A Randomized, Double-Blind, Dose-Finding, Placebo Controlled, Phase II Multicenter Study of Tetrodotoxin in the Treatment of Chemotherapy Induced Neuropathic Pain
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 125
- 试验地点
- 23
- 主要终点
- Change From Baseline in Patient Reported Outcome for Pain at Day 22 to Day 28.
研究概览
简要总结
Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting side effect of many chemotherapeutic agents including vincristine, paclitaxel, cisplatin, oxaliplatin, bortezomib and ixabepilone. Chemotherapy-induced peripheral neuropathy commonly occurs in greater than 40% of patients. To improve the peripheral neuropathy, the chemotherapy dosing is often either decreased or discontinued potentially affecting tumor responsiveness, prognosis, and survival.
There is an unmet medical need for treatment of cancer patients with chemotherapy induced neuropathic pain (CINP) and the proposed study will investigate the efficacy and safety of multiple dose levels of tetrodotoxin (TTX) versus placebo in moderate to severe neuropathic pain caused by chemotherapy.
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
- •If female, not of childbearing potential.
- •Patients with documented neuropathic pain
- •Cancer Patients who have completed a chemotherapy regimen which included taxanes or platinums (or both) and have no evidence actively progressive disease. Concurrent hormonal therapies are allowed
- •Patients with stable moderate to severe neuropathic pain
- •Patients with an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or
- •Patients who are able to complete the study-related questionnaires independently in either English or Spanish.
排除标准
- •History of peripheral neuropathy attributed to any cause other than chemotherapy.
- •Patients receiving any concurrent agents known to cause peripheral neuropathy within 30 days of Randomization.
- •Current use of other therapy (ies), including "alternative" therapies, for treatment of peripheral neuropathy within 30 days of Randomization (with the exception of protocol allowed concurrent medications).
- •Patients who used controlled release opioids within seven days of baseline period or who expect to use controlled release opioids at any time from baseline to end of study.
- •Patients with abnormal kidney function.
- •Patients with bone metastases.
- •Patients scheduled for treatment for their cancer with chemotherapy or radiotherapy between screening and the end of study visit.
- •Current use of lidocaine and other types of antiarrhythmic drugs within 30 days of Randomization.
- •Current use of scopolamine and acetylcholinesterase-inhibiting drugs such as physostigmine within 30 days of Randomization.
- •Current cause of Chemotherapy Induced Neuropathic Pain attributed to Velcade (Bortezomib) or vinca alkaloids or analogues such as vincristine, vinblasine, vinorelbine and vindesine.
- •Current use of tricyclic antidepressant medication, anticonvulsants and monoamine oxidase inhibitors.
- •Patients with current uncontrolled asthma or lung disease.
- •Patients with significant heart disease.
- •Use of an investigational agent within 30 days prior to screening or is scheduled to receive an investigational drug other than TTX during the course of the study.
- •Females who are pregnant or nursing
研究组 & 干预措施
Placebo (twice daily)
Placebo for injection (1 ml volume), twice a day for four consecutive days.
干预措施: Placebo (Drug)
Low dose Tetrodotoxin (twice daily)
Low dose Tetrodotoxin injectable (1 ml volume), twice a day for four consecutive days.
干预措施: Tetrodotoxin (Drug)
Mid-range dose of Tetrodotoxin (twice daily)
Mid-range dose Tetrodotoxin injectable (1 ml volume), twice a day for four consecutive days.
干预措施: Tetrodotoxin (Drug)
Max dose Tetrodotoxin (once daily)
Max dose Tetrodotoxin injectable (1 ml volume), once a day in the morning for four consecutive days and Placebo for injection (1 ml volume), once a day in the afternoon for four consecutive days. Total of 4 treatment days.
干预措施: Placebo (Drug)
Max dose Tetrodotoxin (once daily)
Max dose Tetrodotoxin injectable (1 ml volume), once a day in the morning for four consecutive days and Placebo for injection (1 ml volume), once a day in the afternoon for four consecutive days. Total of 4 treatment days.
干预措施: Tetrodotoxin (Drug)
Max dose Tetrodotoxin (twice daily)
Max dose Tetrodotoxin injectable (1 ml volume), twice a day for four consecutive days.
干预措施: Tetrodotoxin (Drug)
结局指标
主要结局
Change From Baseline in Patient Reported Outcome for Pain at Day 22 to Day 28.
时间窗: Day 22 to Day 28
The primary efficacy endpoint for Part I was the change from baseline in weekly average NPRS scores at 22 to 28 days after treatment. Baseline was defined as the average of NPRS scores for the last 7 days prior to dosing. Pain was assessed using a Numerical Pain Rating Scale (NPRS) with a range of 0 (no pain) to 10 (extreme pain).
次要结局
未报告次要终点