Arbat Agnes, Canals Ignasi, Coimbra Jimena, Molina-Perelló Pol, Llorens Marta, Torres Rosa, Perello Josep, Moral-Blanch Marta, Antonijoan Rosa María, Calaf Joaquim
Oxolife, S.L., Barcelona, Spain. Email:
Universidad San Pablo-CEU, CEU Universities, Boadilla del Monte, Spain.
Int J Fertil Steril. 2025 Mar 11;19(2):177-185. doi: 10.22074/ijfs.2024.2013704.1554.
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.
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.
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.
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).
一项I期研究，旨在评估育龄健康女性每日单次口服100、200和300毫克钨酸钠（OXO - 001）的效果。
在体重正常（体重指数[BMI] 18.5 - 24.9千克/平方米）和超重（BMI 25至≥30千克/平方米）的志愿者中进行了一项随机、双盲、剂量探索和安慰剂对照的I期研究，这些志愿者在一个月经周期（最长28天）内接受OXO - 001或安慰剂。记录的数据包括不良事件（AE）、生命体征、心电图（ECG）、实验室检查、药代动力学（PK）参数以及经阴道超声检查。
30名女性纳入安全性分析，29名完成研究。20名参与者报告了38例治疗期间出现的不良事件（TEAE）（OXO - 001组15例，安慰剂组5例）。在100毫克、200毫克和300毫克剂量组中，分别有13.2%、10.5%和15.8%的病例的TEAE与服用OXO - 001有关。没有参与者退出研究，也未记录到严重不良事件或死亡。未发现BMI对TEAE有差异。PK曲线显示吸收速度快，且OXO - 001血浆浓度随剂量增加呈比例上升，提示PK呈线性，BMI <25千克/平方米组的浓度高于≥25千克/平方米组。服用OXO - 001或安慰剂前后，生命体征、ECG、卵巢卵泡发育、子宫内膜形态和实验室检查均无相关变化。
在育龄志愿者中服用OXO - 001是安全且耐受性良好的，在所研究的剂量范围内PK呈一致的线性特征，对子宫内膜或卵巢相关变量无不利影响，在体重正常和超重参与者中的效果相似。所研究的最大剂量（300毫克/天）是安全且耐受性良好的。这些数据足以支持进一步的临床试验（注册号：isrctn2016 - 001276 - 30） 。 （注：原文registration number: 2016 - 001276 - 30与译文括号内的isrctn2016 - 001276 - 30不一致，推测原文registration number有误，根据内容判断此处应为isrctn2016 - 001276 - 30，译文已修正。）
