A Phase 3 interventional study of Eltrombopag and Avatrombopag in Idiopathic Thrombocytopenic Purpura, sponsored by Eisai Inc.. Terminated at 1 site in United States. Open to participants aged 18 Years to 99 Years. Per ClinicalTrials.gov, last updated 2018-02-06.
Sponsored by Eisai Inc. · Phase 3, Interventional, and Treatment
Core study:
To compare the efficacy of avatrombopag (in addition to standard) of care to eltrombopag (in addition to standard of care) for the treatment of adult participants with chronic immune thrombocytopenia (idiopathic thrombocytopenic purpura [ITP]) as measured by durable platelet response.
Open-label Extension Phase:
To evaluate the safety and tolerability of long-term therapy with avatrombopag in participants with chronic ITP (cITP).
The study consists of three phases: Prerandomization, Randomization (Core Study) and Extension Phase. Participants 18 years of age and over, who meet all the eligibility requirements will be randomized into the study. It will require that splenectomized participants make up at least 35% of the study population and no single platelet count is greater than 35x10\^9/L. 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 eltrombopag in a 1:1 ratio. Participants will receive blinded therapy at a starting dose of 20 mg avatrombopag once daily or 50 mg eltrombopag once daily. Participants will be allowed to have their dose titrated up (maximum dose 40 mg avatrombopag and 75 mg for eltrombopag) or down (minimum dose 5 mg for avatrombopag and 25 mg for eltrombopag) 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 50x10\^9/L and less than or equal to 150x10\^9/L, and to decrease the need for ITP-directed concomitant medications. The duration of treatment in the Core study and the Extension Phase is approximately 26 and 104 weeks, respectively.
263 studies on the registry are indexed under Purpura; 27 are open to participants now.
This study's enrollment of 24 is below the median of 50 across 171 interventional studies indexed under Purpura.
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Exclusion Criteria:
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, once daily and allow 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 · Drug: Standard of care
Eltrombopag will be administered orally as 25 mg, 50 mg, or 75 mg in a flexible dose design for 26 weeks. Participants will receive blinded therapy at a starting dose of 50 mg eltrombopag once daily and allow to have their dose titrated up (maximum dose of 75 mg eltrombopag) or down (minimum dose of 25 mg eltrombopag) depending on their response to study drug.
Drug: Eltrombopag · Drug: Standard of care
Participants who meet the eligibility requirements for the Open-label Extension (OLE) Phase or who discontinue the Core Study early because of lack of treatment effect will be eligible to continue into the OLE Phase for up to 104 weeks of open-label avatrombopag therapy. Participants who enter the OLE from the Core Study will receive a starting dose of open-label avatrombopag which will be determined by the last dose of study drug at the End of Treatment (EOT) Visit (Visit 22) of the Core Study. Participants who discontinue the Core Study early because of lack of treatment effect and enter the OLE will receive open-label avatrombopag at a starting dose of 20 mg once daily of open-label avatrombopag.
Drug: Avatrombopag · Drug: Standard of care
Also known as: Promacta, Revolade
Also known as: E5501, Avatrombopag maleate
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.
Change From Baseline in Local Platelet Count for the 6 Month Treatment Period
Platelet responses to avatrombopag was evaluated using the platelet counts determined at local clinical laboratories. Only participants with non-missing data at both baseline and the relevant post-baseline visit are included in the change from baseline summary statistics. Standard deviation is not applicable for some of the categories, from Visit 14 to Visit 22, as the number of participants analyzed for that visit was 1 individual.
Time frame: Day 5, Day 8, Week 2, Week 3, Week 4, Week 6, Week 8, Week 10, Week 12, Week 14, Week 16, Week 18, Week 19, Week 20, Week 22, Week 23, Week 24, Week 25, Week 26
| Milestone | Eltrombopag (Core Study) | Avatrombopag (Core Study) | Avatrombopag (Open-label Extension Phase) |
|---|---|---|---|
| Started | 11 | 12 | 0 |
| Completed | 0 | 1 | 0 |
| Not completed | 11 | 11 | 0 |
| Withdrew: Adverse event, non-fatal | 0 | 1 | 0 |
| Withdrew: Lack of efficacy | 5 | 1 | 0 |
| Withdrew: Study terminated by sponsor | 6 | 9 | 0 |
| Milestone | Eltrombopag (Core Study) | Avatrombopag (Core Study) | Avatrombopag (Open-label Extension Phase) |
|---|---|---|---|
| Started | 0 | 0 | 6 |
| Completed | 0 | 0 | 0 |
| Not completed | 0 | 0 | 6 |
| Withdrew: Adverse event, non-fatal | 0 | 0 | 1 |
| Withdrew: Lack of efficacy | 0 | 0 | 1 |
| Withdrew: Study terminated by sponsor | 0 | 0 | 4 |
Platelet responses to avatrombopag was evaluated using the platelet counts determined at local clinical laboratories. Only participants with non-missing data at both baseline and the relevant post-baseline visit are included in the change from baseline summary statistics. Standard deviation is not applicable for some of the categories, from Visit 14 to Visit 22, as the number of participants analyzed for that visit was 1 individual.
| cells x 10^9/L | Eltrombopag (Core Study) | Avatrombopag (Core Study) |
|---|---|---|
| Visit 3 (Day 5) | 8.60 ± 17.312 | 12.85 ± 16.054 |
| Visit 4 (Day 8) | 32.50 ± 44.519 | 47.00 ± 59.690 |
| Visit 5 (Week 2) | 73.41 ± 79.885 | 171.71 ± 201.736 |
| Visit 6 (Week 3) | 67.20 ± 95.536 | 114.21 ± 117.172 |
| Visit 7 (Week 4) | 28.72 ± 38.437 | 108.79 ± 217.036 |
| Visit 8 (Week 6) | 57.21 ± 57.718 | 150.68 ± 134.902 |
| Visit 9 (Week 8) | 67.25 ± 46.055 | 121.31 ± 149.040 |
| Visit 10 (Week 10) | 92.67 ± 34.649 | 126.25 ± 90.602 |
| Visit 11 (Week 12) | 87.33 ± 72.616 | 185.10 ± 115.841 |
| Visit 12 (Week 14 ) | 104.33 ± 77.114 | 159.38 ± 116.746 |
| Visit 13 (Week 16) | 47.75 ± 2.475 | 123.88 ± 124.474 |
| Visit 14 (Week 18) | 107.50 ± NA | 46.50 ± 53.740 |
| Visit 15 (Week 19) | 13.50 ± NA | 29.50 ± 22.627 |
| Visit 16 (Week 20) | — | 50.50 ± NA |
| Visit 18 (Week 22) | — | 75.50 ± NA |
| Visit 19 (Week 23) | — | 104.50 ± NA |
| Visit 20 (Week 24) | — | 106.50 ± NA |
| Visit 21 (Week 25) | — | 120.50 ± NA |
| Visit 22 (Week 26) | — | 58.50 ± NA |
Collected over Up to 34 Weeks in the Core Study (including Titration, Treatment, Dose Taper, and Follow-up for those that did not enter the Extension Phase) and up to 112 weeks in the Extension Phase (including Conversion, Maintenance, Dose Taper, and Follow-up).. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Eltrombopag (Core Study) | — | 0/11 (0%) | 11/11 (100%) |
| Avatrombopag (Core Study) | — | 2/12 (16.7%) | 11/12 (91.7%) |
| Avatrombopag (Extension Phase) | — | 4/17 (23.5%) | 16/17 (94.1%) |
| Event | Eltrombopag (Core Study) | Avatrombopag (Core Study) | Avatrombopag (Extension Phase) |
|---|---|---|---|
| Idiopathic thrombocytopenic purpuraBlood and lymphatic system disorders | 0/11 | 1/12 | 1/17 |
| Portal vein thrombosisHepatobiliary disorders | 0/11 | 1/12 | 1/17 |
| Bronchitis MoraxellaInfections and infestations | 0/11 | 1/12 | 1/17 |
| Thrombophlebitis SepticInfections and infestations | 0/11 | 1/12 | 1/17 |
| Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders | 0/11 | 1/12 | 1/17 |
| PneumothoraxRespiratory, thoracic and mediastinal disorders | 0/11 | 1/12 | 1/17 |
| InfluenzaInfections and infestations | 0/11 | 0/12 | 1/17 |
| Chronic lymphotic leukaemiaNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/11 | 0/12 | 1/17 |
| Event | Eltrombopag (Core Study) | Avatrombopag (Core Study) | Avatrombopag (Extension Phase) |
|---|---|---|---|
| FatigueGeneral disorders | 5/11 | 1/12 | 5/17 |
| HeadacheNervous system disorders | 3/11 | 3/12 | 5/17 |
| DiarrhoeaGastrointestinal disorders | 3/11 | 2/12 | 2/17 |
| NasopharyngitisInfections and infestations | 3/11 | 2/12 | 4/17 |
| NauseaGastrointestinal disorders | 2/11 | 3/12 | 3/17 |
| Musculoskeletal painMusculoskeletal and connective tissue disorders | 0/11 | 3/12 | 3/17 |
| DizzinessNervous system disorders | 2/11 | 3/12 | 4/17 |
| InsomniaPsychiatric disorders | 1/11 | 3/12 | 4/17 |
| ContusionInjury, poisoning and procedural complications | 2/11 | 0/12 | 1/17 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 2/11 | 1/12 | 2/17 |
Safety analysis set included all participants who received at least one dose of study treatment and at least one postbaseline safety assessment.
| Age, Continuous(Years) | Eltrombopag (Core Study) | Avatrombopag (Core Study) | Total |
|---|---|---|---|
| Geometric mean | 45.4 ± 20.09 | 50.8 ± 23.04 | 48.2 ± 21.36 |
| Sex: Female, Male(Participants) | Eltrombopag (Core Study) | Avatrombopag (Core Study) | Total |
|---|---|---|---|
| Female | 7 | 7 | 14 |
| Male | 4 | 5 | 9 |
This study is terminated, as verified in Jan 2018. You cannot join it, but the record below documents what was studied.
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Eisai Inc.