Clinical Trial Nuedexta in Subjects With ALS

NCT01806857 | Completed Phase 2 Results

• 2 other identifiers: 2012P0012743FKVAD
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is to determine whether Nuedexta is effective in the treatment of symptoms (impaired speech, swallowing, and saliva control)associated with Amyotrophic Lateral Sclerosis (ALS).

Conditions

Amyotrophic Lateral Sclerosis (ALS)

Keywords

Amyotrophic lateral sclerosis; ALS; Nuedexta; Bulbar function; motor neurons

Outcome Measures

Primary Outcomes (4)

• Bulbar Function Scale (CNS-BFS) Total Score

  The Center for Neurologic Study-Bulbar Function Scale (CNS-BFS) is a 21-item self report scale that assesses three domains of bulbar function: speech, swallowing and salivation. Scores for each question range from 1 (does not apply) to 5 (applies most of the time). The higher the score, the worse the speech, swallowing and salivation (sialorrhea). \[Range of score: 21-105\] The scale was modeled on the Center for Neurologic Study Emotional Lability Scale (CNS-LS) that has been a robust endpoint in four clinical trials. The scale was validated in a large population of ALS patients (n=122) and detects impaired bulbar function at a sensitivity of 90% and a specificity of 0.97%. Test re-test correlation was 0.92% at six-months (n=53).

  Average between Screening Visit to Visit 3

• Bulbar Function Scale (CNS-BFS) Sialorrhea Score

  The Center for Neurologic Study-Bulbar Function Scale (CNS-BFS) is a 21-item self report scale that assesses three domains of bulbar function: speech, swallowing and salivation. Scores for each question range from 1 (does not apply) to 5 (applies most of the time). The higher the score, the worse the salivation (sialorrhea). There are 7 salivation (sialorrhea) questions, with a score range of 7 to 35.

  Average between Screening Visit to Visit 3

• Bulbar Function Scale (CNS-BFS) Speech Score

  The Center for Neurologic Study-Bulbar Function Scale (CNS-BFS) is a 21-item self report scale that assesses three domains of bulbar function: speech, swallowing and salivation. Scores for each question range from 1 (does not apply) to 5 (applies most of the time). The higher the score, the worse the speech. There are 7 speech questions, with a score range of 7 to 35.

  Average between Screening Visit to Visit 3

• Bulbar Function Scale (CNS-BFS) Swallowing Score

  The Center for Neurologic Study-Bulbar Function Scale (CNS-BFS) is a 21-item self report scale that assesses three domains of bulbar function: speech, swallowing and salivation. Scores for each question range from 1 (does not apply) to 5 (applies most of the time). The higher the score, the worse the swallowing. There are 7 swallowing questions, with a score range of 7 to 35.

  Average between Screening Visit to Visit 3

Secondary Outcomes (12)

• Center for Neurologic Study - Lability Scale (CNS-LS) Total Score

  Average between Screening Visit to Visit 3

• ALS Functional Rating Scale- Revised (ALSFRS-R) Total Score

  Average between Screening Visit to Visit 3

• Visual Analog Scale - Speech Scores

  Average between Baseline Visit to Visit 3

• Ashworth Spasticity Scale Score - Right Arm

  Average between Baseline Visit to Visit 3

• Timed Reading of Test Paragraph Result

  Average between Baseline Visit to Visit 3

Study Arms (2)

Nuedexta then Matching Placebo

OTHER

Subjects in this arm will receive treatment with Nuedexta first for 28 days (±3 days) and then crossed over to receive treatment with matching placebo for 28 days (±3 days).

Drug: Nuedexta; Drug: Matching Placebo

Matching Placebo then Nuedexta

OTHER

Subjects in this arm will receive treatment with matching placebo first for 28 days (±3 days) and then crossed over to receive treatment with Nuedexta for 28 days (±3 days).

Drug: Nuedexta; Drug: Matching Placebo

Interventions

Nuedexta DRUG

Nuedexta PO (by mouth) for 28 ± 3 days

Also known as: dextromethorphan hydrobromide and quinidine sulfate

Matching Placebo then Nuedexta; Nuedexta then Matching Placebo

Matching Placebo DRUG

matching placebo PO (by mouth) for 28 ± 3 days

Also known as: sugar pill

Matching Placebo then Nuedexta; Nuedexta then Matching Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ALS diagnosed as possible, laboratory-supported probable, probable, or definite as defined by revised El Escorial criteria
• Age 18 years or older
• Exhibits bulbar dysfunction manifested by dysarthria and/or dysphagia, according to PI judgment, exhibits a score of 55 or above on the CNS-Bulbar Function Scale
• Capable of providing informed consent and following trial procedures
• Geographic accessibility to the site
• Women must not be able to become pregnant for the duration of the study and must be willing to be on two contraceptive therapies
• Slow vital capacity (SVC) measure ≥50% of predicted for gender, height, and age at the screening visit
• Must be able to swallow capsules throughout the course of the study, according to PI judgment
• Subjects must not have taken riluzole for at least 30 days or be on a 50mg BID dose of riluzole for at least 30 days prior to randomization (subjects how have never taken riluzole are permitted in the study)
• Subjects taking anti-sialorrhea medication(s) must be on a stable dose for at least 30 days prior to randomization (anti-sialorrhea naïve subjects are permitted in the study)
• Must be able to safely swallow at least 30 milliliters (mLs) of water for the water swallowing test

You may not qualify if:

• Prior use of Nuedexta®
• Current use of dextromethorphan, quinidine, quinine, mefloquine or opioids
• History of quinidine, quinine, or mefloquine-induced thrombocytopenia, hepatitis, or other hypersensitivity reactions
• History of known sensitivity or intolerability to dextromethorphan
• Use of an mono amine oxidase inhibitor (MAOI) or within 14 days of stopping an MAOI
• Prolonged QT interval, congenital long QT syndrome, history suggestive of torsades de pointes, or heart failure
• Complete atrioventricular (AV) block without implanted pacemaker, or subjects at high risk of complete AV block
• Concomitant use with drugs that both prolong QT interval and are metabolized by cytochrome P 2D6 (CYP2D6) (i.e., thioridazine or pimozide)
• Exposure to any other experimental agent (off-label use or investigational) within 30 days prior to Baseline Visit
• Invasive ventilator dependence, such as tracheostomy
• Any history of either substance abuse within the past year, unstable psychiatric disease, cognitive impairment, or dementia, according to PI judgment
• Placement and/or usage of feeding tube
• Pregnant women or women currently breastfeeding
• Unable to turn diaphragm pacing device off during swallowing tests
• Salivatory Botox within 90 days (3 months) of screening

Sponsors & Collaborators

• Center for Neurologic Study, La Jolla, California,: lead
• ALS Association: collaborator
• State University of New York - Upstate Medical University: collaborator

Study Sites (7)

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Saint Mary's Health Care

Grand Rapids, Michigan, 49503, United States

Location

Hennepin County Medical Center

Minneapolis, Minnesota, 55415, United States

Location

Neurology Associates, P.C.

Lincoln, Nebraska, 68506, United States

Location

The Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Providence ALS Center

Portland, Oregon, 97213, United States

Location

Related Links

• Northeast ALS Consortium Website
• ALS Association Website

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

dextromethorphan - quinidine combination; Dextromethorphan; Quinidine; Sugars

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Cinchona Alkaloids; Quinuclidines; Quinolines; Heterocyclic Compounds, 2-Ring; Carbohydrates

Results Point of Contact

• Title: Richard Smith, MD
• Organization: Center for Neurological Study

cnsonline@ymail.com

858-455-5463

Study Officials

• Richard A Smith, MD

  Center for Neurologic Study (CNS)

  PRINCIPAL INVESTIGATOR

• Jeremy Shefner, MD, PhD

  Barrow Neurological Institute

  PRINCIPAL INVESTIGATOR

• Merit E Cudkowicz, MD, MSc

  Massachusetts General Hospital (MGH)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: March 5, 2013
• First Posted: March 7, 2013
• Study Start: April 1, 2013
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: March 24, 2017
• Results First Posted: March 24, 2017

Record last verified: 2017-02

Locations

US (7)