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

NCT ID: NCT00573443

Last Updated: 2017-04-12

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

326 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-12-31

Study Completion Date

2009-09-30

Brief Summary

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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

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Conditions

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Pseudobulbar Affect (PBA)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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DM 30 mg/Q 10 mg

AVP-923-30/10 Capsules (30 mg dextromethorphan/10 mg quinidine)administered once daily for 1 week and then twice daily for 11 weeks

Group Type EXPERIMENTAL

dextromethorphan hydrobromide 30 mg and quinidine sulfate 10 mg

Intervention Type DRUG

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

DM 20 mg/ Q 10 mg

AVP-923-20/10 Capsules (20 mg dextromethorphan/10 mg quinidine)administered once daily for 1 week and then twice daily for 11 weeks

Group Type EXPERIMENTAL

dextromethorphan hydrobromide 20 mg and quinidine sulfate 10 mg

Intervention Type DRUG

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

Placebo

Placebo Capsules once daily for 1 week and then twice daily for an additional 11 weeks

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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

Interventions

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dextromethorphan hydrobromide 20 mg and quinidine sulfate 10 mg

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 Type DRUG

dextromethorphan hydrobromide 30 mg and quinidine sulfate 10 mg

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 Type DRUG

Placebo

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

Intervention Type DRUG

Other Intervention Names

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AVP-923 Nuedexta™ DM 20 mg/ Q 10 mg DMQ AVP-923 DM 30 mg/ Q 10 mg DMQ

Eligibility Criteria

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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

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.)
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Syneos Health

OTHER

Sponsor Role collaborator

Avanir Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Adrian Hepner, M.D.

Role: STUDY_DIRECTOR

Avanir Pharmaceuticals

Locations

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St. Joseph's Hospital and Medical Center

Phoenix, Arizona, United States

Site Status

Neuromuscular Research Center

Scottsdale, Arizona, United States

Site Status

South Coast Clinical Trials

Anaheim, California, United States

Site Status

UCI Medical Center

Irvine, California, United States

Site Status

Center for Neurologic Study

La Jolla, California, United States

Site Status

UCLA School of Medicine

Los Angeles, California, United States

Site Status

The Forbes Norris MDA/ALS Research Center - California Pacific Medical Center

San Francisco, California, United States

Site Status

The ALS Center at UCSF

San Francisco, California, United States

Site Status

University of Colorado at Denver & Health Science Center

Aurora, Colorado, United States

Site Status

Neuroscience Center

Fort Lauderdale, Florida, United States

Site Status

Mayo Clinic

Jacksonville, Florida, United States

Site Status

University of Miami

Miami, Florida, United States

Site Status

Suncoast Neuroscience Associates

St. Petersburg, Florida, United States

Site Status

The ALS Center at Emory University

Atlanta, Georgia, United States

Site Status

Neurology Specialists of Decatur of Decatur

Decatur, Georgia, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

Consultants in Neurology

Northbrook, Illinois, United States

Site Status

University of Kentucky Health Care - Dept. of Neurology

Lexington, Kentucky, United States

Site Status

The John Hopkins Universitiy

Baltimore, Maryland, United States

Site Status

Massachusets General Hospital

Boston, Massachusetts, United States

Site Status

Baystate Medical Center

Springfield, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

St.Louis University - Neuromuscular Clinic

St Louis, Missouri, United States

Site Status

Advanced Neurology Specialists

Great Falls, Montana, United States

Site Status

Neurology Associates

Lincoln, Nebraska, United States

Site Status

Universitiy of Nevada

Las Vegas, Nevada, United States

Site Status

Upstate Clinical Research

Albany, New York, United States

Site Status

Jacobs Neurological Institute

Buffalo, New York, United States

Site Status

Mount Sinai Medical Center

New York, New York, United States

Site Status

Neurological Institute - Columbia Presbyterian Center

New York, New York, United States

Site Status

Carolinas Medical Center

Charlotte, North Carolina, United States

Site Status

Duke Universitiy Medical Center

Durham, North Carolina, United States

Site Status

Department of Neurology - The Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

Ohio State Universitiy

Columbus, Ohio, United States

Site Status

Oregon Health Science University

Portland, Oregon, United States

Site Status

Drexel University - Department of Neurology

Philadelphia, Pennsylvania, United States

Site Status

The ALS Center - Penn Neurological Institute - The University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Vanderbilt University

Nashville, Tennessee, United States

Site Status

The Methodist Hospital - Baylor College of Medicine

Houston, Texas, United States

Site Status

Department of Neuropsychiatry - Texas Tech University

Lubbock, Texas, United States

Site Status

University of Texas Health Science Center

San Antonio, Texas, United States

Site Status

Universitiy of Vermont

Burlington, Vermont, United States

Site Status

West Virginia University

Morgantown, West Virginia, United States

Site Status

Dean Foundation

Madison, Wisconsin, United States

Site Status

FACENE

Buenos Aires, Buenos Aires F.D., Argentina

Site Status

IADIN

Buenos Aires, Buenos Aires F.D., Argentina

Site Status

Hospital Italiano

Buenos Aires, Buenos Aires F.D., Argentina

Site Status

INEBA

Buenos Aires, Buenos Aires F.D., Argentina

Site Status

Hospital Ramos Mejia

Buenos Aires, Buenos Aires F.D., Argentina

Site Status

Hospital Britanico

Buenos Aires, Buenos Aires F.D., Argentina

Site Status

Policlinico Bancario

Buenos Aires, Buenos Aires F.D., Argentina

Site Status

FLENI

Buenos Aires, Buenos Aires F.D., Argentina

Site Status

Hospital Militar Regional de Cordoba

Córdoba, Córdoba Province, Argentina

Site Status

Instituto Medico Rodriguez Alfici

Godoy Cruz, Mendoza Province, Argentina

Site Status

Instituto de Neurociencias Rosario

Rosario, Santa Fe Province, Argentina

Site Status

Santa Casa de Misericordia de Belo Horizonte

Belo Horizonte, M G, Brazil

Site Status

Hospital de Clínicas-UFPR

Curitiba, Paraná, Brazil

Site Status

Hospital da Restauração

Recife, Pernambuco, Brazil

Site Status

Hospital Universitário Clementino Fraga Filho

Rio de Janeiro, Rio de Janeiro, Brazil

Site Status

Hospital Moinhos de Vento

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Hospital das Clínicas da Faculdade de Medicina da Universidade São Paulo

São Paulo, São Paulo, Brazil

Site Status

Countries

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United States Argentina Brazil

References

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Pioro EP, Brooks BR, Cummings J, Schiffer R, Thisted RA, Wynn D, Hepner A, Kaye R; Safety, Tolerability, and Efficacy Results Trial of AVP-923 in PBA Investigators. Dextromethorphan plus ultra low-dose quinidine reduces pseudobulbar affect. Ann Neurol. 2010 Nov;68(5):693-702. doi: 10.1002/ana.22093.

Reference Type RESULT
PMID: 20839238 (View on PubMed)

Other Identifiers

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07-AVR-123

Identifier Type: -

Identifier Source: org_study_id

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