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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

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ClinicalTrials.gov Identifier: NCT00625443
Recruitment Status : Completed
First Posted : February 28, 2008
Results First Posted : March 16, 2018
Last Update Posted : March 16, 2018
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.

Tracking Information
First Submitted Date  ICMJE February 19, 2008
First Posted Date  ICMJE February 28, 2008
Results First Submitted Date  ICMJE December 4, 2017
Results First Posted Date  ICMJE March 16, 2018
Last Update Posted Date March 16, 2018
Study Start Date  ICMJE May 2007
Actual Primary Completion Date June 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 9, 2018)
  • Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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).
Original Primary Outcome Measures  ICMJE
 (submitted: February 27, 2008)
To assess the safety and tolerability of AKR-501 administered for an additional 6 months in patients with chronic ITP who completed 28 days of treatment in Protocol 501-CL-003. [ Time Frame: Day 1 thru Month 6 while receiving treatment and at Month 7 after discontinuation of treatment. ]
Change History Complete list of historical versions of study NCT00625443 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 9, 2018)
  • Median Platelet Counts at Selected Analysis Timepoints [ 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 ]
    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 [ 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 ]
    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 [ 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 ]
    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 [ 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 ]
    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 [ 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 ]
    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 [ 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 ]
    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 [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 27, 2008)
To evaluate markers of effectiveness, including changes in and maintenance of the peripheral platelet count. [ Time Frame: Day 1 thru Month 6 while receiving treatment and at Month 7 after discontinuation of treatment. ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE A Phase 2, Parallel Group, Rollover Study of AKR-501 in Patients With Chronic Idiopathic Thrombocytopenic Purpura (ITP) Who Completed 28 Days of Study Treatment in Protocol 501-CL-003
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Idiopathic Thrombocytopenic Purpura
Intervention  ICMJE
  • Drug: Blinded (placebo)

    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

  • Drug: Open Label (Avatrombopag tablets)

    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

    Other Names:
    • AKR-501
    • E5501
    • YM477
  • Drug: Blinded (Avatrombopoag tablets)

    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

    Other Names:
    • AKR-501
    • E5501
    • YM477
Study Arms  ICMJE
  • Experimental: Placebo (double-blind)
    Intervention: Drug: Blinded (placebo)
  • Experimental: Avatrombopag tablets (open-label)
    Intervention: Drug: Open Label (Avatrombopag tablets)
  • Experimental: Avatrombopag tablets (double-blind)
    Intervention: Drug: Blinded (Avatrombopoag tablets)
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 23, 2017)
53
Original Estimated Enrollment  ICMJE
 (submitted: February 27, 2008)
65
Actual Study Completion Date  ICMJE October 2009
Actual Primary Completion Date June 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patients who completed 28 days of study treatment in Protocol 501-CL-003.
  2. No significant safety or tolerability concerns from the patient's participation of Protocol 501-CL-003 as determined by the Investigator.
  3. Received medical monitor approval for enrollment into this study.
  4. 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.
  5. 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).
  6. 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).
  7. Willing and able to provide written informed consent.

Exclusion Criteria:

  1. Women who are pregnant and/or lactating.
  2. 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).
  3. 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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00625443
Other Study ID Numbers  ICMJE AKR-501-CL-004
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Eisai Inc.
Study Sponsor  ICMJE Eisai Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pei-Ran Ho, MD Eisai Inc.
PRS Account Eisai Inc.
Verification Date March 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP