Pilot Study to Evaluate Efficacy, Tolerability and Safety Nonracemic Methadone HCl in Patients With Chronic Peripheral Neuropathic Pain: Double-Blind, Placebo-Controlled, Crossover Study Followed by Open-Label, Single-Arm Extension
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 37
- 主要终点
- Change in average daily pain scores
研究概览
简要总结
There is a growing evidence that the d-isomer of methadone is effective in treating neuropathic pain while the l-isomer of methadone is the only effective isomer of methadone for treating somatic pain. This study will examine a combination of different amounts of the d- and l-isomers of methadone specifically tailored to the chronic peripheral neuropathic pain. Non-racemic mixture of methadone isomers will be tested in this pilot efficacy and safety study.
This study will evaluate effect of the three doses of the non-racemic mixture of methadone hydrochloride patients with chronic peripheral neuropathic pain compared with a placebo. The study will also examine the minimally effective and maximally tolerated doses of the non-racemic mixture of methadone. Finally, the safety and tolerability of the non-racemic methadone therapy will be evaluated.
详细描述
Objectives:
- To evaluate effect of the three doses of the non-racemic methadone HCl on the metrics of pain intensity in comparison to placebo.
- To determine minimally effective and maximally tolerated doses of non-racemic methadone HCl for the treatment of diabetic peripheral neuropathic pain.
- To evaluate safety and tolerability of non-racemic methadone HCl therapy.
Study Design:
This is a pilot efficacy and safety study comprised of two parts.
Part I is a double-blind, placebo-controlled, crossover study of three daily doses (15 mg, 30 mg and 40 mg) of non-racemic methadone compared with placebo. Two lower doses (15 mg and 30 mg) will be administered for 1 week. The final dose (40 mg) will be administered for 2 weeks. After receiving three consecutive doses of the assigned drug the subjects will be switched to another regimen. Two 28-day treatment periods will be separated by a 14-day washout (drug-free) interval.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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
- •Male or female 18 years of age or older;
- •Female with a negative serum βhCG pregnancy test
- •Female of non-childbearing potential (postmenopausal or surgically sterile) OR female of child-bearing potential agreed to use the protocol-approved contraceptive method
- •Documented diagnosis of neuropathic pain associated with diabetic peripheral neuropathy for at least 6 months
- •Average daily pain severity score >=4 for the seven days prior to randomization (based on an 11-point numerical rating scale where 0= no pain and 10=worst possible pain)
- •Score >= 40 mm on the VAS of the Short Form McGill Pain Questionnaire (SF-MPQ) at screening and randomization visits
- •Stable doses (for at least three weeks) of non-opioid analgesics including NSAIDS, corticosteroids, gabapentin, pregabalin or antidepressants prescribed for the purposes of pain control or pain treatment naïve
- •Willing to refrain from any pain-relieving drugs other than the protocol-approved rescue medications (acetaminophen, <= 3 g daily or aspirin <= 325 mg daily) during the screening phase and the course of the study
- •Willing to limit alcohol consumption during the study according to protocol requirements
- •Able to understand and complete study diary and questionnaires
- •Willing to give informed consent prior to entry into the study
排除标准
- •A documented neuropathy of any cause other than diabetic peripheral neuropathy
- •A severe intermittent pain for reasons other than radiculopathy (e.g., migraine attacks)
- •History of head injury and/or increased intracranial pressure
- •Any neurologic disorder unrelated to diabetic peripheral neuropathy
- •Non-adequate renal and/or hepatic function as follows: Serum creatinine > 1.5 x ULN (upper limit of normal range) Liver enzymes (ALT and AST) > 2 x ULN
- •Any other know laboratory abnormality that, in the investigator's opinion, would contraindicate study participation
- •Chronic hepatitis B, hepatitis C, or HIV infection
- •Abnormal cognition defined as obvious clinical findings of state of arousal, confusion and memory or concentration deficit.
- •Recent history (within the previous 12 months) of respiratory depression, acute bronchial asthma or hypercarbia, or any other severe pulmonary or respiratory disease
- •Recent history (within the previous 12 months) of sleep apnea
- •Any hemostatic disorders or a current treatment with anticoagulants;
- •Unstable cardiovascular disease or symptomatic peripheral vascular disease
- •Hypotension: sitting or standing systolic blood pressure <= 90 mmHg and/or diastolic blood pressure <= 60 mmHg at screening and/or orthostatic hypotension (defined as a difference between sitting and standing systolic blood pressure >20 mmHg and/or a difference between sitting and standing diastolic blood pressure >10 mmHg)
- •Any clinically important ECG abnormality (including QT interval exceeding 450 ms)
- •Recent history (within the last 12 months) of risk factors for development of prolonged QT interval, including cardiac hypertrophy, concomitant diuretic use, hypocalcemia, hypomagnesemia
研究组 & 干预措施
Non Racemic Methadone
Non-Racemic Methadone Hydrochloride 5 mg Capsules containing a non-racemic mixture of methadone isomers.
干预措施: Non-racemic mixture of methadone HCl (Drug)
Placebo
Matching placebo capsules
干预措施: Non-racemic mixture of methadone HCl (Drug)
结局指标
主要结局
Change in average daily pain scores
时间窗: From Baseline to Week 4
次要结局
未报告次要终点