P-1248. The Effect of Pantoprazole on Doravirine/Islatravir Pharmacokinetics

Abstract Background Doravirine/islatravir (DOR/ISL 100/0.25 mg) is a daily, oral, fixed-dose combination being developed for the treatment of HIV infection. As people living with HIV are commonly prescribed antacids or acid-reducing agents, we investigated the effects of pantoprazole, a proton pump inhibitor (PPI), on DOR/ISL pharmacokinetics (PK). Methods This was a randomized, open-label substudy in participants without HIV. Single-dose DOR/ISL (100/0.75 mg) was administered, followed by a DOR/ISL washout interval of at least 7 days. During the washout period, pantoprazole 40 mg daily was initiated and administered for 5 days, with DOR/ISL coadministered on day 5. Blood was collected to evaluate ISL and DOR PK. Safety and tolerability were assessed throughout the study. Results Twenty-one participants were randomized to receive DOR/ISL; 6 participants completed the DOR/ISL + pantoprazole substudy. Pantoprazole had no clinically meaningful effect on DOR PK after coadministration with DOR/ISL. ISL PK were similar after coadministration of pantoprazole compared with PK after administration of DOR/ISL alone. The geometric least-square mean ratio (GMR) (90% CI) (DOR/ISL + pantoprazole over DOR/ISL) for DOR AUC0-24 and Cmax were 0.93 (0.78-1.11) and 0.98 (0.80-1.20), respectively. The GMR (90% CI) for ISL AUC0-24 and Cmax were 1.05 (0.94-1.16) and 0.99 (0.72-1.35), respectively. DOR/ISL administered alone or in combination with pantoprazole was generally well tolerated. Of participants who received DOR/ISL alone or with pantoprazole, 24% (5/21) had ≥ 1 adverse event (AE). No AE was reported more than once. There were no serious AEs, and one participant discontinued due to an AE (abdominal pain thought to be secondary to pantoprazole). Conclusion Pantoprazole had no clinically meaningful effect on the PK of DOR, and ISL PK was similar after coadministration with pantoprazole, supporting the use of DOR/ISL with acid-reducing agents. The combination was generally well tolerated. Disclosures Randolph P. Matthews, MD, PhD, Merck & Co., Inc.: Employee Nancy Kim, MD, Merck & Co., Inc.: Employee Yang Liu, PhD, Merck & Co., Inc.: Employee Deanne Jackson Rudd, PhD, Merck & Co., Inc.: Employee Graig Garrett, BS, Merck & Co., Inc.: Employee Jocelyn Gilmartin, BS, Merck & Co., Inc.: Employee Ryan Vargo, PhD, Merck & Co., Inc.: Employee S. Aubrey Stoch, MD, Merck & Co., Inc.: Employee Marian Iwamoto, MD, PhD, Merck & Co., Inc.: Former employee