Pharmacokinetic Study on Raltegravir and Lamotrigine (GRANOLA)

This study has been completed.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by:
Radboud University
ClinicalTrials.gov Identifier:
NCT00618241
First received: February 5, 2008
Last updated: June 6, 2011
Last verified: May 2011
  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 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
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:


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
Experimental: A

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
Other Name: Lamictal
Drug: Raltegravir
400 mg BD
Active Comparator: B

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
Other Name: Lamictal
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
Radboud University Medical Center
Nijmegen, Gelderland, Netherlands
Sponsors and Collaborators
Radboud University
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: David M. Burger, PharmD PhD Radboud University
  More Information

Additional Information:
No publications provided

Responsible Party: Dr. D.M. Burger, hospital pharmacist, Radboud University Nijmegen Medical Centre
ClinicalTrials.gov Identifier: NCT00618241     History of Changes
Other Study ID Numbers: UMCN-AKF 07.06
Study First Received: February 5, 2008
Last Updated: June 6, 2011
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:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Lamotrigine
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Anticonvulsants
Central Nervous System Agents

ClinicalTrials.gov processed this record on April 17, 2014