CROSS Research S.A., Clinical Phase I Unit, Via F.A. Giorgioli 14, 6864, Arzo, Switzerland.
CROSS Research S.A., Clinical Projects Unit, Via L. Lavizzari 18, 6850, Mendrisio, Switzerland.
Clin Drug Investig. 2022 Mar;42(3):199-206. doi: 10.1007/s40261-022-01118-w. Epub 2022 Feb 9.
Exogenous human chorionic gonadotropin (hCG) acts on the final phase of the follicle maturation. Choriomon, a highly purified hCG formulation, is approved in many European and extra-European countries for the induction of ovulation after stimulation of follicular development. The present study compares hCG bioavailability of Choriomon (Test product) versus a recombinant hCG preparation (Ovitrelle; Reference product).
In this randomized, two-way cross-over study, 26 healthy women received a single dose of Choriomon (10,000 IU) and Ovitrelle (250 µg; 6500 IU) by subcutaneous injection. hCG was determined in serum up to 192 h post-dose. Dose-normalized peak concentration (C) and area under the concentration-time curve up to the time of the last quantifiable concentration (AUC) and extrapolated to infinity (AUC) were calculated and compared between the two treatments.
Serum hCG concentrations increased rapidly with a very similar pharmacokinetic curve for the two products. The test/reference geometric means ratio (GMR) for AUC and AUC corresponded to 121.31 and 119.81%, and the upper limits of the 90% confidence intervals (CIs) (130.21% and 128.51%, for AUC and AUC, respectively) exceeded the 125% bioequivalence threshold. C GMR was 146.89%, indicating a rate of hCG absorption approximately 50% greater for the test product (90% CI 132.30-163.10). Half-life (t) was very similar (36.77 ± 5.11 h and 38.63 ± 6.08 h), whereas time to achieve C (t) significantly differed, with median values of 16 h and 24 h for Choriomon and Ovitrelle, respectively, (p = 0.0023).
The differences between Choriomon and Ovitrelle pharmacokinetic parameters can be ascribed to the different raw source of the products and are reflected in the approved dose regimens of the two hCG formulations. The observed lack of bioequivalence between the two compounds at the given doses is not clinically relevant, as results from Phase III studies indicated similar clinical efficacy and safety. The safety data are in line with the known safety profile of the two products.
NCT03735030.
外源性人绒毛膜促性腺激素（hCG）作用于卵泡成熟的最后阶段。Choriomon 是一种高度纯化的 hCG 制剂，已在许多欧洲和欧洲以外国家获得批准，用于在刺激卵泡发育后诱导排卵。本研究比较了 Choriomon（试验品）和重组 hCG 制剂（Ovitrelle；参比品）的 hCG 生物利用度。
在这项随机、双交叉研究中，26 名健康女性分别接受单次皮下注射 Choriomon（10000IU）和 Ovitrelle（250μg；6500IU）。在给药后 192 小时内测定血清 hCG。计算并比较了两种治疗方法的剂量标准化峰浓度（C）和至最后可定量浓度时间的浓度-时间曲线下面积（AUC）以及外推至无穷大的 AUC（AUC）。
两种产品的血清 hCG 浓度均迅速升高，药代动力学曲线非常相似。AUC 和 AUC 的试验/参考几何均数比（GMR）分别为 121.31%和 119.81%，90%置信区间（CI）上限（AUC 和 AUC 分别为 128.51%和 130.21%）超过 125%的生物等效性阈值。C GMR 为 146.89%，表明试验产品的 hCG 吸收率约高 50%（90%CI 132.30-163.10）。半衰期（t）非常相似（36.77±5.11h 和 38.63±6.08h），而达到 C 的时间（t）则有显著差异，Choriomon 和 Ovitrelle 的中位数分别为 16h 和 24h（p=0.0023）。
Choriomon 和 Ovitrelle 药代动力学参数的差异可归因于产品的不同原始来源，并反映在两种 hCG 制剂的批准剂量方案中。在给予的剂量下，两种化合物之间观察到的生物等效性缺失无临床意义，因为 III 期研究结果表明两种化合物具有相似的临床疗效和安全性。安全性数据与两种产品已知的安全性特征一致。
NCT03735030。
