Pseudobulbar Affect (PBA) Clinical Trial
Official title:
A Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Assess the Safety and Efficacy and to Determine the Pharmacokinetics of Two Doses of AVP-923 (Dextromethorphan/Quinidine) in the Treatment of Pseudobulbar Affect (PBA) in Patients With Amyotrophic Lateral Sclerosis (ALS) and Multiple Sclerosis (MS)
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.
n/a
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
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