Phase 2, Parallel Group, Rollover Study of AKR-501 in Patients With ChronicITP Who Completed 28 Days of Study Treatment in Protocol 501-CL-003

Phase 2

Completed

Conditions: Idiopathic Thrombocytopenic Purpura

Interventions: Drug: Blinded (Avatrombopoag tablets)
Drug: Blinded (placebo)
Drug: Open Label (Avatrombopag tablets)

Registration Number: NCT00625443

Lead Sponsor: Eisai Inc.

Brief Summary: 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).

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 53

Inclusion Criteria

Patients who completed 28 days of study treatment in Protocol 501-CL-003.
No significant safety or tolerability concerns from the patient's participation of Protocol 501-CL-003 as determined by the Investigator.
Received medical monitor approval for enrollment into this study.
Patients receiving maintenance corticosteroids may be enrolled, as long as the corticosteroids have been administered at a stable dose and the Investigator does not foresee the need to change the steroid dose during study participation. Patients should remain on this stable corticosteroid dose during study participation.
Women of child-bearing potential must have a negative serum pregnancy test at the Day 28 assessment in Protocol 501-CL-003. (Childbearing potential is defined as any woman who has not been surgically sterilized and is pre-menopausal or peri-menopausal i.e., any menstrual flow within 12 months of Screening Visit A for Protocol 501-CL-003).
Women of child-bearing potential must agree to practice a medically approved form of contraception (one of the following must be used: condoms (male or female) with a spermicidal agent, diaphragm or cervical cap with a spermicidal agent, IUD,hormonal contraception, abstinence).
Willing and able to provide written informed consent.

Exclusion Criteria

Women who are pregnant and/or lactating.
Use of the following drugs or treatments:
- Rituximab
- Azathioprine, Cyclosporine A, or other immunosuppressant therapy
- Aspirin, Aspirin-containing compounds, Salicylates,Anticoagulants, Non-steroidal anti-inflammatory drugs(NSAIDs)(including Cyclooxygenase-2 [COX-2] specific NSAIDs), clopidogrel; ticlopidine; and any drugs that affect platelet function.
- Danazol
- Rh0(D) immune globulin (WinRho®) or intravenous immunoglobulin (IVIG).
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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Avatrombopag tablets (double-blind)	Blinded (Avatrombopoag tablets)	-
Placebo (double-blind)	Blinded (placebo)	-
Avatrombopag tablets (open-label)	Open Label (Avatrombopag tablets)	-

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	Day 1 through Month 6 while receiving treatment and at Month 7 after discontinuation of treatment.	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).
Incidence of Severe (Grade 3 or 4) TEAEs	Day 1 through Month 6 while receiving treatment and at Month 7 after discontinuation of treatment.	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).
Incidence of Drug-Related TEAEs	Day 1 through Month 6 while receiving treatment and at Month 7 after discontinuation of treatment.	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).

Secondary Outcome Measures

Name	Time	Method
Median Platelet Counts at Selected Analysis Timepoints	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	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.
Percentage of Participants Who Achieved a Platelet Count of 100,000/mm^3 or Higher by Response Status and Selected Study Visit	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	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.
Percentage of Participants Who Maintained a Platelet Count of 100,000/mm^3 or Higher by Response Status	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	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.
Percentage of Participants Who Achieved Response-Level Platelet Count by Selected Study Visit	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	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.
Percentage of Participants Who Maintained Response-Level Platelet Count	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	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.
Percentage of Participants Who Achieved a Durable, Transient, or Overall Platelet Response	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	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.
Number of Participants With Changes in Concomitant Steroid Use	Day 1 through last 8 weeks of the Treatment Period	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.

Trial Locations

Locations (12): Pacific Cancer Medical Center, Inc
🇺🇸
Anaheim, California, United States
Davis, Posteraro and Wasser, MDs, LLP
🇺🇸
Manchester, Connecticut, United States
Comprehensive Blood and Cancer Center
🇺🇸
Bakersfield, California, United States
John H. Stroger, Jr. Hospital of Cook County, Div. of Hematology and Oncology
🇺🇸
Chicago, Illinois, United States
Florida Cancer Institute
🇺🇸
New Port Richey, Florida, United States
Kansas City Cancer Center, LLC
🇺🇸
Kansas City, Missouri, United States
Cancer Care Center, Inc.
🇺🇸
New Albany, Indiana, United States
Capitol Comprehensive Cancer Care Clinic
🇺🇸
Jefferson 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
Mid Ohio Oncology/Hematology, Inc., dba The Mark H. Zangmeister Center
🇺🇸
Columbus, Ohio, United States
Emerywood Oncology and Hematology
🇺🇸
High Point, North Carolina, United States