Clinical trial NCT00618241: Pharmacokinetic Study on Raltegravir and Lamotrigine
Official title: The Influence of Raltegravir (MK-0518) on the Pharmacokinetics of Single-dose Lamotrigine in Healthy Male Subjects (GRANOLA)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infection
Keywords: interactions
neuropathic pain
pharmacokinetics
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2008-02-19
Enrollment: 24
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Plasma concentrations of lamotrigine, lamotrigine-2N-glucuronide, and raltregravir
timeFrame: 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 outcomes:
measure: Determination of pharmacokinetic parameters (AUC, Cmax, Tmax, Cmin and T 1/2) by noncompartmental analysis
timeFrame: at each sampling time
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
state: Gelderland
Study officials:
affiliation: Radboud University Medical Center
name: David M. Burger, PharmD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: van Luin M, Colbers A, Verwey-van Wissen CP, van Ewijk-Beneken-Kolmer EW, van der Kolk M, Hoitsma A, da Silva HG, Burger DM. The effect of raltegravir on the glucuronidation of lamotrigine. J Clin Pharmacol. 2009 Oct;49(10):1220-7. doi: 10.1177/0091270009345689. Epub 2009 Aug 28.