E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Essential thrombocythaemia |
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E.1.1.1 | Medical condition in easily understood language |
ET is a disorder of the bone marrow, which causes too many platelets to be produced. There is a risk of problems such as blood clots forming unnecessarily and excessive bleeding. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10015493 |
E.1.2 | Term | Essential thrombocythaemia |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the safety of anagrelide and hydroxyurea in short and long term usage of up to three years with particular reference to cardiovascular safety (as assessed by echocardiogram). |
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E.2.2 | Secondary objectives of the trial |
To compare the efficacy of angrelide and hydroxyurea in terms of platelet count after 6 months of treatment.
To compare the efficacy of anagrelide and hydroxyurea in terms of platelet count after 3 months of treatment.
To compare the efficacy of anagrelide and hydroxyurea in terms of the number of patients achieving a complete response.
To compare the cytoreductive impact of anagrelide and hydroxyurea on white blood cell and red blood cell lines.
To investigate the tolerability of anagrelide and hydroxyurea in short term and long term usage of up to three years.
To investigate the effects of anagrelide and hydroxyurea on incidence of disease related thrombotic and haemorrhagic events.
To compare the average time to response following treatment with anagrelide or hydroxyurea.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients must have given written informed consent to participate in the study.
Patients must be aged ≥ 18 years.
Previously untreated with a cytotreductive agent.
Confirmed diagnosis of ET - High Risk Profile.
Satisfactory Medical assessment with no clinically significant and relevant abnormalities.
If patients are female and of childbearing potential they must have a negative serum pregnancy test prior to entering the study and must agree to use effective birth control for the duration of the study. Pregnant or lactating women are excluded from participation.
Patients must be able, willing and likely to comply with the study procedures and restrictions.
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E.4 | Principal exclusion criteria |
Patients with a diagnosis of any other myeloproliferative disorder (MPD).
Any known cause for a secondary thrombocytosis.
Previous or current treatment with cytoreductive therapy.
Anticoagulant therapies.
Anti-aggregant therapies, including aspirin. (Aspirin or other anti-aggregant therapy is allowed up to the point of randomisation).
Known or suspected intolerance to study materials.
Known or suspected Heart Disease.
Left Ventricular Ejection Fraction (LVEF) <55%.
Treatment with any medications known to alter ventricular ejection fraction.
Life threatening malignancy or neoplasia which in the opinion of the investigator is unrelated to thrombocythaemia.
Severe renal impairment defined as creatinine clearance <30ml/min, or severe hepatic impairment defined as elevated transaminases >5xULN.
Clinically significant abnormal laboratory values (excluding markers of essential thrombocythaemia) will exclude the patient from the study as will known infection with hepatitis B, hepatitis C or HIV.
Patients with a history of drug/alcohol abuse (within the previous 2 years).
Patients must not have participated in another investigational study within 30 days prior to enrolment or for a longer duration if specified in local regulations.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome for this study is the safety measurement LVEF. LVEF will be measured at predefined intervals (pre-treatment and Months 1,2,3,6,9,12,18,24,30 and 36) during the study and the response (slope) in LVEF for each patients will be obtained using linear regression. LVEF will be modelled as a linear function of time with a separate slope and intercept for each patient.
The mean slope for each treatment group, the difference in the mean slopes between the two treatment groups, and the associated two-sided 95% confidence intervals will be presented. If the 95% CI for difference lies entirely below 2%/year then it will be concluded that the effect of anagrelide on LVEF is no worse than that observed for hydroxyurea.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Safety with particular reference to cardiovascular safety of anagrelide and hydroxyurea will be performed in short and long term usage of up to 3 years |
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E.5.2 | Secondary end point(s) |
-Mean platelet count at 3 months.
- Mean and percentage platelet count reduction from baseline at 3 and 6 months
- The proportion of patients achieving a complete or partial response will be summarised by treatment group
- The median time to response will be summarised using Kaplan-Meier methodology.The minimum and maximum time to response along with a 95% CI will also be
presented.
- Incidence of disease related thrombotic and haemorrhagic events will be summarised by treatment group at baseline and post-baseline.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Mean platelet count at 3 months.
- Mean and percentage platelet count reduction from baseline at 3 and 6 months
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit of the last subject |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 7 |