Pharmacokinetic Parameters of Co-trimoxazole

September 15, 2014 updated by: JWC Alffenaar, University Medical Center Groningen

Pharmacokinetic Parameters of 960 mg Co-trimoxazole Once Daily in Patients With Tuberculosis

Rationale:

Treatment of multidrug or extensively drug resistant tuberculosis (MDR/XDR-TB) is a real challenge as failure in response to treatment and serious side-effects are frequently encountered. New, more effective drugs with less side effects are therefore urgently needed to solve this problem. Although several new drugs against TB are in the pipeline, physicians currently have limited treatment options for treatment of complicated MDR/XDR-TB cases. Therefore, drugs developed and labeled for other infectious diseases are evaluated for TB. Co-trimoxazole consists of sulfamethoxazole and trimethoprim. Sulfamethoxazole could be effective in the treatment of tuberculosis as shown by Forgacs et al. and Huang et al.

Furthermore, with dried blood spot (DBS) analysis, the exposure to co-trimoxazole could be analyzed with only some blood drops withdrawn with a finger prick on paper. This paper is suitable for storage, transportation and subsequently analysis without additional cooling or storage requirements.

Objective:

The main objective of this prospective clinical trial is to evaluate pharmacokinetics of 960 mg co-trimoxazole in TB patients. This clinical trial will provide important information on PK of co-trimoxazole in TB patients for future studies.

The second objective is to calculate the T>MIC and AUC0-24h/Minimal inhibitory concentration (MIC) ratio as efficacy predicting parameter. Furthermore, the analysis of dried blood spots will be clinically validated by comparing results of blood samples withdrawn from venous blood versus withdrawn by finger prick and transferred to filter paper. Retrospectively, data from this study can be used for limited sampling strategies for co-trimoxazole based on a pharmacokinetic population model constructed from the full PK curves of the patients.

Study design:

A prospective pharmacokinetic study.

Study population: 12 TB patients.

Intervention: on 4 to 6 days, 960 mg co-trimoxazole daily will be added to the normal treatment regimen.

Main study parameters/endpoints:

The pharmacokinetic parameters (Vd, Cl, AUC, etc) of co-trimoxazole are the primary endpoints of the study. The T>MIC and AUC0-24h/Minimal inhibitory concentration (MIC) ratio are most likely the best predictive parameters for efficacy of co-trimoxazole treatment and will be calculated for a range of M tuberculosis isolates.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Phase 2

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
      • Groningen, Netherlands
        • UMCG - Tuberculosis 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

14 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • TB Patients with normal susceptible Mycobacterium tuberculosis
  • Patients older than 17 and younger than 64 years.

Exclusion Criteria:

  • Pregnancy or breast feeding
  • Patients with hypersensitivity to sulfonamide or trimethoprim
  • Concomitant treatment with vitamin K antagonists (acenocoumarol)
  • Patients with preexisting renal dysfunction or concomitant treatment of angiotensin converting enzyme inhibitors and potassium -sparing diuretics) that may exacerbate the hyperkalemic effect of SXT.
  • Patients treated with methotrexate, phenytoin, sulfonylureas (glibenclamide, gliclazide, glimepiride en tolbutamide) or procainamide hydrochloride.
  • Patients that have gastrointestinal complaints like diarrhea and vomiting (observed)
  • Patients that have experienced an adverse effect to SXT or similar antibiotic drugs.
  • Patients with HIV or AIDS.

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

  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: co-trimoxazole
On 4, 5 or 6 consecutive days, 960 mg co-trimoxazole (oral) will be added to the normal treatment of tuberculosis.
Drug: co-trimoxazole
On 4, 5 or 6 consecutive days, co-trimoxazole 960 mg will be added to the normal treatment regimen
Other Names:
  • Sulfamethoxazole/trimethoprim

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
AUC
Time Frame: 4th, 5th or 6th day
Measuring the AUC over 24 hours of sulfamethoxazole, one out of two compounds of co-trimoxazole after obtaining steady state (960 mg co-trimoxazole).
4th, 5th or 6th day

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determination of the AUC/MIC and T>MIC
Time Frame: 4th, 5th or 6th day
Determination of the area under the curve divided by the mean inhibitory concentration and the time above MIC.
4th, 5th or 6th day
Validating DBS analysis
Time Frame: 4th, 5th or 6th day
Validating the analysis of dried blood spots for therapeutic drug monitoring by comparing the concentration measured in venous blood with the concentration measured using the dried blood spot method.
4th, 5th or 6th day

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Population pharmacokinetic model and limited sampling strategies
Time Frame: 4th, 5th or 6th day
Developing a population pharmacokinetic model to predict pharmacokinetic parameters of sulfamethoxazole. With this population pharmacokinetic model, a limited sampling strategy will be developed.
4th, 5th or 6th day

Collaborators and Investigators

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

Sponsor

University Medical Center Groningen

Investigators

  • Principal Investigator: Jan-Willem C Alffenaar, PharmD PhD, UMCG

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

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

October 1, 2013

Primary Completion (Actual)

August 1, 2014

Study Completion (Actual)

August 1, 2014

Study Registration Dates

First Submitted

April 11, 2013

First Submitted That Met QC Criteria

April 15, 2013

First Posted (Estimate)

April 16, 2013

Study Record Updates

Last Update Posted (Estimate)

September 16, 2014

Last Update Submitted That Met QC Criteria

September 15, 2014

Last Verified

September 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SXT8469

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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