Clinical Trial: Anagrelide Retard in Essential Thrombocythemia

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: 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

Brief 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 Summary:

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 me
    Sponsor: AOP Orphan Pharmaceuticals AG

    Current Primary Outcome: Platelet count [ Time Frame: weeks 13-17 ]

    Mean value from three measurements


    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • platelet response [ Time Frame: weeks 13-17 ]
    • Time from randomization to entering maintenance period [ Time Frame: up to 12 weeks ]
    • Study drug administration [ Time Frame: weeks 1-17 ]
    • Change in platelet counts in the titration period [ Time Frame: baseline, week 12 ]
    • Time from randomization until withdrawal [ Time Frame: up to 17 weeks ]
    • Incidence, causality and intensity of adverse events [ Time Frame: weeks 0-21 ]
    • Incidence, intensity and outcomes of events leading to dose reduction or temporary or permanent treatment discontinuation [ Time Frame: weeks 1-18 ]
    • Need of medications to treat adverse events [ Time Frame: weeks 0-21 ]
    • ECG abnormalities [ Time Frame: weeks 0-18 ]
    • Ejection fraction [ Time Frame: baseline, week 17, week 21 ]
    • ECHO normal/abnormal [ Time Frame: baseline, week 17, week 21 ]


    Original Secondary Outcome: Same as current

    Information By: AOP Orphan Pharmaceuticals AG

    Dates:
    Date Received: February 13, 2014
    Date Started: February 2014
    Date Completion:
    Last Updated: July 27, 2015
    Last Verified: July 2015