Clinical Trial Nuedexta in Subjects With ALS
Clinical Trial Nuedexta in Subjects With ALS
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).
Muscle weakness, the cardinal feature of ALS, leads to progressive loss of motor function
 affecting the limbs, tongue, respiratory and pharyngeal muscles. Symptomatic treatments such
 as the placement of a feeding tube, can compensate for the inability to swallow. Riluzole,
 the only approved treatment for ALS, may slow disease progression but no treatment is
 curative and none have improved function.

 Unexpectedly, Nuedexta®, approved for the treatment of labile emotionality that occurs in
 association with ALS and other neurological disorders, has been observed to improve bulbar
 function, primarily speech and swallowing, in a number of neurological disorders, including
 ALS. The basis for this is conjectural but likely due to a direct effect of the drug on motor
 neurons in the part of the brain that controls speech and swallowing. The same part of the
 brain appears to modulate the expression of emotions and interestingly the site of action of
 the drug is the same as a site that has been implicated in a juvenile form of ALS.

 This is a multicenter, randomized double-blind, placebo controlled, cross over study
 evaluating the palliative effect of Nuedexta® on bulbar dysfunction. It is expected that
 approximately 60 ALS patients from 7 clinical centers in the US will be enrolled.
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