Trial Outcomes & Findings for Memantine and Antipsychotics Use (NCT NCT00649220)

NCT ID: NCT00649220

Last Updated: 2011-09-26

Results Overview

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.

• Recruitment status: TERMINATED
• Study phase: PHASE4
• Target enrollment: 19 participants
• Primary outcome timeframe: Week 8-20 post baseline
• Results posted on: 2011-09-26

Participant Flow

Participant milestones

Measure	Memantine Memantine tablets, twice a day (bid).
Overall Study STARTED	19
Overall Study COMPLETED	16
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Measure	Memantine Memantine tablets, twice a day (bid).
Overall Study Adverse Event	2
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Memantine and Antipsychotics Use

Baseline characteristics by cohort

Measure	Memantine n=19 Participants Memantine tablets, twice a day (bid).
Age Continuous	72.4 years STANDARD_DEVIATION 9.7 • n=5 Participants
Age, Customized Between 50 and 85 years	19 participants n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants
Region of Enrollment Germany	19 participants n=5 Participants

PRIMARY outcome

Timeframe: Week 8-20 post baseline

Population: Intention to treat (ITT)

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.

Outcome measures

Measure	Memantine n=19 Participants Memantine tablets, twice a day (bid).
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 • Interval -20.4 to -7.36

SECONDARY outcome

Timeframe: 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

See #1 and #8. Change of <0 reveals a reduction of AP compared to baseline.

Outcome measures

Measure	Memantine n=15 Participants Memantine tablets, twice a day (bid).
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
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
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
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

SECONDARY outcome

Timeframe: Week 20 post baseline

Population: Intention to treat (ITT)

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.

Outcome measures

Measure	Memantine n=15 Participants Memantine tablets, twice a day (bid).
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 • Interval -1.04 to 2.77

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Measure	Memantine n=17 Participants Memantine tablets, twice a day (bid).
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
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
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
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
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 outcome

Timeframe: 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

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.

Outcome measures

Measure	Memantine n=17 Participants Memantine tablets, twice a day (bid).
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
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
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
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
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 outcome

Timeframe: 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

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.

Outcome measures

Measure	Memantine n=18 Participants Memantine tablets, twice a day (bid).
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
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
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
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
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 outcome

Timeframe: 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

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.

Outcome measures

Measure	Memantine n=18 Participants Memantine tablets, twice a day (bid).
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
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
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
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
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 outcome

Timeframe: 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

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.

Outcome measures

Measure	Memantine n=18 Participants Memantine tablets, twice a day (bid).
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
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
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
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

Adverse Events

Memantine

Serious events: 2 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Measure	Memantine n=19 participants at risk Memantine tablets, twice a day (bid).
Psychiatric disorders Depression	5.3% 1/19 • Number of events 1 • All SAEs/AEs from baseline until 4 weeks after end of treatment (in total 20 weeks) The table of "Other Adverse Events" includes all non-serious AEs. The investigator asked the patient for AEs systematically at each visit.
Psychiatric disorders Agitation	5.3% 1/19 • Number of events 1 • All SAEs/AEs from baseline until 4 weeks after end of treatment (in total 20 weeks) The table of "Other Adverse Events" includes all non-serious AEs. The investigator asked the patient for AEs systematically at each visit.
Psychiatric disorders Sleep Disturbances	5.3% 1/19 • Number of events 1 • All SAEs/AEs from baseline until 4 weeks after end of treatment (in total 20 weeks) The table of "Other Adverse Events" includes all non-serious AEs. The investigator asked the patient for AEs systematically at each visit.

Other adverse events

Measure	Memantine n=19 participants at risk Memantine tablets, twice a day (bid).
Psychiatric disorders Agitation	5.3% 1/19 • Number of events 1 • All SAEs/AEs from baseline until 4 weeks after end of treatment (in total 20 weeks) The table of "Other Adverse Events" includes all non-serious AEs. The investigator asked the patient for AEs systematically at each visit.
Psychiatric disorders Anxiety	5.3% 1/19 • Number of events 1 • All SAEs/AEs from baseline until 4 weeks after end of treatment (in total 20 weeks) The table of "Other Adverse Events" includes all non-serious AEs. The investigator asked the patient for AEs systematically at each visit.
Psychiatric disorders Insomnia	5.3% 1/19 • Number of events 1 • All SAEs/AEs from baseline until 4 weeks after end of treatment (in total 20 weeks) The table of "Other Adverse Events" includes all non-serious AEs. The investigator asked the patient for AEs systematically at each visit.
Psychiatric disorders Listless	5.3% 1/19 • Number of events 1 • All SAEs/AEs from baseline until 4 weeks after end of treatment (in total 20 weeks) The table of "Other Adverse Events" includes all non-serious AEs. The investigator asked the patient for AEs systematically at each visit.
Psychiatric disorders Sleep-related eating disorder	5.3% 1/19 • Number of events 1 • All SAEs/AEs from baseline until 4 weeks after end of treatment (in total 20 weeks) The table of "Other Adverse Events" includes all non-serious AEs. The investigator asked the patient for AEs systematically at each visit.
Gastrointestinal disorders Diarrhoea	5.3% 1/19 • Number of events 1 • All SAEs/AEs from baseline until 4 weeks after end of treatment (in total 20 weeks) The table of "Other Adverse Events" includes all non-serious AEs. The investigator asked the patient for AEs systematically at each visit.
Gastrointestinal disorders Epigastric discomfort	5.3% 1/19 • Number of events 1 • All SAEs/AEs from baseline until 4 weeks after end of treatment (in total 20 weeks) The table of "Other Adverse Events" includes all non-serious AEs. The investigator asked the patient for AEs systematically at each visit.
Gastrointestinal disorders Haemorrhoidal haemorrhage	5.3% 1/19 • Number of events 1 • All SAEs/AEs from baseline until 4 weeks after end of treatment (in total 20 weeks) The table of "Other Adverse Events" includes all non-serious AEs. The investigator asked the patient for AEs systematically at each visit.
Gastrointestinal disorders Nausea	5.3% 1/19 • Number of events 1 • All SAEs/AEs from baseline until 4 weeks after end of treatment (in total 20 weeks) The table of "Other Adverse Events" includes all non-serious AEs. The investigator asked the patient for AEs systematically at each visit.
General disorders Fatigue	10.5% 2/19 • Number of events 2 • All SAEs/AEs from baseline until 4 weeks after end of treatment (in total 20 weeks) The table of "Other Adverse Events" includes all non-serious AEs. The investigator asked the patient for AEs systematically at each visit.
Infections and infestations Nasopharyngitis	5.3% 1/19 • Number of events 1 • All SAEs/AEs from baseline until 4 weeks after end of treatment (in total 20 weeks) The table of "Other Adverse Events" includes all non-serious AEs. The investigator asked the patient for AEs systematically at each visit.
Infections and infestations Urinary tract infection	5.3% 1/19 • Number of events 1 • All SAEs/AEs from baseline until 4 weeks after end of treatment (in total 20 weeks) The table of "Other Adverse Events" includes all non-serious AEs. The investigator asked the patient for AEs systematically at each visit.
Injury, poisoning and procedural complications Joint sprain	5.3% 1/19 • Number of events 1 • All SAEs/AEs from baseline until 4 weeks after end of treatment (in total 20 weeks) The table of "Other Adverse Events" includes all non-serious AEs. The investigator asked the patient for AEs systematically at each visit.

Additional Information

Manager Public Disclosure

Merz Pharmaceuticals GmbH

Phone: +49 69 1503 865

Email: matthias.zerm@merz.de

Results disclosure agreements

• Principal investigator is a sponsor employee No results to be published without written agreement by sponsor; manuscripts to be sent to sponsor at least 6 weeks before submission. Sponsor to give written opinion within 30 days. Sponsor is entitled to exert influence on the contents of publications, to postpone publications up to 36 months after end of the study, and to name co-authors. In case of justified doubts of sponsor, the INVESTIGATOR will consider these doubts in the publication as long as the scientific neutrality is not affected.
• Publication restrictions are in place

Restriction type: OTHER