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

Area of Science:

• Pharmacology
• Infectious Diseases
• Drug Development

Background:

• Drug-resistant tuberculosis requires novel therapeutic agents.
• Ganfeborole exhibits bactericidal activity and good tolerability.
• Preclinical studies indicated potential embryofetal developmental effects, necessitating strict contraception measures.

Purpose of the Study:

• To evaluate potential drug-drug interactions between ganfeborole and a combined oral contraceptive (ethinyl estradiol/levonorgestrel).
• To assess the pharmacokinetic impact of steady-state ganfeborole on ethinyl estradiol and levonorgestrel.

Main Methods:

• Phase 1, open-label, fixed-sequence drug-drug interaction study.
• 20 healthy women of non-childbearing potential received ganfeborole (20 mg daily) and a single dose of ethinyl estradiol 0.03 mg/levonorgestrel 15 mg.
• Pharmacokinetic parameters (AUC(0-inf) and Cmax) for ethinyl estradiol and levonorgestrel were measured.

Main Results:

• Geometric mean ratios for ethinyl estradiol Cmax, levonorgestrel AUC(0-inf), and levonorgestrel Cmax met criteria for lack of drug-drug interaction.
• However, the geometric mean ratio for ethinyl estradiol AUC(0-inf) had a 90% confidence interval that did not meet the criteria for lack of interaction.
• Post-hoc analyses of partial AUCs suggested no interaction, but a definitive conclusion could not be reached.

Conclusions:

• A definitive conclusion regarding drug-drug interaction between ganfeborole and combined oral contraceptives could not be established due to variability in ethinyl estradiol pharmacokinetics.
• No treatment-related adverse events were reported.
• Further studies are warranted to fully assess ganfeborole's interaction potential with combined oral contraceptives, and strict contraception will be maintained in future trials.