- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00986128
A Pharmacokinetic Study of Lithium Before and During Topiramate Dosing in Bipolar Disorder Patients
June 8, 2011 updated by: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
A Comparative Study of the Steady State Pharmacokinetics of Lithium Before and During Multiple Oral Daily Topiramate (RWJ-17021) Dosing in Patients With Bipolar Disorders
The purpose of this study is to determine the initial (after 1-week of maintenance dosing) and extended (after 3-weeks of maintenance dosing) effect of topiramate, at doses up to 600 mg/day, on the steady-state pharmacokinetics (absorption, distribution and excretion of the drug by the body) of lithium carbonate in patients with bipolar disorders.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
This was an open-label (both the investigator and the patient knew the identity of the study drug), sequential treatment, multicenter study evaluating the interaction of topiramate and lithium in patients with bipolar disorders.
The study population included 24 patients (12 patients per group) with complete data considered adequate to fully evaluate the extent of the effect of topiramate on lithium pharmacokinetics (PK).
The study consisted of a screening phase, during which patients were maintained on a stable dose of an immediate release lithium carbonate formulation administered every 12 hours, for a minimum of 2 weeks prior to the start of the study, and an open-label treatment phase consisting of a topiramate titration phase and a lithium and topiramate maintenance phase, and 3 PK sampling periods (days when multiple blood and urine samples are taken to estimate the amount of topiramate and /or lithium in the patients blood or urine).
The duration of all of the periods were determined by the investigator.
Patients were sequestered for 48 hours for each of the 3 PK sampling periods.
At each sampling period, blood and urine samples were collected for laboratory safety analyses at the same designated serial sampling times and collection intervals as for PK sampling.
All doses of study medication were administered every 12 hours.
During PK sampling Period 1, patients were maintained on their respective morning and evening doses of lithium carbonate.
Serial blood and urine samples were collected through 12 hours postdose for estimation of lithium serum and urine concentrations.
Patients continued their lithium regimens and subsequently were initiated on topiramate and assigned to either the low-dose Group 1 (200 mg/day) or high-dose Group 2 (up to 600 mg/day).
During the topiramate titration phase, the initial dose of topiramate was 25 mg/day and was titrated upward until the target dose of 200 mg/day was reached (Group 1) or the target dose of 600 mg/day (or maximum tolerated dose greater than 200 mg/day) was reached (Group 2).
Topiramate dose titration was conducted on study Days 2, 4, and 7 for Group 1 and on Days 2, 7, 12, 17, 22, and 27 for Group 2. Once the maximum dose of topiramate was reached, the lithium and topiramate maintenance phase began and lasted for 3 weeks, during which the patients were maintained on a constant daily dose of topiramate and lithium carbonate.
One week after beginning maintenance on topiramate and lithium carbonate, patients entered PK sampling Period 2 of the study, during which serial blood and urine samples were collected through 12 hours postdose for estimation of lithium serum and urine concentrations and for estimation of topiramate plasma concentrations.
At the end of the 3 weeks of lithium and topiramate maintenance, patients entered PK sampling Period 3 of the study, during which serial blood and urine samples were collected through 12 hours postdose for estimation of lithium serum and urine concentrations and for estimation of topiramate plasma concentrations.
Throughout the topiramate titration phase and the lithium and topiramate maintenance phase, serum trough concentrations of lithium (the amount of lithium in the patients blood immediately before their next dose) were determined prior to the morning dose every 3 days, beginning on Day 3 of the topiramate titration phase.
Patients are maintained on a stable dose of an immediate release lithium carbonate formulation for 2 weeks prior to study start.
In the titration phase, topiramate given every 12 hours starting at 25 mg/day.
Patients are titrated to target doses of 200 mg/day (low-dose group) over a period of up to 10 days, or 600 mg/day (high-dose group) over a period of up to 30 days.
The lithium and topiramate maintenance phase lasts for an additional 3 weeks after target doses are reached.
Study Type
Interventional
Enrollment (Actual)
32
Phase
- Phase 1
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 60 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Patients meeting DSM-IV criteria for either Bipolar I, Bipolar II, Cyclothymic Disorder, or Bipolar Disorder NOS
- Patients on monotherapy treatment with lithium carbonate at steady state level for a minimum of two weeks prior to study treatment assignment
- Women are postmenopausal for at least 1 year, or surgically incapable of childbearing, or practicing an acceptable method of birth control (hormonal contraception, intrauterine device, or barrier with spermicide were acceptable) and not pregnant at baseline
Exclusion Criteria:
- Patients with a history of an acquired or hereditary neurologic disease, e.g., epilepsy or significant brain trauma
- Patients on depot medications, including but not limited to haloperidol, decanoate and Depo-Provera
- Patients who had taken acetazolamide, zonisamide, triamterene, dichlorphenamide, chronic antacids, or calcium supplements, or any medication associated with nephrolithiasis (kidney stone formation) in the month prior to beginning topiramate titration
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: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 001
|
100 mg tablet twice daily for 3 weeks
One 100 mg and one 200 mg tablet twice daily for 3 weeks
|
Experimental: 002
|
100 mg tablet twice daily for 3 weeks
One 100 mg and one 200 mg tablet twice daily for 3 weeks
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
To evaluate the potential pharmacokinetic interaction between topiramate and lithium in patients with bipolar disorders
Time Frame: In each sampling period, blood (lithium and topiramate concentrations) is collected pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-morning dose, and urine (lithium concentration) was collected at 0-2, 2-4, 4-8, and 8-12 hours postdose
|
In each sampling period, blood (lithium and topiramate concentrations) is collected pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-morning dose, and urine (lithium concentration) was collected at 0-2, 2-4, 4-8, and 8-12 hours postdose
|
Secondary Outcome Measures
Outcome Measure |
---|
No Secondary Outcomes
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
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.
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
March 1, 2001
Study Completion (Actual)
October 1, 2002
Study Registration Dates
First Submitted
September 25, 2009
First Submitted That Met QC Criteria
September 25, 2009
First Posted (Estimate)
September 29, 2009
Study Record Updates
Last Update Posted (Estimate)
June 10, 2011
Last Update Submitted That Met QC Criteria
June 8, 2011
Last Verified
April 1, 2010
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CR002860
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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