Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
MGH Neuroendocrine and Pituitary Center, Chestnut Hill, MA, USA.
Pituitary. 2021 Dec;24(6):943-953. doi: 10.1007/s11102-021-01163-2. Epub 2021 Jun 25.
Results are presented from 2 to 3 trials investigating oral octreotide capsules (OOC) as an alternative to injectable somatostatin receptor ligands (iSRLs) in the treatment of acromegaly.
CH-ACM-01 was an open-label trial (N = 155) and CHIASMA OPTIMAL was a double-blind placebo-controlled (DPC) trial (N = 56), both investigating OOC as maintenance therapy for patients with acromegaly who were biochemical responders receiving iSRLs.
Baseline characteristics in both trials reflected those expected of patients with acromegaly responding to treatment and were similar between trials, despite differences in inclusion criteria. OOC demonstrated a consistent degree of biochemical response across trials, with 65% of patients in CH-ACM-01 maintaining response during the core period and 64% of patients in CHIASMA OPTIMAL at the end of the DPC. Mean insulin-like growth factor I (IGF-I) levels remained within inclusion criteria at the end of treatment in both trials. Of 110 patients entering the fixed-dose phase in CH-ACM-01, 80% maintained or improved acromegaly symptoms from baseline to the end of treatment. Over 85% of patients in both trials elected to continue into the extension phases. OOC were found to be well tolerated across both trials, and no dose-related adverse events were observed.
OOC demonstrated remarkably consistent results for biochemical response, durability of response, and preference to continue with oral treatment across these 2 complementary landmark phase 3 trials, despite differences in the design of each. Trial registration NCT03252353 (August 2017), NCT01412424 (August 2011).
呈现了 2 至 3 项研究的结果，这些研究调查了口服奥曲肽胶囊（OOC）作为注射用生长抑素受体配体（iSRL）的替代品在治疗肢端肥大症中的作用。
CH-ACM-01 是一项开放标签试验（N=155），CHIASMA OPTIMAL 是一项双盲安慰剂对照（DPC）试验（N=56），均研究了 OOC 作为对接受 iSRL 治疗的生化缓解的肢端肥大症患者的维持治疗。
两项试验的基线特征均反映了预期的对治疗有反应的肢端肥大症患者的特征，并且尽管纳入标准存在差异，但试验之间相似。OOC 在两项试验中均表现出一致程度的生化缓解，CH-ACM-01 核心期有 65%的患者保持缓解，CHIASMA OPTIMAL 结束 DPC 时有 64%的患者保持缓解。两项试验结束时，大多数患者的胰岛素样生长因子 I（IGF-I）水平仍符合纳入标准。在 CH-ACM-01 的固定剂量阶段有 110 名患者进入，80%的患者从基线到治疗结束时保持或改善了肢端肥大症症状。两项试验中超过 85%的患者选择继续进入扩展阶段。OOC 在两项试验中均表现出良好的耐受性，未观察到与剂量相关的不良事件。
OOC 在这两项互补的关键性 3 期试验中均表现出了令人瞩目的生化缓解、缓解持续时间和继续口服治疗的偏好的一致性结果，尽管每个试验的设计存在差异。试验注册 NCT03252353（2017 年 8 月），NCT01412424（2011 年 8 月）。
