Long-term Safety of SPD422 in Japanese Adults With Essential Thrombocythaemia

Study Overview
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Brief Summary
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The purpose of this study is to provide SPD422 to subjects who completed Study SPD422 308 and, in the opinion of the Investigator, will continue to benefit from treatment.

Official Title
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A Phase 3, Multi-centre, Open-label, Extension Study to Investigate the Long-term Safety of SPD422 in Japanese Adults With Essential Thrombocythaemia

Conditions
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Essential Thrombocythemia (ET)

Intervention / Treatment
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* Drug: SPD422 (anagrelide hydrochloride)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have completed Study SPD422 308

Ages Eligible for Study
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Minimum Age: 20 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SPD422 (anagrelide hydrochloride)<br> | Drug: SPD422 (anagrelide hydrochloride)<br>* Subjects will be continued on the dose of anagrelide that controlled their platelet levels in Study 308 and titrated if necessary.<br>* Other names: Agrylin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Platelet Count at Final Assessment | Baseline considered from study SPD422-308 (NCT01214915). Final assessment was defined as the last non-missing data (End of study visit in SPD422-309 [NCT01467661], or early termination visit either in SPD422-308 [NCT01214915] or SPD422-309 [NCT01467661], or last available study visit). | Baseline and final assessment (within 5 days of the last dose of investigational product) | 
| Change From Baseline in Platelet Count During Post-marketing Trial at Final Assessment | Baseline considered from study SPD422-308 (NCT01214915). Final assessment was defined as the last non-missing data (End of study visit in SPD422-309 [NCT01467661], or early termination visit either in SPD422-308 [NCT01214915] or SPD422-309 [NCT01467661], or last available study visit). | Baseline and final assessment (within 5 days of the last dose of investigational product) | 
| Percentage of Participants Who Achieved Platelet Count Less Than (<) 600 | Baseline considered from study SPD422-308 (NCT01214915). Final assessment was defined as the last non-missing data (End of study visit in SPD422-309 [NCT01467661], or early termination visit either in SPD422-308 [NCT01214915] or SPD422-309 [NCT01467661], or last available study visit). Participants who achieved platelet count <600 x 10^9 platelets per liter at each visit were reported. | Baseline, Week 1, Month 1-12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, and final assessment (within 5 days of the last dose of investigational product) | 
| Percentage of Participants Who Achieved Platelet Count Less Than (<) 600 During Post-marketing Trial | Baseline considered from study SPD422-308 (NCT01214915). Final assessment was defined as the last non-missing data (End of study visit in SPD422-309 [NCT01467661], or early termination visit either in SPD422-308 [NCT01214915] or SPD422-309 [NCT01467661], or last available study visit). Participants who achieved platelet count <600 x 10^9 platelets per liter during the post-marketing trial were reported. | Baseline and final assessment (within 5 days of the last dose of investigational product) | 
| Percentage of Participants Who Achieved Shift From Baseline in Platelet Count | Baseline considered from study SPD422-308 (NCT01214915). Final assessment (FA) was defined as the last nonmissing data (End of study visit in SPD422-309 [NCT01467661], or early termination visit either in SPD422-308 [NCT01214915] or SPD422-309 [NCT01467661], or last available study visit). Participants who had platelet count <600 x 10^9 platelet per liter and greater than equal (>=) 600 x 10^9 platelet per liter at the final assessment as a shift from baseline was reported. Percentage of participants with shift = number of participants with shift / Safety analysis set (53 participants) * 100. | Baseline and final assessment (within 5 days of the last dose of investigational product) | 
| Percentage of Participants Who Achieved Shift From Baseline in Platelet Count During Post-marketing Trial | Baseline considered from study SPD422-308 (NCT01214915). Final assessment (FA) was defined as the last non-missing data (End of study visit in SPD422-309 [NCT01467661], or early termination visit either in SPD422-308 [NCT01214915] or SPD422-309 [NCT01467661], or last available study visit). Participants who had platelet count <600 x 10^9 platelet per liter and greater than equal (>=) 600 x 10^9 platelet per liter at the final assessment as a shift from baseline during the post marketing trial was reported. Percentage of participants with shift = number of participants with shift / post-marketing safety analysis set (33 participants) * 100. | Baseline and final assessment (within 5 days of the last dose of investigational product) | 
| Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent adverse event was defined as the onset of any AE or if the severity of a pre-existing AE worsened any time on or after the date of first dose of investigational product in Study SPD422-308 (NCT01214915) and up to and including 12 days after the last dose is taken. | From start of study treatment (SPD422-308) up to 12 days after the last dose of investigational product | 
| Percentage of Participants With TEAEs and TESAEs During Post-marketing Trial | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent adverse event was defined as the onset of any AE or if the severity of a pre-existing AE worsened any time on or after the date of first dose of investigational product in Study SPD422-308 (NCT01214915) and up to and including 12 days after the last dose is taken. | From start of study treatment (SPD422-308) up to 12 days after the last dose of investigational product | 
| Percentage of Participants With TEAEs and TESAEs Related to Clinical Laboratory Result | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent adverse event was defined as the onset of any AE or if the severity of a pre-existing AE worsened any time on or after the date of first dose of investigational product in Study SPD422-308 (NCT01214915) and up to and including 12 days after the last dose is taken. Clinical Laboratory analysis included hematology, biochemistry, and urinalysis. | From start of study treatment (SPD422-308) up to 12 days after the last dose of investigational product | 
| Percentage of Participants With TEAEs and TESAEs Related to Clinical Laboratory Result During Post-marketing Trial | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent adverse event was defined as the onset of any AE or if the severity of a pre-existing AE worsened any time on or after the date of first dose of investigational product in Study SPD422-308 (NCT01214915) and up to and including 12 days after the last dose is taken. Clinical Laboratory analysis included hematology, biochemistry, and urinalysis. | From start of study treatment (SPD422-308) up to 12 days after the last dose of investigational product | 
| Percentage of Participants With TEAEs and TESAEs Related to Vital Signs | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent adverse event was defined as the onset of any AE or if the severity of a pre-existing AE worsened any time on or after the date of first dose of investigational product in Study SPD422-308 (NCT01214915) and up to and including 12 days after the last dose is taken. Vital signs included pulse rate, systolic and diastolic blood pressure, and weight. | From start of study treatment (SPD422-308) up to 12 days after the last dose of investigational product | 
| Percentage of Participants With TEAEs and TESAEs Related to Vital Signs During Post-marketing Trial | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent adverse event was defined as the onset of any AE or if the severity of a pre-existing AE worsened any time on or after the date of first dose of investigational product in Study SPD422-308 (NCT01214915) and up to and including 12 days after the last dose is taken. Vital signs included pulse rate, systolic and diastolic blood pressure, and weight. | From start of study treatment (SPD422-308) up to 12 days after the last dose of investigational product | 
| Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities | Standard 12-Lead ECG analysis was performed to identify the ECG abnormalities. Clinically significant abnormalities like QT prolongation, atrial fibrillation, were decided by the investigator during the study. | From start of study treatment (SPD422-308) up to 12 days after the last dose of investigational product |