The Influence of Raltegravir (MK-0518) on the Pharmacokinetics of Single-dose Lamotrigine in Healthy Male Subjects (GRANOLA)
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
- Plasma concentrations of lamotrigine, lamotrigine-2N-glucuronide, and raltregravir
研究概览
简要总结
The purpose of this study is to determine whether interactions between raltegravir and lamotrigine take place and to study the safety of the combination raltegravir/lamotrigine before used in HIV patients.
详细描述
Lamotrigine is an anticonvulsive drug that is used both for the treatment of HIV-associated neuropathic pain and the treatment of epilepsy in HIV-infected individuals. Lamotrigine is metabolized via glucuronidation.
Raltegravir is a newly developed integrase inhibitor that is also metabolized via glucuronidation.
Since both agents are metabolized via glucuronidation, there is a possibility of competition for glucuronidation, leading to drug-drug interactions between raltegravir and lamotrigine.
This primary objective of this study is to determine the effect of raltegravir on the pharmacokinetics of single dose lamotrigine (by intrasubject comparison). A secondary objective is to determine the effect of single dose lamotrigine on the pharmacokinetics of raltegravir when compared to historical controls. Another secondary objective is to evaluate the safety of combined use of single dose lamotrigine and raltegravir.
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
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Between 18 and 55 years of age
- •Subject does not smoke more than 10 cigarettes, 2 cigars or 2 pipes per day
- •Subject has a Quetelet Index of 18 to 30 kg/m2
- •Subject is able and willing to sign informed consent
- •Subject is in good age-appropriate health condition
- •Subject has a normal blood pressure and pulse rate
排除标准
- •History of sensitivity/idiosyncrasy to medicinal products or excipients
- •Positive HIV test
- •Positive hepatitis B or C test
- •Therapy with any drug (2 weeks preceding dosing) except for paracetamol
- •Relevant history or presence of pulmonary disorders, cardiovascular
- •History of or current abuse of drugs, alcohol or solvents
- •Inability to understand the nature and extent of the trial and procedures
- •Participation in a drug trial within 60 days prior to the first dose
- •Donation of blood within 60 days prior to the first dose
- •Febrile illness within 3 days before the first dose
研究组 & 干预措施
A
Group A: day 1-5 Raltegravir 400 mg oral BD (twice daily). Lamotrigine one oral dose 100 mg on day 4. Wash-out 6-31. Followed by one oral dose Lamotrigine 100 mg on day 34.
5 days Raltegravir 400 mg oral BD. Lamotrigine one oral dose 100mg on day 34.
干预措施: lamotrigine (Drug)
A
Group A: day 1-5 Raltegravir 400 mg oral BD (twice daily). Lamotrigine one oral dose 100 mg on day 4. Wash-out 6-31. Followed by one oral dose Lamotrigine 100 mg on day 34.
5 days Raltegravir 400 mg oral BD. Lamotrigine one oral dose 100mg on day 34.
干预措施: Raltegravir (Drug)
B
Group B: day 4 Lamotrigine one oral dose on day 4. Wash-out day 6-28 followed by Raltegravir 400 mg oral BD day 29-33. One dose Lamotrigine 100 mg oral on day 32.
One dose Lamotrigine 100 mg oral.
干预措施: lamotrigine (Drug)
B
Group B: day 4 Lamotrigine one oral dose on day 4. Wash-out day 6-28 followed by Raltegravir 400 mg oral BD day 29-33. One dose Lamotrigine 100 mg oral on day 32.
One dose Lamotrigine 100 mg oral.
干预措施: Raltegravir (Drug)
结局指标
主要结局
Plasma concentrations of lamotrigine, lamotrigine-2N-glucuronide, and raltregravir
时间窗: just before dosing, at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 24 hours and 48 hours after dosing on study days 4-5 and 32-33.
次要结局
- Determination of pharmacokinetic parameters (AUC, Cmax, Tmax, Cmin and T 1/2) by noncompartmental analysis(at each sampling time)