Abstract Details

Title A Phase 1 Study to Evaluate Bioequivalence Between BHV-0223 40 mg Zydis® Sublingual Formulation and Riluzole 50 mg Oral Tablet in Healthy Volunteers

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) S5 - Therapeutics in ALS and SMA (1:44 PM-1:55 PM)

Poster/Presentation
Number 005

Objective To evaluate rate and extent of absorption of BHV-0223 versus riluzole 50 mg oral tablet (Rilutek®) under fasting conditions (Part I); food-effect on pharmacokinetics (PK) of BHV-0223 (Part II); absorption of Rilutek® when crushed and administered sublingually (Part III).

Background BHV-0223 is a novel, rapidly dissolving Zydis®, 40 mg, sublingual tablet formulation of riluzole that offers an enhanced treatment option for people with ALS.

Design/Methods Part I was an open-label, 2-period, 2-sequence, single-dose crossover study. Fasting healthy volunteers (HVs) were randomized to 1 of 2 treatment sequences (69/sequence): BHV-0223 followed by Rilutek®, or Rilutek® followed by BHV-0223. Parts II and III were each sequential, open-label, 1-period, single-dose studies, in which, fed HVs (n = 67) received BHV-0223, and fasted HVs (n = 6) received crushed Rilutek® administered sublingually, respectively. Safety and plasma PK parameters were evaluated.

Results In Part I, BHV-0223 achieved area under the curve (AUC) and maximum concentration exposures of approximately 90% and 113%, respectively, compared to Rilutek®. The 90% confidence intervals were within the 80%-125% range required by FDA for bioequivalence. Conversely, crushed generic Rilutek® administered sublingually delivered AUC levels with a ratio of 6% compared to orally swallowed Rilutek®. With regard to the assessment of a potential food effect, BHV-0223 demonstrated a fed-to-fasted ratio of 92% with respect to AUC levels.

Conclusions Sublingual BHV-0223 40 mg is bioequivalent to, and thus offers similar efficacy as, Rilutek® 50 mg tablet taken orally; but also potentially increases usability and reduces burden on patients (no need to swallow and no negative food-effect requiring fasting based on AUC); improves safety/tolerability (lower risk of dose-related liver function abnormalities); and enhances the pharmacological profile (less PK variability).

Authors/Disclosures
Irfan Qureshi, MD (Biohaven Pharmaceuticals) PRESENTER	Dr. Qureshi has received personal compensation for serving as an employee of Biohaven. Dr. Qureshi has stock in Biohaven Pharmaceuticals.
Vladimir Coric	Vladimir Coric has received personal compensation for serving as an employee of Biohaven. Vladimir Coric has received personal compensation in the range of $1,000,000+ for serving as an officer or member of the Board of Directors for Bioahven. Vladimir Coric has stock in Biohaven. Vladimir Coric has received intellectual property interests from a discovery or technology relating to health care.
Kimberly Gentile	No disclosure on file
	No disclosure on file
	No disclosure on file
Robert Berman	Robert Berman has received personal compensation for serving as an employee of Biohaven. Robert Berman has received personal compensation in the range of $100,000-$499,999 for serving as an officer or member of the Board of Directors for Biohaven. Robert Berman has received stock or an ownership interest from Biohaven.

��ɫ��

��ɫ��