Clinical trial NCT00573443
Conditions: Pseudobulbar Affect (PBA)
Keywords: Amyotrophic Lateral Sclerosis (Lou Gehrig's disease, ALS) Multiple Sclerosis (MS)
Sponsor: Avanir Pharmaceuticals
Start date: 2007-12-01; Completion date: 2009-09-01
Enrollment: 326 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief 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.

Detailed description:

Arms: arm 1: AVP-923-30/10 Capsules (30 mg dextromethorphan/10 mg quinidine)administered once daily for 1 week and then twice daily for 11 weeks arm 2: AVP-923-20/10 Capsules (20 mg dextromethorphan/10 mg quinidine)administered once daily for 1 week and then twice daily for 11 weeks arm 3: Placebo Capsules once daily for 1 week and then twice daily for an additional 11 weeks
Interventions: intervention 1: dextromethorphan hydrobromide 20 mg and quinidine sulfate 10 mg intervention 2: dextromethorphan hydrobromide 30 mg and quinidine sulfate 10 mg intervention 3: Placebo
Intervention descriptions: intervention 1: Dextromethorphan hydrobromide (DM) and quinidine sulfate (Q) capsules (AVP-923 capsules), containing DM 20 mg/ Q 10 mg, taken once daily for 1 week and then twice daily for 11 consecutive weeks to complete a 12-week period intervention 2: Dextromethorphan hydrobromide (DM) and quinidine sulfate (Q) capsules (AVP-923 capsules), containing DM 30 mg/ Q 10 mg taken once daily for 1 week and then twice daily for 11 consecutive weeks to complete a 12-week period intervention 3: Placebo capsules (identical in appearance to AVP-923 capsules being studied in this trial), taken once daily for 1 week and then twice daily for 11 consecutive weeks to complete a 12-week period

Protocol documents: