Determination of Absorption and Elimination of Lamotrigine-XR

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2010 by University of Minnesota - Clinical and Translational Science Institute.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by:
University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier:
NCT00789113
First received: November 7, 2008
Last updated: February 26, 2010
Last verified: February 2010
  Purpose

People over 65 years of ag break down (metabolize) drugs differently than younger adults. It is not known why this happens or how elderly people absorb or break down these drug differently. These difference may show that elderly individuals need lower doses of medications to avoid possible toxicity. We are interested in studying how yor body absorbs and breaks down your lamotrigine medication. This research may indicate that doses of lamotrigine should be lowered as people get older.


Condition
Epilepsy
Seizures
Bipolar Disorder
Bipolar Depression

Study Type: Observational
Study Design: Observational Model: Case-Crossover
Time Perspective: Prospective
Official Title: Determination of Bioavailability and Clearance of Lamotrigine-XR by a Stable Isotope Technique

Resource links provided by NLM:


Further study details as provided by University of Minnesota - Clinical and Translational Science Institute:

Biospecimen Retention:   Samples With DNA

Blood samples to determine lamotrigine concentration. Urine samples to determine lamotrigine metabolite concentration. DNA from blood sample.


Estimated Enrollment: 15
Study Start Date: November 2008
Estimated Study Completion Date: January 2011
Estimated Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Detailed Description:

If you agree to be in this study you will be admitted in to the General Clinical Research Center (GCRC) for approximately 24 hours on two different days (Part 1 and Part2). We will need you take a portion of your lamotrigine medication in a special form through a needle in your arm (intravenously). The special form of the drug is the same drug as you normally take except that it has a stable label (a NON-radioactive, naturally occurring atom) on the compound so that we can trace a small amount of the drug through your body. No commercial product of lamotrigine for intravenous use is available because of its poor solubility in water. The intravenous formulation used for this study has a chemical, hydroxypropyl-beta-cyclodextrin, that improves the solubility of lamotrigine in water. This formulation is similar to an intravenous formulation approved for another drug, Sporanox® (itraconazole) that is approved by the FDA. We have obtained approval form the FDA for this intravenous lamotrigine product to be used for research purposes and it has been shown to be safe in more than twenty younger individuals. We will collect fourteen (14) blood samples through a small tube placed into a vein in your arm and collect all of your urine over a period of 24 hours. One blood sample will then be drawn each day for 3 days for a total blood collection of seventeen (17 tubes (totaling approximately 170 mL or 11.5 tablespoons). The samples taken from you will be measured for blood chemistries and concentrations of lmaotrigine and its metabolites resulting from the medication that you take to control your disease (epilepsy or depression)

For the second part of the study, you will be switched from your regular lamotrigine (Lamictal®) to once daily morning dosing of an extended-release formulation of Lamictal-XR® (at the same total daily dose). You will remain on the extended-release lamotrigine (Lamictal-XR) for two weeks, after which you will be re-admitted to the GCRC for 24 hours for Part 2 of the study. Study drug administration and blood and urine sampling will be identical to Part I. The extended-release formulation and your regular lamotrigine have been determined by the manufacturer in preliminary studies to be absorbed the same (bioequivalent0. You will not need to change your total daily dose and will only have to take your lamotrigine once daily with the extended-release product. Your blood levels of lamotrigine will be checked to insure that your are achieving the appropriate concentration with new extended-release product. For this study, you will be given a one-month supply free of charge of the extended-release formulation. After the study is completed, you would return to taking your regular lamotrigine dosing. If the FDA has approved the XR formulation at the end of the study, you and your doctor may decide to keep you on the extended-release form of the drug.

With your consent, a genetics sample, consisting of three (3) additional blood tubes (totaling approximately six teaspoonfuls) will also be collected for a genetic analysis. The genetics sample will be identified with a subject number that corresponds to your other samples. We will use this sample to determine the genetic sequence of DNA that you have that is responsible for encoding proteins that are responsible for breaking down or transporting medications like lamotrigine so that they can be eliminated from your body. You can choose to participate in the main study without taking part in the genetics portion of the study. If you withdraw from the main study, the genetics sample will be discarded with the rest of the samples. if you choose to participate in the genetics portion of the study, we will store the genetics sample indefinitely, however, no testing other than for specific DNA sequences will be done unless we have contact you and received permission to do so.

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

15 elderly subjects over the age of 65 taking lamotrigine for control of epilepsy or bipolar disorder

Criteria

Inclusion Criteria:

  • Clinical Diagnosis of Epilepsy or Bipolar Depression
  • able to have a venus catheter implanted for blood withdrawal and for intravenous infusion
  • equal to or over the age of 65

Exclusion Criteria:

  • not on any medication that will interact with lamotrigine e.g. carbamazepine, phenytoin, phenobarbital, valproic acid, St. John's wort, rifampin, tamoxifen
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00789113

Locations
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55404
Sponsors and Collaborators
University of Minnesota - Clinical and Translational Science Institute
GlaxoSmithKline
Investigators
Principal Investigator: Rory P Remmel, PhD University of Minnesota - Clinical and Translational Science Institute
  More Information

No publications provided

Responsible Party: Rory P Remmel/Professor, University of Minnesota
ClinicalTrials.gov Identifier: NCT00789113     History of Changes
Other Study ID Numbers: 0308M51662, IND72642
Study First Received: November 7, 2008
Last Updated: February 26, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Minnesota - Clinical and Translational Science Institute:
lamotrigine
epilepsy
metabolism
bipolar disorder
bipolar depression
glucuronidation

Additional relevant MeSH terms:
Bipolar Disorder
Depression
Depressive Disorder
Epilepsy
Seizures
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders
Behavioral Symptoms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Lamotrigine
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers

ClinicalTrials.gov processed this record on August 26, 2014