Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo, Japan.
Adv Ther. 2013 May;30(5):459-71. doi: 10.1007/s12325-013-0029-0. Epub 2013 May 8.
Pulmonary arterial hypertension (PAH) is associated with poor prognosis despite significant recent advances in its treatment. An intravenous formulation of epoprostenol sodium containing glycine and mannitol (epoprostenol GM; GlaxoSmithKline, London, UK) is widely used to treat PAH. A new formulation of epoprostenol sodium containing arginine and sucrose excipients (epoprostenol AS; Actelion Pharmaceuticals Japan Ltd., Tokyo, Japan) shows better stability at room temperature after preparing diluted solutions. The primary objective of this study was to evaluate the safety and tolerability of switching from epoprostenol GM to epoprostenol AS in Japanese patients with PAH. The authors also evaluated the efficacy and treatment satisfaction after switching formulations.
This was a two-site, open-label, single-arm, Phase 3b study. Eight adult Japanese PAH patients (seven females) treated with a stable dose of epoprostenol GM for ≥30 days were switched to epoprostenol AS and followed for 12 weeks. Outcomes included safety, changes from baseline to 12 weeks in pulmonary hemodynamic factors (pulmonary vascular resistance, mean pulmonary arterial pressure, and cardiac output), and treatment satisfaction, assessed using the Treatment Satisfaction Questionnaire for Medication (TSQM-9).
The mean (range) age and time since diagnosis of PAH were 48 (25-69) years and 6.2 (0.6-13.9) years, respectively. There were no unexpected safety or tolerability concerns after switching formulations. The epoprostenol dose was maintained after switching formulations. There were no significant changes in pulmonary hemodynamic factors from baseline to week 12. Regarding treatment satisfaction, there was a significant improvement in convenience, which is demonstrated in the score of the domain increased from 51.40 ± 10.19 at baseline to 58.33 ± 12.96 at week 12 (P < 0.05).
Switching from epoprostenol GM to the same dose of epoprostenol AS was well tolerated over 12 weeks of treatment, and pulmonary hemodynamics were maintained. Switching to epoprostenol AS was also associated with improvements in treatment satisfaction (convenience). Clinical Trials: JapicCTI-122017.
尽管肺动脉高压 (PAH) 的治疗在最近取得了重大进展，但仍与预后不良相关。含有甘氨酸和甘露醇的依前列醇钠静脉制剂（依前列醇 GM；英国伦敦葛兰素史克公司）被广泛用于治疗 PAH。一种含有精氨酸和蔗糖赋形剂的新型依前列醇钠制剂（日本 Actelion 制药公司的依前列醇 AS）在配制稀释溶液后，在室温下显示出更好的稳定性。本研究的主要目的是评估将 PAH 日本患者从依前列醇 GM 转换为依前列醇 AS 的安全性和耐受性。作者还评估了转换配方后的疗效和治疗满意度。
这是一项在两个地点进行的、开放性、单臂、3b 期研究。8 名接受稳定剂量依前列醇 GM 治疗≥30 天的成年日本 PAH 患者（7 名女性）转换为依前列醇 AS，并随访 12 周。结果包括安全性、从基线到 12 周时肺血流动力学因素（肺血管阻力、平均肺动脉压和心输出量）的变化以及使用治疗满意度问卷药物（TSQM-9）评估的治疗满意度。
平均（范围）年龄和 PAH 确诊后时间分别为 48 岁（25-69 岁）和 6.2 岁（0.6-13.9 岁）。转换配方后没有出现意外的安全性或耐受性问题。转换配方后依前列醇剂量保持不变。从基线到 12 周时，肺血流动力学因素没有显著变化。关于治疗满意度，便利性有显著改善，体现在该领域的评分从基线时的 51.40±10.19 增加到 12 周时的 58.33±12.96（P<0.05）。
在 12 周的治疗中，从依前列醇 GM 转换为相同剂量的依前列醇 AS 耐受性良好，并且肺血流动力学得到维持。转换为依前列醇 AS 还与治疗满意度（便利性）的提高相关。临床试验： JapicCTI-122017。
