Administration of Ondansetron With P-glycoprotein Inhibitor Tariquidar in Patients With Neuropathic Pain
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Concertation-time Profile of Ondansetron in Plasma, Measured by the Area Under the Concentration-time Curve (AUC)
研究概览
简要总结
Prospective, randomized, double-blind, placebo controlled, cross-over proof of concept study.
To determine the pharmacokinetics and tolerability of co-administration of 5-HT3R antagonist ondansetron with a P-glycoprotein inhibitor tariquidar, in patients with neuropathic pain.
详细描述
The investigators hypothesize that co-administration of a 5-HT3 receptor antagonist ondansetron (single 16mg dose) with p-glycoprotein inhibitor tariquidar (single 4mg/kg dose) vs placebo in a cross-over prospective randomized study, will:
- Be tolerable in patients with neuropathic pain.
- Increase the cerebrospinal fluid (CSF) to plasma ratio of ondansetron after intravenous administration, compare to ondansetron alone
- Result in a greater reduction in pain intensity than with ondansetron alone.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented diagnosis of neuropathic pain due to damage or disease affecting the peripheral nervous system;
- •At least Probable neuropathic pain grading1;
- •Pain duration >3 months;
- •Average pain intensity ≥4 on 0-10 numerical rating scale (NRS).
排除标准
- •Current pregnancy or lactation;
- •Moderate-severe kidney or liver dysfunction;
- •Active cardiac arrhythmias (non-sinus rhythm), Long QT syndrome, or QTc interval >450msec;
- •Congestive heart failure
- •Abnormal troponin values at screening visit;
- •Current treatment with MAO inhibitors, mirtazapine, SSRI antidepressants, or SNRI medications duloxetine or venlafaxine;
- •Current treatment with tapentadol, tramadol, or fentanyl;
- •Current treatment with P-glycoprotein substrate drugs with narrow therapeutic window, e.g. digoxin;
- •Current treatment with tricyclic antidepressant medications (e.g. amitriptyline, desipramine, imipramine) at a dose >25mg/day;
- •Ongoing use of any of the following medications with known effects on Pgp function: carbamazepine, phenytoin, phenobarbital, cyclosporine, clarithromycin, erythromycin, ritonavir, verapamil, rifampicin, St. John's wort;
- •Current treatment with QT-prolonging drugs, and drugs known to have a significant interaction with ondansetron or other P-glycoprotein substrates (see section 2.3.3.);
- •Current treatment with anticoagulant drugs;
研究组 & 干预措施
Ondansetron/Placebo first, then Ondansetron/Tariquidar
The study group where patients received Ondansetron with Placebo during Visit 1, and after a washout period of 3 weeks Ondansetron with Tariquidar at Visit 2 per the randomization schedule.
Ondansetron 16 mg was administered IV over 60 minutes with placebo (D5W) or with tariquidar (4mg/kg dose in D5W). Ondansetron was diluted in 100mL 0.9% normal saline, and tariquidar was diluted in 500mL D5W.
干预措施: Ondansetron 16 mg with Tariquidar (Drug)
Ondansetron/Placebo first, then Ondansetron/Tariquidar
The study group where patients received Ondansetron with Placebo during Visit 1, and after a washout period of 3 weeks Ondansetron with Tariquidar at Visit 2 per the randomization schedule.
Ondansetron 16 mg was administered IV over 60 minutes with placebo (D5W) or with tariquidar (4mg/kg dose in D5W). Ondansetron was diluted in 100mL 0.9% normal saline, and tariquidar was diluted in 500mL D5W.
干预措施: Ondansetron 16 mg with Placebo (Drug)
Ondansetron/Tariquidar first, then Ondansetron/Placebo
The study group where patients received Ondansetron with Tariquidar during Visit 1, and after 3 weeks of washout period Ondansetron with Placebo at Visit 2 per the randomization schedule.
Ondansetron 16 mg was administered IV over 60 minutes with tariquidar (4mg/kg dose in D5W) or with placebo (D5W). Ondansetron was diluted in 100mL 0.9% normal saline, and tariquidar was diluted in 500mL D5W.
干预措施: Ondansetron 16 mg with Tariquidar (Drug)
Ondansetron/Tariquidar first, then Ondansetron/Placebo
The study group where patients received Ondansetron with Tariquidar during Visit 1, and after 3 weeks of washout period Ondansetron with Placebo at Visit 2 per the randomization schedule.
Ondansetron 16 mg was administered IV over 60 minutes with tariquidar (4mg/kg dose in D5W) or with placebo (D5W). Ondansetron was diluted in 100mL 0.9% normal saline, and tariquidar was diluted in 500mL D5W.
干预措施: Ondansetron 16 mg with Placebo (Drug)
结局指标
主要结局
Concertation-time Profile of Ondansetron in Plasma, Measured by the Area Under the Concentration-time Curve (AUC)
时间窗: Measurements over 240 minutes, extrapolated to infinity
AUCinf for Ondansetron concentration in plasma based on venous blood sampling for plasma concentrations of ondansetron obtained at 0, 15, 30, 60, 90, 120, 180, and 240 minutes from the beginning of ondansetron infusion.
Cerebrospinal Fluid to Plasma Concentration Ratio of Ondansetron
时间窗: anytime between 0-240 minutes
The level of ondansetron in plasma and CSF (cerebrospinal fluid) in samples, taken around the same time, was measured, and the ratio of the two values was calculated. This ratio (partition coefficient, Kp) of ondansetron, compared between the two sessions, with placebo vs tariquidar
次要结局
- % Change in Pain Intensity(baseline to 90 minutes after ondansetron IV infusion)
- Conditioned Pain Modulation (CPM) Magnitude (ΔCPM)(Baseline and 90 minutes after the end of ondansetron infusion)
- Correlation Between CPM Magnitude (ΔCPM) and Change in Pain Intensity(0-240 min from infusion)
- Change in Neuropathic Pain Symptom Inventory (NPSI) Score(baseline to 70 min after infusion)
研究者
simon.haroutounian
Associate Professor
Washington University School of Medicine