Combined Oral Contraceptive Drug-Drug Interaction Study With Ganfeborole, a New Anti-Tuberculosis Agent.

New drugs are urgently needed to treat drug-resistant tuberculosis in combination regimens. Ganfeborole demonstrated bactericidal activity and good tolerability in clinical trials. In preclinical studies, ganfeborole showed embryofetal developmental effects, currently mandating highly effective non-user dependent contraception in women of childbearing potential. We conducted a Phase 1, open-label, single-center, fixed sequence, 1-way drug-drug interaction (DDI) study in 20 healthy women of non-childbearing potential aged 18-65 years. The primary objective was to assess ganfeborole's effect at steady-state (20 mg daily) on single dose pharmacokinetics of ethinyl estradiol [EE] 0.03 mg/levonorgestrel [LNG] 15 mg (Bayer). Endpoints were EE and LNG area under the plasma concentration-time curve extrapolated to infinity (AUC) and maximum concentration (C). Unexpected fluctuations in individual EE and LNG plasma concentration-time profiles limited the number of acceptable endpoints for the analysis. Geometric mean ratios (GMR; EE/LNG+ganfeborole versus EE/LNG alone) and respective 90% confidence intervals (CI) for EE C(0.96, 0.85-1.09), LNG AUC(1.10, 0.98-1.23) and LNG C(1.08, 0.97-1.19) met criteria for lack of DDI (90% CI 0.80-1.25). However, the GMR for EE AUCwas 0.88, with 90% CI 0.55-1.41. While post-hoc analyses on partial AUCs (up to 8 and 24 h) provided GMR 90% CIs within 0.80-1.25, a lack of DDI could not be concluded. No treatment-related adverse events were reported. Further assessments of potential DDI between ganfeborole and combined oral contraceptives are warranted. Future trials will maintain strict contraception requirements. Clinical Trial Registration: NCT06354257 (registration date: 2024-04-03); EudraCT: 2023-507839-38-00.