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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.

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Idiopathic Thrombocytopenic Purpura
Interventions Drug: Blinded (placebo)
Drug: Open Label (Avatrombopag tablets)
Drug: Blinded (Avatrombopoag tablets)
Enrollment 53
Recruitment Details  
Pre-assignment Details 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.
Arm/Group Title Lower 1/3 Avatromboopag Dose Group Middle 1/3 Avatrombopag Dose Group Upper 1/3 Avatrombopag Dose Group
Hide Arm/Group Description 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. 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. 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.
Period Title: Overall Study
Started 12 26 15
Completed 10 15 10
Not Completed 2 11 5
Reason Not Completed
Adverse Event             1             4             0
Non-compliance with protocol             0             1             0
Platelet count increase >=500,000/mm3             1             0             0
Withdrawal by Subject             0             1             2
Physician Decision             0             4             2
Not specified             0             1             1
Arm/Group Title Lower 1/3 Avatrombopag Dose Group Middle 1/3 Avatrombopag Dose Group Upper 1/3 Avatrombopag Dose Group Total
Hide Arm/Group Description 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. 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. 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. Total of all reporting groups
Overall Number of Baseline Participants 12 26 15 53
Hide Baseline Analysis Population Description
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.
Age, Continuous  
Geometric Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 12 participants 26 participants 15 participants 53 participants
44.7  (21.09) 52.5  (18.44) 50.4  (15.65) 50.1  (18.25)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 26 participants 15 participants 53 participants
Female
7
  58.3%
20
  76.9%
11
  73.3%
38
  71.7%
Male
5
  41.7%
6
  23.1%
4
  26.7%
15
  28.3%
1.Primary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Lower 1/3 Avatrombopag Dose Group Middle 1/3 Avatrombopag Dose Group Upper 1/3 Avatrombopag Dose Group
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 12 26 15
Measure Type: Count of Participants
Unit of Measure: Participants
TEAEs
12
 100.0%
24
  92.3%
14
  93.3%
Severe (Grade 3-4) TEAEs
4
  33.3%
7
  26.9%
6
  40.0%
Treatment-related TEAEs
5
  41.7%
15
  57.7%
7
  46.7%
Serious TEAEs
2
  16.7%
4
  15.4%
3
  20.0%
Serious treatment-related TEAEs
1
   8.3%
2
   7.7%
0
   0.0%
Withdrawal of study drug due to TEAE
2
  16.7%
4
  15.4%
0
   0.0%
Dose interruption due to TEAE
2
  16.7%
3
  11.5%
2
  13.3%
Deaths
0
   0.0%
0
   0.0%
0
   0.0%
2.Primary Outcome
Title Incidence of Severe (Grade 3 or 4) TEAEs
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Lower 1/3 Avatrombopag Dose Group Middle 1/3 Avatrombopag Dose Group Upper 1/3 Avatrombopag Dose Group
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 12 26 15
Measure Type: Count of Participants
Unit of Measure: Participants
Thrombocytopenia
1
   8.3%
2
   7.7%
4
  26.7%
Splenomegaly
0
   0.0%
0
   0.0%
1
   6.7%
Haemorrhagic diathesis
0
   0.0%
1
   3.8%
0
   0.0%
Idiopathic thrombocytopenic purpura
1
   8.3%
0
   0.0%
0
   0.0%
Leukocytosis
0
   0.0%
1
   3.8%
0
   0.0%
Mitral valve incompetence
0
   0.0%
0
   0.0%
1
   6.7%
Diarrhoea
0
   0.0%
0
   0.0%
1
   6.7%
Vomiting
0
   0.0%
0
   0.0%
1
   6.7%
Fatigue
2
  16.7%
0
   0.0%
0
   0.0%
Oedema peripheral
1
   8.3%
0
   0.0%
0
   0.0%
Asthenia
1
   8.3%
0
   0.0%
0
   0.0%
Chest pain
0
   0.0%
0
   0.0%
1
   6.7%
Pyrexia
0
   0.0%
0
   0.0%
1
   6.7%
Platelet count increased
2
  16.7%
1
   3.8%
0
   0.0%
Platelet count decreased
0
   0.0%
2
   7.7%
0
   0.0%
Alanine aminotransferase increased
0
   0.0%
0
   0.0%
1
   6.7%
Aspartate aminotransferase increased
0
   0.0%
0
   0.0%
1
   6.7%
Hyperuricaemia
1
   8.3%
0
   0.0%
0
   0.0%
Back pain
1
   8.3%
0
   0.0%
0
   0.0%
Dizziness
1
   8.3%
0
   0.0%
0
   0.0%
Hypoaesthesia
0
   0.0%
0
   0.0%
1
   6.7%
Cerebrovascular accident
0
   0.0%
0
   0.0%
1
   6.7%
Haemorrhage intercranial
0
   0.0%
1
   3.8%
0
   0.0%
Epistaxis
1
   8.3%
0
   0.0%
0
   0.0%
Hypotension
1
   8.3%
0
   0.0%
0
   0.0%
Pelvic venous thrombosis
0
   0.0%
1
   3.8%
0
   0.0%
3.Primary Outcome
Title Incidence of Drug-Related TEAEs
Hide Description 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).
Time Frame Day 1 through Month 6 while receiving treatment and at Month 7 after discontinuation of treatment.
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Lower 1/3 Avatrombopag Dose Group Middle 1/3 Avatrombopag Dose Group Upper 1/3 Avatrombopag Dose Group
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 12 26 15
Measure Type: Count of Participants
Unit of Measure: Participants
Thrombocytopenia
1
   8.3%
2
   7.7%
0
   0.0%
Splenomegaly
0
   0.0%
1
   3.8%
1
   6.7%
Anaemia
0
   0.0%
1
   3.8%
0
   0.0%
Leukocytosis
0
   0.0%
1
   3.8%
0
   0.0%
Vision blurred
0
   0.0%
1
   3.8%
0
   0.0%
Visual disturbance
0
   0.0%
1
   3.8%
0
   0.0%
Nausea
0
   0.0%
0
   0.0%
2
  13.3%
Abdominal pain upper
0
   0.0%
0
   0.0%
1
   6.7%
Diarrhoea
0
   0.0%
1
   3.8%
0
   0.0%
Vomiting
0
   0.0%
0
   0.0%
1
   6.7%
Fatigue
2
  16.7%
4
  15.4%
1
   6.7%
Oedema peripheral
0
   0.0%
1
   3.8%
0
   0.0%
Platelet count increased
2
  16.7%
2
   7.7%
0
   0.0%
Platelet count decreased
0
   0.0%
2
   7.7%
0
   0.0%
Alanine aminotransferase increased
0
   0.0%
1
   3.8%
0
   0.0%
Hyperlipidaemia
2
  16.7%
1
   3.8%
0
   0.0%
Decreased appetite
0
   0.0%
0
   0.0%
1
   6.7%
Arthralgia
0
   0.0%
1
   3.8%
1
   6.7%
Back pain
0
   0.0%
0
   0.0%
2
  13.3%
Pain in extremity
0
   0.0%
2
   7.7%
0
   0.0%
Arthropathy
0
   0.0%
1
   3.8%
0
   0.0%
Muscular weakness
0
   0.0%
0
   0.0%
1
   6.7%
Headache
2
  16.7%
1
   3.8%
1
   6.7%
Dizziness
1
   8.3%
1
   3.8%
1
   6.7%
Hypoaesthesia
0
   0.0%
0
   0.0%
1
   6.7%
Mood swings
1
   8.3%
0
   0.0%
0
   0.0%
Haematuria
0
   0.0%
1
   3.8%
0
   0.0%
Menorrhagia
1
   8.3%
0
   0.0%
0
   0.0%
Dyspnoea
1
   8.3%
1
   3.8%
0
   0.0%
Epistaxis
1
   8.3%
0
   0.0%
1
   6.7%
Nasal congestion
0
   0.0%
0
   0.0%
1
   6.7%
Rash
0
   0.0%
1
   3.8%
0
   0.0%
4.Secondary Outcome
Title Median Platelet Counts at Selected Analysis Timepoints
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Responders Nonresponders
Hide Arm/Group Description:
Participants continued on their previous blinded dose in study 501-CL-003 at entry into this study. These blinded doses were: avatrombopag 2.5 mg, 5 mg, 10 mg, and 20 mg. The maximum possible escalated dose was a total dose of assigned double-blind avatrombopag plus an additional 20 mg/day open-label avatrombopag. 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.
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.
Overall Number of Participants Analyzed 25 28
Median (Full Range)
Unit of Measure: Platelets x 1000/mm^3
Day 1 Number Analyzed 25 participants 28 participants
55.0
(7 to 316)
23.5
(8 to 240)
Week 2 Number Analyzed 22 participants 28 participants
126.0
(39 to 855)
54.5
(5 to 1207)
Week 4 Number Analyzed 24 participants 27 participants
113.0
(8 to 489)
38.0
(6 to 383)
Week 6 Number Analyzed 23 participants 26 participants
104.0
(18 to 880)
47.0
(10 to 731)
Week 8 Number Analyzed 21 participants 26 participants
137.0
(13 to 571)
45.5
(3 to 263)
Week 10 Number Analyzed 6 participants 16 participants
85.5
(32 to 179)
72.0
(9 to 702)
Week 12 Number Analyzed 14 participants 20 participants
88.0
(4 to 293)
72.0
(2 to 557)
Week 14 Number Analyzed 10 participants 12 participants
84.0
(29 to 296)
77.5
(9 to 368)
Week 16 Number Analyzed 11 participants 17 participants
143.0
(45 to 395)
46.0
(3 to 273)
Week 18 Number Analyzed 17 participants 19 participants
119.0
(28 to 303)
78.0
(17 to 382)
Week 20 Number Analyzed 10 participants 12 participants
92.0
(39 to 322)
68.0
(18 to 481)
Week 22 Number Analyzed 16 participants 16 participants
109.0
(26 to 354)
78.5
(14 to 502)
Week 24 Number Analyzed 21 participants 17 participants
154.0
(28 to 335)
66.0
(19 to 368)
Follow-up Week 1 Number Analyzed 11 participants 11 participants
59.0
(8 to 495)
40.0
(23 to 365)
Follow-up Week 2 Number Analyzed 10 participants 12 participants
25.0
(6 to 86)
22.0
(8 to 426)
Follow-up Week 3 Number Analyzed 12 participants 9 participants
27.0
(3 to 380)
36.0
(14 to 791)
Follow-up Week 4 Number Analyzed 13 participants 15 participants
35.0
(15 to 331)
28.0
(1 to 881)
5.Secondary Outcome
Title Percentage of Participants Who Achieved a Platelet Count of 100,000/mm^3 or Higher by Response Status and Selected Study Visit
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. Data was summarized using the OC method.
Arm/Group Title Responders Nonresponders
Hide Arm/Group Description:
Participants continued on their previous blinded dose in study 501-CL-003 at entry into this study. These blinded doses were: avatrombopag 2.5 mg, 5 mg, 10 mg, and 20 mg. The maximum possible escalated dose was a total dose of assigned double-blind avatrombopag plus an additional 20 mg/day open-label avatrombopag. 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.
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.
Overall Number of Participants Analyzed 25 28
Measure Type: Number
Unit of Measure: Percentage of participants
Week 2 59.1 25.0
Week 4 58.3 18.5
Week 8 52.4 15.4
Week 12 42.9 35.0
Week 16 63.6 17.6
Week 20 40.0 25.0
Week 24 71.4 35.3
Follow up Week 1 18.2 27.3
Follow up Week 2 0 33.3
Follow up Week 3 25.0 11.1
Follow up Week 4 23.1 13.3
6.Secondary Outcome
Title Percentage of Participants Who Maintained a Platelet Count of 100,000/mm^3 or Higher by Response Status
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. Data was summarized using the OC method.
Arm/Group Title Responders Nonresponders
Hide Arm/Group Description:
Participants continued on their previous blinded dose in study 501-CL-003 at entry into this study. These blinded doses were: avatrombopag 2.5 mg, 5 mg, 10 mg, and 20 mg. The maximum possible escalated dose was a total dose of assigned double-blind avatrombopag plus an additional 20 mg/day open-label avatrombopag. 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.
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.
Overall Number of Participants Analyzed 25 28
Measure Type: Number
Unit of Measure: Percentage of participants
32.0 0
7.Secondary Outcome
Title Percentage of Participants Who Achieved Response-Level Platelet Count by Selected Study Visit
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. Data was summarized using the OC method.
Arm/Group Title Responders Nonresponders
Hide Arm/Group Description:
Participants continued on their previous blinded dose study 501-CL-003 at entry into this study. These blinded doses were: avatrombopag 2.5 mg, 5 mg, 10 mg, and 20 mg. The maximum possible escalated dose was a total dose of assigned double-blind avatrombopag plus an additional 20 mg/day open-label avatrombopag. 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.
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.
Overall Number of Participants Analyzed 25 28
Measure Type: Number
Unit of Measure: Percentage of participants
Week 2 86.4 53.6
Week 4 79.2 44.4
Week 8 90.5 46.2
Week 12 85.7 65.0
Week 16 81.8 47.1
Week 20 90.0 66.7
Week 24 81.0 70.6
Follow up Week 1 54.5 45.5
Follow up Week 2 10.0 33.3
Follow up Week 3 41.7 44.4
Follow up Week 4 38.5 33.3
8.Secondary Outcome
Title Percentage of Participants Who Maintained Response-Level Platelet Count
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. Data was summarized using the OC method.
Arm/Group Title Responders Nonresponders
Hide Arm/Group Description:
Participants continued on their previous blinded dose in study 501-CL-003 at entry into this study. These blinded doses were: avatrombopag 2.5 mg, 5 mg, 10 mg, and 20 mg. The maximum possible escalated dose was a total dose of assigned double-blind avatrombopag plus an additional 20 mg/day open-label avatrombopag. 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.
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.
Overall Number of Participants Analyzed 25 28
Measure Type: Number
Unit of Measure: Percentage of participants
56.0 0
9.Secondary Outcome
Title Percentage of Participants Who Achieved a Durable, Transient, or Overall Platelet Response
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. Data was summarized using the OC method.
Arm/Group Title Responders Nonresponders
Hide Arm/Group Description:
Participants continued on their previous blinded dose in study 501-CL-003 at entry into this study. These blinded doses were: avatrombopag 2.5 mg, 5 mg, 10 mg, and 20 mg. The maximum possible escalated dose was a total dose of assigned double-blind avatrombopag plus an additional 20 mg/day open-label avatrombopag. 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.
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.
Overall Number of Participants Analyzed 25 28
Measure Type: Number
Unit of Measure: Percentage of participants
Durable Platelet Response 72.0 35.7
Transient Platelet Response 16.0 28.6
Overall Response 88.0 64.3
10.Secondary Outcome
Title Number of Participants With Changes in Concomitant Steroid Use
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. Data was summarized using the OC method. Only those participants who had data available at both Baseline and post-Baseline were analyzed.
Arm/Group Title Responders Nonresponders
Hide Arm/Group Description:
Participants continued on their previous blinded dose in study 501-CL-003 at entry into this study. These blinded doses were: avatrombopag 2.5 mg, 5 mg, 10 mg, and 20 mg. The maximum possible escalated dose was a total dose of assigned double-blind avatrombopag plus an additional 20 mg/day open-label avatrombopag. 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.
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.
Overall Number of Participants Analyzed 24 24
Measure Type: Number
Unit of Measure: Number of participants
Permanently Discontinued Number Analyzed 12 participants 12 participants
4 4
Decreased by greater than or equal to 50% Number Analyzed 12 participants 12 participants
7 6
Time Frame Approximately 7 months.
Adverse Event Reporting Description 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.
 
Arm/Group Title Lower 1/3 Avatrombopag Dose Group Middle 1/3 Avatrombopag Dose Group Upper 1/3 Avatrombopag Dose Group
Hide Arm/Group Description 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. 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. 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.
All-Cause Mortality
Lower 1/3 Avatrombopag Dose Group Middle 1/3 Avatrombopag Dose Group Upper 1/3 Avatrombopag Dose Group
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/12 (0.00%)   0/26 (0.00%)   0/15 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Lower 1/3 Avatrombopag Dose Group Middle 1/3 Avatrombopag Dose Group Upper 1/3 Avatrombopag Dose Group
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/12 (16.67%)   4/26 (15.38%)   3/15 (20.00%) 
Blood and lymphatic system disorders       
Thrombocytopenia * 1  1/12 (8.33%)  1/26 (3.85%)  2/15 (13.33%) 
Idiopathic thrombocytopenic purpura  1  1/12 (8.33%)  0/26 (0.00%)  0/15 (0.00%) 
Leukocytosis  1  0/12 (0.00%)  1/26 (3.85%)  0/15 (0.00%) 
Cardiac disorders       
Mitral valve incompetence  1  0/12 (0.00%)  0/26 (0.00%)  1/15 (6.67%) 
Gastrointestinal disorders       
Vomiting  1  0/12 (0.00%)  1/26 (3.85%)  1/15 (6.67%) 
Diarrhoea  1  0/12 (0.00%)  0/26 (0.00%)  1/15 (6.67%) 
Nausea  1  0/12 (0.00%)  1/26 (3.85%)  0/15 (0.00%) 
General disorders       
Chest pain  1  0/12 (0.00%)  0/26 (0.00%)  1/15 (6.67%) 
Pyrexia  1  0/12 (0.00%)  0/26 (0.00%)  1/15 (6.67%) 
Investigations       
Platelet count decreased  1  0/12 (0.00%)  1/26 (3.85%)  0/15 (0.00%) 
Musculoskeletal and connective tissue disorders       
Back pain  1  1/12 (8.33%)  0/26 (0.00%)  0/15 (0.00%) 
Nervous system disorders       
Cerebrovascular accident  1  0/12 (0.00%)  0/26 (0.00%)  1/15 (6.67%) 
Haemorrhage intracranial  1  0/12 (0.00%)  1/26 (3.85%)  0/15 (0.00%) 
Lethargy  1  0/12 (0.00%)  1/26 (3.85%)  0/15 (0.00%) 
Vascular disorders       
Pelvic venous thrombosis  1  0/12 (0.00%)  1/26 (3.85%)  0/15 (0.00%) 
Hypotension  1  1/12 (8.33%)  0/26 (0.00%)  0/15 (0.00%) 
1
Term from vocabulary, MedDRA (10.1)
*
Indicates events were collected by non-systematic assessment
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Lower 1/3 Avatrombopag Dose Group Middle 1/3 Avatrombopag Dose Group Upper 1/3 Avatrombopag Dose Group
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   12/12 (100.00%)   24/26 (92.31%)   14/15 (93.33%) 
Blood and lymphatic system disorders       
Thrombocytopenia * 1  1/12 (8.33%)  3/26 (11.54%)  4/15 (26.67%) 
Gastrointestinal disorders       
Gingival bleeding  2  1/12 (8.33%)  3/26 (11.54%)  3/15 (20.00%) 
Diarrhoea  2  1/12 (8.33%)  1/26 (3.85%)  2/15 (13.33%) 
Nausea  2  0/12 (0.00%)  1/26 (3.85%)  3/15 (20.00%) 
Vomiting  2  0/12 (0.00%)  2/26 (7.69%)  2/15 (13.33%) 
Constipation  2  0/12 (0.00%)  3/26 (11.54%)  0/15 (0.00%) 
General disorders       
Fatigue  2  5/12 (41.67%)  4/26 (15.38%)  4/15 (26.67%) 
Oedema peripheral  2  1/12 (8.33%)  2/26 (7.69%)  3/15 (20.00%) 
Oedema  2  1/12 (8.33%)  2/26 (7.69%)  0/15 (0.00%) 
Infections and infestations       
Upper respiratory tract infection  2  1/12 (8.33%)  2/26 (7.69%)  1/15 (6.67%) 
Nasopharyngitis  2  2/12 (16.67%)  1/26 (3.85%)  0/15 (0.00%) 
Injury, poisoning and procedural complications       
Contusion  2  3/12 (25.00%)  3/26 (11.54%)  3/15 (20.00%) 
Investigations       
Platelet count increased  2  2/12 (16.67%)  2/26 (7.69%)  0/15 (0.00%) 
Platelet count decreased  2  0/12 (0.00%)  3/26 (11.54%)  0/15 (0.00%) 
Metabolism and nutrition disorders       
Hyperlipidaemia  2  2/12 (16.67%)  2/26 (7.69%)  0/15 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  2  2/12 (16.67%)  3/26 (11.54%)  2/15 (13.33%) 
Back pain  2  2/12 (16.67%)  1/26 (3.85%)  2/15 (13.33%) 
Musculoskeletal stiffness  2  1/12 (8.33%)  1/26 (3.85%)  1/15 (6.67%) 
Pain in extremity  2  0/12 (0.00%)  2/26 (7.69%)  1/15 (6.67%) 
Nervous system disorders       
Headache  2  2/12 (16.67%)  7/26 (26.92%)  3/15 (20.00%) 
Dizziness  2  1/12 (8.33%)  1/26 (3.85%)  2/15 (13.33%) 
Psychiatric disorders       
Insomnia  2  1/12 (8.33%)  2/26 (7.69%)  1/15 (6.67%) 
Renal and urinary disorders       
Haematuria  2  0/12 (0.00%)  2/26 (7.69%)  1/15 (6.67%) 
Reproductive system and breast disorders       
Menorrhagia  2  1/12 (8.33%)  2/26 (7.69%)  0/15 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Epistaxis  2  2/12 (16.67%)  4/26 (15.38%)  3/15 (20.00%) 
Cough  2  1/12 (8.33%)  1/26 (3.85%)  3/15 (20.00%) 
Dyspnoea  2  2/12 (16.67%)  3/26 (11.54%)  0/15 (0.00%) 
Pharyngolaryngeal pain  2  1/12 (8.33%)  1/26 (3.85%)  1/15 (6.67%) 
Skin and subcutaneous tissue disorders       
Petechiae  2  3/12 (25.00%)  1/26 (3.85%)  2/15 (13.33%) 
Ecchymosis  2  1/12 (8.33%)  1/26 (3.85%)  1/15 (6.67%) 
1
Term from vocabulary, MedDRA (10.0)
2
Term from vocabulary, MedDRA (10.1)
*
Indicates events were collected by non-systematic assessment
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
 
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Eisai Medical Services
Organization: Eisai Inc.
Phone: 1-888-422-4743
Layout table for additonal information
Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT00625443     History of Changes
Other Study ID Numbers: AKR-501-CL-004
First Submitted: February 19, 2008
First Posted: February 28, 2008
Results First Submitted: December 4, 2017
Results First Posted: March 16, 2018
Last Update Posted: March 16, 2018