E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Lymphoblastic Leukaemia |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000844 |
E.1.2 | Term | Acute lymphoblastic leukaemia |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Part A: to characterise the bioavailability of a single 50 mg fixed dose of the O4CP innovative oral liquid formulation versus 50mg registered adult tablets (Purinethol®)
Part B: to assess the pharmacokinetics of an adjusted dose of the O4CP innovative oral liquid formulation given daily for 6 weeks |
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E.2.2 | Secondary objectives of the trial |
Part A and part B : To assess the palatability, the pharmacokinetic and the safety of the new 6MP oral liquid formulation |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria for both parts of the study: • Acute Lymphoblastic Leukaemia in complete remission • Patient under maintenance treatment for at least the last 3 months Stable for at least 3 weeks with the same dosage of 6MP (i.e. not more than a 10% variation in dose over the three weeks) • Informed consent form signed by parents or guardians • Documented assent for children above 6 years
Inclusion criteria specific to part A: • Aged 12-17 years old • Patients treated with a 6MP dose of at least 40 mg per day • TPMT genotyping for the two following polymorphisms (TPMT* 3B 460 G>A and TPMT* 3C 719 A>G) will be performed if not already available. Patient carrying at least one mutant allele for at least one of these two polymorphisms will be excluded
Inclusion criteria specific to part B: • Aged 2-17 years old • TPMT genotyping for the two polymorphisms (TPMT* 3B 460 G>A and TPMT* 3C 719 A>G) will be performed if not already available. Any TPMT deficiency genotype will be authorised to enter part B of the study. But patient carrying out at least one mutant allele for these two polymorphisms needs an adjustment of 6MP dose. The dose of 6MP oral liquid formulation will be adapted according to doctor’s prescription. |
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E.4 | Principal exclusion criteria |
Excluion criteria related to pathologies or treatments • Severe bone marrow suppression(White blood cell below<1.5 109/l, Absolute neutrophil count<0.5 109/l or Platelet count<50 109/l) • Renal/hepatic impairment • Chronic or recurrent infectious disease especially respiratory or urinary tract • Performance level Karnofsky ≤ 50% for patients > 10 years of age and Lansky ≤50 for patients ≤ 10 years of age • Medical history of hypersensitivity to 6MP or drug excipients • Treatment by allopurinol • Treatment by aminosalicylates • Treatment with Probenecid, Trimethoprim, Penicillins, Phenylbutazone, NSAIDs, Phenytoin • Vaccination with live organism vaccines
Exclusion criteria related to the population • Planned travel outside the study area for a substantial portion of the study period • Intake of any experimental treatment during the past three months preceding inclusion or during the study • Patient who, in the judgment of the investigator is not likely to be compliant during the study • Patient linguistically or psychologically unable to understand the information given or formulate his/her assent to be involved • Parents or guardians linguistically or psychologically unable to understand the information given or to give their informed consent or who refuse to give their consent in writing • Patient or parents or guardians who cannot be contacted by phone in case of emergency
Extra exclusion criterion for girls of childbearing potential • Pregnancy or breast-feeding
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E.5 End points |
E.5.1 | Primary end point(s) |
Pharmacokinetics: Cmax, Tmax, AUC0-∞, AUC0-t ; as well as safety, palatability, satisfaction with treatment use, pharmacogenetic analyses
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Bioavailability comparison and description of a new 6MP oral suspension |
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E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
PuriNethol (GSK) 50 mg : same active principle (6-Mercaptopurine) |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The trial will end after the last visit of the last patient. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |