Pharmacokinetic Study on Raltegravir and Lamotrigine (GRANOLA)

October 16, 2020 updated by: Radboud University Medical Center

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • 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 Names:
  • Lamictal
Drug: Raltegravir
400 mg BD

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Radboud University Medical Center

Collaborators

Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2008

Primary Completion (ACTUAL)

October 1, 2008

Study Completion (ACTUAL)

October 1, 2008

Study Registration Dates

First Submitted

February 5, 2008

First Submitted That Met QC Criteria

February 18, 2008

First Posted (ESTIMATE)

February 19, 2008

Study Record Updates

Last Update Posted (ACTUAL)

October 19, 2020

Last Update Submitted That Met QC Criteria

October 16, 2020

Last Verified

May 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UMCN-AKF 07.06

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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