Food Effect and Pharmacokinetic Bridging of Avacopan in Caucasian and Japanese Healthy Participants.

Avacopan 30 mg twice daily (BID) is approved for the treatment of severe active antineutrophil cytoplasmic autoantibody-associated vasculitis (granulomatosis with polyangiitis and microscopic polyangiitis). Food effect on avacopan pharmacokinetics (PKs) and PK bridging in Japanese participants were examined through 2 phase 1 studies involving healthy adult participants. In Study 1, an open-label, crossover trial, participants received oral administration of a single 30-mg dose of avacopan under fasted and fed conditions.

Pharmacokinetic Evaluation of the CYP3A4 and CYP2C9 Drug-Drug Interaction of Avacopan in 2 Open-Label Studies in Healthy Participants.

Avacopan, a complement 5a receptor (C5aR) antagonist approved for treating severe active antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, was evaluated in 2 clinical drug-drug interaction studies. The studies assessed the impact of avacopan on the pharmacokinetics (PK) of CYP3A4 substrates midazolam and simvastatin and CYP2C9 substrate celecoxib, and the influence of CYP3A4 inhibitor itraconazole and inducer rifampin on the PKs of avacopan. The results indicated that twice-daily oral administration of 30 mg of avacopan increased the area under the curve (AUC) of midazolam by 1.

Glucocorticoid Toxicity Index scores by domain in patients with antineutrophil cytoplasmic antibody-associated vasculitis treated with avacopan versus standard prednisone taper: post-hoc analysis of data from the ADVOCATE trial.

Background: The ADVOCATE trial, in which the complement C5a receptor inhibitor avacopan was compared with a standard prednisone taper in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, used the Glucocorticoid Toxicity Index (GTI) to measure glucocorticoid toxicity change. We set out to do a post-hoc analysis of the ADVOCATE data to evaluate changes in individual GTI domains and their ability to differentiate treatment groups.

Methods: The ADVOCATE trial was a phase 3, double-blind, double-dummy, randomised trial comparing oral avacopan (30 mg) twice daily for 52 weeks plus a prednisone-matching placebo for 20 weeks with oral prednisone tapered over 20 weeks plus an avacopan-matching placebo for 52 weeks in patients with ANCA-associated vasculitis.

The impact of treatment with avacopan on health-related quality of life in antineutrophil cytoplasmic antibody-associated vasculitis: a post-hoc analysis of data from the ADVOCATE trial.

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is characterised by inflammation and destruction of small to medium sized blood vessels. In the previously reported ADVOCATE study, a phase 3 double-blind, double-dummy randomised controlled trial of patients with newly diagnosed or relapsing ANCA-associated vasculitis, the oral selective complement 5a receptor inhibitor avacopan was shown to be non-inferior with regard to remission induction at week 26 and superior with regard to sustained remission at week 52, compared with a prednisone taper in a standard of care regimen. In this Article, we report an in-depth analysis of prespecified and exploratory patient-reported outcomes from the ADVOCATE study, measuring health-related quality of life and health utilities.