Safety, Tolerability and Pharmacokinetics of Sodium Tungstate (OXO-001) in Healthy Female Volunteers of Childbearing Age: A Randomized, Double-Blind, Dose-Finding, and Placebo-Controlled Phase I Study.

Abstract

Background: Phase I study to assess the effects of single oral doses of 100, 200, and 300 mg/day of sodium tungstate (OXO-001) in healthy women of childbearing age.

Materials and methods: A randomized, double-blind, dose-finding, and placebo-controlled phase I study was conducted in healthy weight (body mass index [BMI] 18.5-24.9 kg/m2) and overweight (BMI 25 to ≥30 kg/m2) volunteers who received OXO-001 or placebo during a menstrual cycle (maximum 28 days). Data recorded were adverse events (AEs), vital signs, electrocardiogram (ECG), laboratory tests, pharmacokinetics (PK) parameters, and transvaginal ultrasound.

Results: Thirty women were included in the safety analysis, and 29 completed the study. Thirty-eight treatment emergent adverse events (TEAEs) were reported by 20 participants (15 in the OXO-001 group and 5 in the placebo group). TEAEs were related to OXO-001 administration in 13.2, 10.5, and 15.8% of cases of the 100, 200, and 300 mg doses, respectively. None of the participants discontinued the study, and no serious AEs or deaths were recorded. Differences in TEAEs by BMI were not found. The PK profile showed a fast absorption rate and proportional increases of OXO-001 plasma concentration to increasing doses, suggesting linear PK, with higher concentrations in BMI <25 kg/m2 group higher than in the ≥25 kg/m2 group. There were no relevant changes in vital signs, ECG, ovarian follicle development, endometrial morphology, and laboratory tests before and after the administration of OXO-001 or placebo.

Conclusion: The administration of OXO-001 in volunteers of childbearing age was safe and well tolerated, with consistent PK linear profile within doses studied and without detrimental effect on endometrium or ovary-related variables, with similar effects in healthy weight and overweight participants. The maximum studied dose (300 mg/ day) was safe and well tolerated. These data are sufficient to support further clinical trials (registration number: 2016-001276-30).