H. S. Pentikis,1 N. Adetoro,2 C. J. Braun1; 1Symbiomix Therapeutics, SAJE Consulting, Baltimore, MD, 2Symbiomix Therapeutics, Baltimore, MD
BACKGROUND: This study evaluated the effect of a single 2 g dose of SYM-1219 (secnidazole), a new granule formulation in development to treat women with bacterial vaginosis, on the pharmacokinetics (PK) of ethinyl estradiol (EE2) and norethindrone (NET).
METHODS: 54 healthy female subjects, ages 18-65, received EE2/NET alone and in combination, where SYM-1219+ EE2/NET were coadministered on Day 1 (Group B1; N=27) or SYM-1219 on Day 1 and EE2/NET on Day 2 (Group B2; N=27). Blood was drawn to measure plasma concentrations of EE2/NET. A non-compartmental analysis was performed and the PK parameters for each treatment group are reported. Safety was evaluated by recording of adverse events, vital signs, ECGs and standard laboratory tests.
RESULTS: 51 (N=26 for B1 and N=25 for B2) subjects completed the study. EE2 Cmax was reduced by 29% for Group B1; no change in EE2 AUC was seen. EE2 PK was not altered for Group B2. NET Cmax and AUC increased (13%) slightly for Group B1. NET Cmax increased by 16% for Group B2; no change was seen for NET AUC. SYM-1219 was safe and well-tolerated when taken alone or in combination with EE2/NET. The most common adverse events were headache and nausea. All adverse events were mild and resolved without sequelae. There were no significant changes in vital signs, ECG or laboratory parameters.
CONCLUSION: This study characterized the PK of EE2/NET with SYM-1219 coadministration. Minor, not clinically relevant reductions in EE2 exposure were seen when SYM-1219 and EE2/NET were co-administered on the same day. No change in EE2 exposure was seen when the SYM-1219 and EE2/NET doses were staggered by one day. No reductions in drug exposure were evident for NET for either treatment group. These data demonstrate that contraceptive efficacy for EE2/NET would not be altered by SYM-1219 administration.