The purpose of this study is to determine the safety and efficacy of AKR-501 (avatrombopag) administered in participants with chronic Idiopathic Thrombocytopenic Purpura (ITP) who were enrolled into and completed 28 days of study treatment in Protocol 501-CL-003 (NCT00441090).
Participants eligible to enroll into this rollover protocol will begin study treatment within 2-5 days of their Day 28 study termination visit in Protocol 501-CL-003 (NCT00441090). Participants who met the primary efficacy response criterion in Protocol 501-CL-003 will continue receiving the same study treatment to which they were assigned in the previous protocol in a double-blinded manner, these being one of the following 5 treatments: * avatrombopag 2.5 mg daily * avatrombopag 5 mg daily * avatrombopag 10 mg daily * avatrombopag 20 mg daily * placebo Participants who did not meet the primary efficacy response criterion in Protocol 501-CL-003 who otherwise meet the eligibility criteria for this rollover protocol will be offered open label avatrombopag 10 mg daily. This is a parallel group, rollover study.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
53
Placebo Orally, once daily administered under fasting conditions (at least 1 hr prior to or at least 2 hours after a meal or snack) Duration - 6 months
Dose 10 mg Orally, once daily administered under fasting conditions (at least 1 hr prior to or at least 2 hours after a meal or snack) Duration - 6 months
Dose: 2.5, 5, 10, or 20 mg Orally, once daily administered under fasting conditions (at least 1 hr prior to or at least 2 hours after a meal or snack) Duration - 6 months
Pacific Cancer Medical Center, Inc
Anaheim, California, United States
Comprehensive Blood and Cancer Center
Bakersfield, California, United States
Davis, Posteraro and Wasser, MDs, LLP
Manchester, Connecticut, United States
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
A TEAE was defined as 1) the AE started on or after the date of first dose of study drug up to and including 30 days after the last dose of study drug, or 2) the AE started before the first dose of study drug but worsened in severity on or after the date of first dose of study drug up to and including 3 days after the last dose of study drug. For participants having a tapering period of study drug, the last dose day is the last day of study drug during the tapering period. Related AEs included those whose relationship was categorized as possible or probably by the investigator. Dose interruption includes dose decreased, dose previously stopped, permanently stopped, or temporarily stopped. The safety population was divided into three subgroups based on the mean daily dose of active study drug taken; lower 1/3 (less than 8.85 mg avatrombopag), middle 1/3 (greater than or equal to 8.85 mg but less than 13.5 mg avatrombopag), and upper 1/3 (greater than or equal to 13.5 mg avatrombopag).
Time frame: Day 1 through Month 6 while receiving treatment and at Month 7 after discontinuation of treatment.
Incidence of Severe (Grade 3 or 4) TEAEs
A TEAE was defined as 1) the AE started on or after the date of first dose of study drug up to and including 30 days after the last dose of drug, or 2) the AE started before the first dose of study drug but worsened in severity on or after the date of first dose of study drug up to and including 3 days after the last dose of study drug. For participants having a tapering period of study drug, the last dose day is the last day of study drug during the tapering period. The safety population was divided into three subgroups based on the mean daily dose of active study drug taken; lower 1/3 (less than 8.85 mg avatrombopag), middle 1/3 (greater than or equal to 8.85 mg but less than 13.5 mg avatrombopag), and upper 1/3 (greater than or equal to 13.5 mg avatrombopag).
Time frame: Day 1 through Month 6 while receiving treatment and at Month 7 after discontinuation of treatment.
Incidence of Drug-Related TEAEs
Drug-related TEAEs included those whose relationship was categorized as possible or probably by the investigator. A TEAE was defined as 1) the AE started on or after the date of first dose of study drug up to and including 30 days after the last dose of drug, or 2) the AE started before the first dose of study drug but worsened in severity on or after the date of first dose of study drug up to and including 3 days after the last dose of study drug. For participants having a tapering period of study drug, the last dose day is the last day of study drug during the tapering period. The safety population was divided into three subgroups based on the mean daily dose of active study drug taken; lower 1/3 (less than 8.85 mg avatrombopag), middle 1/3 (greater than or equal to 8.85 mg but less than 13.5 mg avatrombopag), and upper 1/3 (greater than or equal to 13.5 mg avatrombopag).
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Florida Cancer Institute
New Port Richey, Florida, United States
John H. Stroger, Jr. Hospital of Cook County, Div. of Hematology and Oncology
Chicago, Illinois, United States
Cancer Care Center, Inc.
New Albany, Indiana, United States
Capitol Comprehensive Cancer Care Clinic
Jefferson City, Missouri, United States
Kansas City Cancer Center, LLC
Kansas City, Missouri, United States
Mount Sinai Medical Center
New York, New York, United States
New York Presbyterian Hospital, Weill Medical College of Cornell University
New York, New York, United States
...and 2 more locations
Time frame: Day 1 through Month 6 while receiving treatment and at Month 7 after discontinuation of treatment.
Median Platelet Counts at Selected Analysis Timepoints
Platelet count (PC) was measured from blood draws. Based on avatrombopag response in study 501-CL-003, participants were divided into two subgroups; 1) "Responders", participants who met the primary efficacy response; pretreatment PC was less than 30,000/mm\^3 and increased to greater than or equal to 50,000/mm\^3 after treatment with avatrombopag, and for participants on steroids, pretreatment PC was greater than or equal to 30,000/mm3 but less than 50,000/mm\^3 and increased to a PC greater than or equal to 20,000/mm\^3 above their pretreatment values and 2) "Nonresponders", participants who did not meet the primary efficacy response and those who were in the placebo arm. Open-label dose escalation of avatrombopag, as well as reductions in ITP-directed concomitant therapy (e.g. steroids) was allowed for all participants. During the periods of avatrombopag dose escalation and/or ITP-directed concomitant medication reduction, platelet sampling was done weekly.
Time frame: Day 1, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, and Follow-up Weeks (after last dose of study drug in this study) 1, 2, 3, 4
Percentage of Participants Who Achieved a Platelet Count of 100,000/mm^3 or Higher by Response Status and Selected Study Visit
Platelet count (PC) was measured from blood draws. Based on avatrombopag response in study 501-CL-003, participants were divided into two subgroups; 1) "Responders", participants who met the primary efficacy response; pretreatment PC was less than 30,000/mm\^3 and increased to greater than or equal to 50,000/mm\^3 after treatment with avatrombopag, and for participants on steroids, pretreatment PC was greater than or equal to 30,000/mm\^3 but less than 50,000/mm\^3 and increased to a PC greater than or equal to 20,000/mm\^3 above their pretreatment values and 2) "Nonresponders", participants who did not meet the primary efficacy response and those who were in the placebo arm. Open-label dose escalation of avatrombopag, as well as reductions in ITP-directed concomitant therapy (e.g. steroids) was allowed for all participants. During the periods of avatrombopag dose escalation and/or ITP-directed concomitant medication reduction, platelet sampling was done weekly.
Time frame: Baseline (last PC before first dose of study drug in previous study), Weeks 2, 4, 8, 12, 16, 20, 24, and Follow-up Weeks (after last dose of study drug in this study) 1, 2, 3, 4
Percentage of Participants Who Maintained a Platelet Count of 100,000/mm^3 or Higher by Response Status
Platelet count (PC) was measured from blood draws. Based on avatrombopag response in study 501-CL-003, participants were divided into two subgroups; 1) "Responders", participants who met the primary efficacy response; pretreatment PC was less than 30,000/mm\^3 and increased to greater than or equal to 50,000/mm\^3 after treatment with avatrombopag, and for participants on steroids, pretreatment PC was greater than or equal to 30,000/mm\^3 but less than 50,000/mm\^3 and increased to a PC greater than or equal to 20,000/mm\^3 above their pretreatment values and 2) "Nonresponders", participants who did not meet the primary efficacy response and those who were in the placebo arm. Open-label dose escalation of avatrombopag, as well as reductions in ITP-directed concomitant therapy (e.g. steroids) was allowed for all participants. During the periods of avatrombopag dose escalation and/or ITP-directed concomitant medication reduction, platelet sampling was done weekly.
Time frame: Baseline (last PC before first dose of study drug in previous study), Weeks 2, 4, 8, 12, 16, 20, 24, and Follow-up Weeks (after last dose of study drug in this study) 1, 2, 3, 4
Percentage of Participants Who Achieved Response-Level Platelet Count by Selected Study Visit
Platelet count (PC) was measured from blood draws. Based on avatrombopag response in study 501-CL-003, participants were divided into two subgroups; 1) "Responders", participants who met the primary efficacy response; pretreatment PC was less than 30,000/mm\^3 and increased to greater than or equal to 50,000/mm\^3 after treatment with avatrombopag, and for participants on steroids, pretreatment PC was greater than or equal to 30,000/mm\^3 but less than 50,000/mm\^3 and increased to a PC greater than or equal to 20,000/mm\^3 above their pretreatment values and 2) "Nonresponders", participants who did not meet the primary efficacy response and those who were in the placebo arm. Open-label dose escalation of avatrombopag, as well as reductions in ITP-directed concomitant therapy (e.g. steroids) was allowed for all participants. During the periods of avatrombopag dose escalation and/or ITP-directed concomitant medication reduction, platelet sampling was done weekly.
Time frame: Baseline (last PC before first dose of study drug in previous study), Weeks 2, 4, 8, 12, 16, 20, 24, and Follow-up Weeks (after last dose of study drug in this study) 1, 2, 3, 4
Percentage of Participants Who Maintained Response-Level Platelet Count
Platelet count (PC) was measured from blood draws. Based on avatrombopag response in study 501-CL-003, participants were divided into two subgroups; 1) "Responders", participants who met the primary efficacy response; pretreatment PC was less than 30,000/mm\^3 and increased to greater than or equal to 50,000/mm\^3 after treatment with avatrombopag, and for participants on steroids, pretreatment PC was greater than or equal to 30,000/mm\^3 but less than 50,000/mm\^3 and increased to a PC greater than or equal to 20,000/mm\^3 above their pretreatment values and 2) "Nonresponders", participants who did not meet the primary efficacy response and those who were in the placebo arm. Open-label dose escalation of avatrombopag, as well as reductions in ITP-directed concomitant therapy (e.g. steroids) was allowed for all participants. During the periods of avatrombopag dose escalation and/or ITP-directed concomitant medication reduction, platelet sampling was done weekly.
Time frame: Baseline (last PC before first dose of study drug in previous study), Weeks 2, 4, 8, 12, 16, 20, 24, and Follow-up Weeks (after last dose of study drug in this study) 1, 2, 3, 4
Percentage of Participants Who Achieved a Durable, Transient, or Overall Platelet Response
Platelet count (PC) was measured from blood draws. Based on avatrombopag response in study 501-CL-003, participants were divided into two subgroups; 1) "Responders", participants who met the primary efficacy response; pretreatment PC was less than 30,000/mm\^3 and increased to greater than or equal to 50,000/mm\^3 after treatment with avatrombopag, and for participants on steroids, pretreatment PC was greater than or equal to 30,000/mm\^3 but less than 50,000/mm\^3 and increased to a PC greater than or equal to 20,000/mm\^3 above their pretreatment values and 2) "Nonresponders", participants who did not meet the primary efficacy response and those who were in the placebo arm. Open-label dose escalation of avatrombopag, as well as reductions in ITP-directed concomitant therapy (e.g. steroids) was allowed for all participants. During the periods of avatrombopag dose escalation and/or ITP-directed concomitant medication reduction, platelet sampling was done weekly.
Time frame: Baseline (last PC before first dose of study drug in previous study), Weeks 2, 4, 8, 12, 16, 20, 24, and Follow-up Weeks (after last dose of study drug in this study) 1, 2, 3, 4
Number of Participants With Changes in Concomitant Steroid Use
A participant who used steroids at study entry was considered to have permanently discontinued steroid use if they had no steroid use during the last 8 weeks of the study Treatment Period. A participant who used steroids at study entry was considered to have decreased concomitant steroid medication by at least 50% if they permanently discontinued steroids, or in no dose of steroid was higher than 50% of their baseline steroid dose during the last 8 weeks of the study Treatment Period.
Time frame: Day 1 through last 8 weeks of the Treatment Period