Findings From a Pharmacokinetic and Pharmacodynamic Study of Sodium Phenylbutyrate and Taurursodiol in Participants With Amyotrophic Lateral Sclerosis


Pre-Clinical Research

Poster Number: M217


James Wymer, MD, University of Florida, Marcelo Gutierrez, PhD, Amylyx Pharmaceuticals, Inc., Maria St. Pierre, MA, Amylyx Pharmaceuticals, Inc., Whitney McNeely, MSN, APRN, University of Florida, Jennifer Steshyn, MABMH, University of Florida, Adeline Yeo, MSc, Amylyx Pharmaceuticals, Inc., Ali Keshavarz, PharmD, PhD, Amylyx Pharmaceuticals, Inc.

Sodium phenylbutyrate and taurursodiol (PB&TURSO) is an oral, fixed dose combination of 3 g PB/1 g TURSO. Per label, PB&TURSO dosing is 1 sachet daily (QD) for the first 3 weeks, then 1 sachet twice daily (BID) thereafter.

Determine pharmacokinetic (PK) parameters of PB, TURSO, and their major metabolites in participants with amyotrophic lateral sclerosis (ALS) after single and multiple oral administrations.

This was a phase 2a, open-label, sequential period study of PB&TURSO PK in participants with ALS. The study comprised a screening period (<42 days), Period 1 (14+4 days), and Period 2 (5-25 days). Urine and blood samples were collected at Period 1 Day 1 (P1D1) after a single dose (treatment naïve), Period 2 Day 1 (P2D1) to evaluate steady state (SS) on QD, and Period 2 Day 15 (P2D15) to evaluate SS on BID. Results The mean age of participants (n=11) was 61.2 years; most were white (81.8%) and male (63.6%). After single administration (P1D1), 15 days of QD (P2D1), and 15 days of BID (P2D15), PB was rapidly absorbed with tmax occurring around 30 mins post-dose, and TURSO tmax values occurring around 3.5 hours on P1D1 and 4.3 hours on P2D1 and P2D15. PB and TURSO Cmax accumulation ratios were 0.92 and 0.98, indicating no accumulation at SS. No differences were observed in Cmax and AUClast for PB, TURSO, and their metabolites after multiple QD or BID administration; age and weight did not affect Cmax or AUClast. After weight adjustment, no difference in the Cmax and AUClast were observed between sexes. Conclusions No differences were observed in the peak concentration (Cmax) and overall plasma exposure (AUClast) of PB, TURSO and their metabolites after multiple QD/BID dosing. Consistent with the known safety profile of PB&TURSO, the most common related adverse events were diarrhea and dizziness.