A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Ascending, Multidose Study To Determine Safety and Tolerability of Orally Administered LX1606 in Subjects With Symptomatic Carcinoid Syndrome Refractory to Stable-Dose Octreotide Long-Acting Release Depot Therapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 23
- 试验地点
- 9
- 主要终点
- Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Drug-related TEAE in the Core Phase
研究概览
简要总结
The purpose of this study is to evaluate the safety and tolerability of telotristat etiprate (LX1606) versus a placebo control in participants with symptomatic carcinoid syndrome not managed by stable-dose long-acting octreotide therapy. Following determination of the maximally tolerated or effective dose, cohort expansion will occur to confirm effect on symptoms and safety profile.
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
- Triple (Participant, 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
- •Males and females, aged 18 and older
- •Biopsy-proven metastatic carcinoid tumor of the gastrointestinal (GI) tract with disease extent confirmed by computed tomography (CT), magnetic resonance imaging (MRI), or radionuclide imaging
- •Symptoms not managed by stable-dose long-acting octreotide therapy (≥4 bowel movements per day)
- •Ability to provide written informed consent
排除标准
- •≥12 high volume, watery bowel movements per day associated with a clinical syndrome of volume contraction, dehydration, or hypotension compatible with a "pancreatic cholera"-type clinical syndrome
- •Sponsor-unacceptable clinical laboratory values for hematology and liver function tests at screening
- •Karnofsky status ≤70% - unable to care for self
- •Surgery within 60 days prior to screening
- •A history of short bowel syndrome
- •Life expectancy <12 months
- •History of substance or alcohol abuse within 2 years prior to screening
- •Previous exposure to a tryptophan hydroxylase (TPH) inhibitor
- •Administration of any investigational drug within 30 days of screening or any therapeutic protein or antibody within 90 days of screening
研究组 & 干预措施
Telotristat Etiprate 150 mg Core Phase
Telotristat etiprate capsules,150 mg orally 3 times daily for 28 days in the double-blind treatment period (core phase) in combination with stable-dose octreotide long-acting release (LAR) depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.
干预措施: Telotristat etiprate (Drug)
Telotristat Etiprate 150 mg Core Phase
Telotristat etiprate capsules,150 mg orally 3 times daily for 28 days in the double-blind treatment period (core phase) in combination with stable-dose octreotide long-acting release (LAR) depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.
干预措施: Octreotide LAR Depot (Drug)
Telotristat Etiprate 250 mg Core Phase
Telotristat etiprate capsules, 250 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.
干预措施: Telotristat etiprate (Drug)
Telotristat Etiprate 250 mg Core Phase
Telotristat etiprate capsules, 250 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.
干预措施: Octreotide LAR Depot (Drug)
Telotristat Etiprate 350 mg Core Phase
Telotristat etiprate capsules, 350 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.
干预措施: Telotristat etiprate (Drug)
Telotristat Etiprate 350 mg Core Phase
Telotristat etiprate capsules, 350 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.
干预措施: Octreotide LAR Depot (Drug)
Telotristat Etiprate 500 mg Core Phase
Telotristat etiprate capsules, 500 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with a stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.
干预措施: Telotristat etiprate (Drug)
Telotristat Etiprate 500 mg Core Phase
Telotristat etiprate capsules, 500 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with a stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.
干预措施: Octreotide LAR Depot (Drug)
Placebo Core Phase
Placebo-matching telotristat etiprate capsules, orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to receive telotristat etiprate in the optional open-label extension period.
干预措施: Octreotide LAR Depot (Drug)
Placebo Core Phase
Placebo-matching telotristat etiprate capsules, orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to receive telotristat etiprate in the optional open-label extension period.
干预措施: Placebo (Drug)
Telotristat Etiprate Open-Label Extension Phase
Telotristat etiprate at assigned dose level for 8 weeks in combination with stable-dose octreotide LAR depot therapy given once per month in the open-label extension period. Upon completion of the 8-week period, participants could enter an additional extension period of 172 weeks, receiving telotristat etiprate at the assigned dose or maximum tolerated dose (500 mg 3 times daily).
干预措施: Telotristat etiprate (Drug)
Telotristat Etiprate Open-Label Extension Phase
Telotristat etiprate at assigned dose level for 8 weeks in combination with stable-dose octreotide LAR depot therapy given once per month in the open-label extension period. Upon completion of the 8-week period, participants could enter an additional extension period of 172 weeks, receiving telotristat etiprate at the assigned dose or maximum tolerated dose (500 mg 3 times daily).
干预措施: Octreotide LAR Depot (Drug)
结局指标
主要结局
Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Drug-related TEAE in the Core Phase
时间窗: Up to 4 Weeks Core Phase
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 Any TEAE in the Open-Label Extension Phase
时间窗: Up to 180 weeks in the open-label extension phase
An 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 receiving treatment.
次要结局
- Change From Baseline in Weekly Mean Stool Form(Baseline to Week 4)
- Change From Baseline in Number of Cutaneous Flushing Episodes(Baseline to Week 4)
- Number of Participants Reporting Improvement in the Subjective Global Assessment of Symptoms Associated With Carcinoid Syndrome(Week 4)
- Number of Participants Experiencing Complete Response at Week 4(Baseline to Week 4)
- Change From Baseline in Mean Number of Bowel Movements (BMs) Per Day(Baseline to Week 4)
- Change From Baseline in Chromogranin A(Baseline to Week 4)
- Change From Baseline in Frequency of Rescue for Short-acting Octreotide Use/Day(Baseline to Week 4)
- Time to First Rescue, Short-acting Octreotide(Baseline to Week 4)
- Change From Baseline in Percentage of Days Per Week Experiencing a Sensation of Urgency to Defecate(Baseline to Week 4)
- Change From Baseline in Severity of Abdominal Pain or Discomfort(Baseline to Week 4)
- Change From Baseline in Urinary 5-hydroxyindoleacetic Acid (u5-HIAA)(Baseline to Week 4)