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Determination of Absorption and Elimination of Lamotrigine-XR

Primary Purpose

Epilepsy, Seizures, Bipolar Disorder

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Extended Release Lamotrigine
Sponsored by
University of Minnesota
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Epilepsy focused on measuring lamotrigine, epilepsy, metabolism, bipolar disorder, bipolar depression, glucuronidation

Eligibility Criteria

65 Years - undefined (Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Minnesota

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Extended Release Lamotrigine

Arm Description

Extended Release Lamotrigine

Outcomes

Primary Outcome Measures

Area Under the Curve (AUC) for Oral Bioavailability of Lamotrigine (LTG
To evaluate the absolute bioavailability of immediate release (IR) and extended release (ER) lamotrigine (LTG) via blood and urine sampling for 24 hour period followed by once a day blood sampling for 3 days following initial dose administration.

Secondary Outcome Measures

Full Information

First Posted
November 7, 2008
Last Updated
December 14, 2015
Sponsor
University of Minnesota
Collaborators
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT00789113
Brief Title
Determination of Absorption and Elimination of Lamotrigine-XR
Official Title
Determination of Bioavailability and Clearance of Lamotrigine-XR by a Stable Isotope Technique
Study Type
Interventional

2. Study Status

Record Verification Date
December 2015
Overall Recruitment Status
Completed
Study Start Date
November 2008 (undefined)
Primary Completion Date
January 2011 (Actual)
Study Completion Date
January 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Minnesota
Collaborators
GlaxoSmithKline

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epilepsy, Seizures, Bipolar Disorder, Bipolar Depression
Keywords
lamotrigine, epilepsy, metabolism, bipolar disorder, bipolar depression, glucuronidation

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Extended Release Lamotrigine
Arm Type
Experimental
Arm Description
Extended Release Lamotrigine
Intervention Type
Drug
Intervention Name(s)
Extended Release Lamotrigine
Primary Outcome Measure Information:
Title
Area Under the Curve (AUC) for Oral Bioavailability of Lamotrigine (LTG
Description
To evaluate the absolute bioavailability of immediate release (IR) and extended release (ER) lamotrigine (LTG) via blood and urine sampling for 24 hour period followed by once a day blood sampling for 3 days following initial dose administration.
Time Frame
1 week

10. Eligibility

Sex
All
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rory P Remmel, PhD
Organizational Affiliation
University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Determination of Absorption and Elimination of Lamotrigine-XR

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