Efficacy and Safety of Brexpiprazole for the Treatment of Agitation in Alzheimer's Dementia: Two 12-Week, Randomized, Double-Blind, Placebo-Controlled Trials.
Am J Geriatr Psychiatry
; 28(4): 383-400, 2020 04.
Article
em En
| MEDLINE
| ID: mdl-31708380
ABSTRACT
OBJECTIVE:
To assess the efficacy, safety, and tolerability of brexpiprazole in patients with agitation in Alzheimer's dementia (AAD).DESIGN:
Two 12-week, randomized, double-blind, placebo-controlled, parallel-arm studies (NCT01862640; NCT01922258).SETTING:
Study 1 81 sites in 7 countries. Study 2 62 sites in 9 countries.PARTICIPANTS:
Patients with AAD (Study 1 433 randomized; Study 2 270 randomized) in a care facility or community-based setting. Stable Alzheimer disease medications were permitted. INTERVENTION Study 1 (fixed dose) brexpiprazole 2 mg/day, brexpiprazole 1 mg/day, or placebo (111) for 12 weeks. Study 2 (flexible dose) brexpiprazole 0.5-2 mg/day or placebo (11) for 12 weeks. MEASUREMENTS Cohen-Mansfield Agitation Inventory (CMAI) (Total score range 29-203; higher scores indicate more frequent agitated behaviors), and Clinical Global Impression - Severity of illness (CGI-S) as related to agitation. Safety was also assessed.RESULTS:
In Study 1, brexpiprazole 2 mg/day demonstrated statistically significantly greater improvement in CMAI Total score from baseline to Week 12 than placebo (adjusted mean difference, -3.77; confidence limits, -7.38, -0.17; t(316)â¯=â¯-2.06; pâ¯=â¯0.040; MMRM). Brexpiprazole 1 mg/day did not show meaningful separation from placebo (0.23; -3.40, 3.86; t(314)â¯=â¯0.12; pâ¯=â¯0.90; MMRM). In Study 2, brexpiprazole 0.5-2 mg/day did not achieve statistical superiority over placebo (-2.34; -5.49, 0.82; t(230)â¯=â¯-1.46; pâ¯=â¯0.15; MMRM). However, a benefit was observed in post hoc analyses among patients titrated to the maximum brexpiprazole dose of 2 mg/day compared with similarly titrated placebo patients (-5.06; -8.99, -1.13; t(144)â¯=â¯-2.54; pâ¯=â¯0.012; MMRM). On the CGI-S, a greater numerical improvement than placebo was demonstrated for brexpiprazole 2 mg/day in Study 1 (-0.16; -0.39, 0.06; t(337)â¯=â¯-1.42; nominal pâ¯=â¯0.16; MMRM), and a greater improvement for brexpiprazole 0.5-2 mg/day in Study 2 (-0.31; -0.55, -0.06; t(222)â¯=â¯-2.42; nominal pâ¯=â¯0.016; MMRM). In Study 1, treatment-emergent adverse events (TEAEs) with incidence ≥5% among patients receiving brexpiprazole 2 mg/day were headache (9.3% versus 8.1% with placebo), insomnia (5.7% versus 4.4%), dizziness (5.7% versus 3.0%), and urinary tract infection (5.0% versus 1.5%). In Study 2, TEAEs with incidence ≥5% among patients receiving brexpiprazole 0.5-2 mg/day were headache (7.6% versus 12.4% with placebo) and somnolence (6.1% versus 3.6%). In both studies, the majority of TEAEs were mild or moderate in severity.CONCLUSIONS:
Brexpiprazole 2 mg/day has the potential to be efficacious, safe, and well tolerated in the treatment of AAD.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Agitação Psicomotora
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Tiofenos
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Quinolonas
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Doença de Alzheimer
Tipo de estudo:
Clinical_trials
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Diagnostic_studies
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Etiology_studies
Limite:
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Am J Geriatr Psychiatry
Assunto da revista:
GERIATRIA
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PSIQUIATRIA
Ano de publicação:
2020
Tipo de documento:
Article