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. 2015 Oct 19;1(3):198-204.
doi: 10.1016/j.trci.2015.10.001. eCollection 2015 Nov.

Combined treatment with memantine and galantamine-CR compared with galantamine-CR only in antidementia drug naïve patients with mild-to-moderate Alzheimer's disease

Oliver Peters  1 , Manuel Fuentes  1 , Lisa Katharina Joachim  1 , Frank Jessen  2 , Christian Luckhaus  3 , Johannes Kornhuber  4 , Johannes Pantel  5 , Michael Hüll  6 , Klaus Schmidtke  6 , Eckart Rüther  7 , Hans-Jürgen Möller  8 , Alexander Kurz  9 , Jens Wiltfang  7 , Wolfgang Maier  2 , Birgitt Wiese  10 , Lutz Frölich  11 , Isabella Heuser  1
Affiliations

Combined treatment with memantine and galantamine-CR compared with galantamine-CR only in antidementia drug naïve patients with mild-to-moderate Alzheimer's disease

Oliver Peters et al. Alzheimers Dement (N Y). .

Abstract

Introduction: Several studies have tested the N-methyl-D-aspartate-receptor antagonist memantine as an add-on to pre-existing treatment with acetylcholinesterase inhibitors. The objective of this study was to evaluate the efficacy and safety of a combined memantine and galantamine-CR de novo regimen compared with galantamine-CR only treatment in never treated patients with mild-to-moderate Alzheimer's disease (AD).

Methods: Antidementia drug-naïve participants (n = 232) with probable, mild-to-moderate AD, and mini-mental state examination scores between 15 and 26 (inclusive) were randomized to receive either 20 mg/day memantine plus 24 mg/day galantamine-CR or 24 mg/day galantamine-CR plus placebo in a 52-week, prospective, double-blind, controlled trial. The primary outcome measurement was the change on the Alzheimer's disease assessment scale-cognition score. Secondary measures comprised the Alzheimer's Disease Cooperative Study-activities of daily living inventory and the clinical dementia rating.

Results: At the end of the trial, there were no statistically significant differences between the galantamine-CR/memantine combination and galantamine-CR only group in primary and secondary outcome measurements. The incidence and the severity of adverse events were similar between the groups.

Discussion: In this trial, memantine in combination with galantamine-CR did not show an advantage with respect to cognition, function, and behavior in previously never treated patients with mild-to-moderate AD. There were no significant differences in tolerability and safety between the groups. Thus, a de novo combination treatment results in no significant improvement in disease progression (current controlled trials number: NCT01921972).

Keywords: Acetylcholinesterase inhibitor; Alzheimer's disease; Combination treatment; Dementia; Galantamine-CR; Memantine.

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Figures

Fig. 1
Fig. 1
Study flow. Abbreviations: GAL-only, galantamine-CR; PP, per protocol; ITT, intention to treat.
Fig. 2
Fig. 2
Primary outcome measure Alzheimer's Disease Assessment Scale (ADAS-cog). Sample size at week 16 (Combi/GAL-only): 184 (91/93); at week 26: 175 (90/85) and at week 52: 170 (86/84). Data are presented as mean and standard deviation. Abbreviations: COMBI group, galantamine-CR/memantine combination; GAL-only group, galantamine-CR; LOCF, last observation carried forward.
Fig. 3
Fig. 3
Secondary outcome measure Alzheimer's Disease Cooperative Study-activities of daily living scale (ADCS-ADL). Sample size at week 16 (Combi/GAL-only): 151 (77/74); at week 26: 149 (72/77) and at week 52: 136 (66/70). Data are presented as mean and standard deviation. Abbreviations: COMBI group, galantamine-CR/memantine combination; GAL-only group, galantamine-CR; LOCF, last observation carried forward.
Fig. 4
Fig. 4
Secondary outcome measure clinical dementia rating scale–sum of boxes. Sample size at week 16 (Combi/GAL-only): 188 (94/94); at week 26: 177 (87/90); at week 39: 177 (86/91) and at week 52: 172 (84/88). Data are presented as mean and standard deviation. Abbreviations: COMBI group, galantamine-CR/memantine combination; GAL-only group, galantamine-CR; LOCF, last observation carried forward.
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