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 safety and pharmacokinetics (PK) of a 1 or 2 g dose of a new granule formulation for SYM-1219, a 5-nitroimidazole being developed for the treatment of women with bacterial vaginosis (BV).
METHODS: 28 healthy female subjects (14/group) ages 18-65 years were randomized to receive a single oral dose of either 1 or 2 grams of SYM-1219, mixed into 4 oz of applesauce. Serial blood samples were collected over 168 hours to determine SYM-1219 plasma concentrations. A non-compartmental analysis was performed and the PK parameters for each treatment group are reported. Safety was evaluated by recording adverse events, vital signs, ECGs and laboratory tests.
RESULTS: All subjects (N=28) completed the study and were evaluable for PK and safety. The PK of SYM-1219 was consistent between individuals, as demonstrated by low %CV estimates. Mean maximum concentrations were 22.6 mcg/mL for the 1 g dose and 45.4 mcg/mL for the 2 g dose and were achieved by approximately 4 hrs in both dose groups. Exposure estimates (AUCinf) were 619 mcg*hr/mL for the 1 g dose and 1331 mcg*hr/mL for the 2 g dose. SYM-1219 was dose proportional when comparing the 1 and 2 g doses. SYM-1219 was safe and well-tolerated. 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 single dose PK of a 1 g and 2 g dose of a new granule formulation of a 5-nitroimidazole, SYM-1219. SYM-1219 was safe and well-tolerated. The consistent PK and resulting exposure, with low variability between subjects, makes this a promising new therapeutic option. Ongoing studies will further evaluate the safety and efficacy of SYM-1219 for the treatment of women with BV.