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Promising Mid-Stage Results Reported for Dextromethorphan/Quinidine Combo in Alzheimer’s-Related Agitation

Study demonstrates significant improvement

Positive results from a phase II trial evaluating AVP-923 (Avanir Pharmaceuticals) for the treatment of agitation in patients with Alzheimer’s disease have been presented at the 2014 American Neurological Association meeting, held October 12–14 in Baltimore, Maryland.

AVP-923 is a combination of two compounds, the active central nervous system ingredient dextromethorphan hydrobromide (a noncompetitive N-methyl-D-aspartate [NMDA] receptor antagonist, sigma-1 receptor agonist, and inhibitor of the serotonin transporter [SERT] and norepinephrine transporter [NET]) plus low-dose quinidine sulfate (a cytochrome P450 2D6 enzyme inhibitor), which serves to increase the bioavailability of dextromethorphan.

AVP-923 is an investigational drug and is not approved by the FDA for the treatment of agitation in patients with Alzheimer’s disease.

In the new study, the compound demonstrated a clinically meaningful and statistically significant improvement in agitation on the trial’s primary endpoint and on most of the secondary endpoints. Key highlights include:

  • AVP-923 showed a statistically significant benefit on the agitation/aggression domain of the Neuropsychiatric Inventory (NPI) (the study's primary endpoint; P = 0.00008).
  • The NPI agitation/aggression score was reduced by 3.3 points from baseline in AVP-923–treated patients at week 5 (stage 1; P = 0.0002 v. placebo) and was reduced by 2.0 points in stage 2 (P = 0.021).
  • The change in the NPI agitation/aggression score corresponded to a mean reduction from baseline of 47% for AVP-923 compared with 22% for placebo in stage 1, and 26% for AVP-923 compared with 6.7% for placebo in stage 2.
  • The treatment benefit with AVP-923 was evident at week 1 and was sustained for the duration of the 10-week study.
  • AVP-923 also demonstrated significant improvements compared with placebo on the following outcomes: NPI total score (P = 0.014); NPI4A (P = 0.001); NPI4D (P < 0.001); clinical global impression of change–agitation (P = 0.0003); patient global impression of change (P = 0.001); and measures of caregiver burden (P ≤ 0.05).

An estimated 6 million Americans have Alzheimer’s disease, a number that has doubled since 1980 and is expected to be as high as 16 million by 2050. The disorder is generally characterized by cognitive decline, impaired performance of daily activities, and behavioral disturbances. Behavioral and psychiatric symptoms develop in up to 60% of community-dwelling dementia patients and in more than 80% of patients with dementia living in nursing homes. Dementia-related behavioral symptoms, including agitation, can be distressing to the patient, to the family, and to caregivers.

Source: Avanir Pharmaceuticals; October 13, 2014.

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