A Study of Anagrelide and Hydroxyurea in High-Risk Essential Thrombocythemia Patients

Study Overview
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Brief Summary
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Essential thrombocythaemia is a disorder of bone marrow, which causes too many platelets to be produced. Platelets are small cells carried around in the blood, which help form blood clots. When patients have too many platelets, there is a risk of blood clots forming unnecessarily and excessive bleeding. The aim of this study is to gain additional information on the safety profile of Anagrelide (Xagrid(r)) and Hydroxyurea (also known as hydroxycarbamide).

Official Title
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A Phase IIIb, Randomized, Open Label Study to Compare the Safety, Efficacy and Tolerability of Anagrelide Hydrochloride Versus Hydroxyurea in High-Risk Essential Thrombocythaemia Patients.

Conditions
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Thrombocythemia, Hemorrhagic

Intervention / Treatment
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* Drug: Anagrelide
* Drug: Hydroxyurea


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of essential thrombocythaemia - high risk profile Previously untreated with a cytoreductive agent Females of childbearing potential must have a negative urine pregnancy test prior to entering the study and must agree to use effective birth control for the duration of the study Exclusion Criteria: Diagnosis of any other myeloproliferative disorder Any known cause for a secondary thrombocytosis Anti-coagulant and anti-aggregant therapies Known or suspected heart disease Left Ventricular Ejection Fraction < 55%

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: Anagrelide<br>* Anagrelide hydrochloride 0.5mg capsules;initial dose administered will be 1.0mg/day administered as 0.5mg bid. The dose will be titrated such that the total daily dose is incremented by no more than 0.5mg per week as required depending on platelet reduction versus adverse event profile.<br>|
| Active Comparator: B<br> | Drug: Hydroxyurea<br>* Hydroxyurea is 500mg hydroxycarbamide capsules; initial dose is 1000mg/day, administered in two divided doses (500mg/dose). Dose titrated to effect to achieve a response.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time | The LVEF was measured by echocardiography and considered a sufficiently sensitive measure to evaluate any changes in cardiac function. | Baseline and Month 1, 2, 3, 6, 9, 12, 18, 24, 30 and 36 | 
| Platelet Count at Month 6 | Platelet count was evaluated. | Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Platelet Counts at Month 3 and 36 | Platelet count was evaluated throughout the study. | Baseline and Month 3 and 36 | 
| Percentage of Participants With Complete Response | A complete response was defined as a platelet count of less than (<) 400x10^9/Liter which was confirmed over 2 consecutive visits at least 28 days apart. | Baseline up to Month 36 | 
| Percentage of Participants With Partial Response | A partial response is defined as a platelet count of 400-600 x 10^9/Liter and a reduction in platelet count of at least 200 x 10^9/Liter from baseline which was confirmed over 2 consecutive visits at least 28 days apart. | Baseline up to Month 36 | 
| Time to Complete Response | Time in days from the date of the first dose of study medication to the date of the first visit at which response was classified. If a participant did not achieve response then they were censored at their last visit in the study (Month 36 or withdrawal). | Baseline up to Month 36 | 
| Time to Partial Response | Time in days from the date of the first dose of study medication to the date of the first visit at which response was classified. If a participant did not achieve response then they were censored at their last visit in the study (Month 36 or withdrawal). | Baseline up to Month 36 | 
| Number of Participants With Thrombotic and Haemorrhagic Events | Thrombohaemorrhagic events are a well-known complication of the underlying essential thrombocythemia (ET) and disease progression. Events such as arterial and venous thrombosis, serious haemorrhage (including gastrointestinal haemorrhage), and death from vascular causes have been reported in participants who received cytoreductive treatment. | From the signing of informed consent until the last study-related visit (Month 36) | 
| Change From Baseline in White Blood Cell Count Over Time | White blood cell count was evaluated throughout the study. | Baseline and Month 6, 12, 18, 24, 30 and 36 | 
| Change From Baseline in Red Blood Cell Count Over Time | Red blood cell count was evaluated throughout the study. | Baseline and Month 6, 12, 18, 24, 30 and 36 |