Alzheimer's Disease
Conditions
Keywords
Alzheimer's, rivastigmine, transdermal, safety, randomized, switch, patch
Brief summary
This study used two doses of rivastigmine transdermal patch (5 cm\^2, 10 cm\^2) to establish the feasibility of 2 switch schedules (with transdermal patch one-step dose titration or without dose titration) from rivastigmine capsules (3 mg bid (bis in die, twice a day), 4,5 mg bid, 6 mg bid) to rivastigmine transdermal patch and to assess safety, tolerability, convenience, and caregivers preferences of rivastigmine transdermal patch versus capsules.
Interventions
DRUGRivastigmine 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).
DRUGRivastigmine patch (9.5 mg/day)
Rivastigmine administered transdermally via patches at a constant dose (9.5 mg/day for the 3 months of treatment).
DRUGRivastigmine 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.
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Meet DSM-IV (Diagnostic & Statistical Manual of Mental Disorders, Version IV) criteria for dementia of Alzheimer type and NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association) criteria for probable Alzheimer's disease (AD), have a MMSE (Mini Mental State Examination) score \> 10 and \< 26 * Have received continuous treatment with rivastigmine capsules at least with 3 mg bid (6 mg of total daily dose) for at least 3 months before entering in the study * Cooperative, willing to complete all aspects of the study, and capable of doing so, either alone or with the aid of a responsible caregiver * Have a primary caregiver willing to accept responsibility for supervising the treatment, (eg, application and removal of the patch daily at approximately the same time of day) and assessing the condition of the patient throughout the study.
Exclusion criteria
* A medical or neurological condition other that AD that could explain the patients dementia (eg, Huntington's disease, Parkinson's Disease, abnormal thyroid function test, B12 or folate deficiency, post-traumatic conditions, syphilis) * Current diagnosis of an active skin lesion/disorder that would prevent accurate assessment of the adhesion and potential skin irritation of the patch (e.g., atopic dermatitis, wounded or scratched skin in the area of the patch application) * History of allergy to topical products containing vitamin E * Taken any of the following substances prior to randomization: * succinylcholine-type muscle relaxants during the previous 2 weeks * an investigational drug during the previous 4 weeks Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Who Had a Gastrointestinal Adverse Event (AE) at Any Time During the Study | Baseline to end of study (Month 3) | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With an AE Involving the Skin (Local Tolerance) Recorded Over the Course of the Study Period (Patch Groups Only) | Baseline to end of study (Month 3) | 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). |
| Percentage of Patients With at Least 1 AE of Any Kind Recorded During the Period of the Study. | Baseline to end of study (Month 3) | 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. |
| Overall Caregiver Satisfaction With Treatment | At end of study (Month 3) | 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. |
| Overall Patient Satisfaction With Treatment | At end of study (Month 3) | 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. |
| Change in the Total Mini-Mental State Examination (MMSE) Score From Baseline to Month 1 and Month 3 | Baseline to Month 1 and Month 3 | 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. |
Countries
Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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). | 43 |
| 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). | 47 |
| 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. | 49 |
| Total | 139 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| 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
| Characteristic | Rivastigmine Patch (4.6 mg/Day Switch to 9.5 mg/Day) | Rivastigmine Patch (9.5 mg/Day) | Rivastigmine Capsules (6 mg to 12 mg/Day) | Total |
|---|---|---|---|---|
| Age Continuous | 77.05 years STANDARD_DEVIATION 4.82 | 75.34 years STANDARD_DEVIATION 7.25 | 77.35 years STANDARD_DEVIATION 6.62 | 76.58 years STANDARD_DEVIATION 6.37 |
| Sex: Female, Male Female | 30 Participants | 29 Participants | 25 Participants | 84 Participants |
| Sex: Female, Male Male | 13 Participants | 18 Participants | 24 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 43 | 7 / 47 | 8 / 49 |
| serious Total, serious adverse events | 2 / 43 | 3 / 47 | 1 / 49 |
Outcome results
Primary
Percentage of Patients Who Had a Gastrointestinal Adverse Event (AE) at Any Time During the Study
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).
Time frame: 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.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Rivastigmine Patch (4.6 mg/Day Switch to 9.5 mg/Day) | Percentage of Patients Who Had a Gastrointestinal Adverse Event (AE) at Any Time During the Study | 4.65 Percentage of participants | 4.65 |
| Rivastigmine Patch (9.5 mg/Day) | Percentage of Patients Who Had a Gastrointestinal Adverse Event (AE) at Any Time During the Study | 4.26 Percentage of participants | 4.26 |
| Rivastigmine Capsules (6 mg to 12 mg/Day) | Percentage of Patients Who Had a Gastrointestinal Adverse Event (AE) at Any Time During the Study | 6.12 Percentage of participants | 6.12 |
Secondary
Change in the Total Mini-Mental State Examination (MMSE) Score From Baseline to Month 1 and Month 3
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.
Time frame: Baseline to Month 1 and Month 3
Population: The Safety population was made up of all the randomized patients who had taken at least one dose of the study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rivastigmine Patch (4.6 mg/Day Switch to 9.5 mg/Day) | 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 2.6 |
| Rivastigmine Patch (4.6 mg/Day Switch to 9.5 mg/Day) | 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 |
| Rivastigmine Patch (9.5 mg/Day) | Change in the Total Mini-Mental State Examination (MMSE) Score From Baseline to Month 1 and Month 3 | Month 1 | 0.59 Units on a scale | Standard Deviation 2.58 |
| Rivastigmine Patch (9.5 mg/Day) | Change in the Total Mini-Mental State Examination (MMSE) Score From Baseline to Month 1 and Month 3 | Month 3 | 0.12 Units on a scale | Standard Deviation 2.85 |
| Rivastigmine Capsules (6 mg to 12 mg/Day) | Change in the Total Mini-Mental State Examination (MMSE) Score From Baseline to Month 1 and Month 3 | Month 1 | 1.00 Units on a scale | Standard Deviation 2.63 |
| Rivastigmine Capsules (6 mg to 12 mg/Day) | Change in the Total Mini-Mental State Examination (MMSE) Score From Baseline to Month 1 and Month 3 | Month 3 | -0.40 Units on a scale | Standard Deviation 2.42 |
Secondary
Overall Caregiver Satisfaction With Treatment
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.
Time frame: At end of study (Month 3)
Population: The Safety population included all randomized patients who received at least one dose of the study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rivastigmine Patch (4.6 mg/Day Switch to 9.5 mg/Day) | Overall Caregiver Satisfaction With Treatment | Very Poor | 0 Participants |
| Rivastigmine Patch (4.6 mg/Day Switch to 9.5 mg/Day) | Overall Caregiver Satisfaction With Treatment | Not Decided (ND) | 1 Participants |
| Rivastigmine Patch (4.6 mg/Day Switch to 9.5 mg/Day) | Overall Caregiver Satisfaction With Treatment | Good | 18 Participants |
| Rivastigmine Patch (4.6 mg/Day Switch to 9.5 mg/Day) | Overall Caregiver Satisfaction With Treatment | Average | 3 Participants |
| Rivastigmine Patch (4.6 mg/Day Switch to 9.5 mg/Day) | Overall Caregiver Satisfaction With Treatment | Very good | 18 Participants |
| Rivastigmine Patch (4.6 mg/Day Switch to 9.5 mg/Day) | Overall Caregiver Satisfaction With Treatment | Poor | 3 Participants |
| Rivastigmine Patch (9.5 mg/Day) | Overall Caregiver Satisfaction With Treatment | Very good | 20 Participants |
| Rivastigmine Patch (9.5 mg/Day) | Overall Caregiver Satisfaction With Treatment | Poor | 2 Participants |
| Rivastigmine Patch (9.5 mg/Day) | Overall Caregiver Satisfaction With Treatment | Very Poor | 3 Participants |
| Rivastigmine Patch (9.5 mg/Day) | Overall Caregiver Satisfaction With Treatment | Average | 5 Participants |
| Rivastigmine Patch (9.5 mg/Day) | Overall Caregiver Satisfaction With Treatment | Not Decided (ND) | 3 Participants |
| Rivastigmine Patch (9.5 mg/Day) | Overall Caregiver Satisfaction With Treatment | Good | 14 Participants |
| Rivastigmine Capsules (6 mg to 12 mg/Day) | Overall Caregiver Satisfaction With Treatment | Very Poor | 0 Participants |
| Rivastigmine Capsules (6 mg to 12 mg/Day) | Overall Caregiver Satisfaction With Treatment | Very good | 10 Participants |
| Rivastigmine Capsules (6 mg to 12 mg/Day) | Overall Caregiver Satisfaction With Treatment | Good | 33 Participants |
| Rivastigmine Capsules (6 mg to 12 mg/Day) | Overall Caregiver Satisfaction With Treatment | Not Decided (ND) | 1 Participants |
| Rivastigmine Capsules (6 mg to 12 mg/Day) | Overall Caregiver Satisfaction With Treatment | Poor | 3 Participants |
| Rivastigmine Capsules (6 mg to 12 mg/Day) | Overall Caregiver Satisfaction With Treatment | Average | 2 Participants |
Secondary
Overall Patient Satisfaction With Treatment
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.
Time frame: At end of study (Month 3)
Population: The Safety population included all randomized patients who received at least one dose of the study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rivastigmine Patch (4.6 mg/Day Switch to 9.5 mg/Day) | Overall Patient Satisfaction With Treatment | Poor | 2 Participants |
| Rivastigmine Patch (4.6 mg/Day Switch to 9.5 mg/Day) | Overall Patient Satisfaction With Treatment | Good | 20 Participants |
| Rivastigmine Patch (4.6 mg/Day Switch to 9.5 mg/Day) | Overall Patient Satisfaction With Treatment | Very Poor | 0 Participants |
| Rivastigmine Patch (4.6 mg/Day Switch to 9.5 mg/Day) | Overall Patient Satisfaction With Treatment | Not Decided (ND) | 0 Participants |
| Rivastigmine Patch (4.6 mg/Day Switch to 9.5 mg/Day) | Overall Patient Satisfaction With Treatment | Average | 3 Participants |
| Rivastigmine Patch (4.6 mg/Day Switch to 9.5 mg/Day) | Overall Patient Satisfaction With Treatment | Very good | 18 Participants |
| Rivastigmine Patch (9.5 mg/Day) | Overall Patient Satisfaction With Treatment | Average | 6 Participants |
| Rivastigmine Patch (9.5 mg/Day) | Overall Patient Satisfaction With Treatment | Poor | 2 Participants |
| Rivastigmine Patch (9.5 mg/Day) | Overall Patient Satisfaction With Treatment | Very good | 14 Participants |
| Rivastigmine Patch (9.5 mg/Day) | Overall Patient Satisfaction With Treatment | Very Poor | 1 Participants |
| Rivastigmine Patch (9.5 mg/Day) | Overall Patient Satisfaction With Treatment | Not Decided (ND) | 3 Participants |
| Rivastigmine Patch (9.5 mg/Day) | Overall Patient Satisfaction With Treatment | Good | 21 Participants |
| Rivastigmine Capsules (6 mg to 12 mg/Day) | Overall Patient Satisfaction With Treatment | Very Poor | 0 Participants |
| Rivastigmine Capsules (6 mg to 12 mg/Day) | Overall Patient Satisfaction With Treatment | Not Decided (ND) | 1 Participants |
| Rivastigmine Capsules (6 mg to 12 mg/Day) | Overall Patient Satisfaction With Treatment | Very good | 12 Participants |
| Rivastigmine Capsules (6 mg to 12 mg/Day) | Overall Patient Satisfaction With Treatment | Good | 29 Participants |
| Rivastigmine Capsules (6 mg to 12 mg/Day) | Overall Patient Satisfaction With Treatment | Average | 5 Participants |
| Rivastigmine Capsules (6 mg to 12 mg/Day) | Overall Patient Satisfaction With Treatment | Poor | 2 Participants |
Secondary
Percentage of Patients With an AE Involving the Skin (Local Tolerance) Recorded Over the Course of the Study Period (Patch Groups Only)
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).
Time frame: 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.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Rivastigmine Patch (4.6 mg/Day Switch to 9.5 mg/Day) | 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 |
| Rivastigmine Patch (9.5 mg/Day) | Percentage of Patients With an AE Involving the Skin (Local Tolerance) Recorded Over the Course of the Study Period (Patch Groups Only) | 17.02 Percentage of participants | 17.02 |
Secondary
Percentage of Patients With at Least 1 AE of Any Kind Recorded During the Period of the Study.
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Rivastigmine Patch (4.6 mg/Day Switch to 9.5 mg/Day) | 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 |
| Rivastigmine Patch (9.5 mg/Day) | Percentage of Patients With at Least 1 AE of Any Kind Recorded During the Period of the Study. | 55.32 Percentage of participants | 55.32 |
| Rivastigmine Capsules (6 mg to 12 mg/Day) | Percentage of Patients With at Least 1 AE of Any Kind Recorded During the Period of the Study. | 53.06 Percentage of participants | 53.06 |