A Randomized, Parallel Group Study to Evaluate the Safety, Pharmacokinetics, and Dose Response of Paltusotine Treatment in Subjects With Carcinoid Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 36
- 试验地点
- 38
- 主要终点
- Safety - Incidence of Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
The purpose of this study is to evaluate the safety, pharmacokinetics (PK), and exploratory dose response of paltusotine treatment in subjects with carcinoid syndrome. This study consists of a Randomized Treatment Phase followed by an Open-Label Extension (OLE) Phase.
详细描述
This is a Phase 2, randomized, open-label, parallel-group, multicenter study designed to evaluate the safety, pharmacokinetics, and efficacy of paltusotine treatment in subjects with carcinoid syndrome. The study was conducted in 2 parts: a Randomized Treatment Phase (RTP) which is completed, and an Open-label Extension (OLE) Phase which is still ongoing. The RTP consisted of paltusotine treatment for 8 weeks. Subjects who completed the RTP were eligible to enter the OLE Phase at the recommendation of the Investigator. In the ongoing OLE Phase, paltusotine is being administered for a further 102 weeks. The total duration of paltusotine treatment for the combined RTP and OLE Phase is up to 110 weeks (28 months).
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
- 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
- •1. Male or female subjects ≥18 years of age.
- •Documented carcinoid syndrome requiring medical therapy.
- •Not currently treated with somatostatin receptor ligands agonists for at least 12 weeks prior to screening and actively symptomatic. This can include treatment-naïve subjects.
- •Subjects currently treated with lanreotide, octreotide long acting release, or short acting octreotide (subcutaneous or oral) who are currently symptomatically controlled
- •Evaluable documentation of locally advanced or metastatic histopathologically confirmed well-differentiated neuroendocrine tumor (NET). Tumors must be Grade 1 (Ki-67 index < 3%, or a mitotic count of < 2 mitoses per 10 high-power fields, if the Ki-67 index is not available) or Grade 2 (Ki-67 index 3-20%, or a mitotic count of 2-20 mitoses per 10 high-power fields, if the Ki-67 index is not available) per the World Health Organization neuroendocrine neoplasm classification (Rindi and Inzani, 2020). Grade 3 tumors are not eligible.
- •No significant disease progression as assessed by the Investigator within the last 6 months before initiation of study drug dosing.
排除标准
- •Diarrhea attributed to any condition(s) other than carcinoid syndrome.
- •Uncontrolled/severe diarrhea associated with significant volume contraction, dehydration, or hypotension.
- •Requires second line treatments (eg, telotristat) for control of carcinoid syndrome symptoms.
- •Treatment with specific NET tumor therapy <4 weeks before Screening (such as everolimus or sunitinib) or hepatic embolization, radiotherapy, peptide receptor radionuclide therapy (PRRT), and/or tumor debulking <12 weeks before Screening.
- •History of another primary malignancy <3 years prior to the date of first dose, except for adequately treated basal or squamous cell carcinoma of the skin, cancer of the breast or cervix in situ, previously treated or concurrent malignancy determined to be clinically stable and not requiring treatment.
- •Diabetes mellitus treated with insulin for less than 6 weeks prior to the study entry.
结局指标
主要结局
Safety - Incidence of Treatment-emergent Adverse Events (TEAEs)
时间窗: First dose of investigational medicine to End of Randomized Treatment Phase (8 weeks)
Incidence of TEAEs, including serious TEAEs and TEAEs leading to discontinuation; change from baseline to the EOR in safety parameters: clinical laboratory tests, physical exam findings, vital signs, 12-lead ECG, and 24-hour continuous cardiac monitoring (only for subjects on 120 mg dose). In addition to all-cause mortality, deaths were categorized by primary cause (e.g., cardiovascular) based on medical adjudication. Events were coded using MedDRA and summarized by treatment group, system organ class, and preferred term. TEAEs were reported per randomized arm. There were 2 randomized arms (40 mg and 80 mg paltusotine, with up-or down-dose titration permitted for symptom control). Results are analyzed based on the initially assigned randomization arm, regardless of the actual dose received.
次要结局
- Pharmacokinetics (PK) of Paltusotine(Measured at each visit (pre and post dose) up to Week 8 (i.e., End of Randomized Treatment Phase [EOR]))