HIV Infection
Conditions
Keywords
interactions, neuropathic pain, pharmacokinetics
Brief summary
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.
Detailed description
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.
Interventions
DRUGlamotrigine
100 mg
DRUGRaltegravir
400 mg BD
Sponsors
Merck Sharp & Dohme LLC
Radboud University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Plasma concentrations of lamotrigine, lamotrigine-2N-glucuronide, and raltregravir | 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. |
Secondary
| Measure | Time frame |
|---|---|
| Determination of pharmacokinetic parameters (AUC, Cmax, Tmax, Cmin and T 1/2) by noncompartmental analysis | at each sampling time |
Countries
Netherlands
Outcome results
None listed