Pharmacokinetic Study on Raltegravir and Lamotrigine

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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HIV Infection

Intervention / Treatment
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* Drug: lamotrigine
* Drug: Raltegravir


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>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. | Drug: lamotrigine<br>* 100 mg<br>* Other names: Lamictal;Drug: Raltegravir<br>* 400 mg BD<br>|
| Active Comparator: B<br>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. | Drug: lamotrigine<br>* 100 mg<br>* Other names: Lamictal;Drug: Raltegravir<br>* 400 mg BD<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of pharmacokinetic parameters (AUC, Cmax, Tmax, Cmin and T 1/2) by noncompartmental analysis |  | at each sampling time | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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interactions, neuropathic pain, pharmacokinetics