Safety and Efficacy of AVP-923 in PBA Patients With ALS or MS (STAR)
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
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 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| 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 |
- 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 ]
- The main secondary endpoint is the mean change in CNS-LS score. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
| Enrollment: | 326 |
| Study Start Date: | December 2007 |
| Study Completion Date: | September 2009 |
| Primary Completion Date: | June 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: A
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
Other Names:
|
|
Experimental: B
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
Other Names:
|
|
Placebo Comparator: C
Placebo Capsules
|
Drug: AVP-923
AVP-923 capsules containing dextromethorphan (DM) and quinidine (Q) taken orally twice-a-day for a 12 week period
Other Names:
|
Eligibility| Ages Eligible for Study: | 18 Years to 80 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Show 62 Study Locations| Study Director: | Adrian Hepner, M.D. | Avanir Pharmaceuticals |
More Information
No publications provided
| Responsible Party: | Adrian J. Hepner, MD - Sr. Director Clinical Research, Avanir Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT00573443 History of Changes |
| Other Study ID Numbers: | 07-AVR-123 |
| Study First Received: | December 13, 2007 |
| Last Updated: | June 24, 2011 |
| 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) |
Additional relevant MeSH terms:
|
Amyotrophic Lateral Sclerosis Multiple Sclerosis Sclerosis Motor Neuron Disease Spinal Cord Diseases Central Nervous System Diseases Nervous System Diseases Neurodegenerative Diseases TDP-43 Proteinopathies Neuromuscular Diseases Proteostasis Deficiencies Metabolic Diseases Demyelinating Autoimmune Diseases, CNS Autoimmune Diseases of the Nervous System Demyelinating Diseases |
Autoimmune Diseases Immune System Diseases Pathologic Processes Dextromethorphan Excitatory Amino Acid Antagonists Excitatory Amino Acid Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Physiological Effects of Drugs Antitussive Agents Central Nervous System Agents Therapeutic Uses Respiratory System Agents |
ClinicalTrials.gov processed this record on May 19, 2013