Trial Outcomes & Findings for Convenience, Tolerability, and Safety of Change in the Administration of Rivastigmine From Capsules to a Transdermal Patch in Patients With Mild to Moderate Alzheimer's Disease (NCT NCT00549601)
NCT ID: NCT00549601
Last Updated: 2011-03-24
Results Overview
Gastrointestinal adverse events (including nausea, vomiting, and diarrhea) were coded using the medical dictionary MedDRA v11.0 and the number of patients who suffered an AE were described by system organ class (SOC) and preferred term (PT).
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
142 participants
Primary outcome timeframe
Baseline to end of study (Month 3)
Results posted on
2011-03-24
Participant Flow
Participant milestones
| Measure |
Rivastigmine Patch (4.6 mg/Day Switch to 9.5 mg/Day)
Rivastigmine administered transdermally via patches at increasing doses (1 patch/day of 4.6 mg for the first month, changing to 1 patch/day of 9.5 mg for the remaining two months).
|
Rivastigmine Patch (9.5 mg/Day)
Rivastigmine administered transdermally via patches at a constant dose (9.5 mg/day for the 3 months of treatment).
|
Rivastigmine Capsules (6 mg to 12 mg/Day)
Rivastigmine administered orally, following the same regime as prior to randomization (doses between 6 mg and 12 mg/day), which remained unchanged throughout the 3 months of treatment.
|
|---|---|---|---|
|
Randomized
STARTED
|
43
|
48
|
51
|
|
Randomized
COMPLETED
|
43
|
47
|
49
|
|
Randomized
NOT COMPLETED
|
0
|
1
|
2
|
|
Received Study Drug
STARTED
|
43
|
47
|
49
|
|
Received Study Drug
COMPLETED
|
36
|
36
|
45
|
|
Received Study Drug
NOT COMPLETED
|
7
|
11
|
4
|
Reasons for withdrawal
| Measure |
Rivastigmine Patch (4.6 mg/Day Switch to 9.5 mg/Day)
Rivastigmine administered transdermally via patches at increasing doses (1 patch/day of 4.6 mg for the first month, changing to 1 patch/day of 9.5 mg for the remaining two months).
|
Rivastigmine Patch (9.5 mg/Day)
Rivastigmine administered transdermally via patches at a constant dose (9.5 mg/day for the 3 months of treatment).
|
Rivastigmine Capsules (6 mg to 12 mg/Day)
Rivastigmine administered orally, following the same regime as prior to randomization (doses between 6 mg and 12 mg/day), which remained unchanged throughout the 3 months of treatment.
|
|---|---|---|---|
|
Randomized
Protocol Violation
|
0
|
0
|
1
|
|
Randomized
Withdrawal by Subject
|
0
|
1
|
1
|
|
Received Study Drug
Adverse Event
|
2
|
5
|
1
|
|
Received Study Drug
Death
|
0
|
1
|
0
|
|
Received Study Drug
Lost to Follow-up
|
0
|
1
|
1
|
|
Received Study Drug
Protocol Violation
|
3
|
4
|
1
|
|
Received Study Drug
Withdrawal by Subject
|
2
|
0
|
1
|
Baseline Characteristics
Convenience, Tolerability, and Safety of Change in the Administration of Rivastigmine From Capsules to a Transdermal Patch in Patients With Mild to Moderate Alzheimer's Disease
Baseline characteristics by cohort
| Measure |
Rivastigmine Patch (4.6 mg/Day Switch to 9.5 mg/Day)
n=43 Participants
Rivastigmine administered transdermally via patches at increasing doses (1 patch/day of 4.6 mg for the first month, changing to 1 patch/day of 9.5 mg for the remaining two months).
|
Rivastigmine Patch (9.5 mg/Day)
n=47 Participants
Rivastigmine administered transdermally via patches at a constant dose (9.5 mg/day for the 3 months of treatment).
|
Rivastigmine Capsules (6 mg to 12 mg/Day)
n=49 Participants
Rivastigmine administered orally, following the same regime as prior to randomization (doses between 6 mg and 12 mg/day), which remained unchanged throughout the 3 months of treatment.
|
Total
n=139 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age Continuous
|
77.05 years
STANDARD_DEVIATION 4.82 • n=99 Participants
|
75.34 years
STANDARD_DEVIATION 7.25 • n=107 Participants
|
77.35 years
STANDARD_DEVIATION 6.62 • n=206 Participants
|
76.58 years
STANDARD_DEVIATION 6.37 • n=7 Participants
|
|
Sex: Female, Male
Female
|
30 Participants
n=99 Participants
|
29 Participants
n=107 Participants
|
25 Participants
n=206 Participants
|
84 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=99 Participants
|
18 Participants
n=107 Participants
|
24 Participants
n=206 Participants
|
55 Participants
n=7 Participants
|
PRIMARY outcome
Timeframe: Baseline to end of study (Month 3)Population: The Safety population included all randomized patients who received at least one dose of the study medication.
Gastrointestinal adverse events (including nausea, vomiting, and diarrhea) were coded using the medical dictionary MedDRA v11.0 and the number of patients who suffered an AE were described by system organ class (SOC) and preferred term (PT).
Outcome measures
| Measure |
Rivastigmine Patch (4.6 mg/Day Switch to 9.5 mg/Day)
n=43 Participants
Rivastigmine administered transdermally via patches at increasing doses (1 patch/day of 4.6 mg for the first month, changing to 1 patch/day of 9.5 mg for the remaining two months).
|
Rivastigmine Patch (9.5 mg/Day)
n=47 Participants
Rivastigmine administered transdermally via patches at a constant dose (9.5 mg/day for the 3 months of treatment).
|
Rivastigmine Capsules (6 mg to 12 mg/Day)
n=49 Participants
Rivastigmine administered orally, following the same regime as prior to randomization (doses between 6 mg and 12 mg/day), which remained unchanged throughout the 3 months of treatment.
|
|---|---|---|---|
|
Percentage of Patients Who Had a Gastrointestinal Adverse Event (AE) at Any Time During the Study
|
4.65 Percentage of participants
4.65
|
4.26 Percentage of participants
4.26
|
6.12 Percentage of participants
6.12
|
SECONDARY outcome
Timeframe: Baseline to end of study (Month 3)Population: The Safety population included all randomized patients who received at least one dose of the study medication.
Adverse events involving the skin included urticaria, pruritus, erythema, and pigmentation disorder. Only the groups administered rivastigmine transdermally via patch were analyzed. The adverse events were coded using the medical dictionary MedDRA v11.0 and the number of patients who suffered an AE were described by system organ class (SOC) and preferred term (PT).
Outcome measures
| Measure |
Rivastigmine Patch (4.6 mg/Day Switch to 9.5 mg/Day)
n=43 Participants
Rivastigmine administered transdermally via patches at increasing doses (1 patch/day of 4.6 mg for the first month, changing to 1 patch/day of 9.5 mg for the remaining two months).
|
Rivastigmine Patch (9.5 mg/Day)
n=47 Participants
Rivastigmine administered transdermally via patches at a constant dose (9.5 mg/day for the 3 months of treatment).
|
Rivastigmine Capsules (6 mg to 12 mg/Day)
Rivastigmine administered orally, following the same regime as prior to randomization (doses between 6 mg and 12 mg/day), which remained unchanged throughout the 3 months of treatment.
|
|---|---|---|---|
|
Percentage of Patients With an AE Involving the Skin (Local Tolerance) Recorded Over the Course of the Study Period (Patch Groups Only)
|
11.63 Percentage of participants
11.63
|
17.02 Percentage of participants
17.02
|
—
|
SECONDARY outcome
Timeframe: Baseline to end of study (Month 3)Population: The Safety population included all randomized patients who received at least one dose of the study medication.
Adverse events were coded using the medical dictionary MedDRA v11.0 and the number of patients who suffered an AE were described by system organ class (SOC) and preferred term (PT). They were also tabulated by severity, relationship with study treatment, and action taken.
Outcome measures
| Measure |
Rivastigmine Patch (4.6 mg/Day Switch to 9.5 mg/Day)
n=43 Participants
Rivastigmine administered transdermally via patches at increasing doses (1 patch/day of 4.6 mg for the first month, changing to 1 patch/day of 9.5 mg for the remaining two months).
|
Rivastigmine Patch (9.5 mg/Day)
n=47 Participants
Rivastigmine administered transdermally via patches at a constant dose (9.5 mg/day for the 3 months of treatment).
|
Rivastigmine Capsules (6 mg to 12 mg/Day)
n=49 Participants
Rivastigmine administered orally, following the same regime as prior to randomization (doses between 6 mg and 12 mg/day), which remained unchanged throughout the 3 months of treatment.
|
|---|---|---|---|
|
Percentage of Patients With at Least 1 AE of Any Kind Recorded During the Period of the Study.
|
48.84 Percentage of participants
48.84
|
55.32 Percentage of participants
55.32
|
53.06 Percentage of participants
53.06
|
SECONDARY outcome
Timeframe: At end of study (Month 3)Population: The Safety population included all randomized patients who received at least one dose of the study medication.
Caregivers were asked to rate their overall degree of satisfaction with the Alzheimer's disease treatment on a scale of 1 to 5 (1 "Very good" - 5 "Very poor") at the end of the study (Month 3). A higher score indicates less satisfaction.
Outcome measures
| Measure |
Rivastigmine Patch (4.6 mg/Day Switch to 9.5 mg/Day)
n=43 Participants
Rivastigmine administered transdermally via patches at increasing doses (1 patch/day of 4.6 mg for the first month, changing to 1 patch/day of 9.5 mg for the remaining two months).
|
Rivastigmine Patch (9.5 mg/Day)
n=47 Participants
Rivastigmine administered transdermally via patches at a constant dose (9.5 mg/day for the 3 months of treatment).
|
Rivastigmine Capsules (6 mg to 12 mg/Day)
n=49 Participants
Rivastigmine administered orally, following the same regime as prior to randomization (doses between 6 mg and 12 mg/day), which remained unchanged throughout the 3 months of treatment.
|
|---|---|---|---|
|
Overall Caregiver Satisfaction With Treatment
Not Decided (ND)
|
1 Participants
|
3 Participants
|
1 Participants
|
|
Overall Caregiver Satisfaction With Treatment
Very good
|
18 Participants
|
20 Participants
|
10 Participants
|
|
Overall Caregiver Satisfaction With Treatment
Good
|
18 Participants
|
14 Participants
|
33 Participants
|
|
Overall Caregiver Satisfaction With Treatment
Average
|
3 Participants
|
5 Participants
|
2 Participants
|
|
Overall Caregiver Satisfaction With Treatment
Poor
|
3 Participants
|
2 Participants
|
3 Participants
|
|
Overall Caregiver Satisfaction With Treatment
Very Poor
|
0 Participants
|
3 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: At end of study (Month 3)Population: The Safety population included all randomized patients who received at least one dose of the study medication.
Patients were asked to rate their overall degree of satisfaction with the Alzheimer's disease treatment on a scale of 1 to 5 (1 "Very good" - 5 "Very poor") at the end of the study (Month 3). A higher score indicates less satisfaction.
Outcome measures
| Measure |
Rivastigmine Patch (4.6 mg/Day Switch to 9.5 mg/Day)
n=43 Participants
Rivastigmine administered transdermally via patches at increasing doses (1 patch/day of 4.6 mg for the first month, changing to 1 patch/day of 9.5 mg for the remaining two months).
|
Rivastigmine Patch (9.5 mg/Day)
n=47 Participants
Rivastigmine administered transdermally via patches at a constant dose (9.5 mg/day for the 3 months of treatment).
|
Rivastigmine Capsules (6 mg to 12 mg/Day)
n=49 Participants
Rivastigmine administered orally, following the same regime as prior to randomization (doses between 6 mg and 12 mg/day), which remained unchanged throughout the 3 months of treatment.
|
|---|---|---|---|
|
Overall Patient Satisfaction With Treatment
Very Poor
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Overall Patient Satisfaction With Treatment
Not Decided (ND)
|
0 Participants
|
3 Participants
|
1 Participants
|
|
Overall Patient Satisfaction With Treatment
Very good
|
18 Participants
|
14 Participants
|
12 Participants
|
|
Overall Patient Satisfaction With Treatment
Good
|
20 Participants
|
21 Participants
|
29 Participants
|
|
Overall Patient Satisfaction With Treatment
Average
|
3 Participants
|
6 Participants
|
5 Participants
|
|
Overall Patient Satisfaction With Treatment
Poor
|
2 Participants
|
2 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Baseline to Month 1 and Month 3Population: The Safety population was made up of all the randomized patients who had taken at least one dose of the study medication.
The Mini Mental State Examination (MMSE) was used to evaluate the patient's cognitive status and how it progressed over time. The 35-point version used in this study was made up of five sections: orientation, fixation, attention and calculation, memory and language, and constructional praxis. The total score for each patient was obtained by adding the score from each of the above sections. The individual receives 1 point for each correct answer. The total score can range from 0 to 30, with a higher score indicating better function. A positive change score indicates improvement.
Outcome measures
| Measure |
Rivastigmine Patch (4.6 mg/Day Switch to 9.5 mg/Day)
n=43 Participants
Rivastigmine administered transdermally via patches at increasing doses (1 patch/day of 4.6 mg for the first month, changing to 1 patch/day of 9.5 mg for the remaining two months).
|
Rivastigmine Patch (9.5 mg/Day)
n=47 Participants
Rivastigmine administered transdermally via patches at a constant dose (9.5 mg/day for the 3 months of treatment).
|
Rivastigmine Capsules (6 mg to 12 mg/Day)
n=49 Participants
Rivastigmine administered orally, following the same regime as prior to randomization (doses between 6 mg and 12 mg/day), which remained unchanged throughout the 3 months of treatment.
|
|---|---|---|---|
|
Change in the Total Mini-Mental State Examination (MMSE) Score From Baseline to Month 1 and Month 3
Month 1
|
0.12 Units on a scale
Standard Deviation 2.60
|
0.59 Units on a scale
Standard Deviation 2.58
|
1.00 Units on a scale
Standard Deviation 2.63
|
|
Change in the Total Mini-Mental State Examination (MMSE) Score From Baseline to Month 1 and Month 3
Month 3
|
-0.59 Units on a scale
Standard Deviation 2.85
|
0.12 Units on a scale
Standard Deviation 2.85
|
-0.40 Units on a scale
Standard Deviation 2.42
|
Adverse Events
Rivastigmine Patch (4.6 mg/Day Switch to 9.5 mg/Day)
Serious events: 2 serious events
Other events: 8 other events
Deaths: 0 deaths
Rivastigmine Patch (9.5 mg/Day)
Serious events: 3 serious events
Other events: 7 other events
Deaths: 0 deaths
Rivastigmine Capsules (6 mg to 12 mg/Day)
Serious events: 1 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Rivastigmine Patch (4.6 mg/Day Switch to 9.5 mg/Day)
n=43 participants at risk
Rivastigmine administered transdermally via patches at increasing doses (1 patch/day of 4.6 mg for the first month, changing to 1 patch/day of 9.5 mg for the remaining two months).
|
Rivastigmine Patch (9.5 mg/Day)
n=47 participants at risk
Rivastigmine administered transdermally via patches at a constant dose (9.5 mg/day for the 3 months of treatment).
|
Rivastigmine Capsules (6 mg to 12 mg/Day)
n=49 participants at risk
Rivastigmine administered orally, following the same regime as prior to randomization (doses between 6 mg and 12 mg/day), which remained unchanged throughout the 3 months of treatment.
|
|---|---|---|---|
|
Infections and infestations
Urinary tract infection
|
2.3%
1/43
|
0.00%
0/47
|
0.00%
0/49
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.00%
0/43
|
0.00%
0/47
|
2.0%
1/49
|
|
Nervous system disorders
Cerebellar haematoma
|
2.3%
1/43
|
0.00%
0/47
|
0.00%
0/49
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/43
|
2.1%
1/47
|
0.00%
0/49
|
|
Nervous system disorders
Transient ischaemic attack
|
0.00%
0/43
|
2.1%
1/47
|
0.00%
0/49
|
|
Vascular disorders
Hypertensive crisis
|
0.00%
0/43
|
2.1%
1/47
|
0.00%
0/49
|
Other adverse events
| Measure |
Rivastigmine Patch (4.6 mg/Day Switch to 9.5 mg/Day)
n=43 participants at risk
Rivastigmine administered transdermally via patches at increasing doses (1 patch/day of 4.6 mg for the first month, changing to 1 patch/day of 9.5 mg for the remaining two months).
|
Rivastigmine Patch (9.5 mg/Day)
n=47 participants at risk
Rivastigmine administered transdermally via patches at a constant dose (9.5 mg/day for the 3 months of treatment).
|
Rivastigmine Capsules (6 mg to 12 mg/Day)
n=49 participants at risk
Rivastigmine administered orally, following the same regime as prior to randomization (doses between 6 mg and 12 mg/day), which remained unchanged throughout the 3 months of treatment.
|
|---|---|---|---|
|
General disorders
Application site erythema
|
7.0%
3/43
|
10.6%
5/47
|
0.00%
0/49
|
|
General disorders
Application site pruritus
|
0.00%
0/43
|
6.4%
3/47
|
0.00%
0/49
|
|
Infections and infestations
Urinary tract infection
|
4.7%
2/43
|
0.00%
0/47
|
12.2%
6/49
|
|
Psychiatric disorders
Agitation
|
7.0%
3/43
|
0.00%
0/47
|
4.1%
2/49
|
Additional Information
Study Director
Novartis Pharmaceuticals
Phone: 862-778-8300
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.
- Publication restrictions are in place
Restriction type: OTHER