Wise Young
08-21-2001, 07:14 PM
Safety/Efficacy of AVP-923 in the Treatment of Emotional Lability (Uncontrolled Crying & Laughing) in Patients With ALS
This study is currently recruiting patients.
Sponsored by
Avanir Pharmaceuticals
Center For Neurologic Study
Purpose
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.
Condition Treatment or Intervention Phase ALS
Drug:AVP-923
Phase III
MEDLINEplusrelated topics:AmyotrophicLateralSclerosis
Study Type:Interventional
Study Design:Treatment,Randomized,Double-Blind Method,Active Control,Parallel Assignment,Safety/Efficacy Study
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
Eligibility
Ages Eligible for Study: 18 Years - 80 Years, Genders Eligible for Study: Both
Participants: Patients
Criteria
Inclusion:
-18 to 80 years of age, inclusive
-Confirmed diagnosis of ALS or probable ALS
-Clinical history of pseudobulbar affect
-CNS-LS score at baseline is > or = 13
-HRSD score is < or = 16 on the 21-item scale
-Normal hematologic, hepatic, and renal function, with no clinically significant deviations, as determined by standard laboratory tests (CBC, SMA-20, and urinalysis)
-Vital capacity of > or = 50%
-EKG (obtained within four weeks prior to entry and read by Biomedical Systems Corporation) with no evidence of a) heart block or any intraventricular conduction delay with QRS duration > or = 120 msec; second degree heart block; or complete heart block; b) prolongation of Q-Tc interval (> or = 450 msec); c) sinus bradycardia (<50 bpm) or history of sick sinus syndrome; or d) ventricular tachycardia or ventricular ectopic beats (>5 per minute)
-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
-Signed and received a copy of an informed consent form after the nature of the study had been fully explained
Exclusion:
-Unwilling or unable to comply with study instructions
-EKG (obtained within four weeks prior to entry and read by Biomedical Systems Corporation) with evidence of a)heart block; second degree heart block; or complete heart block; b) prolongation of Q-Tc interval (>/= 450 msec); c) sinus bradycardia (<50 bpm) or history of sick sinus syndrome; or d) ventricular tachycardia or ventricular ectopic beats (>5 per minute)
-Any history of torsades de pointes
-Known sensitivity to quinidine or opiate drugs (codeine, etc.)
-On concomitant medications which are on the list of disallowed medications or who have been on disallowed concomitant medications within one week prior to Day 1
-HRSD score is >16 on the 21-item scale
-On any anti-depressive medication
-Current or prior history of major psychiatric disturbance. Exclusionary psychiatric diagnoses, as determined by chart review and patient interview, including the following Axis I disorders (DSM-IVR criteria): (i) major depression; (ii) bipolar disorder; (iii) schizophrenia or other psychotic disorder; (iv) somatoform disorders. The Axis II disorder of borderline personality is also excluded.
-Co-existent major systemic diseases that would interfere with interpretation of the results of the study, e.g., malignancy, poorly controlled diabetes, ischemic cardiac disease
-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
-Myasthenia gravis
-Liver, kidney, or pulmonary disease (vital capacity <50%)
-Previously received treatment with co-administration of dextromethorphan and quinidine
-Hypotension (systolic BP <100 mmHg) or history of postural syncope
-History of substance abuse within the past two years
-Women who are pregnant or likely to become pregnant during the course of the study
Expected Total Enrollment: 100
Location and Contact Information
California
Loma Linda University Dept. of Neurology,Loma Linda, California, 92354, United States;Recruiting
Dee Moses 909-558-2236 neuro@jps.net
Carmel Armon, MD, Principal Investigator
California
UCLA School of Medicine Dept. of Neurology,Los Angeles, California, 90095, United States;Recruiting
Linda DeSepulveda 310-825-9816 lbdesepu@ucla.edu Michael Graves, MD, Principal Investigator
California
California Pacific Medical Center Dept. of Neurology,San Francisco, California, 94115, United States;Recruiting
Tracy Stewart 415-923-3963 tracy@cooper.cpmc.org Robert Miller, MD, Principal Investigator
California
University of California, San Francisco,San Francisco, California, 94143, United States;Recruiting
Jason Mass 415-476-7581 jwmass1@itsa.ucsf.edu Richard Olney, MD, Principal Investigator
Colorado
University of Colorado Health Sciences,Denver, Colorado, 80262, United States;Recruiting
Kristen Blackwell 303-315-7046 kristin.howell@UCHSC.edu Hans Neville, MD, Principal Investigator
Florida
University of Miami Dept. of Neurology,Miami, Florida, 33136, United States;Recruiting
Julie Steele 305-243-7424 jsteele@med.miami.edu Walter Bradley, MD, Principal Investigator
Illinois
Northwestern Medical School,Chicago, Illinois, 60611, United States;Recruiting
Pat Casey 312-695-0774 pcasey@nmff.org
Robert Sufit, MD, Principal Investigator
Maryland
Johns Hopkins University,Baltimore, Maryland, 21287, United States;Recruiting
Lora Clawson 410-955-8511
Jeffrey Rothstein, MD, Principal Investigator
Massachusetts
Massachusetts General Hospital,Boston, Massachusetts, 02114, United States;Recruiting
Lauren Bradbury 617-726-8741 lbradbury@partners.org Merit Cudkowicz, MD, Principal Investigator
New Jersey
UMDNJ - Robert Wood Johnson Medical School Neuromuscular & ALS Center,New Brunswick, New Jersey, 08901, United States;Recruiting
Amelia Sherr 732-235-7331 sherram@mumdnj.edu Jerry Belsh, MD, Principal Investigator
New York
Columbia-Presbyterian Center Neurological Institute,New York, New York, 10032, United States;Recruiting
Maura Del Bene 212-305-5105 alscenter@columbia.edu Hiroshi Mitsumoto, MD, Principal Investigator
North Carolina
Wake Forest University,Winston Salem, North Carolina, 27157, United States;Recruiting
Carolyn Ashburn 336-716-9056
Peter Donofrio, MD, Principal Investigator
North Carolina
Carolinas Medical Center Carolinas Neuromuscular/ALS-MDA Center,Charlotte, North Carolina, 28203, United States;Recruiting
Debby Robbins 704-446-6257 jeffrey.rosenfeld@carolinasshealthcare.org Jeffrey Rosenfeld, MD, Ph.D., Principal Investigator
Ohio
Cleveland Clinic Foundation,Cleveland, Ohio, 44195, United States;Recruiting
Terese Wheeler 216-445-1741 pioroe@ccf.org Erik Pioro, MD, Ph.D., Principal Investigator
Pennsylvania
MCP-Hahnemann University Dept. of Neurology,Philadelphia, Pennsylvania, 19107, United States;Recruiting
Kelly Lindheiman@drexel.edu
Terry Hieman-Patterson, MD, Principal Investigator
Pennsylvania
Penn Neurological Institute,Philadelphia, Pennsylvania, 19107, United States;Recruiting
Barb Pyne 215-829-3709 bapyne@pahosp.com Leo McClusky, MD, Principal Investigator
Texas
Baylor College of Medicine Dept. of Neurology,Houston, Texas, 77030, United States;No longer recruiting
Joan Wilson 713-798-4072 joanew@bcm.tmc.edu Stanley Appel, MD, Principal Investigator
Wisconsin
University of Wisconsin ALS Clinical Research Center,Madison, Wisconsin, 53792, United States;Recruiting
Kathy Roelke 608-262-7175 roelke@neurology.wisc.edu Benjamin Brooks, MD, Principal Investigator
More Information
Home page of the Muscular Dystrophy Association
Sponsor's website
Publications
Dark SF, McGrath JJ, Ron MA: Pathological laughing and crying. Australian & New Zealand Journal of Psychiatry 7: 472-479, 1996.
Smith RA, Moore SR, Gresham LS, Manley PE, Licht JM: The treatment of affective lability with dextromethorphan. Neurology 54: 604P, 1995
Gallagher JP. Pathologic laughter and crying in ALS: a search for their origin. Acta Neurol Scand. 1989 Aug;80(2):114-7. PMID: 2816272 [PubMed - indexed for MEDLINE]
Wolf JK, Santana HB, Thorpy M. Treatment of "emotional incontinence" with levodopa. Neurology. 1979 Oct;29(10):1435-6. No abstract available. PMID: 573397 [PubMed - indexed for MEDLINE]
Muller 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. PMID: 10576464 [PubMed - indexed for MEDLINE]
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. PMID: 9221973 [PubMed - indexed for MEDLINE]
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. PMID: 7593709 [PubMed - indexed for MEDLINE]
Study ID Numbers 99-AVR-102; AVP-923
NLM Identifier NCT00021697
Date study started January 2001;
Date Study Completed November 2001 Record last reviewed July 2001
This study is currently recruiting patients.
Sponsored by
Avanir Pharmaceuticals
Center For Neurologic Study
Purpose
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.
Condition Treatment or Intervention Phase ALS
Drug:AVP-923
Phase III
MEDLINEplusrelated topics:AmyotrophicLateralSclerosis
Study Type:Interventional
Study Design:Treatment,Randomized,Double-Blind Method,Active Control,Parallel Assignment,Safety/Efficacy Study
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
Eligibility
Ages Eligible for Study: 18 Years - 80 Years, Genders Eligible for Study: Both
Participants: Patients
Criteria
Inclusion:
-18 to 80 years of age, inclusive
-Confirmed diagnosis of ALS or probable ALS
-Clinical history of pseudobulbar affect
-CNS-LS score at baseline is > or = 13
-HRSD score is < or = 16 on the 21-item scale
-Normal hematologic, hepatic, and renal function, with no clinically significant deviations, as determined by standard laboratory tests (CBC, SMA-20, and urinalysis)
-Vital capacity of > or = 50%
-EKG (obtained within four weeks prior to entry and read by Biomedical Systems Corporation) with no evidence of a) heart block or any intraventricular conduction delay with QRS duration > or = 120 msec; second degree heart block; or complete heart block; b) prolongation of Q-Tc interval (> or = 450 msec); c) sinus bradycardia (<50 bpm) or history of sick sinus syndrome; or d) ventricular tachycardia or ventricular ectopic beats (>5 per minute)
-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
-Signed and received a copy of an informed consent form after the nature of the study had been fully explained
Exclusion:
-Unwilling or unable to comply with study instructions
-EKG (obtained within four weeks prior to entry and read by Biomedical Systems Corporation) with evidence of a)heart block; second degree heart block; or complete heart block; b) prolongation of Q-Tc interval (>/= 450 msec); c) sinus bradycardia (<50 bpm) or history of sick sinus syndrome; or d) ventricular tachycardia or ventricular ectopic beats (>5 per minute)
-Any history of torsades de pointes
-Known sensitivity to quinidine or opiate drugs (codeine, etc.)
-On concomitant medications which are on the list of disallowed medications or who have been on disallowed concomitant medications within one week prior to Day 1
-HRSD score is >16 on the 21-item scale
-On any anti-depressive medication
-Current or prior history of major psychiatric disturbance. Exclusionary psychiatric diagnoses, as determined by chart review and patient interview, including the following Axis I disorders (DSM-IVR criteria): (i) major depression; (ii) bipolar disorder; (iii) schizophrenia or other psychotic disorder; (iv) somatoform disorders. The Axis II disorder of borderline personality is also excluded.
-Co-existent major systemic diseases that would interfere with interpretation of the results of the study, e.g., malignancy, poorly controlled diabetes, ischemic cardiac disease
-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
-Myasthenia gravis
-Liver, kidney, or pulmonary disease (vital capacity <50%)
-Previously received treatment with co-administration of dextromethorphan and quinidine
-Hypotension (systolic BP <100 mmHg) or history of postural syncope
-History of substance abuse within the past two years
-Women who are pregnant or likely to become pregnant during the course of the study
Expected Total Enrollment: 100
Location and Contact Information
California
Loma Linda University Dept. of Neurology,Loma Linda, California, 92354, United States;Recruiting
Dee Moses 909-558-2236 neuro@jps.net
Carmel Armon, MD, Principal Investigator
California
UCLA School of Medicine Dept. of Neurology,Los Angeles, California, 90095, United States;Recruiting
Linda DeSepulveda 310-825-9816 lbdesepu@ucla.edu Michael Graves, MD, Principal Investigator
California
California Pacific Medical Center Dept. of Neurology,San Francisco, California, 94115, United States;Recruiting
Tracy Stewart 415-923-3963 tracy@cooper.cpmc.org Robert Miller, MD, Principal Investigator
California
University of California, San Francisco,San Francisco, California, 94143, United States;Recruiting
Jason Mass 415-476-7581 jwmass1@itsa.ucsf.edu Richard Olney, MD, Principal Investigator
Colorado
University of Colorado Health Sciences,Denver, Colorado, 80262, United States;Recruiting
Kristen Blackwell 303-315-7046 kristin.howell@UCHSC.edu Hans Neville, MD, Principal Investigator
Florida
University of Miami Dept. of Neurology,Miami, Florida, 33136, United States;Recruiting
Julie Steele 305-243-7424 jsteele@med.miami.edu Walter Bradley, MD, Principal Investigator
Illinois
Northwestern Medical School,Chicago, Illinois, 60611, United States;Recruiting
Pat Casey 312-695-0774 pcasey@nmff.org
Robert Sufit, MD, Principal Investigator
Maryland
Johns Hopkins University,Baltimore, Maryland, 21287, United States;Recruiting
Lora Clawson 410-955-8511
Jeffrey Rothstein, MD, Principal Investigator
Massachusetts
Massachusetts General Hospital,Boston, Massachusetts, 02114, United States;Recruiting
Lauren Bradbury 617-726-8741 lbradbury@partners.org Merit Cudkowicz, MD, Principal Investigator
New Jersey
UMDNJ - Robert Wood Johnson Medical School Neuromuscular & ALS Center,New Brunswick, New Jersey, 08901, United States;Recruiting
Amelia Sherr 732-235-7331 sherram@mumdnj.edu Jerry Belsh, MD, Principal Investigator
New York
Columbia-Presbyterian Center Neurological Institute,New York, New York, 10032, United States;Recruiting
Maura Del Bene 212-305-5105 alscenter@columbia.edu Hiroshi Mitsumoto, MD, Principal Investigator
North Carolina
Wake Forest University,Winston Salem, North Carolina, 27157, United States;Recruiting
Carolyn Ashburn 336-716-9056
Peter Donofrio, MD, Principal Investigator
North Carolina
Carolinas Medical Center Carolinas Neuromuscular/ALS-MDA Center,Charlotte, North Carolina, 28203, United States;Recruiting
Debby Robbins 704-446-6257 jeffrey.rosenfeld@carolinasshealthcare.org Jeffrey Rosenfeld, MD, Ph.D., Principal Investigator
Ohio
Cleveland Clinic Foundation,Cleveland, Ohio, 44195, United States;Recruiting
Terese Wheeler 216-445-1741 pioroe@ccf.org Erik Pioro, MD, Ph.D., Principal Investigator
Pennsylvania
MCP-Hahnemann University Dept. of Neurology,Philadelphia, Pennsylvania, 19107, United States;Recruiting
Kelly Lindheiman@drexel.edu
Terry Hieman-Patterson, MD, Principal Investigator
Pennsylvania
Penn Neurological Institute,Philadelphia, Pennsylvania, 19107, United States;Recruiting
Barb Pyne 215-829-3709 bapyne@pahosp.com Leo McClusky, MD, Principal Investigator
Texas
Baylor College of Medicine Dept. of Neurology,Houston, Texas, 77030, United States;No longer recruiting
Joan Wilson 713-798-4072 joanew@bcm.tmc.edu Stanley Appel, MD, Principal Investigator
Wisconsin
University of Wisconsin ALS Clinical Research Center,Madison, Wisconsin, 53792, United States;Recruiting
Kathy Roelke 608-262-7175 roelke@neurology.wisc.edu Benjamin Brooks, MD, Principal Investigator
More Information
Home page of the Muscular Dystrophy Association
Sponsor's website
Publications
Dark SF, McGrath JJ, Ron MA: Pathological laughing and crying. Australian & New Zealand Journal of Psychiatry 7: 472-479, 1996.
Smith RA, Moore SR, Gresham LS, Manley PE, Licht JM: The treatment of affective lability with dextromethorphan. Neurology 54: 604P, 1995
Gallagher JP. Pathologic laughter and crying in ALS: a search for their origin. Acta Neurol Scand. 1989 Aug;80(2):114-7. PMID: 2816272 [PubMed - indexed for MEDLINE]
Wolf JK, Santana HB, Thorpy M. Treatment of "emotional incontinence" with levodopa. Neurology. 1979 Oct;29(10):1435-6. No abstract available. PMID: 573397 [PubMed - indexed for MEDLINE]
Muller 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. PMID: 10576464 [PubMed - indexed for MEDLINE]
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. PMID: 9221973 [PubMed - indexed for MEDLINE]
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. PMID: 7593709 [PubMed - indexed for MEDLINE]
Study ID Numbers 99-AVR-102; AVP-923
NLM Identifier NCT00021697
Date study started January 2001;
Date Study Completed November 2001 Record last reviewed July 2001