A Multicentre , Randomized, Double-blind, Placebo-controlled, Parallel-design Trial of the Efficacy and Safety of Subcutaneous Tetrodotoxin (TTX) for Moderate to Severe Inadequately Controlled Cancer-related Pain
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 165
- 试验地点
- 1
- 主要终点
- Efficacy: Composite-endpoint will be an evaluation that combines pain outcome and quality of life. Pain intensity will be used a co-primary endpoint. Safety as assessed by the analysis of AEs, 12-lead ECG, and abnormal lab values.
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-006) is designed to 1) demonstrate in a double-blind, placebo-controlled trial that the subcutaneous 30 μg b.i.d. dose of TTX for 4 days is effective in reducing pain outcome and improving quality of life; 2) characterize the onset and duration of analgesia, and 3) demonstrate that TTX is well tolerated in patients with inadequately controlled cancer-related pain.
详细描述
Study Objectives:
Male or female subjects with moderate to severe pain (related to cancer or cancer treatment)inadequately controlled by current therapy:
Primary Objectives:
-
To compare the efficacy of subcutaneous tetrodotoxin treatment (TTX) with that of placebo as measured by:
-
pain outcome (pain intensity reduction or use of analgesics)
-
improvement in quality of life (physical and emotional functioning)
-
To compare the safety of subcutaneous tetrodotoxin with that of placebo.
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
- •A subject will be eligible for inclusion in this study only if all of the following criteria apply:
- •Male or female 18 years of age and over.
- •Inpatient or outpatient with a diagnosis of cancer.
- •Stable but inadequately controlled pain with current therapy for at least two weeks.
- •Experiencing somatic, visceral and/or neuropathic pain related to cancer.
- •Baseline pain intensity, as assessed by Question #3 of the Brief Pain Inventory (BPI) that meets the definition of "moderate" (score of 4-5) or "severe" (score of 6-10) pain.
- •Life expectancy of at least 3 months.
- •Ability to communicate well with the investigator and to comply with the requirements (restrictions, appointments, and examination schedule) of the entire study.
- •Signed informed consent document (prior to any study-related procedures being performed).
排除标准
- •A subject 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 randomization.
- •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 could 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.
- •Use of an investigational agent within 30 days prior to screening or 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 serum pregnancy test at screening or positive urine pregnancy test 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.
- •Men with glomerular filtration rate (GRF) less than 60 mL/min/1.73 m2 and women with GFR less than 50 mL/min/1.73 m2
研究组 & 干预措施
Sugar injection
干预措施: Placebo (Biological)
Tetrodotoxin
干预措施: Tetrodotoxin (Biological)
结局指标
主要结局
Efficacy: Composite-endpoint will be an evaluation that combines pain outcome and quality of life. Pain intensity will be used a co-primary endpoint. Safety as assessed by the analysis of AEs, 12-lead ECG, and abnormal lab values.
时间窗: Dec2010
次要结局
- The period of onset of pain response as reported by responders.(Dec2010)
- The number of days a subject meets the definition of pain response.(Dec2010)