NCT02076815

Anagrelide Retard in Essential Thrombocythemia

A Phase III Randomized, Multicenter, Double-blind, Active Controlled Study to Compare the Efficacy and Safety of Two Different Anagrelide Formulations in Patients With Essential Thrombocythemia (TEAM-ET 2.0)

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 106 (actual)
• Sponsor: AOP Orphan Pharmaceuticals AG · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is determine whether Anagrelide Retard is non-inferior to anagrelide immediate release form in treatment of essential thrombocythemia. Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterised by a sustained increase in platelet counts above the normal value (\> 450 x 109/L) and increased megakaryopoiesis in the bone marrow, without secondary causes of thrombocytosis. Anagrelide hydrochloride selectively reduces platelet numbers by inhibiting megakaryocyte development and maturation in humans, without affecting other cell lineages. Anagrelide Retard is a new, prolonged release (PR) tablet formulation of anagrelide developed by AOP Orphan Pharmaceuticals AG. The rationale for developing this new formulation is based on the assumption of having a better tolerability while maintaining an efficacy comparable to that of the immediate release formulation. The effects of Anagrelide Retard and Thromboreductin® will be compared in terms of mean platelet count measured by a central laboratory/centralized method at 3 time points during the maintenance phase.

Detailed description

This is a randomised, multicentre, double-blind, active controlled study to compare the efficacy and safety of two different anagrelide formulations in patients with high-risk essential thrombocythemia (ET). 100 patients, either Anagrelide-treated or Anagrelide-naïve, with an indication to receive Thromboreductin® treatment, will be randomized into one of the two investigational medicinal product (IMP) groups (Anagrelide Retard or Thromboreductin®). Treatment allocation will be balanced within stratum (treated/naive) and age classes by central randomization. Naive patients will start with dose level 2 of the IMPs (i.e., 1 mg Thromboreductin® or 2 mg Anagrelide Retard). Anagrelide-treated patients will be switched to the dose level which is closest to the pre-study anagrelide dose at study start. Dose modifications in the titration phase will be done on a weekly basis (up to a maximum of 12 weeks) until "stable platelet counts" on two consecutive visits is achieved. The periods of the study participation per patient are as follows: * Screening (up to 7 days prior to randomization), ending with randomization/first IMP dose (Baseline Visit) * Titration period (weekly visits for up to 12 weeks): to achieve "stable platelet counts" on two consecutive measurements (i.e. weekly visits) * Maintenance period (weekly visits for 4 weeks): primary endpoint relevant period. The maintenance period for a patient starts at the visit with the second successive platelet count ≤400 G/L (or \<600 G/L, if the dose cannot be increased any more due to intolerance or because the maximal dose allowed has already been reached) if the second platelet value measured lies in the range within ± 30% of the value measured at the previous visit. * End of study (EoS) safety follow-up visit (28 days after the last maintenance visit/EoT for early termination).

Conditions

• Essential Thrombocythemia

Interventions

Type	Name	Description
DRUG	Anagrelide retard	Overencapsulated tablets or matched placebo, twice daily, 2-12 weeks titration to achieve stable platelet count, followed by 4 more weeks
DRUG	Thromboreductin	Overencapsulated capsule, twice daily, 2-12 weeks titration to achieve the stable platelet count, followed by 4 more weeks

Timeline

• Start date: 2014-02-01
• Primary completion: 2015-02-01
• Completion: 2015-04-01
• First posted: 2014-03-04
• Last updated: 2015-07-29

Locations

19 sites across 5 countries: Austria, Bulgaria, Lithuania, Poland, Russia