Acasti says preliminary results of GTX-102 study met all outcome measures

Acasti Pharma announces that the preliminary topline results of the pharmacokinetic bridging study for GTX-102 met all outcome measures. The objectives of the study were to evaluate the bioavailability, pharmacokinetics, and safety of GTX-102, a novel, concentrated oral-mucosal metered spray of betamethasone in healthy volunteers. This new formulation is intended to improve the neurological symptoms of Ataxia Telangiectasia in a pediatric population for which there are currently no FDA-approved therapies. GTX-102 can be sprayed conveniently over the tongue of A-T patients, who often have difficulties swallowing. This PK study was the next step in the proposed 505(b)(2) regulatory pathway for GTX-102. This PK bridging study is a Phase 1, randomized, open-label, crossover study in healthy adult subjects to evaluate the comparative bioavailability, PK, and safety of GTX-102 administered as an oral spray compared to intramuscular betamethasone, and to an oral solution of betamethasone, which is available in Europe but not approved in the US. The betamethasone OS was shown to reduce neurological symptoms in children with A-T in a published multicenter, double-blind, randomized, placebo-controlled crossover trial conducted in Italy. The primary objective of this PK bridging study was to evaluate and characterize the PK profile of GTX-102 as an oral spray. A total of 48 healthy adult subjects were enrolled in this single center, 5-treatment, 8-sequence, 2-period cross-over study. The 5 treatments assessed in the study were: GTX-102: low dose at 0.0125 mg/kg, medium dose at 0.05 mg/kg, and high dose at 0.1 mg/kg; OS betamethasone at 0.1 mg/kg; IM betamethasone at 0.1 mg/kg. Each subject received a single dose of 2 treatments in a cross-over fashion, in a randomized sequence over 2 treatment periods separated by 15 days. The dosing started on September 13, 2022 and ended on November 24, 2022. Betamethasone blood levels were compared between all treatment groups. GTX-102 PK study outcome measures definitions and preliminary topline findings are as follows: Primary outcome measures and their definitions include: AUC0-72 is the area under the concentration time curve up to 72 hours post-dose; AUC is the area under the concentration time curve extrapolated to infinity; Cmax is the maximum concentration occurring between 0 hour to 72 hours after study drug administration. GTX-102 given at doses of 0.0125, 0.5 or 0.1 mg/kg, showed betamethasone blood concentrations that were highly predictable and consistent based on AUC and Cmax, indicating good linearity and dose-proportionality. Following the high dose of GTX-102, betamethasone blood concentrations were within the same range of exposure as IM betamethasone, based on AUC. The IM formulation of betamethasone will serve as a bridge for GTX-102 in the context of the proposed 505(b)(2) regulatory pathway. In addition, Betamethasone blood concentrations following the high dose of GTX-102 were within the same range of exposure as OS betamethasone, based on AUC. This OS formulation was the same one that was used by Zannolli et al and may serve as a clinical comparator for further clinical development of GTX-102. There was statistically no significant difference between GTX-102 when comparing a fast rate of administration to a slow rate, as indicated by Cmax and AUC. This is important because being able to use the fast or the slow rate of administration may provide greater flexibility for patients and caregivers. The Cmax of GTX-102 was within the same range of exposure as the OS, but the Cmax for the IM formulation was lower than both GTX-102 and the OS, as well as what has been reported previously for the IM in the literature. It is important to note that achieving bioequivalence with the IM was not an objective of this study, nor was it expected. No serious adverse events were reported during the study. AEs leading to study discontinuation consisted of cough/fever/body pain/stuffy nose, Covid-19 and elevated creatinine kinase, and all events occurred prior to receiving the second treatment. None were judged as being related to the study drugs by the investigator. The most frequent drug-related AE was mild headache. Based on this data, Acasti will work with our clinical experts and FDA to determine the best final dosing regimen for GTX-102 to incorporate into our Phase 3 study design.