PDF(Pubmed)
Abstract：
Paltusotine is a once-daily, oral, nonpeptide small-molecule somatostatin receptor type 2 (SST2) agonist in clinical development for treatment of acromegaly.
This work aimed to evaluate change in insulin-like growth factor I (IGF-I) levels in patients switched from octreotide long-acting release or lanreotide depot monotherapy to paltusotine.
A phase 2, open-label, prospective, multicenter, multinational, nonrandomized, single-arm exploratory study was conducted in which dosage uptitrations were performed in a double-blinded manner. At 26 global sites, patients with acromegaly switched to paltusotine from injected somatostatin receptor ligand (SRL)-based therapy. Patients received 13-week treatment with once-daily oral paltusotine (10-40 mg/d). The primary end point was change from baseline to week 13 in IGF-I for patients who switched from long-acting octreotide or lanreotide depot monotherapy to paltusotine (group 1). All patients underwent a 4-week paltusotine washout at end of treatment period (wk 13-17). IGF-I, growth hormone (GH), patient-reported outcome, and safety data were collected.
Forty-seven patients enrolled. In group 1 (n = 25), IGF-I and GH showed no significant change between SRL baseline and end of paltusotine treatment at week 13 (median change in IGF-I = -0.03×upper limit of normal [ULN]; P = .6285; GH = -0.05 ng/mL; P = .6285). IGF-I and GH rose significantly in the 4 weeks after withdrawing paltusotine (median change in IGF-I = 0.55×ULN; P < .0001 [median increase 39%]; GH = 0.72 ng/mL; P < .0001 [109.1% increase]). No patients discontinued because of adverse events (AE); no treatment-related serious AEs were reported.
These results suggest once-daily oral paltusotine was effective in maintaining IGF-I values in patients with acromegaly who switched from injected SRLs. Paltusotine was well tolerated with a safety profile consistent with other SRLs.
This work aimed to evaluate change in insulin-like growth factor I (IGF-I) levels in patients switched from octreotide long-acting release or lanreotide depot monotherapy to paltusotine.
A phase 2, open-label, prospective, multicenter, multinational, nonrandomized, single-arm exploratory study was conducted in which dosage uptitrations were performed in a double-blinded manner. At 26 global sites, patients with acromegaly switched to paltusotine from injected somatostatin receptor ligand (SRL)-based therapy. Patients received 13-week treatment with once-daily oral paltusotine (10-40 mg/d). The primary end point was change from baseline to week 13 in IGF-I for patients who switched from long-acting octreotide or lanreotide depot monotherapy to paltusotine (group 1). All patients underwent a 4-week paltusotine washout at end of treatment period (wk 13-17). IGF-I, growth hormone (GH), patient-reported outcome, and safety data were collected.
Forty-seven patients enrolled. In group 1 (n = 25), IGF-I and GH showed no significant change between SRL baseline and end of paltusotine treatment at week 13 (median change in IGF-I = -0.03×upper limit of normal [ULN]; P = .6285; GH = -0.05 ng/mL; P = .6285). IGF-I and GH rose significantly in the 4 weeks after withdrawing paltusotine (median change in IGF-I = 0.55×ULN; P < .0001 [median increase 39%]; GH = 0.72 ng/mL; P < .0001 [109.1% increase]). No patients discontinued because of adverse events (AE); no treatment-related serious AEs were reported.
These results suggest once-daily oral paltusotine was effective in maintaining IGF-I values in patients with acromegaly who switched from injected SRLs. Paltusotine was well tolerated with a safety profile consistent with other SRLs.
摘要：
背景：Paltusotine是每日一次，口服,非肽类小分子生长抑素受体2型(SST2)激动剂在肢端肥大症临床治疗中的应用.
目的：评估从奥曲肽LAR或兰利肽储库单药治疗转为帕司舒汀的患者IGF-I水平的变化。
方法：第二阶段，开放标签，prospective,多中心，跨国公司,非随机化，单臂探索性研究，其中剂量上调以双盲方式进行。
方法：26个全球站点。
方法：肢端肥大症患者从基于SRL的注射治疗转为帕司他汀。
方法：患者接受了13周的治疗，每天一次口服帕舒辛（10-40mg/天）。
方法：主要终点是从长效奥曲肽或兰瑞肽单药治疗转为帕司舒汀（第1组）的患者的IGF-I从基线到第13周的变化。所有患者在治疗期结束时（第13-17周）接受了4周的帕托西汀冲洗。IGF-I,GH,患者报告的结果，并收集安全性数据。
结果：纳入47例患者。在第1组（n=25）中，在第13周，在SRL基线和帕托西汀治疗结束之间，IGF-I和GH没有显着变化（IGF-I的中位数变化=-0.03×正常上限[ULN]，P=0.6285；GH=-0.05ng/mL，P=0.6285)。IGF-I和GH在停用paltusotine后4周内显著上升(IGF-I的中值变化=0.55×ULN,P<0.0001[中位数增加39%]；GH=0.72ng/mL，P<0.0001[109.1%增加])。没有患者因不良事件而停药；没有报告治疗相关的严重不良事件。
结论：这些结果表明每天一次，口服帕司他汀可有效维持肢端肥大症患者的IGF-I值从注射SRL转换。Paltusotine的耐受性良好，安全性与其他SRL一致。
目的：评估从奥曲肽LAR或兰利肽储库单药治疗转为帕司舒汀的患者IGF-I水平的变化。
方法：第二阶段，开放标签，prospective,多中心，跨国公司,非随机化，单臂探索性研究，其中剂量上调以双盲方式进行。
方法：26个全球站点。
方法：肢端肥大症患者从基于SRL的注射治疗转为帕司他汀。
方法：患者接受了13周的治疗，每天一次口服帕舒辛（10-40mg/天）。
方法：主要终点是从长效奥曲肽或兰瑞肽单药治疗转为帕司舒汀（第1组）的患者的IGF-I从基线到第13周的变化。所有患者在治疗期结束时（第13-17周）接受了4周的帕托西汀冲洗。IGF-I,GH,患者报告的结果，并收集安全性数据。
结果：纳入47例患者。在第1组（n=25）中，在第13周，在SRL基线和帕托西汀治疗结束之间，IGF-I和GH没有显着变化（IGF-I的中位数变化=-0.03×正常上限[ULN]，P=0.6285；GH=-0.05ng/mL，P=0.6285)。IGF-I和GH在停用paltusotine后4周内显著上升(IGF-I的中值变化=0.55×ULN,P<0.0001[中位数增加39%]；GH=0.72ng/mL，P<0.0001[109.1%增加])。没有患者因不良事件而停药；没有报告治疗相关的严重不良事件。
结论：这些结果表明每天一次，口服帕司他汀可有效维持肢端肥大症患者的IGF-I值从注射SRL转换。Paltusotine的耐受性良好，安全性与其他SRL一致。
