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

NCT03679975 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: 17MO1R-0012
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Amyotrophic Lateral Sclerosis

Outcome Measures

Primary Outcomes (1)

• 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)

Study Arms (1)

Subjects with ALS

EXPERIMENTAL

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

Interventions

Riluzole Oral Soluble film (ROSF) 50 mg DRUG

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.

Also known as: ROSF, Riluzole Orodispersible Film (ROF)

Subjects with ALS

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• Aquestive Therapeutics: lead
• inVentiv Health Clinical: collaborator
• Covance: collaborator

Study Sites (1)

University of Florida Center for Movement Disorders & Neuroscience

Gainesville, Florida, 32607, United States

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Gary Slatko, Chief Medical Officer
• Organization: Aquestive Therapeutics

clinicaltrials@aquestive.com

908-941-7050

Study Officials

• Cassie Jung

  Aquestive Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 19, 2018
• First Posted: September 21, 2018
• Study Start: April 4, 2018
• Primary Completion: September 26, 2018
• Study Completion: December 21, 2018
• Last Updated: August 18, 2020
• Results First Posted: August 10, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)