A Phase 3, Randomized, Placebo-controlled, Parallel Group, Multicenter, Double-blind Study to Evaluate the Efficacy and Safety of Telotristat Etiprate (LX1606) in Patients With Carcinoid Syndrome Not Adequately Controlled by Somatostatin Analog (SSA) Therapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 135
- 试验地点
- 2
- 主要终点
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Treatment Period
研究概览
简要总结
The primary objective of the study is to confirm that at least 1 or more doses of telotristat etiprate compared to placebo is effective in reducing the number of daily bowel movements (BMs) from baseline averaged over the 12-week double-blind portion (Treatment Period) of the trial in patients not adequately controlled by current SSA therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Histopathologically-confirmed, well-differentiated metastatic neuroendocrine tumor
- •Documented history of carcinoid syndrome and currently experiencing ≥4 bowel movements per day during the Run-in period
- •Currently receiving stable-dose somatostatin analog (SSA) therapy
- •Minimum dose of long-acting release (LAR) or depot SSA therapy
- •Octreotide LAR at 30 mg every 4 weeks
- •Lanreotide Depot at 120 mg every 4 weeks
- •Patients who cannot tolerate SSA therapy at a level indicated above will be allowed to enter at their highest tolerated dose
- •Ability and willingness to provide written informed consent
排除标准
- •Presence of diarrhea attributed to any condition(s) other than carcinoid syndrome
- •Karnofsky Performance status ≤60%
- •Treatment with any tumor directed therapy, including interferon, chemotherapy, mechanistic target of rapamycin (mTOR) inhibitors <4 weeks prior to Screening, or hepatic embolization, radiotherapy, radiolabelled SSA, and/or tumor debulking <12 weeks prior to Screening
- •History of short bowel syndrome (SBS)
- •Clinically significant cardiac arrhythmia, bradycardia, tachycardia that would compromise patient safety or the outcome of the study
- •Previous exposure to telotristat etiprate
研究组 & 干预措施
250 mg Telotristat Etiprate
Following a 3 to 4-week run-in period on stable-dose somatostatin analog (SSA) therapy (octreotide or lanreotide) participants were randomized to receive one 250 mg telotristat etiprate tablet plus one placebo-matching telotristat etiprate tablet administered three times daily for 12 Weeks in the double-blind treatment period, followed by a 36 week open-label extension period.
干预措施: Telotristat etiprate (Drug)
250 mg Telotristat Etiprate
Following a 3 to 4-week run-in period on stable-dose somatostatin analog (SSA) therapy (octreotide or lanreotide) participants were randomized to receive one 250 mg telotristat etiprate tablet plus one placebo-matching telotristat etiprate tablet administered three times daily for 12 Weeks in the double-blind treatment period, followed by a 36 week open-label extension period.
干预措施: Placebo-matching telotristat etiprate (Drug)
500 mg Telotristat Etiprate
Following a 3 to 4-week run-in period on stable-dose SSA therapy (octreotide or lanreotide) participants were randomized to receive, one telotristat etiprate 250 mg plus one placebo-matching telotristat etiprate tablet administered 3 times daily for 1 week, followed by two telotristat etiprate (250 mg) tablets administered three times daily for 11 weeks in the double-blind treatment period, followed by a 36 week open-label extension period.
干预措施: Telotristat etiprate (Drug)
500 mg Telotristat Etiprate
Following a 3 to 4-week run-in period on stable-dose SSA therapy (octreotide or lanreotide) participants were randomized to receive, one telotristat etiprate 250 mg plus one placebo-matching telotristat etiprate tablet administered 3 times daily for 1 week, followed by two telotristat etiprate (250 mg) tablets administered three times daily for 11 weeks in the double-blind treatment period, followed by a 36 week open-label extension period.
干预措施: Placebo-matching telotristat etiprate (Drug)
Placebo
Following a 3 to 4-week run-in period on stable-dose SSA therapy (octreotide or lanreotide) participants were randomized to receive two placebo-matching telotristat etiprate tablets administered three times daily for 12 weeks in the double-blind treatment period, followed by a 36 week open-label extension period.
干预措施: Placebo-matching telotristat etiprate (Drug)
Telotristat Etiprate Open-Label Extension
Patients previously assigned to 250 mg or 500 mg three times daily of telotristat etiprate were administered two 250 mg telotristat etiprate tablets three times daily in a 36 week open-label extension (OLE) period. Patients previously assigned to placebo were administered one 250 mg telotristat etiprate tablet plus one placebo-matching tablet three times daily for one week, followed by two 250 mg telotristat etiprate tablets three times daily for 35 weeks.
干预措施: Telotristat etiprate (Drug)
Telotristat Etiprate Open-Label Extension
Patients previously assigned to 250 mg or 500 mg three times daily of telotristat etiprate were administered two 250 mg telotristat etiprate tablets three times daily in a 36 week open-label extension (OLE) period. Patients previously assigned to placebo were administered one 250 mg telotristat etiprate tablet plus one placebo-matching tablet three times daily for one week, followed by two 250 mg telotristat etiprate tablets three times daily for 35 weeks.
干预措施: Placebo-matching telotristat etiprate (Drug)
结局指标
主要结局
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Treatment Period
时间窗: First dose of study drug to within 30 days of last dose of study drug in the Double-Blind Treatment Period (Up to 17.6 Weeks)
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A TEAE was an AE reported after the first dose of randomized treatment on Day 1.
Number of Participants With TEAEs in the Open-Label Extension Period
时间窗: First dose of study drug to within 30 days of last dose of study drug in the Open-Label Extension Period (Up to 54.3 Weeks)
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A TEAE was an AE reported after the first dose of randomized treatment on Day 1.
Change From Baseline in the Number of Bowel Movements (BMs) Per Day Averaged Over 12 Weeks
时间窗: Baseline and 12 Weeks
Participants recorded the number of bowel movements per day in a daily diary. The total number of BMs per day were averaged over the 12-week period. A negative change from Baseline indicates improvement.
次要结局
- Change From Baseline in Urinary 5-hydroxyindoleacetic Acid (u5-HIAA) Levels(Baseline and Week 12)
- Change From Baseline in the Number of Daily Cutaneous Flushing Episodes Averaged Across All Time-Points(Baseline and 12 Weeks)
- Change From Baseline in Abdominal Pain Averaged Across All Time-Points(Baseline and 12 Weeks)