Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 78 of 1359 for:    Area Under Curve AND tablet

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01906671
Recruitment Status : Recruiting
First Posted : July 24, 2013
Last Update Posted : April 20, 2018
Sponsor:
Collaborator:
Danish Cancer Society
Information provided by (Responsible Party):
Kjeld Schmiegelow, Rigshospitalet, Denmark

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Acute Lymphoblastic Leukemia 6-mercaptopurine Therapy Drug: Xaluprine Drug: Puri-Nethol Phase 4

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Plasma Kinetics of Tablet and Liquid Formulations of 6-mercaptopurine in Childhood Acute Lymphoblastic Leukemia.
Actual Study Start Date : June 2013
Estimated Primary Completion Date : September 2018
Estimated Study Completion Date : November 2018


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.




Primary Outcome Measures :
  1. 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)


Secondary Outcome Measures :
  1. Area under curve(AUC) [ Time Frame: Will be measured within six months after collection of the blood samples ]
    Area under curve(AUC)

  2. Maximum concentration (Cmax) [ Time Frame: Will be measured within six months after collection of the blood samples ]
    Maximum concentration (Cmax)

  3. Time to half-life (T½) [ Time Frame: Will be measured within six months after collection of the blood samples ]
    Time to half-life (T½)



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01906671


Locations
Layout table for location information
Denmark
Juliane Marie Centret, Rigshospitalet Recruiting
Copenhagen, DK-, Denmark, 2100
Contact: Kjeld Schmiegelow, Professor    +45 35451357    kjeld.schmiegelow@regionh.dk   
Contact: Rikke Hebo Larsen, MD    +45 35457932    rikke.hebo.larsen.01@regionh.dk   
Principal Investigator: Kjeld Schmiegelow, Professor         
Sub-Investigator: Rikke Hebo Larsen, MD         
Sponsors and Collaborators
Kjeld Schmiegelow
Danish Cancer Society
Investigators
Layout table for investigator information
Principal Investigator: Kjeld Schmiegelow, Professor Pediatric Clinic II, Rigshospitalet, Copenhagen

Layout table for additonal information
Responsible Party: Kjeld Schmiegelow, Professor in Pediatrics and Pediatric Oncology, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT01906671     History of Changes
Other Study ID Numbers: 6-MP formulation
2013-001236-21 ( EudraCT Number )
First Posted: July 24, 2013    Key Record Dates
Last Update Posted: April 20, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Kjeld Schmiegelow, Rigshospitalet, Denmark:
6-mercaptopurine
Drug formulation

Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Mercaptopurine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors