Efficacy, Safety, Tolerability and Pharmacokinetics of Concomitant Administration of Tramadol With Duloxetine or Pregabalin: a Randomized Controlled Flexible-dose Study in Patients With Neuropathic Pain
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Concentration of O-desmethyltramadol
研究概览
简要总结
Tramadol is an opioid analgesic, which is widely used in the treatment of acute and neuropathic pain. Treatment of neuropathic pain often requires a combination of pain medications due to the complex nature of neuropathic pain and frequent inadequate response to drug treatment. Common drugs used concomitantly with tramadol are SNRI antidepressant duloxetine and anticonvulsants such as pregabalin. Both tramadol and duloxetine have serotonergic effects and duloxetine has also a potential to inhibit metabolism of tramadol. The objective of the study is to investigate the pharmacokinetics and pharmacodynamic interaction of oral tramadol with duloxetine and pregabalin in patients with chronic neuropathic pain due to postherpetic neuralgia or diabetic polyneuropathy. All subjects will receive tramadol and duloxetine or tramadol and pregabalin in a randomized double-blind order. Primary end point is O-desmethyltramadol concentration.
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, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Chronic (≥ 6 months) neuropathic pain due to postherpetic neuralgia or diabetic polyneuropathy
- •Pain intensity ≥ 4 on a numerical scale of 0-10
- •Informed consent
排除标准
- •Clinically significant abnormalities in laboratory screening
- •Pregnancy
- •Depression
- •Use of strong opioids (morphine, oxycodone, fentanyl, hydromorphone, methadone)
- •A previous history of intolerance or allergy to the study drugs or to related compounds and additives
- •Existing or history of seizures, haematological disorders, clinically significant renal, hepatic, respiratory, cardiac or psychiatric disease, dementia, drug allergy
- •Previous or present alcoholism, drug abuse, psychological or other emotional problems or cognitive impairment that are likely to invalidate informed consent or limit the ability of the subject to comply with protocol requirements
- •Concomitant drug therapy known to cause significant enzyme induction or inhibition of CYP 1A2, 2D6, 3A4, 2B6, drugs metabolised by CYP2D6 enzyme, antidepressants, MAO-inhibitors, non-steroidal anti-inflammatory analgesics.
研究组 & 干预措施
Duloxetine and tramadol
To ascertain the double-blinding of subjects and investigators, duloxetine and pregabalin will be administered as 2 similar capsules twice a day. Each of these capsules will contain either 30mg of duloxetine, 75 mg of pregabalin or placebo. Capsules will be prepared at the hospital pharmacy.
干预措施: Tramadol (Drug)
Duloxetine and tramadol
To ascertain the double-blinding of subjects and investigators, duloxetine and pregabalin will be administered as 2 similar capsules twice a day. Each of these capsules will contain either 30mg of duloxetine, 75 mg of pregabalin or placebo. Capsules will be prepared at the hospital pharmacy.
干预措施: Duloxetine (Drug)
Pregabalin and tramadol
To ascertain the double-blinding of subjects and investigators, duloxetine and pregabalin will be administered as 2 similar capsules twice a day. Each of these capsules will contain either 30mg of duloxetine, 75 mg of pregabalin or placebo. Capsules will be prepared at the hospital pharmacy.
干预措施: Tramadol (Drug)
Pregabalin and tramadol
To ascertain the double-blinding of subjects and investigators, duloxetine and pregabalin will be administered as 2 similar capsules twice a day. Each of these capsules will contain either 30mg of duloxetine, 75 mg of pregabalin or placebo. Capsules will be prepared at the hospital pharmacy.
干预措施: Pregabalin (Drug)
结局指标
主要结局
Concentration of O-desmethyltramadol
时间窗: 3 weeks
次要结局
- Platelet function(baseline and 3 weeks)
- Plasma 5-HT concentration(baseline, 1, 2 and 3 weeks)
- Pain intensity(daily for 3 weeks)
- Use of rescue medication(1,2 and 3 weeks)
- Behavioral serotonergic effects(1, 2 and 3 weeks)
- Concentration of O-desmethyltramadol(baseline, 1 and 2 weeks)