Combined Oral Contraceptive Drug–Drug Interaction Study With Ganfeborole, a New Anti‐Tuberculosis Agent

Abstract 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 (0‐inf) ) and maximum concentration ( C max ). 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 max (0.96, 0.85‐1.09), LNG AUC (0‐inf) (1.10, 0.98‐1.23) and LNG C max (1.08, 0.97‐1.19) met criteria for lack of DDI (90% CI 0.80‐1.25). However, the GMR for EE AUC (0‐inf) was 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