Safety/Efficacy of AVP-923 in the Treatment of Emotional Lability (Uncontrolled Crying & Laughing) in Patients With ALS

Amyotrophic Lateral Sclerosis Clinical Trial

Official title:

A Double-Blind Controlled, Multicenter Phase II/III Study to Assess the Safety and Efficacy of AVP-923 (Dextromethorphan/Quinidine) in the Treatment of Pseudobulbar Affect in Patients With Amyotrophic Lateral Sclerosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00021697
• Other study ID #: 99-AVR-102
• Secondary ID: AVP-923
• Status: Completed
• Phase: Phase 3
• First received: August 1, 2001
• Last updated: July 13, 2016
• Start date: January 2001
• Est. completion date: April 2002

Study information

• Verified date: July 2016
• Source: Avanir Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare and evaluate the safety of AVP-923 (dextromethorphan/quinidine) for the treatment of emotional lability in ALS patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: April 2002
• Est. primary completion date: April 2002
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion:

• 18 to 80 years of age, inclusive

• Confirmed diagnosis of ALS or probable ALS

• Clinical history of pseudobulbar affect

• If female, must not be pregnant, breast-feeding, or planning a pregnancy during the course of the study, and must have a negative urine pregnancy test prior to start of study

• If female, must have been practicing an established method of birth control for at least the prior month (oral contraceptive tablets, hormonal implant device, intrauterine device, diaphragm and contraceptive cream or foam, condom with spermicide, tubal ligation, or abstinence) or be surgically sterile or post-menopausal

• Must be willing to not take any prohibited medications during participation in the study

Exclusion:

• Known sensitivity to quinidine or opiate drugs (codeine, etc.)

• On any anti-depressive medication

• Recently (within two months) diagnosed with ALS

• Currently participating in, or who within the past 30 days have participated in, the study of another investigational new drug

• Previously received treatment with co-administration of dextromethorphan and quinidine

• History of substance abuse within the past two years

• Women who are pregnant or likely to become pregnant during the course of the study

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• AVP-923

Locations

Country	Name	City	State
United States	Johns Hopkins University	Baltimore	Maryland
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Carolinas Medical Center Carolinas Neuromuscular/ALS-MDA Center	Charlotte	North Carolina
United States	Northwestern Medical School	Chicago	Illinois
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	University of Colorado Health Sciences	Denver	Colorado
United States	Loma Linda University Dept. of Neurology	Loma Linda	California
United States	UCLA School of Medicine Dept. of Neurology	Los Angeles	California
United States	University of Wisconsin ALS Clinical Research Center	Madison	Wisconsin
United States	University of Miami Dept. of Neurology	Miami	Florida
United States	Columbia-Presbyterian Center Neurological Institute	New York	New York
United States	MCP-Hahnemann University Dept. of Neurology	Philadelphia	Pennsylvania
United States	Penn Neurological Institute	Philadelphia	Pennsylvania
United States	University of Texas Health Science Center @ San Antonio	San Antonio	Texas
United States	University of California, San Francisco	San Francisco	California
United States	State University of New York	Syracuse	New York
United States	Wake Forest University	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Avanir Pharmaceuticals

Country where clinical trial is conducted

United States, 

References & Publications (9)

Brooks BR, Crumpacker D, Fellus J, Kantor D, Kaye RE. PRISM: a novel research tool to assess the prevalence of pseudobulbar affect symptoms across neurological conditions. PLoS One. 2013 Aug 21;8(8):e72232. doi: 10.1371/journal.pone.0072232. eCollection 2013. — View Citation

Brooks BR, Thisted RA, Appel SH, Bradley WG, Olney RK, Berg JE, Pope LE, Smith RA; AVP-923 ALS Study Group. Treatment of pseudobulbar affect in ALS with dextromethorphan/quinidine: a randomized trial. Neurology. 2004 Oct 26;63(8):1364-70. — View Citation

Dark FL, McGrath JJ, Ron MA. Pathological laughing and crying. Aust N Z J Psychiatry. 1996 Aug;30(4):472-9. Review. — View Citation

Gallagher JP. Pathologic laughter and crying in ALS: a search for their origin. Acta Neurol Scand. 1989 Aug;80(2):114-7. — View Citation

Moore SR, Gresham LS, Bromberg MB, Kasarkis EJ, Smith RA. A self report measure of affective lability. J Neurol Neurosurg Psychiatry. 1997 Jul;63(1):89-93. — View Citation

Müller U, Murai T, Bauer-Wittmund T, von Cramon DY. Paroxetine versus citalopram treatment of pathological crying after brain injury. Brain Inj. 1999 Oct;13(10):805-11. — View Citation

Schadel M, Wu D, Otton SV, Kalow W, Sellers EM. Pharmacokinetics of dextromethorphan and metabolites in humans: influence of the CYP2D6 phenotype and quinidine inhibition. J Clin Psychopharmacol. 1995 Aug;15(4):263-9. — View Citation

Smith RA, Moore SR, Gresham LS, Manley PE, Licht JM: The treatment of affective lability with dextromethorphan. Neurology 54: 604P, 1995

Wolf JK, Santana HB, Thorpy M. Treatment of "emotional incontinence" with levodopa. Neurology. 1979 Oct;29(10):1435-6. — View Citation

External Links

•   Homepage for ALSA/ALS
•   Sponsor's website