Effect of Upadacitinib on the Pharmacokinetics of Rosuvastatin or Atorvastatin in Healthy Subjects

This phase 1, 2‐part, 2‐period, open‐label, drug‐drug interaction study evaluated the potential for pharmacokinetic interactions between upadacitinib and rosuvastatin, an organic anion transporting polypeptide (OATP) 1B1 and breast cancer resistance protein substrate, or atorvastatin, a cytochrome P450 3A, OATP1B1, and OATP1B3 substrate, in 36 healthy volunteers. During period 1, a single dose of rosuvastatin (5 mg; part 1) or atorvastatin (10 mg; part 2) was administered on day 1, followed by a washout period of 5 days. During period 2, once‐daily doses of upadacitinib extended‐release (30 mg) were administered on days 1 to 10, and a single dose of rosuvastatin (5 mg; part 1) or atorvastatin (10 mg; part 2) was administered 1 hour after the upadacitinib dose on day 7. Serial blood samples were collected for assays of drug concentrations. In Part 1, rosuvastatin maximum observed plasma concentration (C(max)) and area under the plasma concentration–time curve from time 0 to infinity (AUC(inf)) were 23% and 33% lower, respectively, when administered with upadacitinib relative to when administered alone. In part 2, atorvastatin C(max) and AUC(inf) was 11% and 23% lower, respectively, when administered with upadacitinib relative to when administered alone. The C(max) and AUC(inf) of the active metabolite ortho‐hydroxyatorvastatin remained unchanged. Administration of a single 5‐mg dose of rosuvastatin or a single 10‐mg dose of atorvastatin had no relevant effect on upadacitinib C(max) or area under the plasma concentration–time curve. These results demonstrated that upadacitinib has no clinically relevant effect on the pharmacokinetics of rosuvastatin and atorvastatin or on substrates transported by OATP1B or breast cancer resistance protein.