0/107
|
0.93%
1/108
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/107
|
0.93%
1/108
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/107
|
0.93%
1/108
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer
|
0.00%
0/107
|
0.93%
1/108
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.93%
1/107
|
0.00%
0/108
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
0.00%
0/107
|
0.93%
1/108
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.93%
1/107
|
0.00%
0/108
|
|
Nervous system disorders
Dyslalia
|
0.00%
0/107
|
0.93%
1/108
|
Other adverse events
| Measure |
Rivastigmine Patch 1-step
n=107 participants at risk
Rivastigmine patch 1-step
|
Rivastigmine Patch 3-step
n=108 participants at risk
Rivastigmine patch 3-step
|
|---|---|---|
|
Gastrointestinal disorders
Constipation
|
2.8%
3/107
|
1.9%
2/108
|
|
Gastrointestinal disorders
Diarrhoea
|
4.7%
5/107
|
2.8%
3/108
|
|
Gastrointestinal disorders
Nausea
|
3.7%
4/107
|
5.6%
6/108
|
|
Gastrointestinal disorders
Vomiting
|
4.7%
5/107
|
2.8%
3/108
|
|
General disorders
Application site dermatitis
|
3.7%
4/107
|
2.8%
3/108
|
|
General disorders
Application site erythema
|
15.9%
17/107
|
15.7%
17/108
|
|
General disorders
Application site pruritus
|
22.4%
24/107
|
22.2%
24/108
|
|
General disorders
Application site rash
|
2.8%
3/107
|
5.6%
6/108
|
|
Infections and infestations
Gastroenteritis
|
1.9%
2/107
|
2.8%
3/108
|
|
Infections and infestations
Influenza
|
2.8%
3/107
|
0.00%
0/108
|
|
Infections and infestations
Nasopharyngitis
|
8.4%
9/107
|
11.1%
12/108
|
|
Injury, poisoning and procedural complications
Contusion
|
1.9%
2/107
|
2.8%
3/108
|
|
Investigations
Electrocardiogram QT prolonged
|
0.93%
1/107
|
2.8%
3/108
|
|
Investigations
Weight decreased
|
3.7%
4/107
|
1.9%
2/108
|
|
Metabolism and nutrition disorders
Decreased appetite
|
4.7%
5/107
|
4.6%
5/108
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.93%
1/107
|
2.8%
3/108
|
|
Psychiatric disorders
Restlessness
|
3.7%
4/107
|
0.93%
1/108
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
12.1%
13/107
|
11.1%
12/108
|
|
Skin and subcutaneous tissue disorders
Eczema
|
1.9%
2/107
|
2.8%
3/108
|
|
Vascular disorders
Hypertension
|
2.8%
3/107
|
4.6%
5/108
|
Additional Information
Study Director
Novartis Pharmaceuticals
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 (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety
- Publication restrictions are in place
Restriction type: OTHER