Details

Autor(en) / Beteiligte

• Kletzl, Heidemarie
• Ajmi, Hassan
• Antys, Izabela
• Heinig, Katja
• Jaber, Birgit
• Marbury, Thomas C.
• Young, Annie
• Günther, Andreas

Titel

Effect of mild or moderate hepatic impairment on the pharmacokinetics of risdiplam

Ist Teil von

• British journal of clinical pharmacology, 2022-08, Vol.88 (8), p.3749-3759

Ort / Verlag

England

Erscheinungsjahr

2022

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• 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.