A Phase II Trial to Assess the Efficacy and Safety of Pasireotide s.c. Alone or in Combination With Cabergoline in Patients With Cushing's Disease
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 68
- 试验地点
- 3
- 主要终点
- Percentage of Responders With Mean Urinary Free Cortisol (mUFC) ≤ 1.0xULN Collected or Imputed at Week 35
研究概览
简要总结
The main purpose of this prospective, multicenter, open-label phase II study, was to evaluate the efficacy and safety of pasireotide alone or in combination with cabergoline in patients with Cushing's disease.
详细描述
This was an open-label, multi-center, international, non-comparative study with adult patients with confirmed diagnosis of Cushing's disease. Given the fact that CD patients may need a multimodality treatment approach, the trial design aimed to mimic CD treatment by using a medical stepwise approach. Therefore, the whole patient population started treatment with Pasireotide and only in patients within this population who did not achieve biochemical control, cabergoline was added.
The whole patient population had never received pasireotide or had received it in the past (reasons of discontinuation not related to safety).
Core Phase
- Pasireotide naïve patients started pasireotide monotherapy at the dose of 0.6 mg s.c. bid. If at the end of the 8 week treatment period, the biochemical control was not achieved and the 0.6mg bid dose was well tolerated, the pasireotide dose was increased to 0.9mg bid. If the 0.9mg bid dose of pasireotide did not lead to biochemical control, cabergoline was added with a starting dose of 0.5mg qd. If the combination dose of 0.9mg bid of pasireotide plus 0.5mg qd cabergolinedid not achieve biochemical control, the cabergoline dose will be increased to 1.0mg qd.
- Patients who were currently being treated with maximal tolerated doses of pasireotide monotherapy for at least 8 weeks at screening without achieving normal mUFC, entered the study with a combination therapy starting with cabergoline 0.5mg qd.
Extension Phase
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
pasireotide +/- cabergoline
pasireotide alone or with cabergoline
干预措施: Pasireotide with or without cabergoline (Drug)
结局指标
主要结局
Percentage of Responders With Mean Urinary Free Cortisol (mUFC) ≤ 1.0xULN Collected or Imputed at Week 35
时间窗: Baseline up to week 35
Participants who attained mUFC ≤ 1.0 x ULN (upper limit of normal) with pasireotide alone or in combination with cabergoline. The 24h-UFC concentration results from three samples, collected during the screening period, were averaged to obtain the Baseline urinary free cortisol level. mean 24h-UFC was determined from two 24-hour urine collections collected on two consecutive days that occurred before the visit. Imputation: subjects who completed the end of treatment visit at Week 35, but had missing evaluation of mean urinary free cortisol (mUFC). The last available mUFC assessment at or after previous visit (week) before last week was carried forward as the last week mUFC assessment.
次要结局
- Serum Cortisol Levels(Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 8 weeks during extension)
- Sitting Diastolic Blood Pressure at Week 35(Baseline and week 35)
- Body Weight at Week 35(Baseline and week 35)
- Body Mass Index at Week 35(Baseline and week 35)
- Percentage of Responders With Mean Urinary Free Cortisol (mUFC) ≤ 1.0xULN(Baseline up to week 235)
- Mean Urinary Free Cortisol (mUFC) at Scheduled Visits(Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 8 weeks during extension)
- Duration (Weeks) of Controlled or Partially Controlled Response(from the date patient's first normalization (mUFC ≤ 1.0xULN) or at least 50% reduction from baseline up to the date when the patient's mUFC > 1.0 x ULN)
- Sitting Systolic Blood Pressure at Week 35(Baseline and week 35)
- Percentage of Participants Who Attain mUFC ≤ 1.0 x ULN or Have at Least 50% Reduction From Baseline in mUFC(Baseline up to week 235)
- Mean Scores of Cushing QoL Standardized Score at Week 17 and 35(Baseline and week 17 and 35)
- Number of Participants With Improvement in Clinical Symptom of Hypercortisolism From Baseline - Facial Rubor(Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 16 weeks during extension)
- Number of Participants With Improvement in Clinical Symptom of Hypercortisolism From Baseline - Hirsutism(Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 16 weeks during extension)
- Number of Participants With Improvement in Clinical Symptom of Hypercortisolism From Baseline - Striae(Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 16 weeks during extension)
- Plasma Adrenocorticotropic Hormone (ACTH)(Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 8 weeks during extension)
- Waist Circumference at Week 35(Baseline and week 35)
- LDL, HDL and Total Cholesterol at Week 35(Baseline and week 35)
- Mean Scores of SF-12v2 Domain Scores at Week 17 and 35(Baseline, week 17 and 35)
- Number of Participants With Improvement in Clinical Symptom of Hypercortisolism From Baseline - Dorsal Fat Pad(Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 16 weeks during extension)
- Number of Participants With Shift From Mild to Severe in Clinical Signs of Hypercortisolism(Baseline, weeks 1, 2, 4, every 4 or 5 weeks during core, every 8 weeks during extension)
- Number of Participants With Improvement in Clinical Symptom of Hypercortisolism From Baseline - Supraclavicular Fat Pad(Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 8 weeks during extension)
- Number of Patients With Shift From Standing Easily to Not Being Able to Stand(Baseline up to week 267)