Safety and Efficacy of AVP-923 in PBA Patients With ALS or MS
Status:
Completed
Trial end date:
2009-09-01
Target enrollment:
Participant gender:
Summary
Objectives of the study are to evaluate the safety, tolerability, and efficacy of two
different doses of AVP-923 (capsules containing either 30 mg of dextromethorphan hydrobromide
and 10 mg of quinidine sulfate [AVP-923-30] or 20 mg of dextromethorphan hydrobromide and 10
mg of quinidine sulfate [AVP-923-20]) when compared to placebo, for the treatment of PBA in a
population of patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS)
over a 12-week period. An additional objective is to determine the pharmacokinetic parameters
of the two different doses of AVP-923 in a subset of the study population.
Pseudobulbar Affect (PBA) is a condition characterized by involuntary, sudden and frequent
episodes of laughing and/or crying out of proportion or incongruous to the underlying emotion
of happiness or sadness Other terms used to describe this condition include emotional
lability, emotionalism, emotional incontinence, emotional discontrol, excessive emotionalism,
and pathological laughing and crying. The outbursts can occur spontaneously or in response to
provocative stimuli such as questions or events.
A body of evidence suggests that PBA can be modulated through pharmacologic intervention.
Dextromethorphan (DM) is a low-affinity uncompetitive antagonist of the N-Methyl-D-aspartate
(NMDA) receptor, reducing the level of excitatory activity. DM also acts at the
phencyclidine-binding site, which is part of the NMDA receptor complex. DM is a sigma
receptor agonist, suppressing the release of excitatory neurotransmitters.
Quinidine (Q) is a known potent inhibitor of cytochrome P450 2D6 (CYP2D6), that decreases the
metabolism of dextromethorphan and helps to achieve sustained and therapeutic levels of this
drug.