A Multicentre, Open-label, Long-term Efficacy and Safety Continuation Study of Subcutaneous Tetrodotoxin (TTX) for Moderate to Severe Cancer-related Pain
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 113
- 试验地点
- 2
- 主要终点
- Efficacy: long-term efficacy of tetrodotoxin (TTX) in reducing pain and improving quality of life. Safety: long-term safety and tolerability of s.c. TTX
研究概览
简要总结
Different pathophysiologic mechanisms are responsible for the development of chronic pain disorders. Pain pathways are triggered in part by ectopic discharges of voltage-sensitive sodium channels, which are in abundance in both the peripheral and the central nervous systems. Tetrodotoxin (TTX) is a selective blocker of Na+ channels and causes analgesia either by decreasing the propagation of action potentials by Na+ channels and/or by blocking of ectopic discharges associated with chronic pain. TTX is extracted from the puffer fish (fugu). Results from animal pharmacology studies revealed that TTX is a more potent analgesic than standard analgesic agents such as aspirin, morphine or meperidine.
At present, the management of severe cancer pain generally includes the use of opiates. This can often result in undesirable side effects, and treatment with this type of medication is not always effective. Because currently available pain-relieving therapy is unsatisfactory for many patients, there is a need for new therapeutic approaches for the management of moderate or severe cancer pain.
Recent studies indicate that intramuscular (into a muscle) or subcutaneous (under the skin) injections of tetrodotoxin (TTX) may reduce pain in cancer patients who did not respond to standard therapies.
The current proposed study (TEC-006OL) is designed to provide the option for all patients who participated in the TEC-006 study (both tetrodotoxin and placebo-treated) to receive or continue to receive tetrodotoxin treatment.
详细描述
Study Objectives: In cancer patients with moderate to severe pain who participated in the TEC-006 study:
Primary Objectives:
- To assess the long-term efficacy of subcutaneous tetrodotoxin (TTX) treatment in reducing the pain outcome and improving the quality of life (physical and emotional functioning).
- To assess the long-term safety and tolerability of subcutaneous tetrodotoxin (TTX).
Secondary Objective:
• To assess the duration of analgesia following repeated cycles of tetrodotoxin (TTX) treatment.
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
- •All patients who participated in the TEC-006 study (tetrodotoxin and placebo-treated) will be eligible for inclusion in this study provided they wish to continue to receive treatment and meet the inclusion and exclusion criteria.
- •NOTE: The blinded treatment assignment of patients in the TEC-006 will not be revealed to either the investigator or the patient. Patients will not be aware which treatment they received in the TEC-006 study. All patients will receive tetrodotoxin treatment in the TEC-006OL study.
- •A patient will be eligible or continue to be eligible for inclusion in this study (First Treatment Cycle and subsequent Treatment Cycles) only if all of the following criteria apply:
- •Male or female 18 years of age and over
- •In-patients or out-patients with a diagnosis of cancer
- •Patients must be experiencing somatic, visceral and/or neuropathic pain related to cancer.
- •Compliant to the requirements of the TEC-006 Protocol.
- •Inadequately controlled pain: Pain intensity described as 'moderate', 'severe' or 'excruciating', as assessed by the VRS during the screening/baseline period of the First Treatment Cycle, and a baseline pain intensity score of ≥4 as assessed by NRS (worst, average, or component-specific pain).
- •Meet the Responder or Clinical Responder definition for repeat cycle treatment (cycle #2 to cycle #4)
- •Life expectancy of > 3 months.
- •Ability to communicate well with the Investigator and to comply with the requirements of the entire study.
- •Willingness to give written informed consent (prior to any study-related procedures being performed) and to be able to adhere to the study restrictions, appointments and examination schedule.
排除标准
- •A patient will not be eligible for inclusion in this study if any of the following criteria apply:
- •Planned initiation of chemotherapy, radiotherapy or bisphosphonates within 30 days prior to enrolment.
- •Known renal disease.
- •If it has been more than 14 days since their TEC_006 End of Study Visit or their pain returned to baseline since their last tetrodotoxin treatment cycle (for repeat cycle).
- •Patient has previously completed 4 cycles of tetrodotoxin
- •If it has been more than 6 months since patient signed consent to participate in the TEC-006 OL study.
- •Use of anaesthetics.
- •Use of lidocaine, and other types of antiarrhythmic drugs.
- •Use of scopolamine and acetylcholinesterase-inhibiting drugs such as physostigmine.
- •History of CO2 retention, or SaO2 <80% either on room air or O2 of not greater than 2-4 L/min by nasal cannula.
- •Second or third degree heart block or prolonged QTc interval (corrected for rate) on screening ECG (confirmed > 450 msec on repeated occasion) or any other active cardiac arrhythmia or abnormality that would constitute a clinical risk.
- •Coagulation or bleeding defects if in the opinion of the Investigator this represents a risk to the subject considering the subcutaneous (s.c.) route of administration.
- •Known hypersensitivity to puffer fish, tetrodotoxin and/or its derivatives.
- •Received an investigational agent other than tetrodotoxin within 30 days prior to screening or who is scheduled to receive an investigational drug other than tetrodotoxin during the course of the study.
- •Females who are lactating or at risk of pregnancy (i.e., sexually active with fertile males and not using an adequate form of birth control).
- •Females with a positive pregnancy test at screening or on admission to study site.
- •Any other condition that, in the opinion of the investigators, is likely to interfere with the successful collection of the measures required for the study or poses a risk to the patient.
结局指标
主要结局
Efficacy: long-term efficacy of tetrodotoxin (TTX) in reducing pain and improving quality of life. Safety: long-term safety and tolerability of s.c. TTX
时间窗: Repeat treatment for patients with meaningful analgesic response
次要结局
- For each Treatment Cycle: the total number of days a subject meets the definition of pain response.(Repeat treatment for subjects with meaningful analgesic response)