A Phase I, Randomized, SAD, MAD, and PK Study of Risvodetinib in Older Adults and Parkinson's Disease.
J Parkinsons Dis
; 14(2): 325-334, 2024.
Article
en En
| MEDLINE
| ID: mdl-38251063
ABSTRACT
Background:
Pre-clinical studies suggest that c-Abl activation may play an important role in the etiology of Parkinson's disease, making c-Abl an important target to evaluate for potential disease-modification.Objective:
To assess safety, tolerability, and pharmacokinetics of the c-Abl inhibitor risvodetinib (IkT-148009) in healthy subjects and participants with Parkinson's disease.Methods:
Part 1 (single ascending dose (SAD)) and Part 2 (7-day multiple ascending dose (MAD)) studies were in healthy volunteers. Participants were randomized 3ââ1 across 9 SAD doses and 3 MAD doses of risvodetinib (IkT-148009) or placebo. Part 3 was a MAD study conducted at two doses in 14 participants with mild-to-moderate PD (MAD-PD). Primary outcome measures were safety, tolerability and pharmacokinetics. Exploratory outcomes in PD participants included clinical measures of PD state, GI function, and cerebrospinal fluid (CSF) concentration.Results:
108 patients were treated with no dropouts. The SAD tested doses ranging from 12.5 to 325âmg, while the MAD tested 25 to 200âmg and MAD-PD tested 50 to 100âmg in Parkinson's participants. All active doses had a favorable safety profile with no clinically meaningful adverse events. Single dose pharmacokinetics were approximately linear between 12.5âmg and 200âmg for both Cmax and AUC0 - inf without distinction between healthy volunteers and participants with PD. Exposures at each dose were high relative to other drugs in the same kinase inhibitor class.Conclusions:
Risvodetinib (IkT-148009) was well tolerated, had a favorable safety and pharmacology profile over 7-day dosing, did not induce serious adverse events and did not appear to induce deleterious side-effects in participants administered anti-PD medications.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Enfermedad de Parkinson
Tipo de estudio:
Clinical_trials
Límite:
Aged
/
Humans
Idioma:
En
Revista:
J Parkinsons Dis
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos