Riluzole Oral Soluble Film (ROSF) Swallowing Safety in Amyotrophic Lateral Sclerosis (ALS)

Study Overview
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Brief Summary
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The primary objective is to evaluate the effect, if any, of a single 50 mg dose of Riluzole Oral Soluble Film (ROSF) on swallowing safety in individuals with amyotrophic lateral sclerosis.

Detailed Description
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This was a single site, single dose, open-label study with one group of male or female patients between 18-80 years old with a diagnosis of Probable or Definite Amyotrophic Lateral Sclerosis (ALS) according to revised El-Escorial Criteria. Patients seen in the ALS Clinic at the University of Florida were screened to determine eligibility for participation in the study according to the specified inclusion/exclusion criteria. Following informed consent and enrollment, subjects were given a complete physical and neurological examination including the validated Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R). Swallowing safety was assessed using the gold standard Videofluoroscopic Swallowing Study (VFSS) to allow direct visualization of the swallowing process and any episodes of penetration or aspiration were quantified using the validated Penetration Aspiration Scale (PAS). Subjects participated in a standardized protocol that includes 11 bolus stimuli presentations of different liquid and food materials to test swallowing function using a progression of textures and materials. Immediately following this assessment, subjects were given a single dose of ROSF 50 mg, placed on the median lingual sulcus of the dorsum of the tongue (area under the tongue on the midline groove that separates the surface of the tongue into right and left halves). Three minutes after the administration of ROSF, the identical standardized VFSS protocol was re-administered to allow a comparison of swallowing safety (using the PAS scale) pre- versus post-ROSF administration. The original plan was to enroll 30 patients for a final sample size of 25 completed patients. The protocol stipulated that, depending upon the study enrollment rate, the Sponsor could elect to perform an interim analysis using available data from the subset of subjects who had completed the study at that time. An interim assessment of the data was performed after 8 subjects had completed the study and a ninth patient had been screened and was awaiting VFSS. With agreement from the FDA, the Sponsor decided to terminate the study after 9 completed patients, based on the analysis of the first 8 completed patients showing no evidence of a harmful effect of one dose of ROSF 50 mg on swallowing function.

Official Title
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A Single Center Study to Evaluate the Effect of Riluzole Oral Soluble Film on Swallowing Safety in Individuals With Amyotrophic Lateral Sclerosis

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Drug: Riluzole Oral Soluble film (ROSF) 50 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects between 18-80 years of age, inclusive Subjects with a diagnosis of probable or definite ALS in accordance with the Revised El-Escorial Criteria 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. Subjects with no known allergy to barium, riluzole or inactive ingredients in ROSF Subject or subject's legally authorized representative must be willing and able to give informed consent/assent and HIPAA authorization. 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. 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). Availability to volunteer for the entire study duration and willing to adhere to all protocol requirements 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: Subjects who score 2 or below on the Functional Oral Intake Scale. Subjects with a prior swallowing study that has shown a Penetration Aspiration Scale score of 3 or greater Subjects with a history of 2 or more episodes of aspiration pneumonia requiring hospitalization Subjects with a history of clinically significant liver disease, renal disease, or any other medical condition judged to be exclusionary by the Investigator 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 Female subjects who had a positive urine pregnancy test (βhCG) at screening or Visit 1, were trying to become pregnant, or were breastfeeding. Subjects with active cancer within the previous 2 years, except treated basal cell carcinoma of the skin 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. Subjects with known history of moderate or severe renal impairment as defined by a calculated creatinine clearance of ≤50 mL/minute 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.) 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). Use of potentially hepatotoxic drugs: (e.g., allopurinol, methyldopa, sulfasalazine). Subjects with clinically significant abnormal laboratory values in the judgment of the Investigator 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. 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. Employee or immediate relative of an employee of the investigator, Aquestive Therapeutics, any of its affiliates or partners, or inVentiv Health.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Interventional Model Description: The original plan was to enroll 30 patients for a final sample size of 25 completed patients. With agreement from the FDA, the Sponsor decided to terminate the study after 9 completed patients, based on an interim analysis of the first 8 completed patients with no evidence of a harmful effect of one dose of 50 mg Riluzole Oral Film on swallowing function.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Subjects with ALS<br>Subjects with a diagnosis of probable or definite ALS in accordance with the Revised El-Escorial Criteria were administered a single dose of the Riluzole Oral Soluble Film (ROSF) 50 mg. | Drug: Riluzole Oral Soluble film (ROSF) 50 mg<br>* Enrolled subjects underwent an instrumental evaluation of swallowing safety before and after administration of a single dose of the ROSF formulation containing 50 mg of riluzole.<br>* Other names: Riluzole Orodispersible Film (ROF);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Categorized by Differences From Baseline in Penetration Aspiration Scale (PAS) - Sum of Scores Method | Swallowing safety was assessed using the gold standard Videofluoroscopic Swallowing Study (VFSS) to allow direct visualization of the swallowing process and any episodes of penetration or aspiration were quantified using the validated Penetration Aspiration Scale (PAS). The PAS is an 8-point validated scale of swallowing safety that takes into account both degree/level of airway invasion during swallowing and the patients' response to the penetration or aspiration episode. The assessment is performed via videofluoroscope. Scores of 1 and 2 indicate airway safe swallowing with no airway invasion or ability to clear airway invasion. Scores 3 through 8 indicate airway unsafe swallowing based on penetration of the airway, level of penetration, and the patient's ability to respond. An increase in score/higher score means a worse outcome. A decrease in score/lower score means a better outcome. | Before and after administration of ROSF 50 mg on day 1 (visit 1) |