Effect of mild or moderate hepatic impairment on the pharmacokinetics of risdiplam.
Br J Clin Pharmacol
; 88(8): 3749-3759, 2022 08.
Article
en En
| MEDLINE
| ID: mdl-35301746
ABSTRACT
AIM:
This phase I, multicentre, open-label, nonrandomised, parallel-group, two-part study aimed to evaluate the effect of mild to moderate hepatic impairment on the pharmacokinetics (PK), safety and tolerability of a single oral dose of risdiplam.METHODS:
Adult subjects (aged 18-70 years) with mild (Child-Pugh Class A; Part 1) or moderate (Child-Pugh Class B; Part 2) hepatic impairment were matched with subjects with normal hepatic function on sex, age, body mass index and smoking status. Each subject received a single oral dose of 5 mg of risdiplam. Plasma concentrations of risdiplam and its metabolite M1 were measured and PK parameters were compared. Adverse events, laboratory abnormalities, vital signs and electrocardiogram measurements were assessed.RESULTS:
After a single dose (5 mg) of risdiplam, the risdiplam PK parameters area under the plasma concentration-time curve from time zero to infinity and maximum observed plasma concentration were approximately 20% and 5% lower, respectively, in subjects with mild hepatic impairment and approximately 8% and 20% higher, respectively, in subjects with moderate hepatic impairment compared with subjects with normal hepatic function. These differences were not statistically significant; all 90% confidence intervals for geometric least squares-means ratios spanned unity. No new risdiplam-related safety findings were observed in subjects with mild or moderate hepatic impairment.CONCLUSION:
Mild or moderate hepatic impairment did not have a clinically relevant impact on the PK of risdiplam. Therefore, no dose adjustment is required in patients with mild or moderate hepatic impairment when receiving risdiplam.Palabras clave
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Base de datos:
MEDLINE
Asunto principal:
Hepatopatías
Tipo de estudio:
Clinical_trials
/
Prognostic_studies
Idioma:
En
Revista:
Br J Clin Pharmacol
Año:
2022
Tipo del documento:
Article