WASHINGTON — A combination of dextromethorphan 20 mg and quinidine 10 mg, dubbed AVP-923, significantly reduced agitation in patients with Alzheimer’s disease within one week of treatment, according to researchers.
Currently FDA-approved for treating pseudo bulbar affect, the drug’s benefit for agitation in Alzheimer’s patients was sustained for 10 weeks, findings from a phase 2, double-blind, placebo controlled study indicate.
“Our study suggests that AVP-923 has meaningful effects in reducing agitation, and further studies are warranted,” Jeffrey Cummings, MD, of the Cleveland Clinic Lou Ruvo Center said at the 2015 Alzheimer’s International Conference. “If future studies support these findings, we believe this type of pharmacological approach may play a useful role in the management of Alzheimer’s.”
Cummings and colleagues used a two-stage Sequential Parallel Comparison (SPCD) study design to minimize placebo effect and analyze the drugs effects in people with probable Alzheimer’s disease and agitation.
They randomly assigned patients 4:3 to receive either AVP-923 20/10 mg once daily titrated to 30/10 mg twice daily or placebo during stage one (weeks 3-5). In stage two (weeks 6-10), patients in the AVP-923 group continued on 30/10 mg twice daily, and those in the placebo group were stratified based on whether or not they improved (indicating a placebo effect) and re-randomized 1:1 to either placebo or AVP-923.
For the primary analysis, the researchers combined data from stages one and two and found that AVP-923 significantly reduced agitation in patients with Alzheimer’s disease compared with placebo (P<0.001).
In the secondary analysis, NPI Agitation/Agression domain scores declined from 7.1 to 3.5 in the AV-923 group (n=93) compared with a reduction from 7.2 to 5.1 in the placebo group (n=66; P=0.001) over 10 weeks.
“This is a nearly twofold reduction in NPI Agitation/Agression domain scores in the AVP-923 group compared with the placebo group, and that is statistically significant and clinically meaningful,” Cumming said.
Significant improvements from baseline in the AVP-923 group occurred on NPI composite domains including:
- Agitation/Aggression, Irritability/Lability, and Aberrant Motor Behavior with Disinhibition (NPI-4D; P=0.022), or Anxiety (NPI4-A; P=0.014)
- Aberrant Motor Behavior (P=0.026) and Sleep /Nighttime Behavior (P=0.013) domains
- Alzheimer’s Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC; P=0.015)
- Patient Global Impression of Change (PGI-C; P=0.007)
- Caregiver Strain Index (P=0.004) and Cornell Scale for Depression in Dementia (P=0.031)
Compared with placebo, the most common adverse events in the AVP-923 group included falls (8.6% vs. 3.9%), diarrhea (5.9% vs. 3.1%), and urinary tract infection (5.3% vs. 3.9%).
A phase-3 trial of AVP-923 is scheduled to begin in 2015.
- Cummings J et al. #04-09-05. “Dextromethorphan/Quinidine (AVP-923) for Treatment of Agitation in Patients with Alzheimer’s Disease: Analysis of Week 10 Results for Patients Treated Only with AVP-923 Versus Patients Receiving Only Placebo (NCT01584440).” Presented at: Alzheimer’s Association International Conference; July 18-23, 2015; Washington, DC.