Abstract: SA-PO0238
Pharmacokinetics (PK) of Avacopan in Participants with ESKD Requiring Hemodialysis (HD)
Session Information
- Pharmacology
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
- 2000 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
Authors
- Oberoi, Rajneet K, Amgen Inc, Thousand Oaks, California, United States
- Mohrmann, Caroline, Amgen Inc, Thousand Oaks, California, United States
- Flach, Stephen D, Fortrea Inc, Durham, North Carolina, United States
- Marbury, Thomas C., Orlando Clinical Research Center, Orlando, Florida, United States
- Hernandez, Pedro, Floridian Clinical Research, Miami Lakes, Florida, United States
- Gokhale, Manoj, Fortrea Inc, Durham, North Carolina, United States
- MacElrevey, Celeste R, Fortrea Inc, Durham, North Carolina, United States
- Sampson, Caitlin, Amgen Inc, Thousand Oaks, California, United States
- Amouzadeh, Hamid, Amgen Inc, Thousand Oaks, California, United States
- Hudson, Krischan, Amgen Inc, Thousand Oaks, California, United States
- Upreti, Vijay V, Amgen Inc San Francisco, South San Francisco, California, United States
- Ward, Jessica A, Amgen Inc, Thousand Oaks, California, United States
Background
Avacopan is approved as an adjunctive treatment for severe active granulomatosis with polyangiitis (GPA)/microscopic polyangiitis (MPA) at 30-mg BID with food for adults with mild, moderate or severe kidney impairment. It has not been studied in patients on dialysis. This Phase 1, open label study investigated the PK of avacopan and its active metabolite M1 in participants without GPA/MPA with ESKD requiring HD (estimated glomerular filtration rate [eGFR]<15 mL/min/1.73 m2) and healthy participants (HP; eGFR≥90 mL/min/1.73 m2) following single avacopan 30-mg oral dose.
Methods
The ESKD group (n=7) received avacopan on two occasions 18 days apart: 4 hours before the HD session (on-HD), and on a nondialysis day (off-HD). Demographically (age, sex, BMI) matched HP (n=6) received one dose of avacopan. PK samples for avacopan and M1 were collected through day 18 post-dose. PK of avacopan and M1 were compared between the ESKD group (off-HD) and HP, and between on- and off-HD within the ESKD group. Total active moiety (TAM, avacopan + M1 metabolite) was calculated as molar potency-adjusted exposures.
Results
Avacopan area under the concentration-time curve (AUC; partial area of AUC0-48 hours between two consecutive HD sessions) was 14% lower with minimal effect on maximum plasma concentration (Cmax, 3% increase) in the ESKD group off-HD vs HP, while M1 AUC0-48 and Cmax were 34% lower. TAM AUC0-48 was 18% lower in the ESKD group off-HD vs HP, with no difference in Cmax (<1% difference). In the ESKD group, AUC0-48 and Cmax were 9% and 20% lower, respectively, on- vs off-HD, while M1 AUC0-48 and Cmax were similar on- vs off-HD (<5% difference). TAM AUC and Cmax in the ESKD group decreased by 7% and 18%, respectively. Overall, avacopan and M1 individual exposures overlapped between the ESKD group and HP. Avacopan was well-tolerated and no serious adverse events were reported.
Conclusion
Given the PK variability of avacopan (23% to 54%), this study indicates no clinically meaningful effect of ESKD on avacopan, M1 and TAM exposures. No dose adjustment is warranted for avacopan due to ESKD or HD status.
Funding
- Commercial Support – Amgen Inc.