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Pharmacokinetic Study on Raltegravir and Lamotrigine

Phase 1
Completed
Conditions
HIV Infection
Interventions
Registration Number
NCT00618241
Lead Sponsor
Radboud University Medical Center
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
24
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
AlamotrigineGroup 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.
BRaltegravirGroup 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.
ARaltegravirGroup 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.
BlamotrigineGroup 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.
Primary Outcome Measures
NameTimeMethod
Plasma concentrations of lamotrigine, lamotrigine-2N-glucuronide, and raltregravirjust 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
NameTimeMethod
Determination of pharmacokinetic parameters (AUC, Cmax, Tmax, Cmin and T 1/2) by noncompartmental analysisat each sampling time

Trial Locations

Locations (1)

Radboud University Medical Center

🇳🇱

Nijmegen, Gelderland, Netherlands

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