Study on Two Different Formulations of 6-mercaptopurine. Tablet Versus Oral Liquid

April 19, 2018 updated by: Kjeld Schmiegelow

Plasma Kinetics of Tablet and Liquid Formulations of 6-mercaptopurine in Childhood Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) accounts for 30 % of all childhood malignancies. The patients undergo four phases of treatment, finishing with a late maintenance phase in which 6-mercaptopurine and Methotrexate are essential components. Insufficient treatment intensity in this phase is associated with increased risk of relapse. Excessive variation in the bioavailability of 6-mercaptopurine has been observed which can cause both risks of undertreatment/relapse as well as overtreatment with severe side effects.

In the attempt to achieve individualized 6-mercaptopurine dosing different approaches have been pursued. Nonetheless variation in bioavailability remains a problem.

Earlier, oral tablets of 50 mg (Purinethol) were the only administration form of 6-mercaptopurine and it was primarily designed for adult patients. Challenges with accurate dosing and getting the children to swallow the tablets have been a widespread problem, forcing the caregivers to divide or crush the tablets as well as having to administer different dosages over 2-3 days. Due to these problems, an oral liquid formulation of 6-mercaptopurine (Xaluprine) has been developed. However this oral liquid has only been tested on healthy adult volunteers, and not on the target group, childhood patients. This project will assess the bioavailability and plasma kinetics of oral liquid and tablet formulation of 6-mercaptopurine in children with acute lymphoblastic leukemia.

The investigators hypothesize to observe comparable plasma kinetics, in children with acute lymphoblastic leukemia when treated with 6-mercaptopurine in the form of a tablet and oral liquid formulation, as previously observed in healthy adults.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

16

Phase

  • Phase 4

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

  • Denmark
    • DK-
      • Copenhagen, DK-, Denmark, 2100
        • Recruiting
        • Juliane Marie Centret, Rigshospitalet
        • Contact:
        • Contact:
        • Principal Investigator:
          • Kjeld Schmiegelow, Professor
        • Sub-Investigator:
          • Rikke Hebo Larsen, MD

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

No older than 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Childhood acute lymphoblastic leukemia patients, age 0-18 years at diagnosis, treated at the department of pediatrics and adolescent medicine, Rigshospitalet.
  • Informed consent

Exclusion Criteria:

  • None

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 Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Puri-Nethol
Tablet formulation of 6-mercaptopurine
Drug: Xaluprine
Comparison of plasma kinetics after administration of 6-mercaptopurine in the form of a tablet (Puri-Nethol) and in the form of an oral liquid formulation (Xaluprine). Each patient will be included in both arms of the study, because of the cross-over design.
Drug: Puri-Nethol
Comparison of plasma kinetics after administration of 6-mercaptopurine in the form of a tablet (Puri-Nethol) and in the form of an oral liquid formulation (Xaluprine). Each patient will be included in both arms of the study, because of the cross-over design.
Experimental: Xaluprine
Oral liquid formulation of 6-mercaptopurine
Drug: Xaluprine
Comparison of plasma kinetics after administration of 6-mercaptopurine in the form of a tablet (Puri-Nethol) and in the form of an oral liquid formulation (Xaluprine). Each patient will be included in both arms of the study, because of the cross-over design.
Drug: Puri-Nethol
Comparison of plasma kinetics after administration of 6-mercaptopurine in the form of a tablet (Puri-Nethol) and in the form of an oral liquid formulation (Xaluprine). Each patient will be included in both arms of the study, because of the cross-over design.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to maximum concentration (Tmax)
Time Frame: Will be measured within a six months after collection of the blood samples
Time to maximum concentration (Tmax)
Will be measured within a six months after collection of the blood samples

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area under curve(AUC)
Time Frame: Will be measured within six months after collection of the blood samples
Area under curve(AUC)
Will be measured within six months after collection of the blood samples
Maximum concentration (Cmax)
Time Frame: Will be measured within six months after collection of the blood samples
Maximum concentration (Cmax)
Will be measured within six months after collection of the blood samples
Time to half-life (T½)
Time Frame: Will be measured within six months after collection of the blood samples
Time to half-life (T½)
Will be measured within six months after collection of the blood samples

Collaborators and Investigators

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

Sponsor

Kjeld Schmiegelow

Collaborators

Danish Cancer Society

Investigators

  • Principal Investigator: Kjeld Schmiegelow, Professor, Pediatric Clinic II, Rigshospitalet, Copenhagen

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 (Actual)

June 1, 2013

Primary Completion (Anticipated)

September 1, 2018

Study Completion (Anticipated)

November 1, 2018

Study Registration Dates

First Submitted

July 16, 2013

First Submitted That Met QC Criteria

July 23, 2013

First Posted (Estimate)

July 24, 2013

Study Record Updates

Last Update Posted (Actual)

April 20, 2018

Last Update Submitted That Met QC Criteria

April 19, 2018

Last Verified

April 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 6-MP formulation
  • 2013-001236-21 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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.

Clinical Trials on Acute Lymphoblastic Leukemia

Clinical Trials on Xaluprine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Zambia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe