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
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Placebo (double-blind)
|
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
|
| Experimental: Avatrombopag tablets (open-label)
|
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:
|
| Experimental: Avatrombopag tablets (double-blind)
|
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:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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.
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Pacific Cancer Medical Center, Inc | Anaheim | California | United States | 92801 |
| 2 | Comprehensive Blood and Cancer Center | Bakersfield | California | United States | 93309 |
| 3 | Davis, Posteraro and Wasser, MDs, LLP | Manchester | Connecticut | United States | 06105 |
| 4 | Florida Cancer Institute | New Port Richey | Florida | United States | 34655 |
| 5 | John H. Stroger, Jr. Hospital of Cook County, Div. of Hematology and Oncology | Chicago | Illinois | United States | 60612 |
| 6 | Cancer Care Center, Inc. | New Albany | Indiana | United States | 47150 |
| 7 | Capitol Comprehensive Cancer Care Clinic | Jefferson City | Missouri | United States | 65109 |
| 8 | Kansas City Cancer Center, LLC | Kansas City | Missouri | United States | 64131 |
| 9 | Mount Sinai Medical Center | New York | New York | United States | 10029 |
| 10 | New York Presbyterian Hospital, Weill Medical College of Cornell University | New York | New York | United States | 10032 |
| 11 | Emerywood Oncology and Hematology | High Point | North Carolina | United States | 27262 |
| 12 | Mid Ohio Oncology/Hematology, Inc., dba The Mark H. Zangmeister Center | Columbus | Ohio | United States | 43219 |
Sponsors and Collaborators
- Eisai Inc.
Investigators
- Study Director: Pei-Ran Ho, MD, Eisai Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- AKR-501-CL-004
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 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 |
|---|---|---|---|
| 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 |
Baseline Characteristics
| Arm/Group Title | Lower 1/3 Avatrombopag Dose Group | Middle 1/3 Avatrombopag Dose Group | Upper 1/3 Avatrombopag Dose Group | Total |
|---|---|---|---|---|
| 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 Participants | 12 | 26 | 15 | 53 |
| Age (Years) [Geometric Mean (Standard Deviation) ] | ||||
| Geometric Mean (Standard Deviation) [Years] |
44.7
(21.09)
|
52.5
(18.44)
|
50.4
(15.65)
|
50.1
(18.25)
|
| Sex: Female, Male (Count of 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%
|
Outcome Measures
| Title | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) |
|---|---|
| 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. |
Outcome Measure Data
| 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 |
|---|---|---|---|
| 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. |
| Measure Participants | 12 | 26 | 15 |
| TEAEs |
12
100%
|
24
92.3%
|
14
93.3%
|
| Severe (Grade 3-4) TEAEs |
4
33.3%
|
7
26.9%
|
6
40%
|
| Treatment-related TEAEs |
5
41.7%
|
15
57.7%
|
7
46.7%
|
| Serious TEAEs |
2
16.7%
|
4
15.4%
|
3
20%
|
| Serious treatment-related TEAEs |
1
8.3%
|
2
7.7%
|
0
0%
|
| Withdrawal of study drug due to TEAE |
2
16.7%
|
4
15.4%
|
0
0%
|
| Dose interruption due to TEAE |
2
16.7%
|
3
11.5%
|
2
13.3%
|
| Deaths |
0
0%
|
0
0%
|
0
0%
|
| Title | Incidence of Severe (Grade 3 or 4) TEAEs |
|---|---|
| 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. |
Outcome Measure Data
| 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 |
|---|---|---|---|
| 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. |
| Measure Participants | 12 | 26 | 15 |
| Thrombocytopenia |
1
8.3%
|
2
7.7%
|
4
26.7%
|
| Splenomegaly |
0
0%
|
0
0%
|
1
6.7%
|
| Haemorrhagic diathesis |
0
0%
|
1
3.8%
|
0
0%
|
| Idiopathic thrombocytopenic purpura |
1
8.3%
|
0
0%
|
0
0%
|
| Leukocytosis |
0
0%
|
1
3.8%
|
0
0%
|
| Mitral valve incompetence |
0
0%
|
0
0%
|
1
6.7%
|
| Diarrhoea |
0
0%
|
0
0%
|
1
6.7%
|
| Vomiting |
0
0%
|
0
0%
|
1
6.7%
|
| Fatigue |
2
16.7%
|
0
0%
|
0
0%
|
| Oedema peripheral |
1
8.3%
|
0
0%
|
0
0%
|
| Asthenia |
1
8.3%
|
0
0%
|
0
0%
|
| Chest pain |
0
0%
|
0
0%
|
1
6.7%
|
| Pyrexia |
0
0%
|
0
0%
|
1
6.7%
|
| Platelet count increased |
2
16.7%
|
1
3.8%
|
0
0%
|
| Platelet count decreased |
0
0%
|
2
7.7%
|
0
0%
|
| Alanine aminotransferase increased |
0
0%
|
0
0%
|
1
6.7%
|
| Aspartate aminotransferase increased |
0
0%
|
0
0%
|
1
6.7%
|
| Hyperuricaemia |
1
8.3%
|
0
0%
|
0
0%
|
| Back pain |
1
8.3%
|
0
0%
|
0
0%
|
| Dizziness |
1
8.3%
|
0
0%
|
0
0%
|
| Hypoaesthesia |
0
0%
|
0
0%
|
1
6.7%
|
| Cerebrovascular accident |
0
0%
|
0
0%
|
1
6.7%
|
| Haemorrhage intercranial |
0
0%
|
1
3.8%
|
0
0%
|
| Epistaxis |
1
8.3%
|
0
0%
|
0
0%
|
| Hypotension |
1
8.3%
|
0
0%
|
0
0%
|
| Pelvic venous thrombosis |
0
0%
|
1
3.8%
|
0
0%
|
| Title | Incidence of Drug-Related TEAEs |
|---|---|
| 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. |
Outcome Measure Data
| 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 |
|---|---|---|---|
| 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. |
| Measure Participants | 12 | 26 | 15 |
| Thrombocytopenia |
1
8.3%
|
2
7.7%
|
0
0%
|
| Splenomegaly |
0
0%
|
1
3.8%
|
1
6.7%
|
| Anaemia |
0
0%
|
1
3.8%
|
0
0%
|
| Leukocytosis |
0
0%
|
1
3.8%
|
0
0%
|
| Vision blurred |
0
0%
|
1
3.8%
|
0
0%
|
| Visual disturbance |
0
0%
|
1
3.8%
|
0
0%
|
| Nausea |
0
0%
|
0
0%
|
2
13.3%
|
| Abdominal pain upper |
0
0%
|
0
0%
|
1
6.7%
|
| Diarrhoea |
0
0%
|
1
3.8%
|
0
0%
|
| Vomiting |
0
0%
|
0
0%
|
1
6.7%
|
| Fatigue |
2
16.7%
|
4
15.4%
|
1
6.7%
|
| Oedema peripheral |
0
0%
|
1
3.8%
|
0
0%
|
| Platelet count increased |
2
16.7%
|
2
7.7%
|
0
0%
|
| Platelet count decreased |
0
0%
|
2
7.7%
|
0
0%
|
| Alanine aminotransferase increased |
0
0%
|
1
3.8%
|
0
0%
|
| Hyperlipidaemia |
2
16.7%
|
1
3.8%
|
0
0%
|
| Decreased appetite |
0
0%
|
0
0%
|
1
6.7%
|
| Arthralgia |
0
0%
|
1
3.8%
|
1
6.7%
|
| Back pain |
0
0%
|
0
0%
|
2
13.3%
|
| Pain in extremity |
0
0%
|
2
7.7%
|
0
0%
|
| Arthropathy |
0
0%
|
1
3.8%
|
0
0%
|
| Muscular weakness |
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%
|
1
6.7%
|
| Mood swings |
1
8.3%
|
0
0%
|
0
0%
|
| Haematuria |
0
0%
|
1
3.8%
|
0
0%
|
| Menorrhagia |
1
8.3%
|
0
0%
|
0
0%
|
| Dyspnoea |
1
8.3%
|
1
3.8%
|
0
0%
|
| Epistaxis |
1
8.3%
|
0
0%
|
1
6.7%
|
| Nasal congestion |
0
0%
|
0
0%
|
1
6.7%
|
| Rash |
0
0%
|
1
3.8%
|
0
0%
|
| Title | Median Platelet Counts at Selected Analysis Timepoints |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 25 | 28 |
| Day 1 |
55.0
|
23.5
|
| Week 2 |
126.0
|
54.5
|
| Week 4 |
113.0
|
38.0
|
| Week 6 |
104.0
|
47.0
|
| Week 8 |
137.0
|
45.5
|
| Week 10 |
85.5
|
72.0
|
| Week 12 |
88.0
|
72.0
|
| Week 14 |
84.0
|
77.5
|
| Week 16 |
143.0
|
46.0
|
| Week 18 |
119.0
|
78.0
|
| Week 20 |
92.0
|
68.0
|
| Week 22 |
109.0
|
78.5
|
| Week 24 |
154.0
|
66.0
|
| Follow-up Week 1 |
59.0
|
40.0
|
| Follow-up Week 2 |
25.0
|
22.0
|
| Follow-up Week 3 |
27.0
|
36.0
|
| Follow-up Week 4 |
35.0
|
28.0
|
| Title | Percentage of Participants Who Achieved a Platelet Count of 100,000/mm^3 or Higher by Response Status and Selected Study Visit |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS. Data was summarized using the OC method. |
| Arm/Group Title | Responders | Nonresponders |
|---|---|---|
| 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. |
| Measure Participants | 25 | 28 |
| Week 2 |
59.1
492.5%
|
25.0
96.2%
|
| Week 4 |
58.3
485.8%
|
18.5
71.2%
|
| Week 8 |
52.4
436.7%
|
15.4
59.2%
|
| Week 12 |
42.9
357.5%
|
35.0
134.6%
|
| Week 16 |
63.6
530%
|
17.6
67.7%
|
| Week 20 |
40.0
333.3%
|
25.0
96.2%
|
| Week 24 |
71.4
595%
|
35.3
135.8%
|
| Follow up Week 1 |
18.2
151.7%
|
27.3
105%
|
| Follow up Week 2 |
0
0%
|
33.3
128.1%
|
| Follow up Week 3 |
25.0
208.3%
|
11.1
42.7%
|
| Follow up Week 4 |
23.1
192.5%
|
13.3
51.2%
|
| Title | Percentage of Participants Who Maintained a Platelet Count of 100,000/mm^3 or Higher by Response Status |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS. Data was summarized using the OC method. |
| Arm/Group Title | Responders | Nonresponders |
|---|---|---|
| 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. |
| Measure Participants | 25 | 28 |
| Number [Percentage of participants] |
32.0
266.7%
|
0
0%
|
| Title | Percentage of Participants Who Achieved Response-Level Platelet Count by Selected Study Visit |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS. Data was summarized using the OC method. |
| Arm/Group Title | Responders | Nonresponders |
|---|---|---|
| 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. |
| Measure Participants | 25 | 28 |
| Week 2 |
86.4
720%
|
53.6
206.2%
|
| Week 4 |
79.2
660%
|
44.4
170.8%
|
| Week 8 |
90.5
754.2%
|
46.2
177.7%
|
| Week 12 |
85.7
714.2%
|
65.0
250%
|
| Week 16 |
81.8
681.7%
|
47.1
181.2%
|
| Week 20 |
90.0
750%
|
66.7
256.5%
|
| Week 24 |
81.0
675%
|
70.6
271.5%
|
| Follow up Week 1 |
54.5
454.2%
|
45.5
175%
|
| Follow up Week 2 |
10.0
83.3%
|
33.3
128.1%
|
| Follow up Week 3 |
41.7
347.5%
|
44.4
170.8%
|
| Follow up Week 4 |
38.5
320.8%
|
33.3
128.1%
|
| Title | Percentage of Participants Who Maintained Response-Level Platelet Count |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS. Data was summarized using the OC method. |
| Arm/Group Title | Responders | Nonresponders |
|---|---|---|
| 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. |
| Measure Participants | 25 | 28 |
| Number [Percentage of participants] |
56.0
466.7%
|
0
0%
|
| Title | Percentage of Participants Who Achieved a Durable, Transient, or Overall Platelet Response |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS. Data was summarized using the OC method. |
| Arm/Group Title | Responders | Nonresponders |
|---|---|---|
| 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. |
| Measure Participants | 25 | 28 |
| Durable Platelet Response |
72.0
600%
|
35.7
137.3%
|
| Transient Platelet Response |
16.0
133.3%
|
28.6
110%
|
| Overall Response |
88.0
733.3%
|
64.3
247.3%
|
| Title | Number of Participants With Changes in Concomitant Steroid Use |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 24 | 24 |
| Permanently Discontinued |
4
33.3%
|
4
15.4%
|
| Decreased by greater than or equal to 50% |
7
58.3%
|
6
23.1%
|
Adverse Events
| 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 | |||
| 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 (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/12 (0%) | 0/26 (0%) | 0/15 (0%) | |||
Serious Adverse Events |
||||||
| Lower 1/3 Avatrombopag Dose Group | Middle 1/3 Avatrombopag Dose Group | Upper 1/3 Avatrombopag Dose Group | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/12 (16.7%) | 4/26 (15.4%) | 3/15 (20%) | |||
| Blood and lymphatic system disorders | ||||||
| Thrombocytopenia | 1/12 (8.3%) | 1/26 (3.8%) | 2/15 (13.3%) | |||
| Idiopathic thrombocytopenic purpura | 1/12 (8.3%) | 0/26 (0%) | 0/15 (0%) | |||
| Leukocytosis | 0/12 (0%) | 1/26 (3.8%) | 0/15 (0%) | |||
| Cardiac disorders | ||||||
| Mitral valve incompetence | 0/12 (0%) | 0/26 (0%) | 1/15 (6.7%) | |||
| Gastrointestinal disorders | ||||||
| Vomiting | 0/12 (0%) | 1/26 (3.8%) | 1/15 (6.7%) | |||
| Diarrhoea | 0/12 (0%) | 0/26 (0%) | 1/15 (6.7%) | |||
| Nausea | 0/12 (0%) | 1/26 (3.8%) | 0/15 (0%) | |||
| General disorders | ||||||
| Chest pain | 0/12 (0%) | 0/26 (0%) | 1/15 (6.7%) | |||
| Pyrexia | 0/12 (0%) | 0/26 (0%) | 1/15 (6.7%) | |||
| Investigations | ||||||
| Platelet count decreased | 0/12 (0%) | 1/26 (3.8%) | 0/15 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Back pain | 1/12 (8.3%) | 0/26 (0%) | 0/15 (0%) | |||
| Nervous system disorders | ||||||
| Cerebrovascular accident | 0/12 (0%) | 0/26 (0%) | 1/15 (6.7%) | |||
| Haemorrhage intracranial | 0/12 (0%) | 1/26 (3.8%) | 0/15 (0%) | |||
| Lethargy | 0/12 (0%) | 1/26 (3.8%) | 0/15 (0%) | |||
| Vascular disorders | ||||||
| Pelvic venous thrombosis | 0/12 (0%) | 1/26 (3.8%) | 0/15 (0%) | |||
| Hypotension | 1/12 (8.3%) | 0/26 (0%) | 0/15 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Lower 1/3 Avatrombopag Dose Group | Middle 1/3 Avatrombopag Dose Group | Upper 1/3 Avatrombopag Dose Group | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 12/12 (100%) | 24/26 (92.3%) | 14/15 (93.3%) | |||
| Blood and lymphatic system disorders | ||||||
| Thrombocytopenia | 1/12 (8.3%) | 3/26 (11.5%) | 4/15 (26.7%) | |||
| Gastrointestinal disorders | ||||||
| Gingival bleeding | 1/12 (8.3%) | 3/26 (11.5%) | 3/15 (20%) | |||
| Diarrhoea | 1/12 (8.3%) | 1/26 (3.8%) | 2/15 (13.3%) | |||
| Nausea | 0/12 (0%) | 1/26 (3.8%) | 3/15 (20%) | |||
| Vomiting | 0/12 (0%) | 2/26 (7.7%) | 2/15 (13.3%) | |||
| Constipation | 0/12 (0%) | 3/26 (11.5%) | 0/15 (0%) | |||
| General disorders | ||||||
| Fatigue | 5/12 (41.7%) | 4/26 (15.4%) | 4/15 (26.7%) | |||
| Oedema peripheral | 1/12 (8.3%) | 2/26 (7.7%) | 3/15 (20%) | |||
| Oedema | 1/12 (8.3%) | 2/26 (7.7%) | 0/15 (0%) | |||
| Infections and infestations | ||||||
| Upper respiratory tract infection | 1/12 (8.3%) | 2/26 (7.7%) | 1/15 (6.7%) | |||
| Nasopharyngitis | 2/12 (16.7%) | 1/26 (3.8%) | 0/15 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Contusion | 3/12 (25%) | 3/26 (11.5%) | 3/15 (20%) | |||
| Investigations | ||||||
| Platelet count increased | 2/12 (16.7%) | 2/26 (7.7%) | 0/15 (0%) | |||
| Platelet count decreased | 0/12 (0%) | 3/26 (11.5%) | 0/15 (0%) | |||
| Metabolism and nutrition disorders | ||||||
| Hyperlipidaemia | 2/12 (16.7%) | 2/26 (7.7%) | 0/15 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 2/12 (16.7%) | 3/26 (11.5%) | 2/15 (13.3%) | |||
| Back pain | 2/12 (16.7%) | 1/26 (3.8%) | 2/15 (13.3%) | |||
| Musculoskeletal stiffness | 1/12 (8.3%) | 1/26 (3.8%) | 1/15 (6.7%) | |||
| Pain in extremity | 0/12 (0%) | 2/26 (7.7%) | 1/15 (6.7%) | |||
| Nervous system disorders | ||||||
| Headache | 2/12 (16.7%) | 7/26 (26.9%) | 3/15 (20%) | |||
| Dizziness | 1/12 (8.3%) | 1/26 (3.8%) | 2/15 (13.3%) | |||
| Psychiatric disorders | ||||||
| Insomnia | 1/12 (8.3%) | 2/26 (7.7%) | 1/15 (6.7%) | |||
| Renal and urinary disorders | ||||||
| Haematuria | 0/12 (0%) | 2/26 (7.7%) | 1/15 (6.7%) | |||
| Reproductive system and breast disorders | ||||||
| Menorrhagia | 1/12 (8.3%) | 2/26 (7.7%) | 0/15 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Epistaxis | 2/12 (16.7%) | 4/26 (15.4%) | 3/15 (20%) | |||
| Cough | 1/12 (8.3%) | 1/26 (3.8%) | 3/15 (20%) | |||
| Dyspnoea | 2/12 (16.7%) | 3/26 (11.5%) | 0/15 (0%) | |||
| Pharyngolaryngeal pain | 1/12 (8.3%) | 1/26 (3.8%) | 1/15 (6.7%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Petechiae | 3/12 (25%) | 1/26 (3.8%) | 2/15 (13.3%) | |||
| Ecchymosis | 1/12 (8.3%) | 1/26 (3.8%) | 1/15 (6.7%) | |||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Results Point of Contact
| Name/Title | Eisai Medical Services |
|---|---|
| Organization | Eisai Inc. |
| Phone | 1-888-422-4743 |
- AKR-501-CL-004