Efficacy and Safety of Oral E5501 Plus Standard of Care for the Treatment of Thrombocytopenia in Adults With Chronic Immune Thrombocytopenia (Amendment 02)
Study Details
Study Description
Brief Summary
Core Study:
To demonstrate that the efficacy of avatrombopag (in addition to standard of care) is superior to placebo (in addition to standard of care) for the treatment of adult participants with chronic immune thrombocytopenia (idiopathic thrombocytopenic purpura) (ITP) as measured by cumulative number of weeks of platelet response over 6 months of once daily treatment in adults participants who received at least 1 prior ITP therapy.
Extension Phase:
To evaluate the safety and tolerability of long-term therapy with avatrombopag in participants with chronic ITP (cITP).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
This study consists three phases: Prerandomization, Randomization (Core Study) and Extension study. The overall duration of treatment (Core and Extension) is approximately 104 weeks with the Core study being 26 weeks and the Extension study being 76 weeks. Approximately 45 participants 18 years of age and over who meet all the eligibility requirements will be randomized. No single platelet count should be greater than 35x109/L (liter). Participants will be centrally stratified at randomization by splenectomy status, baseline platelet count, and use of concomitant ITP medication at baseline, and randomized to receive either double-blind avatrombopag or placebo in a 2:1 ratio. Participants will receive blinded therapy at a starting dose of 20 mg avatrombopag or placebo once daily. Participants will be allowed to have their dose titrated up (maximum dose 40 mg avatrombopag or matching placebo) or down (minimum dose 5 mg for avatrombopag or matching placebo) depending on their response to study drug. The goal of dose modification is to maintain the platelet count at levels greater than or equal to 50x109/L and less than or equal to 150x10^9/L, and to decrease the need for ITP-directed concomitant medications.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Avatrombopag (Core Study) Avatrombopag will be administered orally as 5 mg, 10 mg, 20 mg, 30 mg, or 40 mg in a flexible dose design for 26 weeks. Participants will receive blinded therapy at a starting dose of 20 mg avatrombopag, one daily and allowed to have their dose titrated up (maximum dose of 40 mg avatrombopag) or down (minimum dose of 5 mg avatrombopag) depending on their response to study drug. |
Drug: Avatrombopag
Other Names:
Drug: Standard of care
Permitted ITP concomitant background therapies are as follows:
Corticosteroids and/or azathioprine taken at a stable dose for 4 weeks before randomization;
Mycophenolate mofetil (MMF) or danazol taken at a stable dose for at least 12 weeks before randomization;
Cyclosporine A (CsA) (due to the fact that it is a P-glycoprotein-mediated transport [P-gp] inhibitor) is to be avoided unless deemed medically necessary; CsA taken at a stable dose for at least 12 weeks before randomization.
At the discretion of the investigator, participants will be allowed to use aspirin, other salicylates, or approved adenosine diphosphate (ADP) receptor antagonists, (eg, clopidogrel, prasugrel) during the study once their platelet count had risen.
Participants treated with proton pump inhibitors (PPIs) and H2 antagonist therapy will receive a stable dose for at least 6 weeks prior to randomization. Treatment with these therapies must have been completed at least 2 weeks prior to randomization.
|
| Placebo Comparator: Placebo (Core Study) Placebo will be administered as 5 mg, 10 mg, 20 mg, 30 mg or 40 mg in a flexible dose design for 26 weeks. Placebo will be administered orally at a starting dose of 20 mg, once daily. Afterwards the dose can be titrated up (maximum dose of 40 mg avatrombopag) or down (minimum dose of 5 mg avatrombopag) depending on the participant's response to the study drug; placebo titration will be used to maintain the blind. |
Drug: Placebo
Drug: Standard of care
Permitted ITP concomitant background therapies are as follows:
Corticosteroids and/or azathioprine taken at a stable dose for 4 weeks before randomization;
Mycophenolate mofetil (MMF) or danazol taken at a stable dose for at least 12 weeks before randomization;
Cyclosporine A (CsA) (due to the fact that it is a P-glycoprotein-mediated transport [P-gp] inhibitor) is to be avoided unless deemed medically necessary; CsA taken at a stable dose for at least 12 weeks before randomization.
At the discretion of the investigator, participants will be allowed to use aspirin, other salicylates, or approved adenosine diphosphate (ADP) receptor antagonists, (eg, clopidogrel, prasugrel) during the study once their platelet count had risen.
Participants treated with proton pump inhibitors (PPIs) and H2 antagonist therapy will receive a stable dose for at least 6 weeks prior to randomization. Treatment with these therapies must have been completed at least 2 weeks prior to randomization.
|
| Experimental: Avatrombopag (Open-Label Extension) Participants who meet all eligibility criteria requirements of extension phase and who discontinue the core study because of lack of treatment effect will continue into the extension phase. Avatrombopag will be administered to participants who enter extension phase, with a starting dose of 20 mg avatrombopag, once daily for 76 weeks and undergo dose titration. |
Drug: Avatrombopag
Other Names:
Drug: Standard of care
Permitted ITP concomitant background therapies are as follows:
Corticosteroids and/or azathioprine taken at a stable dose for 4 weeks before randomization;
Mycophenolate mofetil (MMF) or danazol taken at a stable dose for at least 12 weeks before randomization;
Cyclosporine A (CsA) (due to the fact that it is a P-glycoprotein-mediated transport [P-gp] inhibitor) is to be avoided unless deemed medically necessary; CsA taken at a stable dose for at least 12 weeks before randomization.
At the discretion of the investigator, participants will be allowed to use aspirin, other salicylates, or approved adenosine diphosphate (ADP) receptor antagonists, (eg, clopidogrel, prasugrel) during the study once their platelet count had risen.
Participants treated with proton pump inhibitors (PPIs) and H2 antagonist therapy will receive a stable dose for at least 6 weeks prior to randomization. Treatment with these therapies must have been completed at least 2 weeks prior to randomization.
|
Outcome Measures
Primary Outcome Measures
- Number of Weeks With Platelet Count Greater Than or Equal to 50 x 10^9/L During 6-Month Treatment Period [Week 1 to Week 26]
The cumulative number of weeks of platelet response is defined as the total numbers of weeks in which the platelet count is greater than or equal to 50 x 10^ 9/L during 6 months of treatment of core study in the absence of rescue therapy.
Secondary Outcome Measures
- Number of Participants With a Reduction in Use of Concomitant Immune/Idiopathic Thrombocytopenic Purpura (ITP) Medication [Week 1 through Week 26]
Only participants on concomitant ITP medications at baseline were included.
- Number of Participants With Platelet Count Greater Than or Equal to 50 x 10^9/L at Day 8 [Week 1 (Day 8)]
Participants with platelet response at Day 8 are defined as those who had a platelet count greater than or equal to 50 x 10^9/L at day 8 in the absence of rescue therapy on or before Day 8.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Men and women greater than or equal to 18 years of age
-
Participants diagnosed with cITP (greater than or equal to 12 months duration) according to the American Society for Hematology/British Committee for Standards in Hematology (ASH/BCSH) guidelines, and an average of 2 platelet counts greater than 30x10^9/L). The physical exam should not suggest any disease which may cause thrombocytopenia other than ITP
-
Participants who previously received one or more ITP therapies (including, but not limited to corticosteroids, immunoglobulins, azathioprine, danazol, cyclophosphamide and/or rituximab).
-
Participants must have had either initially responded (platelet count greater than 50x10^9/L) to a previous ITP therapy or have had a bone marrow examination consistent with ITP within 3 years to rule out myelodysplastic syndrome (MDS) or other causes of thrombocytopenia
-
Prothrombin time/International Normalized Ratio (PT/INR) and activated partial thromboplastin time (aPTT) must have been within 80% to 120% of the normal range with no history of hypercoagulable state
-
A complete blood count within the reference range (including white blood count [WBC] differential not indicative of a disorder other than ITP), with the following exceptions: hemoglobin: participants with hemoglobin levels between 10 g/dL (100 g/L) and the lower limit of normal (LLN) are eligible for inclusion, if anemia was clearly attributable to ITP (excessive blood loss); Absolute neutrophil count (ANC) greater than or equal to 1500/uL (1.5x10^9/L) (elevated WBC/ANC due to corticosteroid treatment is acceptable)
Exclusion Criteria:
-
Participants with known secondary immune thrombocytopenia (e.g., with known Helicobacter pylori-induced ITP participants infected with known human immunodeficiency virus [HIV] or hepatitis C virus [HCV] or participants with known systemic lupus erythematosus). (Revised per Amendment 01)
-
Participants with significant medical conditions that may impact on the safety of the participant or interpretation of the study results (e.g., acute hepatitis, active chronic hepatitis; lymphoproliferative disease; myeloproliferative disorders, leukemia)
-
History of MDS
-
History of gastric atrophy (added per Amendment 01)
-
History of pernicious anemia or participants with vitamin B12 deficiency (defined as less than LLN) who have not had pernicious anemia excluded as a cause (added per Amendment 01)
-
Any prior history of arterial or venous thrombosis (stroke, transient ischemic attack, myocardial infarction, deep vein thrombosis or pulmonary embolism), and more than two of the following risk factors: hormone replacement therapy, estrogen-containing hormone replacement or contraceptive therapies, smoking, diabetes, hypercholesterolemia, medication for hypertension, cancer, hereditary thrombophilic disorders (e.g., Factor V Leiden, antithrombin III deficiency, etc.), or any other family history of arterial or venous thrombosis
-
Participants with a history of significant cardiovascular disease (e.g., congestive heart failure [CHF] New York Heart Association Grade III/IV, arrhythmia known to increase the risk of thromboembolic events [e.g., atrial fibrillation], participants with a QT interval corrected for heart rate of >450 msec, angina, coronary artery stent placement, angioplasty, coronary artery bypass grafting)
-
Participants with a history of cirrhosis, portal hypertension, and chronic active hepatitis
-
Participants with concurrent malignant disease
-
Use of immunoglobulins (IVIg and anti-D) within 1 week of randomization
-
Splenectomy or use of rituximab within 12 weeks of randomization
-
Use of romiplostim or eltrombopag within 4 weeks of randomization
-
Participants who are currently treated with corticosteroids or azathioprine but have not been receiving a stable dose for at least 4 weeks prior to randomization or have not completed these therapies more than 4 weeks prior to randomization
-
Participants who are currently treated with MMF, CsA, or danazol but have not been receiving a stable dose for at least 12 weeks prior to randomization or have not completed these therapies more than 4 weeks prior to randomization
-
Use of cyclophosphamide or vinca alkaloid regimens within 4 weeks of randomization
-
Participants who are currently treated with PPIs or H2 antagonist therapy but have not been receiving a stable dose for at least 6 weeks prior to randomization or have not completed these therapies more than 2 weeks prior to randomization
-
Fasting gastrin-17 blood levels exceeding the ULN at Screening for participants not on PPIs or H2 antagonists (Revised per Amendment 01)
-
Fasting gastrin-17 blood levels exceeding 1.5 times the upper limit of normal (ULN) at Screening for participants on PPIs or H2 antagonists (Added per Amendment 01)
-
Blood creatinine exceeding ULN by more than 20% OR total albumin below the lower limit of normal (LLN) by 10%
-
Alanine aminotransferase (ALT) OR aspartate aminotransferase (AST) levels exceeding 3 times the ULN or total bilirubin exceeding 2 times the ULN
-
Participants with a history of cancer treatment with cytotoxic chemotherapy and/or radiotherapy.
-
Participants with a history of ITP treatment with cytotoxic chemotherapy are still eligible for enrollment.
-
Females who are pregnant (positive beta-human chorionic gonadotropin positive [B-hCG] test) or breastfeeding
-
Participants with a known allergy to avatrombopag (E5501) or its excipients
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Adelaide | Australia | |||
| 2 | Bedford Park | Australia | |||
| 3 | Antwerpen | Belgium | |||
| 4 | Plovdiv | Bulgaria | |||
| 5 | Sofia | Bulgaria | |||
| 6 | Brno | Czechia | |||
| 7 | Hradec Kralove | Czechia | |||
| 8 | Praha | Czechia | |||
| 9 | Rotterdam | Netherlands | |||
| 10 | Christchurch | New Zealand | |||
| 11 | Palmerston North | New Zealand | |||
| 12 | Bialystok | Poland | |||
| 13 | Chorzow | Poland | |||
| 14 | Gdansk | Poland | |||
| 15 | Krakow | Poland | |||
| 16 | Lodz | Poland | |||
| 17 | Wroclaw | Poland | |||
| 18 | Singapore | Singapore | |||
| 19 | Bratislava | Slovakia | |||
| 20 | Johannesburg | South Africa | |||
| 21 | Dnipropetrovsk | Ukraine | |||
| 22 | Donetsk | Ukraine | |||
| 23 | Ivano-Frankivsk | Ukraine | |||
| 24 | Kyiv | Ukraine | |||
| 25 | Lviv | Ukraine |
Sponsors and Collaborators
- Eisai Inc.
Investigators
- Study Director: Joe McIntosh, Eisai Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- E5501-G000-302
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | A total of 100 participants were screened in study. Of these 100 participants, 51 were screen failures and 49 were randomized into the study. |
| Arm/Group Title | Placebo (Core Study) | Avatrombopag (Core Study) | Avatrombopag (Extension Phase) |
|---|---|---|---|
| Arm/Group Description | Placebo was administered as 5 mg, 10 mg, 20 mg, 30 mg or 40 mg in a flexible dose design for 26 weeks. Placebo was administered orally at a starting dose of 20 mg, once daily. Afterwards the dose could be titrated up (maximum dose of 40 mg avatrombopag) or down (minimum dose of 5 mg avatrombopag) depending on the participant's response to the study drug; placebo titration was used to maintain the blind. | Avatrombopag was administered orally as 5 mg, 10 mg, 20 mg, 30 mg, or 40 mg in a flexible dose design for 26 weeks. Participants received blinded therapy at a starting dose of 20 mg avatrombopag, one daily and they were allowed to have their dose titrated up (maximum dose of 40 mg avatrombopag) or down (minimum dose of 5 mg avatrombopag) depending on their response to study drug. | Participants who met all the eligibility criteria requirements of extension phase and who discontinued the core study because of lack of treatment effect continued into the extension phase. Avatrombopag was administered to participants who entered extension phase, with a starting dose of 20 mg avatrombopag, once daily for 76 weeks and underwent dose titration. |
| Period Title: Core Study | |||
| STARTED | 17 | 32 | 0 |
| COMPLETED | 1 | 22 | 0 |
| NOT COMPLETED | 16 | 10 | 0 |
| Period Title: Core Study | |||
| STARTED | 0 | 0 | 39 |
| COMPLETED | 0 | 0 | 29 |
| NOT COMPLETED | 0 | 0 | 10 |
Baseline Characteristics
| Arm/Group Title | Placebo (Core Study) | Avatrombopag (Core Study) | Total |
|---|---|---|---|
| Arm/Group Description | Placebo was administered as 5 mg, 10 mg, 20 mg, 30 mg or 40 mg in a flexible dose design for 26 weeks. Placebo was administered orally at a starting dose of 20 mg, once daily. Afterwards the dose could be titrated up (maximum dose of 40 mg avatrombopag) or down (minimum dose of 5 mg avatrombopag) depending on the participant's response to the study drug; placebo titration was used to maintain the blind. | Avatrombopag was administered orally as 5 mg, 10 mg, 20 mg, 30 mg, or 40 mg in a flexible dose design for 26 weeks. Participants received blinded therapy at a starting dose of 20 mg avatrombopag, one daily and they were allowed to have their dose titrated up (maximum dose of 40 mg avatrombopag) or down (minimum dose of 5 mg avatrombopag) depending on their response to study drug. | Total of all reporting groups |
| Overall Participants | 17 | 32 | 49 |
| Age (Years) [Geometric Mean (Standard Deviation) ] | |||
| Geometric Mean (Standard Deviation) [Years] |
41.2
(14.7)
|
46.4
(14.2)
|
44.6
(14.44)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
8
47.1%
|
23
71.9%
|
31
63.3%
|
| Male |
9
52.9%
|
9
28.1%
|
18
36.7%
|
Outcome Measures
| Title | Number of Weeks With Platelet Count Greater Than or Equal to 50 x 10^9/L During 6-Month Treatment Period |
|---|---|
| Description | The cumulative number of weeks of platelet response is defined as the total numbers of weeks in which the platelet count is greater than or equal to 50 x 10^ 9/L during 6 months of treatment of core study in the absence of rescue therapy. |
| Time Frame | Week 1 to Week 26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (Core Study): All participants who were randomized into the study. |
| Arm/Group Title | Placebo (Core Study) | Avatrombopag (Core Study) |
|---|---|---|
| Arm/Group Description | Placebo was administered as 5 mg, 10 mg, 20 mg, 30 mg or 40 mg in a flexible dose design for 26 weeks. Placebo was administered orally at a starting dose of 20 mg, once daily. Afterwards the dose could be titrated up (maximum dose of 40 mg avatrombopag) or down (minimum dose of 5 mg avatrombopag) depending on the participant's response to the study drug; placebo titration was used to maintain the blind. | Avatrombopag was administered orally as 5 mg, 10 mg, 20 mg, 30 mg, or 40 mg in a flexible dose design for 26 weeks. Participants received blinded therapy at a starting dose of 20 mg avatrombopag, one daily and they were allowed to have their dose titrated up (maximum dose of 40 mg avatrombopag) or down (minimum dose of 5 mg avatrombopag) depending on their response to study drug. |
| Measure Participants | 17 | 32 |
| Median (Full Range) [Weeks] |
0
|
12.4
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo (Core Study), Avatrombopag (Core Study) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Title | Number of Participants With a Reduction in Use of Concomitant Immune/Idiopathic Thrombocytopenic Purpura (ITP) Medication |
|---|---|
| Description | Only participants on concomitant ITP medications at baseline were included. |
| Time Frame | Week 1 through Week 26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (Core Study): All participants who were randomized into the study. |
| Arm/Group Title | Placebo (Core Study) | Avatrombopag (Core Study) |
|---|---|---|
| Arm/Group Description | Placebo was administered as 5 mg, 10 mg, 20 mg, 30 mg or 40 mg in a flexible dose design for 26 weeks. Placebo was administered orally at a starting dose of 20 mg, once daily. Afterwards the dose could be titrated up (maximum dose of 40 mg avatrombopag) or down (minimum dose of 5 mg avatrombopag) depending on the participant's response to the study drug; placebo titration was used to maintain the blind. | Avatrombopag was administered orally as 5 mg, 10 mg, 20 mg, 30 mg, or 40 mg in a flexible dose design for 26 weeks. Participants received blinded therapy at a starting dose of 20 mg avatrombopag, one daily and they were allowed to have their dose titrated up (maximum dose of 40 mg avatrombopag) or down (minimum dose of 5 mg avatrombopag) depending on their response to study drug. |
| Measure Participants | 7 | 15 |
| Yes |
0
0%
|
5
15.6%
|
| No |
7
41.2%
|
10
31.3%
|
| Title | Number of Participants With Platelet Count Greater Than or Equal to 50 x 10^9/L at Day 8 |
|---|---|
| Description | Participants with platelet response at Day 8 are defined as those who had a platelet count greater than or equal to 50 x 10^9/L at day 8 in the absence of rescue therapy on or before Day 8. |
| Time Frame | Week 1 (Day 8) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (Core Study): All participants who were randomized into the study. |
| Arm/Group Title | Placebo (Core Study) | Avatrombopag (Core Study) |
|---|---|---|
| Arm/Group Description | Placebo was administered as 5 mg, 10 mg, 20 mg, 30 mg or 40 mg in a flexible dose design for 26 weeks. Placebo was administered orally at a starting dose of 20 mg, once daily. Afterwards the dose could be titrated up (maximum dose of 40 mg avatrombopag) or down (minimum dose of 5 mg avatrombopag) depending on the participant's response to the study drug; placebo titration was used to maintain the blind. | Avatrombopag was administered orally as 5 mg, 10 mg, 20 mg, 30 mg, or 40 mg in a flexible dose design for 26 weeks. Participants received blinded therapy at a starting dose of 20 mg avatrombopag, one daily and they were allowed to have their dose titrated up (maximum dose of 40 mg avatrombopag) or down (minimum dose of 5 mg avatrombopag) depending on their response to study drug. |
| Measure Participants | 17 | 32 |
| Yes |
0
0%
|
21
65.6%
|
| No |
17
100%
|
11
34.4%
|
Adverse Events
| Time Frame | Core Study: up to 39 Weeks (including Screening, Titration, Treatment, Dose Taper, and Follow-up for those who did not enter the Extension Phase). Extension Phase: up to 104 weeks (including Conversion, Maintenance Period, Dose Taper, and Follow-up). | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Treatment emergent adverse events were collected. Core Study Safety Analysis Set (SAS): All participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment. Extension Phase SAS: All participants who received at least 1 dose of avatrombopag (either Core or Extension Phase) and had a postdose safety assessment. | |||||
| Arm/Group Title | Placebo (Core Study) | Avatrombopag (Core Study) | Avatrombopag (Extension Phase) | |||
| Arm/Group Description | Placebo was administered as 5 mg, 10 mg, 20 mg, 30 mg or 40 mg in a flexible dose design for 26 weeks. Placebo was administered orally at a starting dose of 20 mg, once daily. Afterwards the dose could be titrated up (maximum dose of 40 mg avatrombopag) or down (minimum dose of 5 mg avatrombopag) depending on the participant's response to the study drug; placebo titration was used to maintain the blind. | Avatrombopag was administered orally as 5 mg, 10 mg, 20 mg, 30 mg, or 40 mg in a flexible dose design for 26 weeks. Participants received blinded therapy at a starting dose of 20 mg avatrombopag, one daily and they were allowed to have their dose titrated up (maximum dose of 40 mg avatrombopag) or down (minimum dose of 5 mg avatrombopag) depending on their response to study drug. | Participants who met all eligibility criteria requirements of extension phase and who discontinued the core study because of lack of treatment effect continued into the extension phase. Avatrombopag was administered to participants who entered extension phase, with a starting dose of 20 mg avatrombopag, once daily for 76 weeks and underwent dose titration. | |||
All Cause Mortality |
||||||
| Placebo (Core Study) | Avatrombopag (Core Study) | Avatrombopag (Extension Phase) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Placebo (Core Study) | Avatrombopag (Core Study) | Avatrombopag (Extension Phase) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/17 (5.9%) | 9/32 (28.1%) | 15/47 (31.9%) | |||
| Blood and lymphatic system disorders | ||||||
| Idiopathic thrombocytopenic purpura | 1/17 (5.9%) | 0/32 (0%) | 0/47 (0%) | |||
| Thrombocytopenia | 0/17 (0%) | 1/32 (3.1%) | 3/47 (6.4%) | |||
| Gastrointestinal disorders | ||||||
| Food poisoning | 0/17 (0%) | 1/32 (3.1%) | 1/47 (2.1%) | |||
| Mouth haemorrhage | 0/17 (0%) | 1/32 (3.1%) | 1/47 (2.1%) | |||
| Nausea | 0/17 (0%) | 1/32 (3.1%) | 1/47 (2.1%) | |||
| Vomiting | 0/17 (0%) | 2/32 (6.3%) | 2/47 (4.3%) | |||
| Erosive duodenitis | 0/17 (0%) | 0/32 (0%) | 1/47 (2.1%) | |||
| Gastritis haemorrhagic | 0/17 (0%) | 0/32 (0%) | 1/47 (2.1%) | |||
| Gingival bleeding | 0/17 (0%) | 0/32 (0%) | 1/47 (2.1%) | |||
| General disorders | ||||||
| Polyserositis | 0/17 (0%) | 1/32 (3.1%) | 1/47 (2.1%) | |||
| Infections and infestations | ||||||
| Urinary tract infection | 0/17 (0%) | 1/32 (3.1%) | 1/47 (2.1%) | |||
| Investigations | ||||||
| Platelet count decreased | 0/17 (0%) | 1/32 (3.1%) | 2/47 (4.3%) | |||
| Alanine aminotransferase increased | 0/17 (0%) | 0/32 (0%) | 1/47 (2.1%) | |||
| Aspartate aminotransferase increased | 0/17 (0%) | 0/32 (0%) | 1/47 (2.1%) | |||
| Gamma-glutamyltransferase increased | 0/17 (0%) | 0/32 (0%) | 1/47 (2.1%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Intervertebral disc disorder | 0/17 (0%) | 0/32 (0%) | 1/47 (2.1%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Chronic myelomonocytic leukaemia | 0/17 (0%) | 0/32 (0%) | 1/47 (2.1%) | |||
| Nervous system disorders | ||||||
| Cerebrovascular accident | 0/17 (0%) | 1/32 (3.1%) | 1/47 (2.1%) | |||
| Headache | 0/17 (0%) | 2/32 (6.3%) | 2/47 (4.3%) | |||
| Dizziness | 0/17 (0%) | 0/32 (0%) | 1/47 (2.1%) | |||
| Reproductive system and breast disorders | ||||||
| Uterine haemorrhage | 0/17 (0%) | 1/32 (3.1%) | 1/47 (2.1%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Epistaxis | 0/17 (0%) | 1/32 (3.1%) | 1/47 (2.1%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Petechiae | 0/17 (0%) | 1/32 (3.1%) | 1/47 (2.1%) | |||
| Vascular disorders | ||||||
| Deep vein thrombosis | 0/17 (0%) | 1/32 (3.1%) | 1/47 (2.1%) | |||
| Jugular vein thrombosis | 0/17 (0%) | 0/32 (0%) | 1/47 (2.1%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Placebo (Core Study) | Avatrombopag (Core Study) | Avatrombopag (Extension Phase) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 10/17 (58.8%) | 31/32 (96.9%) | 45/47 (95.7%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 0/17 (0%) | 2/32 (6.3%) | 2/47 (4.3%) | |||
| Idiopathic thrombocytopenic purpura | 1/17 (5.9%) | 0/32 (0%) | 0/47 (0%) | |||
| Iron deficiency anaemia | 1/17 (5.9%) | 0/32 (0%) | 0/47 (0%) | |||
| Thrombocytopenia | 0/17 (0%) | 2/32 (6.3%) | 9/47 (19.1%) | |||
| Gastrointestinal disorders | ||||||
| Dyspepsia | 1/17 (5.9%) | 1/32 (3.1%) | 1/47 (2.1%) | |||
| Gingival bleeding | 0/17 (0%) | 4/32 (12.5%) | 8/47 (17%) | |||
| Mouth Haemorrhage | 0/17 (0%) | 3/32 (9.4%) | 4/47 (8.5%) | |||
| Nausea | 0/17 (0%) | 3/32 (9.4%) | 3/47 (6.4%) | |||
| Vomiting | 0/17 (0%) | 2/32 (6.3%) | 2/47 (4.3%) | |||
| General disorders | ||||||
| Fatigue | 1/17 (5.9%) | 4/32 (12.5%) | 7/47 (14.9%) | |||
| Infections and infestations | ||||||
| Influenza | 0/17 (0%) | 2/32 (6.3%) | 4/47 (8.5%) | |||
| Nasopharyngitis | 0/17 (0%) | 3/32 (9.4%) | 5/47 (10.6%) | |||
| Pharyngitis | 1/17 (5.9%) | 0/32 (0%) | 6/47 (12.8%) | |||
| Upper respiratory tract infection | 1/17 (5.9%) | 6/32 (18.8%) | 11/47 (23.4%) | |||
| Urinary tract infection | 0/17 (0%) | 1/32 (3.1%) | 3/47 (6.4%) | |||
| Injury, poisoning and procedural complications | ||||||
| Contusion | 4/17 (23.5%) | 10/32 (31.3%) | 19/47 (40.4%) | |||
| Joint injury | 1/17 (5.9%) | 0/32 (0%) | 0/47 (0%) | |||
| Investigations | ||||||
| Blood gastrin increased | 0/17 (0%) | 2/32 (6.3%) | 2/47 (4.3%) | |||
| Blood urine present | 1/17 (5.9%) | 0/32 (0%) | 0/47 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 0/17 (0%) | 4/32 (12.5%) | 5/47 (10.6%) | |||
| Back pain | 0/17 (0%) | 3/32 (9.4%) | 4/47 (8.5%) | |||
| Pain in extremity | 1/17 (5.9%) | 1/32 (3.1%) | 3/47 (6.4%) | |||
| Nervous system disorders | ||||||
| Dizziness | 1/17 (5.9%) | 0/32 (0%) | 2/47 (4.3%) | |||
| Headache | 2/17 (11.8%) | 12/32 (37.5%) | 14/47 (29.8%) | |||
| Somnolence | 1/17 (5.9%) | 0/32 (0%) | 0/47 (0%) | |||
| Psychiatric disorders | ||||||
| Insomnia | 1/17 (5.9%) | 3/32 (9.4%) | 3/47 (6.4%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 0/17 (0%) | 2/32 (6.3%) | 3/47 (6.4%) | |||
| Epistaxis | 3/17 (17.6%) | 4/32 (12.5%) | 8/47 (17%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Petechiae | 1/17 (5.9%) | 4/32 (12.5%) | 7/47 (14.9%) | |||
| Vascular disorders | ||||||
| Hypertension | 1/17 (5.9%) | 2/32 (6.3%) | 5/47 (10.6%) | |||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Results Point of Contact
| Name/Title | Eisai Inc. |
|---|---|
| Organization | Eisai Call Center |
| Phone | 888-422-4743 |
- E5501-G000-302