|
Parameter
|
MRZ-90001-9605 [
6
]
|
MEM-MD-01 [
8
]
|
MEM-MD-02 [
7
]
|
MEM-MD-50 [
5
]
|
|---|
|
MEM monotherapy
|
MEM monotherapy
|
MEM added to DON
|
MEM added to ChEI
|
|---|
|
10 mg b.i.d. IR
|
10 mg b.i.d. IR
|
10 mg b.i.d. IR
|
28 mg q.d. ER
|
|---|
|
PBO
|
MEM
|
PBO
|
MEM
|
PBO/DON
|
MEM/DON
|
PBO/ChEI
|
MEM/ChEI
|
|---|
|
(number = 126)
|
(number = 126)
|
(number = 172)
|
(number = 178)
|
(number = 201)
|
(number = 202)
|
(number = 335)
|
(number = 341)
|
|---|
|
Baseline patient characteristics
| | | | | | | |
|
Age, yearsa
|
76.3 ± 7.8
|
75.9 ± 8.4
|
78.3 ± 7.6
|
78.1 ± 8.2
|
75.5 ± 8.7
|
75.5 ± 8.4
|
76.8 ± 7.8
|
76.2 ± 8.4
|
|
Women, number (%)
|
79 (63)
|
91 (72)
|
121 (70)
|
129 (72)
|
134 (67)
|
128 (63)
|
243 (72)
|
244 (72)
|
|
White, number (%)
|
115 (91)
|
112 (89)
|
141 (82)
|
142 (80)
|
186 (92)
|
182 (90)
|
312 (93)
|
324 (95)
|
|
Weight, kga
|
66.1 ± 14.1
|
64.5 ± 12.4
|
65.9 ± 12.8
|
64.5 ± 13.5
|
66.2 ± 14.1
|
70.5 ± 14.3
|
64.6 ± 13.3
|
65.1 ± 12.8
|
|
MMSE scorea
|
8.1 ± 3.6
|
7.7 ± 3.7
|
10.3 ± 3.1
|
10.0 ± 2.8
|
10.2 ± 3.0
|
9.9 ± 3.1
|
10.6 ± 2.9
|
10.9 ± 2.9
|
|
MMSE rangeb
|
1 to 14
| |
5 to 16
| |
5 to 16
| |
3 to 17
| |
|
Concomitant anti-dementia treatment
|
none
| |
none
| |
donepezil
| |
ChEI
| |
|
PBO/DON: number = 217
| |
|
MEM/DON: number = 219
| |
|
Duration, weeks
|
28
| |
24
| |
24
| |
24
| |
|
Score changes from baseline at study endpoint (LOCF)a
| | | | | | | | |
|
SIB (number)
|
−9.8 ± 13.4 (126)
|
−3.9 ± 11.3 (126)
|
−2.6 ± 8.6 (165)
|
−1.7 ± 11.4 (170)
|
−2.3 ± 9.0 (196)
|
1.0 ± 7.9 (198)
|
0.3 ± 11.5 (327)
|
2. ± 11.2 (332)
|
|
P valuec
|
<0.001
| |
0.62
| |
<0.001
| |
0.001
| |
|
ADCS-ADL19 (number)
|
−5.1 ± 6.3 (126)
|
−3.0 ± 6.8 (126)
|
−2.1 ± 5.5 (165)
|
−1.5 ± 6.8 (171)
|
−3.2 ± 6.0 (197)
|
−1.8 ± 6.5 (198)
|
−1.3 ± 7.7 (328)
|
−0.7 ± 6.9 (331)
|
|
P valuec
|
0.022
| |
0.28
| |
0.028
| |
0.18
| |
|
NPI (number)
|
3.6 ± 15.6 (126)
|
0.4 ± 15.4 (126)
|
−0.2 ± 14.5 (154)
|
−1.0 ± 15.9 (161)
|
3.6 ± 14.0 (189)
|
−0.2 ± 11.2 (193)
|
−1.6 ± 12.7 (321)
|
−4.3. ± 14.6 (318)
|
|
P valuec
|
0.37
| |
0.96
| |
0.002
| |
0.005
| |
|
CIBIC-Plusd (number)
|
4.7 ± 1.1 (126)
|
4.5 ± 1.1 (126)
|
4.6 ± 1.0 (163)
|
4.3 ± 1.0 (171)
|
4.7 ± 1.0 (196)
|
4.4 ± 1.0 (198)
|
4.1 ± 1.2 (328)
|
3.8 ± 1.2 (333)
|
|
P valuee
|
0.06
| |
0.18
| |
0.027
| |
0.008
| |
-
aMean ± SD; bMMSE range shown is actual, which may differ from protocol-specified range; c
P values for continuous variables (ADCS-ADL19, SIB, NPI) were generated using ANCOVA models for all trials except for MRZ-90001-9605, in which the Wilcoxon-Mann–Whitney test was used. For the categorical variable (CIBIC-Plus), P values were generated using a Cochran-Mantel-Haenszel test, except for the MRZ-90001-9605 trial, in which Wilcoxon-Mann–Whitney test was used; dCIBIC-Plus rating reflects a change from baseline; therefore, endpoint values are used; e
P values for CIBIC-Plus are based on the CMH test. AD, Alzheimer’s disease; ADCS-ADL19, 19-item Alzheimer’s Disease Cooperative Study – Activities of Daily Living scale; ANCOVA, analysis of covariance; b.i.d., twice daily; ChEI, cholinesterase inhibitor; CIBIC-Plus, Clinician’s Interview-Based Impression of Change – Plus Caregiver Input scale; DON, donepezil; ER, extended release; IR, immediate release; MEM, memantine; MMSE, Mini-Mental State Examination; NPI, Neuropsychiatric Inventory; OC, observed cases; PBO, placebo; q.d., once daily; SD, standard deviation; SIB, Severe Impairment Battery.
