Alzheimer's Disease
Conditions
Brief summary
To investigate the potential to reduce concomitant antipsychotic medication use in subjects with moderate dementia of Alzheimer's type, treated with memantine.
Interventions
DRUGMemantine
memantine tablets, twice a day (bid), for 20 weeks
Sponsors
Merz Pharmaceuticals GmbH
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Current diagnosis of probable Alzheimer's disease consistent with NINCDS-ADRDA criteria or with DSM IV TR criteria for Dementia of the Alzheimer's type. * MRI or CT scan supporting the diagnosis of DAT without indications of any relevant other CNS disorders. * Patients treated with any acetylcholinesterase inhibitor (AChEI) man be included. * The patient should have German as a mother-tongue or at least speak the language fluently.
Exclusion criteria
* Evidence (including CT/MRI results) of any clinically significant central nervous system disease other than Alzheimer's disease. * Modified Hachinski Ischemia score greater than 4 at screening. * Intake of any medication that is contra-indicated in combination with memantine. * Treatment with depot antipsychotics. * History of severe drug allergy, or hypersensitivity, or patients with known hypersensitivity to memantine, amantadine or lactose. * Known or suspected history of alcoholism or drug abuse within the past 10 years. * Previous treatment with memantine or participation in an investigational study with memantine.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Dose Reduction of Antipsychotics (AP) in Percent of Defined Daily Dose (DDD) From Baseline to a Post-baseline Visit at Which the Value of the Visual Analogue Scale (VAS) Compared With the Baseline Value Was =< 15 Percent. | Week 8-20 post baseline | VAS: see #8. Mean percent of the total Defined Daily Dose (DDD), averaged over one week, was calculated. Total DDD was calculated as sum of DDD for each AP drug. DDD is the assumed average maintenance dose per day defined by WHO. The reduction of AP Δ \[percent\] was calculated as a difference between the mean total DDD recorded at baseline and the mean total DDD recorded at the respective week. Measurements from those post-baseline visits were taken into account only when the value of the VAS was not substantially worse compared to baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Mini-Mental State Examination (MMSE) Score Value From Baseline to Week 20. | Week 20 post baseline | MMSE is a brief, physician-administered scale, designed for measuring the cognitive functions, such as: orientation, memory, attention, naming, and comprehension. The scoring range of MMSE is 0 to 30 points. A score of 23 or lower is indicative of cognitive impairment. Change of \>0 reveals an improvement compared to baseline. |
| Change of Test for the Early Detection of Dementia With Discrimination From Depression [TE4D] Score Value From Baseline to Week 4, 8, 12, 16, and/or 20 - First Part: Total Dementia | Week 4-20 post baseline | TE4D is a psychometric, physician-administered test that is used for both screening subjects with early dementia and monitoring the clinical progress of the disease. The first part consists of 9 items, which assess different symptoms associated with dementia such as memory, time-orientation, etc. The scoring range is 0 to 50 points. A score of 35 or lower is an indication of dementia. A change \>0 represents an improvement. |
| Change of Test for the Early Detection of Dementia With Discrimination From Depression [TE4D] Score Value From Baseline to Week 4, 8, 12, 16, and/or 20 - Second Part: Total Depression | Week 4-20 post Baseline | TE4D is a psychometric, physician-administered test that is used for both screening subjects with early dementia and monitoring the clinical progress of the disease. The second part consists of a proxy rating and a self-assessment rating. The scoring range of each rating is 1 to 10. The maximum total score of 10 corresponds to severe depression. A change \<0 reveals an improvement compared to baseline. |
| Reduction of Antipsychotic Drug Dose From Baseline to Week 8, 12, 16 and/or 20. | Week 8-20 post Baseline | See #1 and #8. Change of \<0 reveals a reduction of AP compared to baseline. |
| Change of Nurses' Observation Scale for Geriatric Patients [NOSGER] Total Score Value From Baseline to Week 4, 8, 12, 16, and/or 20 | Week 4-20 post Baseline | NOSGER is a comprehensive scale, which contains 30 items of behavior, each rated on a 5-point scale according to the frequency of occurrence by direct observation. Item scores are summarized into 6 dimension scores: memory, instrumental activities of daily life, self-care, mood, social behavior, and disturbing behavior. The NOSGER has a scoring range of 30 to 150 with the higher scores indicating worse subject's status. The items in each group are rated for their frequency ranging from 1 (never) to 5 (always). A change of \<0 reveals an improvement compared to baseline. |
| Change in the VAS Score From Baseline to Week 8, 12, 16 and/or 20. | Week 8-20 post Baseline | VAS is a report device to measure the subject's burden caused by behavioral symptoms. To measure the burden on the VAS only the first 3 items of the Neuropsychiatric Inventory (NPI) Questionnaire were considered (delusions, hallucinations (visual and auditory), and agitation / aggression). The VAS consists of a 100 mm horizontal line, anchored at the ends with the reference not at all and extremely. The VAS score was determined by measuring in mm from the left hand end of the line to the point, where the investigator had marked the magnitude of a subject's burden. |
| Change of Modified Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADLB19) Score Value From Baseline to Week 4, 8, 12, 16, and/or 20. | Week 4-20 post Baseline | The modified ADCS-ADL19 is comprehensive battery of ADL questions aimed to measure the functional ability of subjects with Dementia of Alzheimer's type over a broad range of dementia severity. It has a scoring range of 0 to 54 with the lower scores indicating greater functional impairment. Each ADL item was rated from the highest level of independent performance to complete loss. Change of \>0 reveals an improvement compared to baseline. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Memantine Memantine tablets, twice a day (bid). | 19 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Memantine |
|---|---|
| Age Continuous | 72.4 years STANDARD_DEVIATION 9.7 |
| Age, Customized Between 50 and 85 years | 19 participants |
| Region of Enrollment Germany | 19 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 7 / 19 |
| serious Total, serious adverse events | 2 / 19 |
Outcome results
Primary
Maximum Dose Reduction of Antipsychotics (AP) in Percent of Defined Daily Dose (DDD) From Baseline to a Post-baseline Visit at Which the Value of the Visual Analogue Scale (VAS) Compared With the Baseline Value Was =< 15 Percent.
VAS: see #8. Mean percent of the total Defined Daily Dose (DDD), averaged over one week, was calculated. Total DDD was calculated as sum of DDD for each AP drug. DDD is the assumed average maintenance dose per day defined by WHO. The reduction of AP Δ \[percent\] was calculated as a difference between the mean total DDD recorded at baseline and the mean total DDD recorded at the respective week. Measurements from those post-baseline visits were taken into account only when the value of the VAS was not substantially worse compared to baseline.
Time frame: Week 8-20 post baseline
Population: Intention to treat (ITT)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Memantine | Maximum Dose Reduction of Antipsychotics (AP) in Percent of Defined Daily Dose (DDD) From Baseline to a Post-baseline Visit at Which the Value of the Visual Analogue Scale (VAS) Compared With the Baseline Value Was =< 15 Percent. | -13.9 Percent of daily dose [DDD] | Standard Deviation 13.58 |
Comparison: Two-side, paired t-test on the null hypothesis that antipsychotics are reduced by 10% compared to baselinep-value: 0.22626t-test, 2 sided
Comparison: Wilcoxon signed rank test on the null hypothesis that antipsychotics are reduced by 10% compared to baselinep-value: 0.34192Wilcoxon signed rank test
Secondary
Change in the Mini-Mental State Examination (MMSE) Score Value From Baseline to Week 20.
MMSE is a brief, physician-administered scale, designed for measuring the cognitive functions, such as: orientation, memory, attention, naming, and comprehension. The scoring range of MMSE is 0 to 30 points. A score of 23 or lower is indicative of cognitive impairment. Change of \>0 reveals an improvement compared to baseline.
Time frame: Week 20 post baseline
Population: Intention to treat (ITT)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Memantine | Change in the Mini-Mental State Examination (MMSE) Score Value From Baseline to Week 20. | 0.9 units on a scale | Standard Deviation 3.44 |
Secondary
Change in the VAS Score From Baseline to Week 8, 12, 16 and/or 20.
VAS is a report device to measure the subject's burden caused by behavioral symptoms. To measure the burden on the VAS only the first 3 items of the Neuropsychiatric Inventory (NPI) Questionnaire were considered (delusions, hallucinations (visual and auditory), and agitation / aggression). The VAS consists of a 100 mm horizontal line, anchored at the ends with the reference not at all and extremely. The VAS score was determined by measuring in mm from the left hand end of the line to the point, where the investigator had marked the magnitude of a subject's burden.
Time frame: Week 8-20 post Baseline
Population: Intention to treat (ITT).~Week 8: n=17; Week 12: n=16; Week 16: n=16; Week 20: n=18
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Memantine | Change in the VAS Score From Baseline to Week 8, 12, 16 and/or 20. | Week 8 | -1.5 Units on a scale [cm] | Standard Deviation 1.94 |
| Memantine | Change in the VAS Score From Baseline to Week 8, 12, 16 and/or 20. | Week 12 | -1.7 Units on a scale [cm] | Standard Deviation 2.53 |
| Memantine | Change in the VAS Score From Baseline to Week 8, 12, 16 and/or 20. | Week 16 | -1.2 Units on a scale [cm] | Standard Deviation 2.86 |
| Memantine | Change in the VAS Score From Baseline to Week 8, 12, 16 and/or 20. | Week 20 | -1.4 Units on a scale [cm] | Standard Deviation 2.46 |
Secondary
Change of Modified Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADLB19) Score Value From Baseline to Week 4, 8, 12, 16, and/or 20.
The modified ADCS-ADL19 is comprehensive battery of ADL questions aimed to measure the functional ability of subjects with Dementia of Alzheimer's type over a broad range of dementia severity. It has a scoring range of 0 to 54 with the lower scores indicating greater functional impairment. Each ADL item was rated from the highest level of independent performance to complete loss. Change of \>0 reveals an improvement compared to baseline.
Time frame: Week 4-20 post Baseline
Population: Intention to treat (ITT).~Week 4: n=18; Week 8: n=17; Week 12: n=16; Week 16: n=16; Week 20: n=18
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Memantine | Change of Modified Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADLB19) Score Value From Baseline to Week 4, 8, 12, 16, and/or 20. | Week 4 | -0.7 Units on a Scale | Standard Deviation 6.33 |
| Memantine | Change of Modified Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADLB19) Score Value From Baseline to Week 4, 8, 12, 16, and/or 20. | Week 8 | 2.2 Units on a Scale | Standard Deviation 8.09 |
| Memantine | Change of Modified Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADLB19) Score Value From Baseline to Week 4, 8, 12, 16, and/or 20. | Week 12 | 3.8 Units on a Scale | Standard Deviation 11.07 |
| Memantine | Change of Modified Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADLB19) Score Value From Baseline to Week 4, 8, 12, 16, and/or 20. | Week 16 | 3.8 Units on a Scale | Standard Deviation 11.27 |
| Memantine | Change of Modified Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADLB19) Score Value From Baseline to Week 4, 8, 12, 16, and/or 20. | Week 20 | 2.4 Units on a Scale | Standard Deviation 11.08 |
Secondary
Change of Nurses' Observation Scale for Geriatric Patients [NOSGER] Total Score Value From Baseline to Week 4, 8, 12, 16, and/or 20
NOSGER is a comprehensive scale, which contains 30 items of behavior, each rated on a 5-point scale according to the frequency of occurrence by direct observation. Item scores are summarized into 6 dimension scores: memory, instrumental activities of daily life, self-care, mood, social behavior, and disturbing behavior. The NOSGER has a scoring range of 30 to 150 with the higher scores indicating worse subject's status. The items in each group are rated for their frequency ranging from 1 (never) to 5 (always). A change of \<0 reveals an improvement compared to baseline.
Time frame: Week 4-20 post Baseline
Population: Intention to treat (ITT).~Week 4: n=18; Week 8: n=17; Week 12: n=16; Week 16: n=16; Week 20: n=17
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Memantine | Change of Nurses' Observation Scale for Geriatric Patients [NOSGER] Total Score Value From Baseline to Week 4, 8, 12, 16, and/or 20 | Week 4 | -0.4 Units on a scale | Standard Deviation 10.9 |
| Memantine | Change of Nurses' Observation Scale for Geriatric Patients [NOSGER] Total Score Value From Baseline to Week 4, 8, 12, 16, and/or 20 | Week 8 | -2.1 Units on a scale | Standard Deviation 10.31 |
| Memantine | Change of Nurses' Observation Scale for Geriatric Patients [NOSGER] Total Score Value From Baseline to Week 4, 8, 12, 16, and/or 20 | Week 12 | -5.4 Units on a scale | Standard Deviation 13.29 |
| Memantine | Change of Nurses' Observation Scale for Geriatric Patients [NOSGER] Total Score Value From Baseline to Week 4, 8, 12, 16, and/or 20 | Week 16 | -8.4 Units on a scale | Standard Deviation 18.74 |
| Memantine | Change of Nurses' Observation Scale for Geriatric Patients [NOSGER] Total Score Value From Baseline to Week 4, 8, 12, 16, and/or 20 | Week 20 | -7.9 Units on a scale | Standard Deviation 19.02 |
Secondary
Change of Test for the Early Detection of Dementia With Discrimination From Depression [TE4D] Score Value From Baseline to Week 4, 8, 12, 16, and/or 20 - First Part: Total Dementia
TE4D is a psychometric, physician-administered test that is used for both screening subjects with early dementia and monitoring the clinical progress of the disease. The first part consists of 9 items, which assess different symptoms associated with dementia such as memory, time-orientation, etc. The scoring range is 0 to 50 points. A score of 35 or lower is an indication of dementia. A change \>0 represents an improvement.
Time frame: Week 4-20 post baseline
Population: Intent to treat (ITT).~Week 4: n=18; Week 8: n=17; Week 12: n=16; Week 16: n=16; Week 20: n=17
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Memantine | Change of Test for the Early Detection of Dementia With Discrimination From Depression [TE4D] Score Value From Baseline to Week 4, 8, 12, 16, and/or 20 - First Part: Total Dementia | Week 4 | -2.3 units on a scale | Standard Deviation 7.64 |
| Memantine | Change of Test for the Early Detection of Dementia With Discrimination From Depression [TE4D] Score Value From Baseline to Week 4, 8, 12, 16, and/or 20 - First Part: Total Dementia | Week 8 | -0.3 units on a scale | Standard Deviation 5.31 |
| Memantine | Change of Test for the Early Detection of Dementia With Discrimination From Depression [TE4D] Score Value From Baseline to Week 4, 8, 12, 16, and/or 20 - First Part: Total Dementia | Week 12 | -1.3 units on a scale | Standard Deviation 4.48 |
| Memantine | Change of Test for the Early Detection of Dementia With Discrimination From Depression [TE4D] Score Value From Baseline to Week 4, 8, 12, 16, and/or 20 - First Part: Total Dementia | Week 16 | 0.7 units on a scale | Standard Deviation 5.39 |
| Memantine | Change of Test for the Early Detection of Dementia With Discrimination From Depression [TE4D] Score Value From Baseline to Week 4, 8, 12, 16, and/or 20 - First Part: Total Dementia | Week 20 | 1.4 units on a scale | Standard Deviation 4.2 |
Secondary
Change of Test for the Early Detection of Dementia With Discrimination From Depression [TE4D] Score Value From Baseline to Week 4, 8, 12, 16, and/or 20 - Second Part: Total Depression
TE4D is a psychometric, physician-administered test that is used for both screening subjects with early dementia and monitoring the clinical progress of the disease. The second part consists of a proxy rating and a self-assessment rating. The scoring range of each rating is 1 to 10. The maximum total score of 10 corresponds to severe depression. A change \<0 reveals an improvement compared to baseline.
Time frame: Week 4-20 post Baseline
Population: Intention to treat (ITT).~Week 4: n=18; Week 8: n=17; Week 12: n=16; Week 16: n=16; Week 20: n=17
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Memantine | Change of Test for the Early Detection of Dementia With Discrimination From Depression [TE4D] Score Value From Baseline to Week 4, 8, 12, 16, and/or 20 - Second Part: Total Depression | Week 4 | 2.5 units on a scale | Standard Deviation 4.84 |
| Memantine | Change of Test for the Early Detection of Dementia With Discrimination From Depression [TE4D] Score Value From Baseline to Week 4, 8, 12, 16, and/or 20 - Second Part: Total Depression | Week 8 | 1.6 units on a scale | Standard Deviation 3.97 |
| Memantine | Change of Test for the Early Detection of Dementia With Discrimination From Depression [TE4D] Score Value From Baseline to Week 4, 8, 12, 16, and/or 20 - Second Part: Total Depression | Week 12 | -0.1 units on a scale | Standard Deviation 3.26 |
| Memantine | Change of Test for the Early Detection of Dementia With Discrimination From Depression [TE4D] Score Value From Baseline to Week 4, 8, 12, 16, and/or 20 - Second Part: Total Depression | Week 16 | -0.2 units on a scale | Standard Deviation 2.07 |
| Memantine | Change of Test for the Early Detection of Dementia With Discrimination From Depression [TE4D] Score Value From Baseline to Week 4, 8, 12, 16, and/or 20 - Second Part: Total Depression | Week 20 | -0.4 units on a scale | Standard Deviation 2.09 |
Secondary
Reduction of Antipsychotic Drug Dose From Baseline to Week 8, 12, 16 and/or 20.
See #1 and #8. Change of \<0 reveals a reduction of AP compared to baseline.
Time frame: Week 8-20 post Baseline
Population: Intention to treat (ITT).~Week 8: n=16; Week 12: n=14; Week 16: n=13; Week 20: n=15
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Memantine | Reduction of Antipsychotic Drug Dose From Baseline to Week 8, 12, 16 and/or 20. | Week 8 | -4.4 Percent of daily dose [DDD] | Standard Deviation 5.53 |
| Memantine | Reduction of Antipsychotic Drug Dose From Baseline to Week 8, 12, 16 and/or 20. | Week 12 | -8.2 Percent of daily dose [DDD] | Standard Deviation 12.38 |
| Memantine | Reduction of Antipsychotic Drug Dose From Baseline to Week 8, 12, 16 and/or 20. | Week 16 | -10.6 Percent of daily dose [DDD] | Standard Deviation 13.49 |
| Memantine | Reduction of Antipsychotic Drug Dose From Baseline to Week 8, 12, 16 and/or 20. | Week 20 | -14.9 Percent of daily dose [DDD] | Standard Deviation 15.05 |