Clinical Trial Nuedexta in Subjects With ALS
Condition: Amyotrophic Lateral Sclerosis (ALS)
MeSH terms: Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis
Intervention: Nuedexta; Matching Placebo
Intervention description: Nuedexta PO (by mouth) for 28 ± 3 days; matching placebo PO (by mouth) for 28 ± 3 days
Intervention MeSH terms: Quinidine; Dextromethorphan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 90.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Amyotrophic lateral sclerosis; ALS; Nuedexta; Bulbar function; motor neurons

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).
    

Eligibility criteria:

        Inclusion Criteria:

          -  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

        Exclusion Criteria:

          -  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

          -  Salivatory radiation within 180 days (6 months) of screening