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

Primary outcomes

1. Change From Baseline in Platelet Count at Final Assessment

   Time frame: Baseline and final assessment (within 5 days of the last dose of investigational product)

   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).

2. Change From Baseline in Platelet Count During Post-marketing Trial at Final Assessment

   Time frame: Baseline and final assessment (within 5 days of the last dose of investigational product)

   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).

3. Percentage of Participants Who Achieved Platelet Count Less Than (<) 600

   Time frame: 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)

   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.

4. Percentage of Participants Who Achieved Platelet Count Less Than (<) 600 During Post-marketing Trial

   Time frame: Baseline and final assessment (within 5 days of the last dose of investigational product)

   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.

5. Percentage of Participants Who Achieved Shift From Baseline in Platelet Count

   Time frame: Baseline and final assessment (within 5 days of the last dose of investigational product)

   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.

6. Percentage of Participants Who Achieved Shift From Baseline in Platelet Count During Post-marketing Trial

   Time frame: Baseline and final assessment (within 5 days of the last dose of investigational product)

   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.

7. Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

   Time frame: From start of study treatment (SPD422-308) up to 12 days after the last dose of investigational product

   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.

8. Percentage of Participants With TEAEs and TESAEs During Post-marketing Trial

   Time frame: From start of study treatment (SPD422-308) up to 12 days after the last dose of investigational product

   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.

9. Percentage of Participants With TEAEs and TESAEs Related to Clinical Laboratory Result

   Time frame: From start of study treatment (SPD422-308) up to 12 days after the last dose of investigational product

   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.

10. Percentage of Participants With TEAEs and TESAEs Related to Clinical Laboratory Result During Post-marketing Trial

    Time frame: From start of study treatment (SPD422-308) up to 12 days after the last dose of investigational product

    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.

11. Percentage of Participants With TEAEs and TESAEs Related to Vital Signs

    Time frame: From start of study treatment (SPD422-308) up to 12 days after the last dose of investigational product

    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.

12. Percentage of Participants With TEAEs and TESAEs Related to Vital Signs During Post-marketing Trial

    Time frame: From start of study treatment (SPD422-308) up to 12 days after the last dose of investigational product

    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.

13. Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities

    Time frame: From start of study treatment (SPD422-308) up to 12 days after the last dose of investigational product

    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.