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

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ClinicalTrials.gov Identifier: NCT01906671
Recruitment Status : Unknown
Verified April 2018 by Kjeld Schmiegelow, Rigshospitalet, Denmark.
Recruitment status was:  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

Tracking Information
First Submitted Date  ICMJE July 16, 2013
First Posted Date  ICMJE July 24, 2013
Last Update Posted Date April 20, 2018
Actual Study Start Date  ICMJE June 2013
Estimated Primary Completion Date September 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 10, 2017)
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)
Original Primary Outcome Measures  ICMJE
 (submitted: July 23, 2013)
Time to maximum concentration (Tmax) [ Time Frame: Will be measured within a two months after collection of the blood samples ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 10, 2017)
  • Area under curve(AUC) [ Time Frame: Will be measured within six months after collection of the blood samples ]
    Area under curve(AUC)
  • Maximum concentration (Cmax) [ Time Frame: Will be measured within six months after collection of the blood samples ]
    Maximum concentration (Cmax)
  • Time to half-life (T½) [ Time Frame: Will be measured within six months after collection of the blood samples ]
    Time to half-life (T½)
Original Secondary Outcome Measures  ICMJE
 (submitted: July 23, 2013)
  • Area under curve(AUC) [ Time Frame: Will be measured within two months after collection of the blood samples ]
  • Maximum concentration (Cmax) [ Time Frame: Will be measured within two months after collection of the blood samples ]
  • Time to half-life (T½) [ Time Frame: Will be measured within two months after collection of the blood samples ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study on Two Different Formulations of 6-mercaptopurine. Tablet Versus Oral Liquid
Official Title  ICMJE Plasma Kinetics of Tablet and Liquid Formulations of 6-mercaptopurine in Childhood Acute Lymphoblastic Leukemia.
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Lymphoblastic Leukemia
  • 6-mercaptopurine Therapy
Intervention  ICMJE
  • 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.
Study Arms  ICMJE
  • Experimental: Puri-Nethol
    Tablet formulation of 6-mercaptopurine
    Interventions:
    • Drug: Xaluprine
    • Drug: Puri-Nethol
  • Experimental: Xaluprine
    Oral liquid formulation of 6-mercaptopurine
    Interventions:
    • Drug: Xaluprine
    • Drug: Puri-Nethol
Publications * Larsen RH, Hjalgrim LL, Grell K, Kristensen K, Pedersen LG, Brünner ED, Als-Nielsen B, Schmiegelow K, Nersting J. Pharmacokinetics of tablet and liquid formulations of oral 6-mercaptopurine in children with acute lymphoblastic leukemia. Cancer Chemother Pharmacol. 2020 Jul;86(1):25-32. doi: 10.1007/s00280-020-04097-x. Epub 2020 Jun 9.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: May 10, 2017)
16
Original Estimated Enrollment  ICMJE
 (submitted: July 23, 2013)
30
Estimated Study Completion Date  ICMJE November 2018
Estimated Primary Completion Date September 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Denmark
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01906671
Other Study ID Numbers  ICMJE 6-MP formulation
2013-001236-21 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Kjeld Schmiegelow, Rigshospitalet, Denmark
Study Sponsor  ICMJE Kjeld Schmiegelow
Collaborators  ICMJE Danish Cancer Society
Investigators  ICMJE
Principal Investigator: Kjeld Schmiegelow, Professor Pediatric Clinic II, Rigshospitalet, Copenhagen
PRS Account Rigshospitalet, Denmark
Verification Date April 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP