A phase III randomized, multicentre, double blind, active controlled trial to compare the efficacy and safety of two different anagrelide formulations in patients with essential thrombocythaemia – the TEAM‐ET 2·0 trial

• Published in: British journal of haematology Vol. 185; no. 4; pp. 691 - 700
• Main Authors: Gisslinger, Heinz, Buxhofer‐Ausch, Veronika, Hodisch, Juri, Radinoff, Atanas, Karyagina, Elena, Kyrcz‐Krzemień, Slawomira, Abdulkadyrov, Kudrat, Gerbutavicius, Rolandas, Melikyan, Anait, Burgstaller, Sonja, Hus, Marek, Kłoczko, Janusz, Yablokova, Vera, Tzvetkov, Nikolay, Całbecka, Malgorzata, Shneyder, Tatyana, Warzocha, Krzysztof, Jurgutis, Mindaugas, Kaplanov, Kamil, Jilma, Bernd, Schoergenhofer, Christian, Klade, Christoph
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.05.2019; John Wiley and Sons Inc
• Subjects: anagrelide; Delayed-Action Preparations; Dosage; Dose-Response Relationship, Drug; Double-Blind Method; Double-blind studies; Drug Compounding; Drug delivery; essential thrombocythaemia; Female; Formulations; Haematological Malignancy; Hematology; Humans; Male; Middle Aged; pharmacodynamics; pharmacokinetics; Platelet Aggregation Inhibitors - administration & dosage; Platelet Aggregation Inhibitors - adverse effects; Platelet Aggregation Inhibitors - pharmacokinetics; Platelet Count; Platelets; Quality of Life; Quinazolines - administration & dosage; Quinazolines - adverse effects; Quinazolines - pharmacokinetics; Randomization; Research Paper; Safety; Schedules; Thrombocythemia, Essential - drug therapy; Titration; Treatment Outcome; pharmacokinetics; anagrelide; pharmacodynamics; safety; essential thrombocythaemia
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/bjh.15824

Summary Anagrelide is an established treatment option for essential thrombocythaemia (ET). A prolonged release formulation was developed with the aim of reducing dosing frequency and improving tolerability, without diminishing efficacy. This multicentre, randomized, double blind, active‐controlled, non‐inferiority trial investigated the efficacy, safety and tolerability of anagrelide prolonged release (A‐PR) over a reference product in high‐risk ET patients, either anagrelide‐naïve or ‐experienced. In a 6 to 12‐week titration period the individual dose for the consecutive 4‐week maintenance period was identified. The primary endpoint was the mean platelet count during the maintenance period (3 consecutive measurements, day 0, 14, 28). Of 112 included patients 106 were randomized. The mean screening platelet counts were 822 × 109/l (95% confidence interval (CI) 707–936 × 109/l) and 797 × 109/l (95% CI 708–883 × 109/l) for A‐PR and the reference product, respectively. Both treatments effectively reduced platelet counts, to mean 281 × 109/l for A‐PR (95% CI 254–311) and 305 × 109/l (95% CI 276–337) for the reference product (P < 0·0001, for non‐inferiority). Safety and tolerability were comparable between both drugs. The novel prolonged‐release formulation was equally effective and well tolerated compared to the reference product. A‐PR provides a more convenient dosing schedule and will offer an alternative to licensed immediate‐release anagrelide formulations.