Background and Objectives

Osteoarthritis (OA) is a major public health burden. While knee and hip joints are most commonly affected, the glenohumoral (shoulder) joint is also frequently involved. We evaluated the pharmacokinetics and safety/tolerability of triamcinolone acetonide extended-release (TA-ER) and triamcinolone acetonide crystalline suspension (TAcs) in patients with shoulder OA.

Methods

In this phase 2, randomized, open-label, single-dose study (NCT03382262), adults with moderately-to-severely symptomatic shoulder OA for ≥ 6 months randomly received a single ultrasound-guided intra-articular (IA) injection of TA-ER 32 mg or TAcs 40 mg. Safety was evaluated throughout 12 weeks post-injection; blood samples for pharmacokinetic evaluations were collected pre-injection and through Day 85 post-injection.

Results

Among 25 randomized patients, 12 received TA-ER and 13 received TAcs. Most patients were female (60%), and all had moderate (72%) or severe (28%) shoulder OA. Adverse events (AEs) were reported by four (33%) patients following TA-ER and three (23%) following TAcs injection. No AE was serious or led to study discontinuation. Systemic exposure following TAcs was approximately 1.5-fold higher than that following TA-ER injection (geometric mean [GM] AUC_0–last 873,543 vs 557,602 h × pg/mL). GM C_max was also higher in TAcs- than TA-ER-treated patients (2034 vs 1283 pg/mL). Bioequivalence testing confirmed lower systemic TA exposure following TA-ER than TAcs IA injection.

Conclusion

These pharmacokinetic data confirm protracted release of TA from TA-ER following IA injection in patients with shoulder OA. Lower peak and systemic TA exposure following TA-ER suggests TA-ER could potentially confer an improved systemic safety profile over TAcs.

Trial Registration Number

NCT03382262 (December 22, 2017 retrospectively registered).

中文翻译：

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肩骨关节炎患者超声引导关节内注射曲安奈德缓释剂或标准曲安奈德后的安全性和全身暴露：一项开放标签、随机研究

背景和目标

骨关节炎（OA）是一项重大的公共卫生负担。虽然膝关节和髋关节最常受到影响，但盂体（肩）关节也经常受累。我们评估了曲安奈德缓释剂 (TA-ER) 和曲安奈德结晶混悬液 (TAcs) 在肩部 OA 患者中的药代动力学和安全性/耐受性。

方法

在这项 2 期、随机、开放、单剂量研究 (NCT03382262) 中，患有中度至重度肩部 OA ≥ 6 个月的成人随机接受单次超声引导关节内 (IA) 注射 TA- ER 32 mg 或 TAcs 40 mg。注射后 12 周内评估安全性；在注射前和注射后第85天收集用于药代动力学评估的血样。

结果

在 25 名随机患者中，12 名接受 TA-ER，13 名接受 TAcs。大多数患者为女性（60%），并且全部患有中度（72%）或重度（28%）肩部骨关节炎。TA-ER 后四名 (33%) 患者报告了不良事件 (AE)，TAcs 注射后三名 (23%) 患者报告了不良事件 (AE)。没有出现严重的 AE 或导致研究中止的情况。TAcs 后的全身暴露量比 TA-ER 注射后的全身暴露量高约 1.5 倍（几何平均 [GM] AUC _{0 – 最后}873,543 vs 557,602 h × pg/mL）。TAcs 治疗患者的GM C _max也高于 TA-ER 治疗患者（2034 vs 1283 pg/mL）。生物等效性测试证实，与 TAcs IA 注射相比，TA-ER 后的全身 TA 暴露量较低。

结论

这些药代动力学数据证实，肩部 OA 患者注射 IA 后，TA 从 TA-ER 中持续释放。TA-ER 后较低的峰值和全身 TA 暴露表明 TA-ER 可能比 TAc 具有更好的系统安全性。

试用注册号

NCT03382262（2017年12月22日追溯注册）。