Anagrelide Retard in Essential Thrombocythemia

• Status: Completed
• Trial end date: 2015-04-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: AOP Orphan Pharmaceuticals AG
• Treatments: Anagrelide

Criteria

Inclusion Criteria:

• willing and able to give written informed consent prior to any study specific procedures and able to comply with the trial protocol

• confirmed diagnosis of ET according to 2008 WHO diagnostic criteria* (Swerdlow et al, 2008), defined as meeting all four criteria

• at high risk of experiencing ET-related events, indicated for Thromboreductin® treatment as defined by one or more of the following criteria: age ≥ 60 years, platelet counts ≥ 1000 G/L, increase of platelet count ≥ 300 G/L within 3 months, severe thrombohemorrhagic or ischemic symptoms in anamnesis

• either currently treated with anagrelide

• or ET treatment naive

• or anagrelide naive

Exclusion Criteria:

• Diagnosis of any myeloproliferative disorder other than ET

• Any known cause for a secondary thrombocytosis

• ET currently well controlled by another cytoreductive treatment than Anagrelide and the opportunity to continue to receive this treatment

• ET currently treated with combination of any two of the following agents: anagrelide, hydroxyurea, interferons, busulfan

• Hypersensitivity to either active or non-active ingredients of anagrelide or to any other excipients of the investigational products

• Known hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption

• Cardiovascular disease grade 3 with a negative benefit/risk assessment or grade 4 (South West Oncology Group; Green and Weiss, 1992)

• Clinically significant abnormal laboratory values (excluding markers for ET) in investigator's opinion

• Severe renal insufficiency (creatinine clearance <30 ml/min)

• Moderate to severe hepatic insufficiency (ALT or AST > 5 times upper normal limit [UNL])

• White blood count (WBC) ≥ 15 G/L at screening

• Diagnosis of any malignancy, other than ET (except basal cell and squamous cell carcinomas of the skin and carcinoma in situ of the cervix that have been completely excised and are considered cured), within the last 3 years, or coexisting malignant, systemic disease

• Poorly controlled diabetes mellitus

• Known infection with hepatitis B, hepatitis C or HIV

• Pregnant or lactating women

• Women of childbearing potential or male patients, who have sexual intercourse with females of childbearing potential, not willing to use an effective method of contraception during the study.

• History of drug/alcohol abuse within the previous 2 years

• Participation in another investigational study within 4 weeks prior to informed consent signed or for a longer duration if specified in local regulations

• Any significant psychiatric disorder that, in the opinion of the investigator, might prohibit the understanding and giving of informed consent, or that might prevent the patient from completing the trial.