Drug-Drug Interactions With the Hepatitis B Virus Capsid Assembly Modulator JNJ-56136379 (Bersacapavir).

ABSTRACT

The capsid assembly modulator JNJ-56136379 (bersacapavir) disrupts hepatitis B virus replication. It is metabolized via cytochrome P450 (CYP) 3A, but little is known about the drug-drug interactions of JNJ-56136379 when combined with drugs that inhibit or are metabolized by CYP3A. In a phase 1, open-label trial (NCT03945539), healthy adults received 1 dose of JNJ-56136379 with and without 21 days of prior exposure to itraconazole 200 mg (CYP3A inhibitor). In a second phase 1, open-label trial (NCT03111511), healthy women received 1 dose of drospirenone/ethinyl estradiol and midazolam before and after 15 days of JNJ-56136379. Itraconazole increased the area under the plasma concentration-time curve (AUC) of JNJ-56136379 by 38%. JNJ-56136379 reduced the maximum observed concentration and AUC of midazolam (CYP3A substrate) by 42%-54%, increased AUC of ethinyl estradiol by 1.6-fold, but had no effect on drospirenone pharmacokinetics. Overall, these results demonstrated that a strong CYP3A inhibitor (itraconazole) modestly increased JNJ-56136379 exposure. Furthermore, JNJ-56136379 was a weak inducer of CYP3A (midazolam) and increased ethinyl estradiol exposure; coadministration of high-dose estrogen-based contraceptives and JNJ-56136379 is not recommended.