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Safety and Efficacy of AVP-923 in PBA Patients With ALS or MS (STAR)

This study is currently recruiting participants.
Verified by Avanir Pharmaceuticals, September 2008

Sponsors and Collaborators: Avanir Pharmaceuticals
Kendle International
Information provided by: Avanir Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00573443
  Purpose

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 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 is a known potent inhibitor of cytochrome CYP2D6, that decreases the metabolism of dextromethorphan and helps to achieve sustained and therapeutic levels of this drug.


Condition Intervention Phase
Pseudobulbar Affect (PBA)
Drug: AVP-923
Phase III

Genetics Home Reference related topics:   amyotrophic lateral sclerosis   

MedlinePlus related topics:   Amyotrophic Lateral Sclerosis    Multiple Sclerosis   

ChemIDplus related topics:   Dextromethorphan    Dextromethorphan hydrobromide    Levomethorphan    Racemethorphan    Quinidine    Avp 923   

U.S. FDA Resources

Study Type:   Interventional
Study Design:   Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
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 and Multiple Sclerosis

Further study details as provided by Avanir Pharmaceuticals:

Primary Outcome Measures:
  • The primary efficacy endpoint is the number of laughing and/or crying episodes as recorded in the patient diary. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The main secondary endpoint is the mean change in CNS-LS score. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:   306
Study Start Date:   December 2007
Estimated Study Completion Date:   June 2009
Estimated Primary Completion Date:   March 2009 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
A: Experimental
AVP-923-30/10 Capsules (30 mg DM/10 mg Q)
Drug: AVP-923
AVP-923 capsules containing dextromethorphan (DM) and quinidine (Q) taken orally twice-a-day for a 12 week period
B: Experimental
AVP-923-20/10 Capsules (20 mg DM/10 mg Q)
Drug: AVP-923
AVP-923 capsules containing dextromethorphan (DM) and quinidine (Q) taken orally twice-a-day for a 12 week period
C: Placebo Comparator
Placebo Capsules
Drug: AVP-923
AVP-923 capsules containing dextromethorphan (DM) and quinidine (Q) taken orally twice-a-day for a 12 week period

  Eligibility
Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Criteria

Main Inclusion Criteria:

  • The patient has a diagnosis of Amyotrophic Lateral Sclerosis (according to El Escorial Criteria, WFN, 1998) and the time from diagnosis of ALS is not be longer than 30 months, or the patient has a diagnosis of multiple sclerosis or probable multiple sclerosis (according to McDonald criteria, 2001)
  • The patient has a clinical history and clinical relevant symptoms of Pseudobulbar Affect (PBA)
  • CNS-LS score at baseline is 13 or greater

Main Exclusion Criteria:

  • Patients with myasthenia gravis
  • Any personal history of complete heart block, QTc prolongation, or torsades de pointes
  • Any family history of congenital QT interval prolongation syndrome
  • Patients with known sensitivity to quinidine, dextromethorphan or opiate drugs (codeine, etc.)
  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00573443

Show 59 study locations  Show 59 Study Locations

Sponsors and Collaborators
Avanir Pharmaceuticals
Kendle International

Investigators
Study Director:     Adrian Hepner, M.D.     Avanir Pharmaceuticals    
  More Information

Responsible Party:   Avanir Pharmaceuticals ( Adrian J. Hepner, MD - Sr. Director Clinical Research )
Study ID Numbers:   07-AVR-123
First Received:   December 13, 2007
Last Updated:   September 3, 2008
ClinicalTrials.gov Identifier:   NCT00573443
Health Authority:   United States: Food and Drug Administration;   Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica;   Argentina: Human Research Bioethics Committee;   Brazil: Ministry of Health;   Brazil: National Committee of Ethics in Research

Keywords provided by Avanir Pharmaceuticals:
Amyotrophic Lateral Sclerosis (Lou Gehrig's disease, ALS)  
Multiple Sclerosis (MS)  

Study placed in the following topic categories:
Spinal Cord Diseases
Demyelinating diseases
Neurodegenerative Diseases
Naphazoline
Multiple Sclerosis
Neuromuscular Diseases
Phenylephrine
Phenylpropanolamine
Motor Neuron Disease
Autoimmune Diseases of the Nervous System
Excitatory Amino Acids
Autoimmune Diseases
Demyelinating Diseases
Central Nervous System Diseases
Sclerosis
Degenerative motor system disease
Motor neuron disease
Oxymetazoline
Amyotrophic lateral sclerosis
Amyotrophic Lateral Sclerosis
Guaifenesin
Quinidine
Dextromethorphan
Demyelinating Autoimmune Diseases, CNS
Lou Gehrig's disease

Additional relevant MeSH terms:
Respiratory System Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Therapeutic Uses
Physiological Effects of Drugs
Nervous System Diseases
Excitatory Amino Acid Agents
Antitussive Agents
Central Nervous System Agents
Pharmacologic Actions
Excitatory Amino Acid Antagonists

ClinicalTrials.gov processed this record on September 05, 2008




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