Pharmacokinetic Study on Raltegravir and Lamotrigine (GRANOLA)

Radboud University Medical Center

Status and phase: Completed; Phase 1

Conditions: HIV Infection

Treatments: Drug: lamotrigine; Drug: Raltegravir

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00618241

UMCN-AKF 07.06

Details and patient eligibility

About

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.

Full 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.

Enrollment: 24 patients

Sex: Male

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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24 participants in 2 patient groups

A

Experimental group

Description:

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.

Treatment:

Drug: Raltegravir

Drug: lamotrigine

B

Active Comparator group

Description:

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.

Treatment:

Drug: Raltegravir

Drug: lamotrigine