CLINICAL TRIAL: PASIREOTIDE IN PATIENTS WITH PERSISTENT OR RECURRENT CUSHING'S D

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 Psirebit是一种新型的环六肽类生长抑素类似物，是奥曲肽(SMS201-955，Sandostatin)的后续产品，具有良好的内分泌特性。5种已知的人生长抑素受体(SST-1-5)中的4种具有高亲和力，显示出独特的结合谱。与hsst1和-5受体亚型的亲和力是奥曲肽的30-40倍，与sst-3的亲和力是奥曲肽的5倍。 主要目标： O根据对派西肽600 mg S.C.的反应来评估其疗效。B.i.d。和900 mg S.C.B.i.d。在治疗6个月后，根据UFC&lt；1.5×ULN和&gt；50%的尿游离皮质醇(UFC)测定，库欣病患者的尿中游离皮质醇(UFC)水平下降了50%。 研究设计： 在2-4周的筛查期后，符合入选标准的患者将以双盲方式随机接受帕西瑞肽S.C.剂量为600或900毫克S.C.B.i.d。通过交互式语音应答系统(IVRS)进行三个月的培训。在头三个月的治疗后，对指定的盲法治疗剂量(UFC 1.5×ULN和&GT；将UFC减少50%)有反应的患者将在接下来的三个月继续接受相同的剂量。没有回应的患者将被调查员解盲。接受600 mg S.C.的患者。B.i.d。剂量将被要求将他们的剂量增加到900 mg S.C.B.i.d。在接下来的3个月里。患者在900 mg S.C.中。B.i.d。没有反应的剂量组将被允许将他们的剂量增加到1200 mg S.C.B.i.d.那些没有选择增加剂量的人将被停止参与研究。初步分析将在治疗六个月后进行。如果两个剂量水平在6个月时都提供了帕西瑞肽治疗成功的证据，则初步疗效分析将完成。否则，可以执行顺序降级分析。此后将有6个月的开放标签期，届时患者将继续使用相同的吡西诺酮剂量。接受600 mg S.C.的患者。B.i.d，可以将剂量增加到900 mg S.C.B.i.d。在开放标签期间的任何时间，如果没有保持响应。同样，接受900 mg S.C.的患者。B.i.d。将被允许将他们的剂量增加到1200 mg S.C.B.i.d。在开放标签期间的任何时间，如果没有保持反应，如果他们已经耐受了900 mg S.C.B.i.d。剂量。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Pasireotide is a novel cyclohexapeptide, somatostatin analogue developed as a follow-up to octreotide (SMS 201-955, Sandostatin) with a superior endocrine profile. Pasireotide exhibits a unique binding profile with a high affinity binding to four of the five known human somatostatin receptors (sst-1-5). Pasireotide binds with a 30 to 40 fold higher affinity than octreotide to the hsst1 and -5 receptor subtypes and a fivefold higher affinity to sst-3. Primary Objectives: o To assess the efficacy in terms of response to pasireotide 600 mg s.c. b.i.d. and 900 mg s.c. b.i.d. independently in patients with Cushing's disease as measured by UFC <1.5 X ULN and >50% reduction of urinary free cortisol (UFC) from baseline after 6 months of treatment. Study Design: After a 2-4 week screening period, patients who fulfill the entrance criteria will be randomized in a double-blinded manner to receive pasireotide s.c. at a dose of either 600 or 900 mg s.c. b.i.d. for three months via an Interactive Voice Response System (IVRS). After the first three months of treatment, patients who have responded to the assigned blinded treatment dose (UFC 1.5 X ULN and >50% reduction of UFC) will continue to receive the same dose for the following 3 months. Patients who have not responded will be unblinded by the investigator. Patients who received the 600 mg s.c. b.i.d. dose will be required to have their dose increased to 900 mg s.c. b.i.d. for the following 3 months. Patients in the 900 mg s.c. b.i.d. dose group who did not respond will be permitted to have their dose increased to 1200 mg s.c. b.i.d.. Those not electing to increase the dose will be discontinued from the study. The primary analysis will be performed after six months of treatment. Should both dose levels provide evidence of pasireotide treatment success at month 6, the primary efficacy analysis will be complete. Otherwise, a sequential step-down analysis may be performed. There will be a 6-month open-label period thereafter when patients will continue with the same pasireotide dose. Patients receiving the 600 mg s.c. b.i.d., can have their dose increased to receive 900 mg s.c. b.i.d. at any time during the open-label period if the response is not maintained. In the same way, patients receiving 900 mg s.c. b.i.d. will be permitted to have their dose increased to 1200 mg s.c. b.i.d. at any time during the open-label period if the response is not maintained, and if they have tolerated the 900 mg s.c. b.i.d. dose.