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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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo (double-blind) | Experimental |
| |
| Avatrombopag tablets (open-label) | Experimental |
| |
| Avatrombopag tablets (double-blind) | Experimental |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Blinded (placebo) | Drug | 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 |
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| Measure | Description | Time Frame |
|---|---|---|
| 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). | 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). | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
Women who are pregnant and/or lactating.
Use of the following drugs or treatments:
Inability to comply with protocol requirements or give informed consent, as determined by the Investigator.
For more information regarding inclusion/exclusion criteria, please see record for AKR 501-CL-003 Protocol.
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| Name | Affiliation | Role |
|---|---|---|
| Pei-Ran Ho, MD | Eisai Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Pacific Cancer Medical Center, Inc | Anaheim | California | 92801 | United States | ||
| Comprehensive Blood and Cancer Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24802775 | Derived | Bussel JB, Kuter DJ, Aledort LM, Kessler CM, Cuker A, Pendergrass KB, Tang S, McIntosh J. A randomized trial of avatrombopag, an investigational thrombopoietin-receptor agonist, in persistent and chronic immune thrombocytopenia. Blood. 2014 Jun 19;123(25):3887-94. doi: 10.1182/blood-2013-07-514398. Epub 2014 May 6. |
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After Protocol Amendment 4, this study implemented a flexible dose regimen and was considered to have an open-label, uncontrolled, single-arm design. Due to these limitations in study design, a single grouping method with 3 subgroups was implemented for reporting participant disposition.
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| ID | Title | Description |
|---|---|---|
| FG000 | Lower 1/3 Avatromboopag Dose Group | Participants in this group took less than 8.85 mg avatrombopag orally once daily under fasting conditions (at least 1 hour before and 2 hours after a meal or snack). Grouping of avatrombopag dose into lower 1/3, middle 1/3, and upper 1/3 was based on the average daily dose received during the combined active treatment periods of studies 501-CL-003 and 501-CL-004. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Open Label (Avatrombopag tablets) | Drug | 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 |
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| Blinded (Avatrombopoag tablets) | Drug | 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 |
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| Day 1 through Month 6 while receiving treatment and at Month 7 after discontinuation of treatment. |
| 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. | 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. | 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. | 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. | 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. | 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. | Day 1 through last 8 weeks of the Treatment Period |
| Bakersfield |
| California |
| 93309 |
| United States |
| Davis, Posteraro and Wasser, MDs, LLP | Manchester | Connecticut | 06105 | United States |
| Florida Cancer Institute | New Port Richey | Florida | 34655 | United States |
| John H. Stroger, Jr. Hospital of Cook County, Div. of Hematology and Oncology | Chicago | Illinois | 60612 | United States |
| Cancer Care Center, Inc. | New Albany | Indiana | 47150 | United States |
| Capitol Comprehensive Cancer Care Clinic | Jefferson City | Missouri | 65109 | United States |
| Kansas City Cancer Center, LLC | Kansas City | Missouri | 64131 | United States |
| Mount Sinai Medical Center | New York | New York | 10029 | United States |
| New York Presbyterian Hospital, Weill Medical College of Cornell University | New York | New York | 10032 | United States |
| Emerywood Oncology and Hematology | High Point | North Carolina | 27262 | United States |
| Mid Ohio Oncology/Hematology, Inc., dba The Mark H. Zangmeister Center | Columbus | Ohio | 43219 | United States |
| FG001 | Middle 1/3 Avatrombopag Dose Group | Participants in this group took greater than or equal to 8.85 mg avatrombopag to less than 13.5 mg avatrombopag orally once daily under fasting conditions (at least 1 hour before and 2 hours after a meal or snack). Grouping of avatrombopag dose into lower 1/3, middle 1/3, and upper 1/3 was based on the average daily dose received during the combined active treatment periods of studies 501-CL-003 and 501-CL-004. |
| FG002 | Upper 1/3 Avatrombopag Dose Group | Participants in this group took greater than or equal to 13.5 mg avatrombopag orally once daily under fasting conditions (at least 1 hour before and 2 hours after a meal or snack). Grouping of avatrombopag dose into lower 1/3, middle 1/3, and upper 1/3 was based on the average daily dose received during the combined active treatment periods of studies 501-CL-003 and 501-CL-004. |
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| NOT COMPLETED |
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Full analysis set (FAS) included all participants who completed 501-CL-003 and received study drug in 501-CL-004, except baseline values and ITP-directed medications taken during the 2-week period before the first dose of avatrombopag in 501-CL-004. Data was summarized using the observed case (OC) method.
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| ID | Title | Description |
|---|---|---|
| BG000 | Lower 1/3 Avatrombopag Dose Group | Participants in this group took less than 8.85 mg avatrombopag orally once daily under fasting conditions (at least 1 hour before and 2 hours after a meal or snack). Grouping of avatrombopag dose into lower 1/3, middle 1/3, and upper 1/3 was based on the average daily dose received during the combined active treatment periods of studies 501-CL-003 and 501-CL-004. |
| BG001 | Middle 1/3 Avatrombopag Dose Group | Participants in this group took greater than or equal to 8.85 mg avatrombopag to less than 13.5 mg avatrombopag orally once daily under fasting conditions (at least 1 hour before and 2 hours after a meal or snack). Grouping of avatrombopag dose into lower 1/3, middle 1/3, and upper 1/3 was based on the average daily dose received during the combined active treatment periods of studies 501-CL-003 and 501-CL-004. |
| BG002 | Upper 1/3 Avatrombopag Dose Group | Participants in this group took greater than or equal to 13.5 mg avatrombopag orally once daily under fasting conditions (at least 1 hour before and 2 hours after a meal or snack). Grouping of avatrombopag dose into lower 1/3, middle 1/3, and upper 1/3 was based on the average daily dose received during the combined active treatment periods of studies 501-CL-003 and 501-CL-004. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Geometric Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
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| Primary | 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). | Safety population included all participants who received at least one dose of study drug and had at least one post-treatment safety assessment. The term "post-treatment" refers to any assessment timepoint after the participant received at least one dose of study drug. | Posted | Count of Participants | Participants | Day 1 through Month 6 while receiving treatment and at Month 7 after discontinuation of treatment. |
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| Primary | 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). | Safety population included all participants who received at least one dose of study drug and had at least one post-treatment safety assessment. The term "post-treatment" refers to any assessment timepoint after the participant received at least one dose of study drug. | Posted | Count of Participants | Participants | Day 1 through Month 6 while receiving treatment and at Month 7 after discontinuation of treatment. |
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| Primary | 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). | Safety population included all participants who received at least one dose of study drug and had at least one post-treatment safety assessment. The term "post-treatment" refers to any assessment timepoint after the participant received at least one dose of study drug. | Posted | Count of Participants | Participants | Day 1 through Month 6 while receiving treatment and at Month 7 after discontinuation of treatment. |
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| Secondary | 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. | Full analysis set (FAS) included all participants who completed 501-CL-003 and received study drug in the current study, except baseline values and ITP-directed medications taken during the 2-week period before the first dose of avatrombopag in the current study. Data was summarized using the observed case (OC) method. | Posted | Median | Full Range | Platelets x 1000/mm^3 | 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 |
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| Secondary | 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. | FAS. Data was summarized using the OC method. | Posted | Number | Percentage of participants | 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 |
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| Secondary | 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. | FAS. Data was summarized using the OC method. | Posted | Number | Percentage of participants | 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 |
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| Secondary | 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. | FAS. Data was summarized using the OC method. | Posted | Number | Percentage of participants | 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 |
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| Secondary | 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. | FAS. Data was summarized using the OC method. | Posted | Number | Percentage of participants | 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 |
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| Secondary | 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. | FAS. Data was summarized using the OC method. | Posted | Number | Percentage of participants | 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 |
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| Secondary | 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. | FAS. Data was summarized using the OC method. Only those participants who had data available at both Baseline and post-Baseline were analyzed. | Posted | Number | Number of participants | Day 1 through last 8 weeks of the Treatment Period |
|
Approximately 7 months.
Treatment-emergent adverse events and treatment-emergent serious adverse events were reported. Safety population included all participants who received at least one dose of study drug and had at least one post-treatment safety assessment. The term "post-treatment" refers to any assessment timepoint after the participant received at least one dose of study drug.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Lower 1/3 Avatrombopag Dose Group | Participants in this group took less than 8.85 mg avatrombopag orally once daily under fasting conditions (at least 1 hour before and 2 hours after a meal or snack). Grouping Method A of avatrombopag dose into lower 1/3, middle 1/3, and upper 1/3 was based on the average daily dose received during the combined active treatment periods of studies 501-CL-003 and 501-CL-004. | 0 | 12 | 2 | 12 | 12 | 12 |
| EG001 | Middle 1/3 Avatrombopag Dose Group | Participants in this group took greater than or equal to 8.85 mg avatrombopag to less than 13.5 mg avatrombopag orally once daily under fasting conditions (at least 1 hour before and 2 hours after a meal or snack). Grouping Method A of avatrombopag dose into lower 1/3, middle 1/3, and upper 1/3 was based on the average daily dose received during the combined active treatment periods of studies 501-CL-003 and 501-CL-004. | 0 | 26 | 4 | 26 | 24 | 26 |
| EG002 | Upper 1/3 Avatrombopag Dose Group | Participants in this group took greater than or equal to 13.5 mg avatrombopag orally once daily under fasting conditions (at least 1 hour before and 2 hours after a meal or snack). Grouping Method A of avatrombopag dose into lower 1/3, middle 1/3, and upper 1/3 was based on the average daily dose received during the combined active treatment periods of studies 501-CL-003 and 501-CL-004. | 0 | 15 | 3 | 15 | 14 | 15 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (10.1) | Non-systematic Assessment |
| |
| Mitral valve incompetence | Cardiac disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA (10.1) | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Haemorrhage intracranial | Nervous system disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Lethargy | Nervous system disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Pelvic venous thrombosis | Vascular disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Idiopathic thrombocytopenic purpura | Blood and lymphatic system disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Leukocytosis | Blood and lymphatic system disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (10.1) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Gingival bleeding | Gastrointestinal disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Oedema | General disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
| |
| Platelet count increased | Investigations | MedDRA (10.1) | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA (10.1) | Systematic Assessment |
| |
| Hyperlipidaemia | Metabolism and nutrition disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Menorrhagia | Reproductive system and breast disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Pharyngolaryngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA (10.1) | Systematic Assessment |
|
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Eisai Medical Services | Eisai Inc. | 1-888-422-4743 |
| ID | Term |
|---|---|
| D016553 | Purpura, Thrombocytopenic, Idiopathic |
| ID | Term |
|---|---|
| D011696 | Purpura, Thrombocytopenic |
| D011693 | Purpura |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D057049 | Thrombotic Microangiopathies |
| D013921 | Thrombocytopenia |
| D001791 | Blood Platelet Disorders |
| D000095542 | Cytopenia |
| D006474 | Hemorrhagic Disorders |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D006470 | Hemorrhage |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012877 | Skin Manifestations |
| D012816 | Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| C533238 | avatrombopag |
Not provided
Not provided
Not provided
| Male |
|
| Title | Measurements |
|---|---|
|
| Treatment-related TEAEs |
|
| Serious TEAEs |
|
| Serious treatment-related TEAEs |
|
| Withdrawal of study drug due to TEAE |
|
| Dose interruption due to TEAE |
|
| Deaths |
|
| OG001 | Middle 1/3 Avatrombopag Dose Group | Participants in this group took greater than or equal to 8.85 mg avatrombopag to less than 13.5 mg avatrombopag orally once daily under fasting conditions (at least 1 hour before and 2 hours after a meal or snack). Grouping of avatrombopag dose into lower 1/3, middle 1/3, and upper 1/3 was based on the average daily dose received during the combined active treatment periods of studies 501-CL-003 and 501-CL-004. |
| OG002 | Upper 1/3 Avatrombopag Dose Group | Participants in this group took greater than or equal to 13.5 mg avatrombopag orally once daily under fasting conditions (at least 1 hour before and 2 hours after a meal or snack). Grouping of avatrombopag dose into lower 1/3, middle 1/3, and upper 1/3 was based on the average daily dose received during the combined active treatment periods of studies 501-CL-003 and 501-CL-004. |
|
|
| OG001 | Middle 1/3 Avatrombopag Dose Group | Participants in this group took greater than or equal to 8.85 mg avatrombopag to less than 13.5 mg avatrombopag orally once daily under fasting conditions (at least 1 hour before and 2 hours after a meal or snack). Grouping of avatrombopag dose into lower 1/3, middle 1/3, and upper 1/3 was based on the average daily dose received during the combined active treatment periods of studies 501-CL-003 and 501-CL-004. |
| OG002 | Upper 1/3 Avatrombopag Dose Group | Participants in this group took greater than or equal to 13.5 mg avatrombopag orally once daily under fasting conditions (at least 1 hour before and 2 hours after a meal or snack). Grouping of avatrombopag dose into lower 1/3, middle 1/3, and upper 1/3 was based on the average daily dose received during the combined active treatment periods of studies 501-CL-003 and 501-CL-004. |
|
|
| OG001 | Nonresponders | Participants began treatment with open-label 10 mg avatrombopag daily. The maximum possible escalated dose was 40 mg/day open-label. Grouping Method B of dividing participants into Responders and Non-Responders was based on both treatment received and Day 28 platelet response to study drug in study 501-CL-004. |
|
|
| OG001 | Nonresponders | Participants began treatment with open-label 10 mg avatrombopag daily. The maximum possible escalated dose was 40 mg/day open-label. Grouping Method B of dividing participants into Responders and Non-Responders was based on both treatment received and Day 28 platelet response to study drug in study 501-CL-004. |
|
|
| OG001 | Nonresponders | Participants began treatment with open-label 10 mg avatrombopag daily. The maximum possible escalated dose was 40 mg/day open-label. Grouping Method B of dividing participants into Responders and Non-Responders was based on both treatment received and Day 28 platelet response to study drug in study 501-CL-004. |
|
|
| OG001 | Nonresponders | Participants began treatment with open-label 10 mg avatrombopag daily. The maximum possible escalated dose was 40 mg/day open-label. Grouping Method B of dividing participants into Responders and Non-Responders was based on both treatment received and Day 28 platelet response to study drug in study 501-CL-004. |
|
|
| OG001 | Nonresponders | Participants began treatment with open-label 10 mg avatrombopag daily. The maximum possible escalated dose was 40 mg/day open-label. Grouping Method B of dividing participants into Responders and Non-Responders was based on both treatment received and Day 28 platelet response to study drug in study 501-CL-004. |
|
|
| OG001 | Nonresponders | Participants began treatment with open-label 10 mg avatrombopag daily. The maximum possible escalated dose was 40 mg/day open-label. Grouping Method B of dividing participants into Responders and Non-Responders was based on both treatment received and Day 28 platelet response to study drug in study 501-CL-004. |
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