一项针对嗜酸细胞性食管炎的布地奈德（布地奈德混悬液）研究制剂的安全性：六项 1-3 期临床试验的综合安全性分析。
Safety of an investigational formulation of budesonide (budesonide oral suspension) for eosinophilic oesophagitis: an integrated safety analysis of six phase 1-3 clinical trials.
机构信息
Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
出版信息
Aliment Pharmacol Ther. 2023 May;57(10):1117-1130. doi: 10.1111/apt.17430. Epub 2023 Mar 8.
BACKGROUND
Questions remain regarding the safety of swallowed topical corticosteroids in eosinophilic oesophagitis (EoE).
AIM
To assess the safety of an investigational formulation of budesonide (budesonide oral suspension; BOS) from six trials.
METHODS
Safety data were integrated from six trials (healthy adults: SHP621-101 [phase 1]; patients with EoE: MPI 101-01 and MPI 101-06 [phase 2]; SHP621-301, SHP621-302 and SHP621-303 [phase 3]) for participants who received ≥1 dose of study drug (BOS 2.0 mg twice daily [b.i.d.], BOS any dose [including BOS 2.0 mg b.i.d.] and placebo). Adverse events (AEs), laboratory testing, bone density and adrenal AEs were assessed. Exposure-adjusted incidence rates were calculated for AEs and AEs of special interest (AESIs).
RESULTS
Overall, 514 unique participants were included (BOS 2.0 mg b.i.d., n = 292; BOS any dose, n = 448; placebo, n = 168). The BOS 2.0 mg b.i.d., BOS any dose and placebo groups totalled 93.7, 122.4 and 25.0 participant-years of exposure (PY), respectively. Proportions of treatment-emergent AEs (TEAEs) and AESIs (any) reported were higher for BOS than placebo; however, most were mild/moderate in severity. The most commonly reported AESIs (exposure-adjusted incidence rates [per 100 PY]) in the BOS 2.0 mg b.i.d., BOS any dose and placebo groups were infections (133.5, 154.4 and 136.2, respectively) and gastrointestinal AEs (84.3, 80.9 and 92.1, respectively). Adrenal AEs were more frequent with BOS 2.0 mg b.i.d. and BOS any dose than placebo (44.8, 34.3 and 24.0, respectively). TEAEs and AESIs related to study drug or leading to discontinuation were infrequent.
CONCLUSIONS
BOS was well-tolerated; most TEAEs with BOS were mild/moderate in severity.
GOV NUMBERS
SHP621-101 (no clinical trials registration number), MPI 101-01 (NCT00762073), MPI 101-06 (NCT01642212), SHP621-301 (NCT02605837), SHP621-302 (NCT02736409) and SHP621-303 (NCT03245840).
背景
关于吞服局部皮质类固醇在嗜酸性食管炎（EoE）中的安全性问题仍存在疑问。
目的
评估研究性布地奈德制剂（布地奈德口服混悬液；BOS）在六项试验中的安全性。
方法
从六项试验（健康成年人：SHP621-101[I 期]；EoE 患者：MPI 101-01 和 MPI 101-06[II 期]；SHP621-301、SHP621-302 和 SHP621-303[III 期]）中整合了接受至少一剂研究药物（BOS 2.0mg 每日两次[b.i.d.]、BOS 任何剂量[包括 BOS 2.0mg b.i.d.]和安慰剂）的参与者的安全性数据。评估不良事件（AE）、实验室检查、骨密度和肾上腺 AE。计算 AE 和特别关注的 AE（AESI）的暴露调整发生率。
结果
共有 514 名独特的参与者被纳入（BOS 2.0mg b.i.d.，n=292；BOS 任何剂量，n=448；安慰剂，n=168）。BOS 2.0mg b.i.d.、BOS 任何剂量和安慰剂组的暴露年限分别为 93.7、122.4 和 25.0 人年。与安慰剂相比，BOS 报告的治疗中出现的 AE（TEAE）和 AESI（任何）的比例更高；然而，大多数为轻度/中度严重程度。BOS 2.0mg b.i.d.、BOS 任何剂量和安慰剂组中报告的最常见的 AESI（暴露调整后的发病率[每 100 人年]）分别为感染（133.5、154.4 和 136.2）和胃肠道 AE（84.3、80.9 和 92.1）。BOS 2.0mg b.i.d.和 BOS 任何剂量的肾上腺 AE 发生率均高于安慰剂（分别为 44.8、34.3 和 24.0）。与研究药物相关或导致停药的 TEAE 和 AESI 较为少见。
结论
BOS 耐受性良好；BOS 大多数 TEAE 为轻度/中度严重程度。
政府编号
SHP621-101（无临床试验注册号）、MPI 101-01（NCT00762073）、MPI 101-06（NCT01642212）、SHP621-301（NCT02605837）、SHP621-302（NCT02736409）和 SHP621-303（NCT03245840）。
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