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Pseudobulbar Affect (PBA)Phase 3STARNCT00573443

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

A Phase 3 study testing dextromethorphan hydrobromide 20 mg and quinidine sulfate 10 mg and dextromethorphan hydrobromide 30 mg and quinidine sulfate 10 mg in people with Pseudobulbar Affect (PBA), run by Avanir Pharmaceuticals at 62 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Pseudobulbar Affect (PBA)
What is being tested?
dextromethorphan hydrobromide 20 mg and quinidine sulfate 10 mg and dextromethorphan hydrobromide 30 mg and quinidine sulfate 10 mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
326 participants
Where
62 sitesin 3 countries
Study dates
Dec 2007to Sep 2009
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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.)

Trial locations and contacts

62 sites in 3 countries.

62 sites in 3 countries

United States45 sites

  • Upstate Clinical Research

    Albany, New York, 12205

  • South Coast Clinical Trials

    Anaheim, California, 92804

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • The ALS Center at Emory University

    Atlanta, Georgia, 30322

  • University of Colorado at Denver & Health Science Center

    Aurora, Colorado, 80045

  • The John Hopkins Universitiy

    Baltimore, Maryland, 21287

  • Massachusets General Hospital

    Boston, Massachusetts, 02129

  • Jacobs Neurological Institute

    Buffalo, New York, 14203

  • Universitiy of Vermont

    Burlington, Vermont, 05405

  • Carolinas Medical Center

    Charlotte, North Carolina, 28207

  • Northwestern University

    Chicago, Illinois, 60611

  • Department of Neurology - The Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Ohio State Universitiy

    Columbus, Ohio, 43210

  • Neurology Specialists of Decatur of Decatur

    Decatur, Georgia, 30033

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • Duke Universitiy Medical Center

    Durham, North Carolina, 27710

  • Neuroscience Center

    Fort Lauderdale, Florida, 33334

  • Advanced Neurology Specialists

    Great Falls, Montana, 59405

  • The Methodist Hospital - Baylor College of Medicine

    Houston, Texas, 77030

  • UCI Medical Center

    Irvine, California, 92868

  • Mayo Clinic

    Jacksonville, Florida, 32224

  • Center for Neurologic Study

    La Jolla, California, 92103

  • Universitiy of Nevada

    Las Vegas, Nevada, 89102

  • University of Kentucky Health Care - Dept. of Neurology

    Lexington, Kentucky, 40536

  • Neurology Associates

    Lincoln, Nebraska, 68506

  • UCLA School of Medicine

    Los Angeles, California, 90095

  • Department of Neuropsychiatry - Texas Tech University

    Lubbock, Texas, 79430

  • Dean Foundation

    Madison, Wisconsin, 53715

  • University of Miami

    Miami, Florida, 33136

  • West Virginia University

    Morgantown, West Virginia, 26506

  • Vanderbilt University

    Nashville, Tennessee, 37232

  • Mount Sinai Medical Center

    New York, New York, 10029

  • Neurological Institute - Columbia Presbyterian Center

    New York, New York, 10032

  • Consultants in Neurology

    Northbrook, Illinois, 60062

  • Drexel University - Department of Neurology

    Philadelphia, Pennsylvania, 19107

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

    Philadelphia, Pennsylvania, 19107

  • St. Joseph's Hospital and Medical Center

    Phoenix, Arizona, 85013

  • Oregon Health Science University

    Portland, Oregon, 97239

  • University of Texas Health Science Center

    San Antonio, Texas, 78229

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

    San Francisco, California, 94115

  • The ALS Center at UCSF

    San Francisco, California, 94117

  • Neuromuscular Research Center

    Scottsdale, Arizona, 85258

  • Baystate Medical Center

    Springfield, Massachusetts, 01199

  • St.Louis University - Neuromuscular Clinic

    St Louis, Missouri, 63110

  • Suncoast Neuroscience Associates

    St. Petersburg, Florida, 33701

Other trials in United States

Argentina11 sites

  • FACENE

    Buenos Aires, Buenos Aires F.D., 1117ABD

  • IADIN

    Buenos Aires, Buenos Aires F.D., C1055AAD

  • Hospital Italiano

    Buenos Aires, Buenos Aires F.D., C1181ACH

  • INEBA

    Buenos Aires, Buenos Aires F.D., C1192AAW

  • Hospital Ramos Mejia

    Buenos Aires, Buenos Aires F.D., C1221ADC

  • Hospital Britanico

    Buenos Aires, Buenos Aires F.D., C1280AEB

  • Policlinico Bancario

    Buenos Aires, Buenos Aires F.D., C1416DRJ

  • FLENI

    Buenos Aires, Buenos Aires F.D., C1428AQK

  • Hospital Militar Regional de Cordoba

    Córdoba, Córdoba Province, X5000HGX

  • Instituto Medico Rodriguez Alfici

    Godoy Cruz, Mendoza Province, M5501AAP

  • Instituto de Neurociencias Rosario

    Rosario, Santa Fe Province, 2002KQJ

Other trials in Argentina

Brazil6 sites

  • Santa Casa de Misericordia de Belo Horizonte

    Belo Horizonte, M G, 30.150-221

  • Hospital de Clínicas-UFPR

    Curitiba, Paraná, 80.060.900

  • Hospital Moinhos de Vento

    Porto Alegre, Rio Grande do Sul, 90.560.030

  • Hospital da Restauração

    Recife, Pernambuco, 52.010-040

  • Hospital Universitário Clementino Fraga Filho

    Rio de Janeiro, Rio de Janeiro, 21941-913

  • Hospital das Clínicas da Faculdade de Medicina da Universidade São Paulo

    São Paulo, São Paulo, 05.403-000

Other trials in Brazil

About this 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 (ALS) and Multiple Sclerosis (MS)

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.

Read more

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.

Being tested
dextromethorphan hydrobromide 20 mg and quinidine sulfate 10 mg, dextromethorphan hydrobromide 30 mg and quinidine sulfate 10 mg, Placebo
Keywords
Amyotrophic Lateral Sclerosis (Lou Gehrig's disease, ALS), Multiple Sclerosis (MS)
Medical subject headings
Amyotrophic Lateral Sclerosis, Multiple Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • dextromethorphan hydrobromide 20 mg and quinidine sulfate 10 mgDrug

    Also called AVP-923, Nuedexta™, DM 20 mg/ Q 10 mg, DMQ

    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

  • dextromethorphan hydrobromide 30 mg and quinidine sulfate 10 mgDrug

    Also called AVP-923, DM 30 mg/ Q 10 mg, DMQ

    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

  • PlaceboDrug

    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

Study groups in NCT00573443
Study groupRoleWhat they receive
DM 30 mg/Q 10 mgExperimentalAVP-923-30/10 Capsules (30 mg dextromethorphan/10 mg quinidine)administered once daily for 1 week and then twice daily for 11 weeks
Receives: Drug: dextromethorphan hydrobromide 30 mg and quinidine sulfate 10 mg
DM 20 mg/ Q 10 mgExperimentalAVP-923-20/10 Capsules (20 mg dextromethorphan/10 mg quinidine)administered once daily for 1 week and then twice daily for 11 weeks
Receives: Drug: dextromethorphan hydrobromide 20 mg and quinidine sulfate 10 mg
PlaceboPlacebo comparatorPlacebo Capsules once daily for 1 week and then twice daily for an additional 11 weeks
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. PBA Episode Rate Ratio (Post/Pre), Regression Adjusted

    Episodes were counted each day and recorded in a daily diary. The outcome measure is the ratio of the episode rate over the 84-day treatment period to the rate during the baseline period, adjusted for study site, and underlying disease using longitudinal negative binomial regression.

    Measured: Baseline to Day 84

Secondary outcomes (6)

  1. Mean Change From Baseline in CNS-LS Total Score by Visit

    Center for Neurologic Studies-Lability Scale (CNS-LS) is an instrument for the measurement of PBA that has been validated for the use in patients with ALS and MS. It is a 7-item self-report questionnaire that measures the frequency and severity of PBA episodes, including assessments of labile laughter and labile tearfulness,and provides a score for total PBA (total score can range from 7-35). The following 5-point scoring was used: 1=Applies never, 2=Applies rarely, 3=Applies occasionally, 4=Applies frequently, 5=Applies most of the time. A score of 13 or higher may suggest PBA, and the higher the score the more severe the episodes.

    Measured: Baseline, Day 15, Day 29, Day 57, Day 84

  2. Mean Change From Baseline to Day 84 in Neuropsychiatric Inventory (NPI-Q) Frequency and Severity Score (EE Population)

    The NPI is a retrospective (to 1 month) caregiver-informant interview assessing frequency and severity of 12 neuropsychiatric symptom domains. The NPI score is based on the sum of the severity ratings (0=absent, 1=mild, 3=severe). The 12 symptom domains include delusions, hallucinations, agitation/aggression, dysphoria/depression, anxiety, euphoria/elation, apathy/indifference, disinhibition, irritability/lability, aberrant motor behaviors, nighttime behavioral disturbances, and appetite/eating abnormalities. The NPI severity score is based on severity ratings (0=absent, 1=mild to 3=severe).

    Measured: Baseline to Day 84

  3. Mean Change From Baseline to Day 84 in Neuropsychiatric Inventory (NPI-Q) Frequency and Severity Score (ITT Population)

    The NPI is a retrospective (to 1 month) caregiver-informant interview assessing frequency and severity of 12 neuropsychiatric symptom domains. The NPI score is based on the sum of the severity ratings (0=absent, 1=mild, 3=severe). The 12 symptom domains include delusions, hallucinations, agitation/aggression, dysphoria/depression, anxiety, euphoria/elation, apathy/indifference, disinhibition, irritability/lability, aberrant motor behaviors, nighttime behavioral disturbances, and appetite/eating abnormalities. The NPI severity score is based on severity ratings (0=absent, 1=mild to 3=severe).

    Measured: Baseline to Day 84

  4. Mean Change From Baseline at Day 84 in SF-36 (Short-Form) Health Survey Medical Outcome Score by Category

    The SF-36 is designed to examine a person's perceived health status. The SF-36 includes one multi-item scale measuring eight health concepts: vitality, physical functioning, bodily pain, general health perceptions, physical role-, emotional role-, social role functioning, and mental health. Answers to each question are scored and summed to produce raw scale scores for each health concept which are then transformed to a 0 - 100 scale, a high score defining a more favorable health state. An aggregate summary measure is calculated by averaging the scores from the eight health concepts.

    Measured: Baseline and Day 84

  5. Mean Change From Baseline at Day 84 in Beck Depression Inventory (BDI-II) Total Score

    The BDI-II is a 21-item self report instrument intended to assess the existence and severity of symptoms of depression, summed to give a single score. The BDI-II uses a 4-point for each item ranging from 0 to 3. A total score of 0-13 is considered minimal range, 14 to 19 is mild, 20 to 28 is moderate, and 29 to 63 is severe.

    Measured: Baseline and Day 84

  6. Mean Change From Baseline to Day 84 in Pain Rating Scale (PRS) of MS Subjects

    Subjects with MS were instructed to also record daily the pain they experienced using the PRS. After evaluating the subject's ability to comply with these requirements, the investigator determined if a caregiver should complete the study diary and assessments. Subjects rated their pain over the past 12 hours on a scale of 0 to 10 (0=none, 10=worst pain ever experienced).

    Measured: Baseline, Day 15, Day 29, Day 57, Day 84

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Dec 2007 (estimated)
  2. Study startDec 2007
  3. Primary completionJun 2009
  4. Study completionSep 2009

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
326 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00573443
Sponsor's protocol ID
07-AVR-123
Acronym
STAR
Status last verified
Mar 2017
First submitted
13 Dec 2007
Last updated
12 Apr 2017
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 20839238

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing dextromethorphan hydrobromide 20 mg and quinidine sulfate 10 mg and dextromethorphan hydrobromide 30 mg and quinidine sulfate 10 mg in people with Pseudobulbar Affect (PBA), run by Avanir Pharmaceuticals at 62 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 62 sites in United States, Argentina, Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Jul 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

PBA Episode Rate Ratio (Post/Pre), Regression Adjusted (time frame: Baseline to Day 84). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00573443, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2017.

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