Official Title: “The Influence of Raltegravir (MK-0518) on the Pharmacokinetics of Single-Dose Lamotrigine in Healthy Male Subjects (GRANOLA)”

The purpose of this study is to determine whether interactions between raltegravir and lamotrigne take place and to study the safety of the combination raltegravir/lamotrigine before used in HIV patients.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Dose Comparison, Crossover Assignment, Pharmacokinetics Study

Study Primary Completion Date: October 2008

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.

Intervention(s) in this Clinical Trial

• Drug: lamotrigine alone or combined with raltegravir vise versa
  • Group A: day 1-5 Raltegravir 400mg oral BD. Lamotrigine one oral dose 100mg on day 4. Wash-out 6-31. Followed by one oral dose Lamotrigine 100mg on day 34. Group B: day 4 Lamotrigine one oral dose on day 4. Wash-out day 6-28 followed by Raltegravir 400mg oral BD day 29-33. One dose Lamotrigine 100mg oral on day 32.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: A
  • 5 days Raltegravir 400mg oral BD. Lamotrigine one oral dose 100mg on day 4.
• Active Comparator: B
  • One dose Lamotrigine 100mg oral.

Primary Measures

• Plasma concentrations of lamotrigine, lamotrigine-2N-glucuronide, and raltregravir
  • Time Frame: 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.
    Safety Issue?: No

Secondary Measures

• Determination of pharmacokinetic parameters (AUC, Cmax, Tmax, Cmin and T 1/2) by noncompartmental analysis
  • Time Frame: at each sampling time
    Safety Issue?: No

Inclusion Criteria:

• between 18 and 55 years of age
• subj does not smoke more than 10 cigarettes, 2 cigars of 2 pipes per day
• subj has a quetelet index of 18 to 30kg/m2
• subj is able and willing to sign informed consent
• subj is in a good age-appropriate health condition
• subj 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

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 55 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Radboud University

Overall Clinical Trial Officials and Contacts

David m Burger, PharmD PhD Principal Investigator Radboud University  

Information obtained from ClinicalTrials.gov on November 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00618241

Study ID Number: UMCN-AKF 07.06

ClinicalTrials.gov Identifier: NCT00618241

Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)