Melmed Shlomo, Popovic Vera, Bidlingmaier Martin, Mercado Moises, van der Lely Aart Jan, Biermasz Nienke, Bolanowski Marek, Coculescu Mihail, Schopohl Jochen, Racz Karoly, Glaser Benjamin, Goth Miklos, Greenman Yona, Trainer Peter, Mezosi Emese, Shimon Ilan, Giustina Andrea, Korbonits Márta, Bronstein Marcello D, Kleinberg David, Teichman Sam, Gliko-Kabir Irit, Mamluk Roni, Haviv Asi, Strasburger Christian
Cedars-Sinai Medical Center (S.M.), Los Angeles, California 90048; Clinical Center of Serbia (V.P.), Belgrade 11080, Serbia; Medizinische Klinik IV (M.Bi., J.S.), LMU, Munich 80336, Germany; ABC Medical Center (M.M.), Mexico City 00-16, Mexico; Erasmus Medical Center (A.J.V.D.L.), Rotterdam 3000, The Netherlands; Leiden University Medical Center (N.B.), Leiden 2333 ZA, The Netherlands; Wroclaw Medical University (M.Bo.), Wroclaw 50-345, Poland; National Institute of Endocrinology (M.C.), Bucharest 11420, Romania; Semmelweis University (K.R.), Budapest 1085, Hungary; Hadassah-Hebrew University Medical Center (B.G.), Jerusalem 9112001, Israel; Health Center (M.G.), Hungarian Defense Forces, Budapest 1134, Hungary; Sourasky Medical Center (Y.G.), Tel Aviv 64239, Israel; The Christie Hospital (P.T.), Manchester M20 4BX, United Kingdom; University of Pecs (E.M.), Pecs 7600, Hungary; Rabin Medical Center (I.S.), Petah-Tikva 4941492, Israel; University of Brescia (A.G.), Brescia 25100, Italy; Queen Mary University of London (M.K.), London E1 4NS, United Kingdom; Sao Paulo University (M.D.B.), Sao Paulo 03071-000, Brazil; New York University Langone Medical Center (D.K.), New York, New York 10016; Chiasma (S.T., I.G.-K., R.M., A.H.), Newton, Massachusetts 02459; and Charite Universitätsmedizin (C.S.), Berlin 10098, Germany.
J Clin Endocrinol Metab. 2015 Apr;100(4):1699-708. doi: 10.1210/jc.2014-4113. Epub 2015 Feb 9.
A novel oral octreotide formulation was tested for efficacy and safety in a phase III, multicenter, open-label, dose-titration, baseline-controlled study in patients with acromegaly.
We enrolled 155 complete or partially controlled patients (IGF-1 <1.3 × upper limit of normal [ULN], and 2-h integrated GH <2.5 ng/mL) receiving injectable somatostatin receptor ligand (SRL) for ≥ 3 months. Subjects were switched to 40 mg/d oral octreotide capsules (OOCs), and the dose escalated to 60 and then up to 80 mg/d to control IGF-1. Subsequent fixed doses were maintained for a 7-month core treatment, followed by a voluntary 6-month extension.
Of 151 evaluable subjects initiating OOCs, 65% maintained response and achieved the primary endpoint of IGF-1 <1.3 × ULN and mean integrated GH <2.5 ng/mL at the end of the core treatment period and 62% at the end of treatment (up to 13 mo). The effect was durable, and 85 % of subjects initially controlled on OOCs maintained this response up to 13 months. When controlled on OOCs, GH levels were reduced compared to baseline, and acromegaly-related symptoms improved. Of 102 subjects completing the core treatment, 86% elected to enroll in the 6-month extension. Twenty-six subjects who were considered treatment failures (IGF-1 ≥ 1.3 × ULN) terminated early, and 23 withdrew for adverse events, consistent with those known for octreotide or disease related.
OOC, an oral therapeutic peptide, achieves efficacy in controlling IGF-1 and GH after switching from injectable SRLs for up to 13 months, with a safety profile consistent with approved SRLs. OOC appears to be effective and safe as an acromegaly monotherapy.
在一项针对肢端肥大症患者的III期多中心、开放标签、剂量滴定、基线对照研究中，对一种新型口服奥曲肽制剂的疗效和安全性进行了测试。
我们纳入了155例完全或部分得到控制的患者（胰岛素样生长因子-1[IGF-1]<正常上限[ULN]的1.3倍，且2小时整合生长激素[GH]<2.5 ng/mL），这些患者接受注射用生长抑素受体配体（SRL）治疗≥3个月。受试者改用40 mg/d的口服奥曲肽胶囊（OOC），剂量逐步增至60 mg/d，然后增至80 mg/d以控制IGF-1。随后维持固定剂量进行7个月的核心治疗，之后进行为期6个月的自愿延长治疗。
在151例开始服用OOC的可评估受试者中，65%维持了反应，并在核心治疗期结束时达到了IGF-1<正常上限的1.3倍且平均整合生长激素<2.5 ng/mL的主要终点，在治疗结束时（最长13个月）达到该终点的比例为62%。这种效果是持久的，85%最初在OOC治疗下得到控制的受试者在长达13个月的时间里维持了这种反应。在OOC治疗下得到控制时，生长激素水平较基线降低，与肢端肥大症相关的症状得到改善。在102例完成核心治疗的受试者中，86%选择参加6个月的延长治疗。26例被视为治疗失败（IGF-1≥正常上限的1.3倍）的受试者提前终止治疗，23例因不良事件退出，这些不良事件与奥曲肽已知的不良事件或疾病相关不良事件一致。
OOC作为一种口服治疗性肽，从注射用SRL转换后，在长达13个月的时间里能够有效控制IGF-1和生长激素，其安全性与已获批的SRL一致。OOC作为肢端肥大症的单一疗法似乎有效且安全。
