E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
High risk Essential thrombocythaemia |
Trombocitemia essenziale ad alto rischio |
|
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 | 14.1 |
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) |
|
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). |
Confrontare la sicurezza di anagrelide e idrossiurea a breve ed a lungo termine (fino a 3 anni di trattamento) con particolare attenzione alla sicurezza cardiovascolare (valutata mediante ecocardiografia) |
|
E.2.2 | Secondary objectives of the trial |
To compare the efficacy of anagrelide and hydroxyurea in terms of the platelet count after 6 months of treatment. To compare the efficacy of anagrelide and hydroxyurea in terms of the 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 hydroyxurea in short 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. |
Confrontare l'efficacia di anagrelide e idrossiurea in termini di conta piastrinica dopo 6 rispettivamente 3 mesi di trattamento,e numero di pazienti con risposta completa.Confrontare l'azione citoriduttiva dei due farmaci sulle cellule bianche e rosse del sangue.Valutare la tollerabilita' dei due farmaci nell'uso a breve ed a lungo termine (fino a 3 anni).Confrontare gli effetti dei due farmaci sull'incidenza di eventi trombotici o emorragici correlati alla patologia.Confrontare il tempo medio di risposta dopo trattamento con anagrelide o idrossiurea. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients must be aged ≥ 18 years. Male, or female patients who are postmenopausal, or surgically or biologically sterile. Females of childbearing potential with a negative urine pregnancy test prior to entering the study and using acceptable forms of contraception for the duration of the study.Satisfactory medical assessment with no clinically significant and relevant abnormalities. Diagnosis of essential thrombocythaemia. The patient must have given written personally signed and dated informed consent to participate in the study. |
ND |
|
E.4 | Principal exclusion criteria |
Concurrent disease 1. Known or suspected heart disease 2. Left ventricular ejection fraction (LVEF) <55% 3. History of life threatening malignancy or neoplasia, which in the opinion of the investigator is unrelated to thrombocythaemia 4. Moderate to severe renal impairment defined as creatinine clearance <50ml/min , or moderate to severe hepatic impairment defined as elevated transaminases >5x ULN 5. 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 6. Current or relevant previous history of serious, severe or unstable (acute or progressive) physical or psychiatric illness, any medical disorder that may require treatment or make the patient unlikely to fully complete the study, or any condition that presents undue risk from the study medication or procedures. Concomitant medications 1. Previous or current treatment with cytoreductive therapy 2. Anti-aggregant therapies, including aspirin. (Aspirin or other anti-aggregant therapy is allowed up to the point of randomisation) 3. Anticoagulant therapies 4. Treatment with any agents known to effect ventricular ejection fraction including but not limited to the following: positive inotropes, diuretics, anti-arrhythmic drugs, beta blockers, antihypertensives, drugs effecting the renin-angiotensin system, nitrates, calcium channel blockers, potassium channel activators, and sympathomimetics. Allergy / intolerance Known or suspected intolerance or hypersensitivity to the study materials [or closely related compounds] or any of their excipients. Substance abuse Patients with a history of alcohol or other substance abuse within the last 2-years will be excluded. Other clinical trials / experimental medications Patients must not have used another investigational agent or taken part in a clinical trial within the last 30-days prior to enrolment. Patients may however participate in study SPD422-203 whilst still enrolled in this study. Others Female patients who are pregnant or lactating including females with a positive pregnancy test at screening must be excluded. Patients that have previously been enrolled into this study and subsequently withdrawn must also be excluded. |
ND |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome for this study is 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 patient 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 slopes between the two treatment groups, and the associated two-sided 95% confidence intervals will be presented. If the 95% confidence interval (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. The assumption that LVEF decline is linear will also be checked and alternative analysis assumptions will be considered (details to be provided in the SAP). This analysis will be performed using the FAS and PP population; results from both populations will be contrasted. Summary statistics for LVEF at each visit and changes from baseline at each visit will also be presented by treatment group. Individual patient graphs of LVEF will also be generated. |
Outcome primario dello studio: effetto sulla frazione di eiezione del ventricolo sinistro, quale valutazione di sicurezza. Outcome di efficacia primario: conta piastrinica a 6 mesi. Altri endpoint di sicurezza: parametri cardiovascolari (valutati mediante ecocardiogramma), eventi avversi, alterazioni valori di laboratorio. |
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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 | No |
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.8.2.4 | 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 44 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 8 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |