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

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

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.

Study Overview

• Status: Completed
• Conditions: Essential Thrombocythemia (ET)
• Intervention / Treatment: Drug: SPD422 (anagrelide hydrochloride)

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan, 160-8582
    • Keio University Hospital
  • Akita
    • Akita-shi, Akita, Japan, 010-8543
      • Akita University Hospital
  • Bunkyo-ku
    • Honkomagome 3-18-22, Bunkyo-ku, Japan, 13 113-8677
      • Tokyo Metropolitan Cancer and Infectious diseases Center Kom
    • Sendagi 1-1-5, Bunkyo-ku, Japan, 13 113-8603
      • Nippon Medical School Hospital
  • Chiba-shi
    • Chuo-ku Inohana 1-8-1, Chiba-shi, Japan, 12 260-8677
      • Chiba University Hospital
  • Hokkaidō Prefecture
    • Sapporo-shi, Hokkaidō Prefecture, Japan, 01 060-8648
      • Hokkaido University Hospital
  • Kanagawa Prefecture
    • Isehara-shi, Kanagawa Prefecture, Japan, 259-1143
      • Tokai University Hospital
  • Maebashi-shi
    • Showa-machi 3-39-15, Maebashi-shi, Japan, 10 371-8511
      • Gunma University Hospital
  • Meguro-ku
    • Higashigaoka 2-5-1, Meguro-ku, Japan, 13 152-8902
      • NHO Tokyo Medical Center
  • Mie
    • Tsu-shi, Mie, Japan, 514-8507
      • Mie University Hospital
  • Miyazaki
    • Miyazaki-shi, Miyazaki, Japan, 889-1692
      • University of Miyazaki Hospital
  • Niigata
    • Niigata-shi, Niigata, Japan, 951-8566
      • Niigata Cancer Centre
  • Okayama Prefecture
    • Okayama-shi, Okayama Prefecture, Japan, 33 700-8558
      • Okayama University Hospital
  • Osaka
    • Osaka-shi, Osaka, Japan, 545-0051
      • Osaka City University Hospital
    • Suita-shi, Osaka, Japan, 565-0871
      • Osaka University Hospital
  • Shizuoka Prefecture
    • Izunokuni-shi, Shizuoka Prefecture, Japan, 22 410-2295
      • Juntendo University Shizuoka Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects must have completed Study SPD422 308

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• Kanakura Y, Shirasugi Y, Yamaguchi H, Koike M, Chou T, Okamoto S, Achenbach H, Wu J, Nakaseko C. A phase 3b, multicenter, open-label extension study of the long-term safety of anagrelide in Japanese adults with essential thrombocythemia. Int J Hematol. 2018 Nov;108(5):491-498. doi: 10.1007/s12185-018-2510-7. Epub 2018 Aug 18.

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2010
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: October 31, 2011
• First Submitted That Met QC Criteria: November 4, 2011
• First Posted (Estimate): November 9, 2011

Study Record Updates

• Last Update Posted (Actual): June 9, 2021
• Last Update Submitted That Met QC Criteria: May 24, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Hemorrhagic Disorders; Myeloproliferative Disorders; Blood Coagulation Disorders; Blood Platelet Disorders; Thrombocytosis; Thrombocythemia, Essential; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Anagrelide
• Other Study ID Numbers: SPD422-309