Abstracts
3427235
(#12) Clinical Profile of AXS-05 in Treating Alzheimer's Disease Agitation: Results From the ADVANCE-1 and ACCORD-1 Randomized, Placebo-Controlled Studies
Abstract: Background: Alzheimer's disease (AD) agitation is characterized by emotional distress, aggression, and disinhibition. AXS-05 (dextromethorphan-bupropion) is a novel, oral NMDA receptor antagonist and sigma-1 receptor agonist approved for treating major depressive disorder in adults. Here, we present two Phase 3 randomized, controlled studies evaluating AXS-05 in AD agitation: ADVANCE-1 and ACCORD-1.
Methods: Eligible patients had probable AD. In ADVANCE-1, patients took AXS-05 (n=152), bupropion (n=49), or placebo (n=156) twice-daily for 5 weeks. Primary endpoint was change from baseline in the Cohen-Mansfield Agitation Inventory (CMAI) score. ACCORD-1 was a randomized discontinuation study with an open-label period where patients received AXS-05 until sustained CMAI response. In the double-blind period, patients took AXS-05 (n=53) or placebo (n=55) for ≤26 weeks or until relapse. Primary endpoint was time to agitation relapse.
Results: In ADVANCE-1, AXS-05 significantly reduced CMAI scores vs bupropion or placebo at Week 5. The most common treatment-emergent adverse events (TEAEs) for AXS-05 included somnolence (8.2%), dizziness (6.3%), and diarrhea (4.4%). In ACCORD-1, AXS-05 treatment was associated with improved CMAI scores as early as Week 1 of the open-label period. In the double-blind period, AXS-05 significantly improved time-to-relapse and relapse rates versus placebo; relapse risk was 3.6-fold lower. The most common TEAEs for AXS-05 included diarrhea (7.5%), fall (7.5%), and back pain (5.7%). AXS-05 was not associated with cognitive impairment or sedation.
Conclusions: AXS-05 led to a substantial, rapid reduction in AD agitation symptoms and was generally well tolerated. Long-term treatment significantly increased AD agitation time-to-relapse, supporting the potential benefit of AXS-05.
Short Description: Two clinical trials, ADVANCE-1 and ACCORD-1, evaluated the safety and efficacy of AXS-05 (dextromethorphan-bupropion; a novel, oral NMDA receptor antagonist and sigma-1 receptor agonist) in the treatment of Alzheimer's disease (AD) agitation. Compared to controls, AXS-05 was associated with substantial, rapid reduction in agitation symptoms. Longer-term AXS-05 treatment was associated with greater time-to-relapse and reduced risk of relapse. AXS-05 was generally well tolerated, supporting its role as a treatment option for AD agitation.
Name of Sponsoring Organization(s): Axsome Therapeutics, Inc
Methods: Eligible patients had probable AD. In ADVANCE-1, patients took AXS-05 (n=152), bupropion (n=49), or placebo (n=156) twice-daily for 5 weeks. Primary endpoint was change from baseline in the Cohen-Mansfield Agitation Inventory (CMAI) score. ACCORD-1 was a randomized discontinuation study with an open-label period where patients received AXS-05 until sustained CMAI response. In the double-blind period, patients took AXS-05 (n=53) or placebo (n=55) for ≤26 weeks or until relapse. Primary endpoint was time to agitation relapse.
Results: In ADVANCE-1, AXS-05 significantly reduced CMAI scores vs bupropion or placebo at Week 5. The most common treatment-emergent adverse events (TEAEs) for AXS-05 included somnolence (8.2%), dizziness (6.3%), and diarrhea (4.4%). In ACCORD-1, AXS-05 treatment was associated with improved CMAI scores as early as Week 1 of the open-label period. In the double-blind period, AXS-05 significantly improved time-to-relapse and relapse rates versus placebo; relapse risk was 3.6-fold lower. The most common TEAEs for AXS-05 included diarrhea (7.5%), fall (7.5%), and back pain (5.7%). AXS-05 was not associated with cognitive impairment or sedation.
Conclusions: AXS-05 led to a substantial, rapid reduction in AD agitation symptoms and was generally well tolerated. Long-term treatment significantly increased AD agitation time-to-relapse, supporting the potential benefit of AXS-05.
Short Description: Two clinical trials, ADVANCE-1 and ACCORD-1, evaluated the safety and efficacy of AXS-05 (dextromethorphan-bupropion; a novel, oral NMDA receptor antagonist and sigma-1 receptor agonist) in the treatment of Alzheimer's disease (AD) agitation. Compared to controls, AXS-05 was associated with substantial, rapid reduction in agitation symptoms. Longer-term AXS-05 treatment was associated with greater time-to-relapse and reduced risk of relapse. AXS-05 was generally well tolerated, supporting its role as a treatment option for AD agitation.
Name of Sponsoring Organization(s): Axsome Therapeutics, Inc
