Pharmacokinetic Study on Raltegravir and Lamotrigine - Full Text View

Sponsor:	Radboud University
Collaborator:	Merck
Information provided by:	Radboud University
ClinicalTrials.gov Identifier:	NCT00618241

Purpose

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.

Condition	Intervention	Phase
HIV Infection	Drug: lamotrigine Drug: Raltegravir	Phase I

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Dose Comparison, Crossover Assignment, Pharmacokinetics Study
Official Title:	The Influence of Raltegravir (MK-0518) on the Pharmacokinetics of Single-Dose Lamotrigine in Healthy Male Subjects (GRANOLA)

Resource links provided by NLM:

MedlinePlus related topics: AIDS

Drug Information available for: Lamotrigine Raltegravir

U.S. FDA Resources

Further study details as provided by Radboud University:

Primary Outcome 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. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Determination of pharmacokinetic parameters (AUC, Cmax, Tmax, Cmin and T 1/2) by noncompartmental analysis [ Time Frame: at each sampling time ] [ Designated as safety issue: No ]

Enrollment:	24
Study Start Date:	February 2008
Study Completion Date:	October 2008
Primary Completion Date:	October 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental 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 100 mg Drug: Raltegravir 400 mg BD
B: Active Comparator 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 100 mg Drug: Raltegravir 400 mg BD

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

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	Yes

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00618241

Locations

Netherlands, Gelderland
Radboud University Medical Center
Nijmegen, Gelderland, Netherlands

Sponsors and Collaborators

Radboud University

Merck

Investigators

Principal Investigator:

David M. Burger, PharmD PhD

Radboud University

More Information

No publications provided

Responsible Party:	Radboud University Nijmegen Medical Centre ( Dr. D.M. Burger, hospital pharmacist )
Study ID Numbers:	UMCN-AKF 07.06
Study First Received:	February 5, 2008
Last Updated:	February 24, 2009
ClinicalTrials.gov Identifier:	NCT00618241 History of Changes
Health Authority:	Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:

interactions
neuropathic pain
pharmacokinetics

Additional relevant MeSH terms:

RNA Virus Infections
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Acquired Immunodeficiency Syndrome
Calcium Channel Blockers
Cardiovascular Agents
Infection
Pharmacologic Actions
Immunologic Deficiency Syndromes

Membrane Transport Modulators
Virus Diseases
HIV Infections
Therapeutic Uses
Sexually Transmitted Diseases
Lentivirus Infections
Lamotrigine
Central Nervous System Agents
Retroviridae Infections
Anticonvulsants

ClinicalTrials.gov processed this record on February 08, 2010