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Clinical Trial
. 2019 May;185(4):691-700.
doi: 10.1111/bjh.15824. Epub 2019 Mar 28.

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

Heinz Gisslinger  1 , Veronika Buxhofer-Ausch  2 , Juri Hodisch  3 , Atanas Radinoff  4 , Elena Karyagina  5 , Slawomira Kyrcz-Krzemień  6 , Kudrat Abdulkadyrov  7 , Rolandas Gerbutavicius  8 , Anait Melikyan  9 , Sonja Burgstaller  10 , Marek Hus  11 , Janusz Kłoczko  12 , Vera Yablokova  13 , Nikolay Tzvetkov  14 , Malgorzata Całbecka  15 , Tatyana Shneyder  16 , Krzysztof Warzocha  17 , Mindaugas Jurgutis  18 , Kamil Kaplanov  19 , Bernd Jilma  20 , Christian Schoergenhofer  20 , Christoph Klade  3
Affiliations
Clinical Trial

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

Heinz Gisslinger et al. Br J Haematol. 2019 May.

Abstract

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.

Keywords: anagrelide; essential thrombocythaemia; pharmacodynamics; pharmacokinetics; safety.

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Conflict of interest statement

JH and CK are employees of AOP. HG, VBA, and SB received honoraria and consulted AOP.

Figures

Figure 1
Figure 1
Trial design and flowchart. Trial Design (upper panel) and flowchart of the TEAM‐ET trial (lower panel). M1 represents Day 0, M3 represents Day 14 and M5 Day 28 of the Maintenance period. AE, adverse event; ET, essential thrombocythaemia; PLT, platelet. [Colour figure can be viewed at wileyonlinelibrary.com].
Figure 2
Figure 2
Dose levels in the titration period. Dose levels in the titration period of all patients for the test substance (anagrelide prolonged release, A‐PR) and the reference product. n = 52 for A‐PR and n = 54 for reference product.
Figure 3
Figure 3
Adverse events divided by system organ class. The figure displays the adverse events reported throughout the trial. Gastrointestinal disorders occurred more frequently in the Anagrelide Prolonged Release group compared to the Reference Product group (P = 0·048). There was no significant difference in other system organ classes (n = 52 for anagrelide prolonged release and n = 54 for reference product).
See this image and copyright information in PMC

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