Riluzole Oral Soluble Film Swallowing Safety in Amyotrophic Lateral Sclerosis

This is a single site, single dose, open-label safety study. Approximately thirty (30)
individuals with amyotrophic lateral sclerosis (ALS) will be enrolled. Subjects seen in the
ALS Clinic at the University of Florida will be screened to determine eligibility according
to the specified inclusion/exclusion criteria. Following enrollment and informed consent,
subjects will undergo a clinical evaluation including the validated Amyotrophic Lateral
Sclerosis Functional Rating Scale-Revised (ALSFRS- R). Swallowing safety will be assessed
using the gold standard Videofluoroscopic Swallowing Study to afford direct visualization of
the swallowing process and any episodes of penetration or aspiration quantified using the
validated Penetration Aspiration Scale (PAS). Subjects will undergo a standardized protocol
that includes 12 bolus stimuli presentations of different liquid and food materials to test
the swallow across a continuum of textures and materials. Immediately following, subjects
will be given a single dose of riluzole oral soluble film (ROSF) 50mg, placed on the median
lingual sulcus of the dorsum of the tongue. Three minutes after the administration of ROSF,
the identical standardized VFSS protocol will be re- administered to allow a comparison of
swallowing safety (using the PAS scale) pre vs. post ROSF administration.

Inclusion Criteria:

1. Male or female subjects between 18-80 years of age, inclusive

2. Subjects with a diagnosis of probable or definite ALS in accordance with the Revisited
El-Escorial Criteria (Cedarbaum, 1999)

3. Subjects must be currently on an oral diet and able to take foods and liquids by mouth
equivalent to a score of 3 or above on the Functional Oral Intake Scale (Crary, 2005).

4. Subjects with no known allergy to barium, riluzole or inactive ingredients* in ROSF

5. Subjects or subject's legally authorized representative must be willing and able to
give informed consent/assent and HIPAA authorization.

6. Subjects must have the ability to comprehend and be informed of the nature of the
study, as assessed by the PI or Sub-Investigator.

7. Subjects prescribed riluzole at or before the dose of study drug. (The study is open
to subjects currently taking riluzole at screening, subjects who are not currently
taking riluzole at screening who have taken riluzole in the past, and subjects to be
newly started on riluzole (given as ROSF in this study.)

8. Female subjects of childbearing potential must have a negative urine pregnancy test at
Screening and Visit 1. Female subjects of childbearing potential (i.e. not surgically
sterile, not 2 years postmenopausal, or not with a sterile partner) must have a
negative pregnancy test at screening and Visit 1, agree to abstinence, be practicing
double barrier contraception or using an FDA approved contraceptive (e.g., licensed
hormonal or barrier methods) for greater than 2 months prior to screening visit and
commit to an acceptable form of birth control for the duration of the study and for 30
days after participation in the study

9. Availability to volunteer for the entire study duration and willing to adhere to all
protocol requirements

Exclusion Criteria:

1. Subjects who score 2 or below on the Functional Oral Intake Scale (Crary, 2005)

2. Subjects with a prior swallowing study that has shown a PAS of 3 or greater

3. Subjects with a history of two or more episodes of aspiration pneumonia requiring
hospitalization

4. Subjects with a history of clinically significant liver disease, renal disease, or any
other medical condition judged to be exclusionary by the investigator

5. Subjects who are unwilling to sign informed consent or subjects who for any other
reason in the judgment of investigator are unable to complete the study

6. Female subjects who have a positive urine pregnancy test (βhCG) at screening or Visit
1, are trying to become pregnant or are breastfeeding.

7. Subjects with active cancer within the previous 2 years, except treated basal cell
carcinoma of the skin

8. Subjects who have taken any experimental drug within 30 days prior to enrollment or
within 5 half-lives of the investigational drug -whichever is the longer period.
However, subjects who have previously completed other MonoSol Rx sponsored ROSF
clinical studies within the last 30 days prior to enrollment may be eligible for
consideration for entry into this study.

9. Subjects with moderate or severe renal impairment as defined by a calculated
creatinine clearance of ≤50 mL/minute

10. Subjects currently taking riluzole with ALT levels greater than 5 times upper limit of
normal or with evidence of clinical jaundice. (Riluzole should be discontinued in
these patients.)

11. Subjects who will be receiving riluzole for the first time who exhibit baseline
elevations of several LFTs (especially elevated bilirubin). (These findings at
baseline should preclude the use of riluzole including ROSF).

12. Use of potentially hepatotoxic drugs: (e.g., allopurinol, methyldopa, sulfasalazine).

13. Subjects with clinically significant abnormal laboratory values in the judgment of the
investigator

14. Use of strong or moderate CYP1A2 inhibitors (e.g., ciprofloxacin, enoxacin,
fluvoxamine, methoxsalen, mexiletine, thiabendazole, vemurafenib, zileuton) and CYP1A2
inducers (e.g. rifampin and barbiturates) in the previous 30 days before first drug
administration.

15. Anything else that, in the opinion of the investigator, would place the subject at
increased risk or preclude the subject's full compliance with or completion of the
study

16. Employee or immediate relative of an employee of the investigator, MonoSol Rx LLC, any
of its affiliates or partners, or inVentiv Health.