Clinical trial: Riluzole Oral Soluble Film (ROSF) Swallowing Safety in Amyotrophic Lateral Sclerosis (ALS) (NCT03679975)

Eligibility criteria:
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 Revised
             El-Escorial Criteria

          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.

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

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

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

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

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

          9. 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 barrier method contraceptive (e.g., licensed hormonal or
             barrier methods) for more than 2 months prior to the 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.

        Exclusion Criteria:

          1. Subjects who score 2 or below on the Functional Oral Intake Scale.

          2. Subjects with a prior swallowing study that has shown a Penetration Aspiration Scale
             score of 3 or greater

          3. Subjects with a history of 2 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 were unwilling to sign informed consent or subjects who for any other
             reason in the judgment of investigator were unable to complete the study

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

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

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

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

         10. Subjects currently taking riluzole with alanine aminotransferase 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 would be receiving riluzole for the first time who exhibited baseline
             elevations of several liver function tests (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, Aquestive
             Therapeutics, any of its affiliates or partners, or inVentiv Health.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.
Subject must be at most 80 Years

Patient description (medical language): A 47-year-old man comes to the clinic for the follow up of his neuromuscular disease. He experienced gradual, progressive weakness of the left upper extremity over the last year.  Over the last few months, he has also noticed weakness in the right upper extremity.  BP is 120/75, PR is 80 and temperature is 37 C. Reflexes are brisk in the upper extremities, and the plantar responses are extensor.  Mild gait ataxia is present. The patient is under treatment of Riluzole 50 mg BID with the diagnosis of ALS.

Patient description (patient's own words): I've been suffering from a neuromuscular disease for a while now, and I went to my doctor's office. I'm now a 47-year-old man and over the past year I experienced a progressive and gradual weakness of my left upper extremity, and over the past month, I also noticed a weakness over my right upper extremity. My heart rate was 120/75, and my  PR was 80 with 37°C for temperature. My reflexes are not good in my upper extremities, and I have trouble with my balance. I'm also under Exservan 50 mg for my sclerosis.

Does the patient match the trial criteria? Entailment