Alzheimer Dementia (AD)
Conditions
Brief summary
Evaluation of the safety and tolerability of a 20 mg once daily dose of memantine compared with 10 mg given twice daily in patients with dementia of Alzheimer's type and MMSE range 5-18.
Interventions
DRUGMemantine (once daily)
DRUGMemantine (twice daily)
Sponsors
H. Lundbeck A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* The patient has a knowledgeable and reliable caregiver who will accompany the patient to all clinical visits during the study. * The patient has a diagnosis of probable AD consistent with the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria. * The patient has a Mini Mental State Examination (MMSE) score ≥ 5 and ≤ 18 at Screening visit * The dose of Memantine has been stable at 20 mg once a day for at least 3 month prior to screening
Exclusion criteria
* The patient has one or more of the following conditions: Evidence and/or history of any clinically significant neurodegenerative disease or other serious neurological disorders other than Alzheimer's disease including, but not limited to, Lewy body dementia, Fronto-Temporal dementia, Parkinson's disease, Huntington's disease, major cortical stroke, Multiple Sclerosis, major head trauma and primary or secondary cerebral neoplasm. * The patient has a modified Hachinski ischemia score greater than 4 at the screening visit. * The patient has any current psychiatric disorder or Axis I disorder (DSM-IV-TR™ criteria), established as the primary diagnosis, other than AD * The patient is currently receiving treatment with an unstable dose of acetyl cholinesterase inhibitor Other protocol defined inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | baseline to week 16 (end of study) | Number of patients who reported adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ADCS - CGIC Score at Week 12 | ADCS - CGIC score at Week 12 | The Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) is a semi-structured interview designed to assess clinically relevant changes in patients with Alzheimer's disease. Items in the ADCS-CGIC interview provide general information, and information about cognition, behaviour, social and daily functioning. Responses to ADCS-CGIC interview result in a global clinical judgement of severity (at baseline) and clinically relevant change at subsequent visits. Severity rated at baseline is only used for reference. The severity at baseline is rated on a 7-point Likert-type scale from 1(normal, not ill at all) to 7 (among the most extremely ill patients). The ADCS-CGIC relevant change is rated on a 7-point Likert-type scale from 1 (marked improvement) to 7 (marked worsening). |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Memantine (Once Daily) Memantine 20 mg once daily, tablets, orally AND Placebo tablets once daily, orally | 30 |
| Memantine (Twice Daily) 10 mg given twice daily, tablets, orally AND Placebo tablets twice daily, orally | 32 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative reason(s) | 0 | 1 |
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | Memantine (Once Daily) | Memantine (Twice Daily) | Total |
|---|---|---|---|
| Age, Continuous | 69.1 years STANDARD_DEVIATION 9.3 | 70.3 years STANDARD_DEVIATION 8.1 | 69.7 years STANDARD_DEVIATION 8.6 |
| Duration of Alzheimer's Disease | 2.1 years STANDARD_DEVIATION 1.9 | 2.3 years STANDARD_DEVIATION 1.9 | 2.2 years STANDARD_DEVIATION 1.9 |
| MMSE Total Score | 11.4 units on a scale STANDARD_DEVIATION 4.2 | 11.4 units on a scale STANDARD_DEVIATION 4.5 | 11.4 units on a scale STANDARD_DEVIATION 4.3 |
| Modified Hachinski Ischemia Total Score | 1.6 units on a scale STANDARD_DEVIATION 1.2 | 1.8 units on a scale STANDARD_DEVIATION 0.9 | 1.7 units on a scale STANDARD_DEVIATION 1 |
| Race/Ethnicity, Customized Asian | 30 Participants | 32 Participants | 62 Participants |
| Sex: Female, Male Female | 17 Participants | 17 Participants | 34 Participants |
| Sex: Female, Male Male | 13 Participants | 15 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 30 | 2 / 32 |
| serious Total, serious adverse events | 0 / 30 | 1 / 32 |
Outcome results
Primary
Adverse Events
Number of patients who reported adverse events
Time frame: baseline to week 16 (end of study)
Population: All patients treated
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Memantine (Once Daily) | Adverse Events | 15 Participants |
| Memantine (Twice Daily) | Adverse Events | 16 Participants |
Secondary
ADCS - CGIC Score at Week 12
The Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) is a semi-structured interview designed to assess clinically relevant changes in patients with Alzheimer's disease. Items in the ADCS-CGIC interview provide general information, and information about cognition, behaviour, social and daily functioning. Responses to ADCS-CGIC interview result in a global clinical judgement of severity (at baseline) and clinically relevant change at subsequent visits. Severity rated at baseline is only used for reference. The severity at baseline is rated on a 7-point Likert-type scale from 1(normal, not ill at all) to 7 (among the most extremely ill patients). The ADCS-CGIC relevant change is rated on a 7-point Likert-type scale from 1 (marked improvement) to 7 (marked worsening).
Time frame: ADCS - CGIC score at Week 12
Population: Full analysis set - all randomised patients who took at least one dose of investigational medicinal product, and who had a valid baseline assessment and at least one valid post-baseline assessment of the ADCS-CGIC.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Memantine (Once Daily) | ADCS - CGIC Score at Week 12 | 3.92 units on a scale | Standard Error 0.14 |
| Memantine (Twice Daily) | ADCS - CGIC Score at Week 12 | 3.60 units on a scale | Standard Error 0.14 |
Comparison: The ADCS-CGIC was analyzed based on an analysis of covariance (ANCOVA) of ADCS-CGIC score at Week 12, with treatment and site as fixed factors, and baseline score as a covariate using observed cases.p-value: 0.09795% CI: [-0.06, 0.69]ANCOVA