This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Phase 3, Multicenter, Randomized, Double-blind,Active-controlled, Parallel-group Trial With an Open-labelExtension Phase to Evaluate the Efficacy and Safety of OralE5501 Versus Eltrombopag, in Adults With Chronic ImmuneThrombocytopenia (Idiopathic Thrombocytopenic Purpura) (NCT01433978), a randomized phase 3 study. The primary outcome is Change From Baseline in Local Platelet Count for the 6 Month Treatment Period.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01433978 |
| Phase | Phase 3 |
| Condition | Idiopathic Thrombocytopenic Purpura |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 24 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Eisai Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Adults with chronic immune thrombocytopenia, also called idiopathic thrombocytopenic purpura. The registry record states that the Full Analysis Set included all randomized participants, while the primary outcome summaries used only participants with non-missing measurements at baseline and the relevant follow-up visit.
Intervention
Avatrombopag, given with standard of care in the core study. The arm description specifies a flexible oral dosing design for 26 weeks, beginning at 20 mg once daily, with dose adjustment permitted. Eligible participants could enter an open-label extension with avatrombopag therapy for up to 104 weeks.
Comparator
Eltrombopag, also given with standard of care in the core study. The description specifies a flexible oral dosing design for 26 weeks, beginning at 50 mg once daily, with dose adjustment permitted. The registry record does not report a numerical treatment comparison for the primary outcome.
Primary question
The registry’s core-study summary frames the question as a comparison of durable platelet response between avatrombopag plus standard of care and eltrombopag plus standard of care. The listed primary outcome is instead titled as change from baseline in local platelet count during the 6 month treatment period. The registry record does not provide numerical results for that outcome, so the size or precision of a treatment difference cannot be assessed.
3. Trial Design
This was a phase 3, multicenter, randomized, parallel-group trial with an open-label extension. The registry record reports enrollment of 24 participants and lists the study status as terminated. It does not report why the trial was terminated. The study began on 2012-03-26, and the primary completion date is recorded as 2013-09.
The core study compared avatrombopag with eltrombopag, with both treatments described as being given in addition to standard of care. The core treatment period was 26 weeks. Both arm descriptions specify flexible oral dosing and dose adjustment. Avatrombopag was described as starting at 20 mg once daily, with a maximum dose of 40 mg. Eltrombopag was described as starting at 50 mg once daily, with a maximum dose of 75 mg. The registry record does not give the actual dose histories of participants.
The title describes the study as double-blind, while the registry’s masking field records triple masking. The record does not explain which roles were masked or reconcile these descriptions. The extension phase was open-label and offered avatrombopag for up to 104 weeks to participants meeting its eligibility requirements, as well as to participants who discontinued the core study early because of lack of treatment effect. The record does not provide a complete account of extension entry or follow-up.
The core-study groups listed for adverse-event reporting included 11 participants in the eltrombopag group and 12 in the avatrombopag group. The extension adverse-event group included 17 participants. These are the denominators reported for those safety summaries; the record does not explain how they relate to the enrollment total or give a participant flow accounting. Randomization procedures, allocation concealment, and the detailed protocol are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: One screen-failed participant was randomized into the study in error, but not dosed.
Core Study
| Stage | Eltrombopag (Core Study) | Avatrombopag (Core Study) | Avatrombopag (Open-label Extension Phase) |
|---|---|---|---|
| STARTED | 11 | 12 | 0 |
| COMPLETED | 0 | 1 | 0 |
| NOT COMPLETED | 11 | 11 | 0 |
Reasons for not completing this period:
| Reason | Eltrombopag (Core Study) | Avatrombopag (Core Study) | Avatrombopag (Open-label Extension Phase) |
|---|---|---|---|
| Adverse Event, Non-Fatal | 0 | 1 | 0 |
| Lack of Efficacy | 5 | 1 | 0 |
| Study Terminated by Sponsor | 6 | 9 | 0 |
Extension Phase
| Stage | Eltrombopag (Core Study) | Avatrombopag (Core Study) | Avatrombopag (Open-label Extension Phase) |
|---|---|---|---|
| STARTED | 0 | 0 | 6 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 6 |
Reasons for not completing this period:
| Reason | Eltrombopag (Core Study) | Avatrombopag (Core Study) | Avatrombopag (Open-label Extension Phase) |
|---|---|---|---|
| Adverse Event, Non-Fatal | 0 | 0 | 1 |
| Lack of Efficacy | 0 | 0 | 1 |
| Study Terminated by Sponsor | 0 | 0 | 4 |
Analysis population for the primary outcome, as defined in the registry: The Full Analysis Set (FAS) included all participants who were randomized into the study. Only participants with non-missing data at both baseline and the relevant post-baseline visit are included in the change from baseline summary statistics.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
Population: Safety analysis set included all participants who received at least one dose of study treatment and at least one postbaseline safety assessment.
| Characteristic | Unit | Eltrombopag (Core Study) | Avatrombopag (Core Study) | Total |
|---|---|---|---|---|
| Participants analysed | 11 | 12 | 23 | |
| Age, Continuous | Years | 45.4 (SD 20.09) | 50.8 (SD 23.04) | 48.2 (SD 21.36) |
| Sex: Female, Male: Female | Participants | 7 | 7 | 14 |
| Sex: Female, Male: Male | Participants | 4 | 5 | 9 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in Local Platelet Count for the 6 Month Treatment Period, measured over 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.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Standard Deviation |
| Unit | cells x 10^9/L |
| Endpoint classification | not reduced to a single comparison |
The listed primary outcome is change from baseline in local platelet count during the 6 month treatment period. Counts were determined at local clinical laboratories. The registry lists measurement times from Day 5 and Day 8 through Week 26, with several visits in between. It states that each change-from-baseline summary includes only participants with non-missing data at both baseline and the relevant follow-up visit.
Platelet count is a laboratory measure of the quantity of platelets in blood. In general, repeated measurements can describe how that quantity changes during treatment and whether changes are sustained across follow-up visits. The registry’s core-study summary also identifies durable platelet response as the intended efficacy comparison, but the listed outcome title and description focus on visit-specific changes in platelet count. The record does not define durable response within the outcome description or explain how that concept maps to the listed summaries.
The outcome identifies the geometric mean as its summary measure and standard deviation as its dispersion measure. The registry notes that a standard deviation was not applicable for some categories from Visit 14 to Visit 22 because only one participant was analyzed at those visits. No numerical endpoint estimates, uncertainty intervals, or treatment comparisons are reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the intended comparison and identifies the primary outcome, but it does not report numerical results for that outcome. It therefore does not allow readers to determine the direction or magnitude of change in local platelet count, compare the treatment groups, or judge the precision of any difference. The primary outcome is listed across many visits, but no visit-level estimates are included in the record.
This absence is especially important because the core-study summary refers to durable platelet response, whereas the primary outcome title refers to change from baseline in local platelet count. These may represent related ways of evaluating platelet response, but the registry record does not explain their relationship or supply a durable-response result. It would be inappropriate to treat the stated study objective as evidence that one treatment had a larger or more sustained response.
The record lists 24 participants enrolled, and the safety summaries use group denominators of 11, 12, and 17 for the eltrombopag core study, avatrombopag core study, and avatrombopag extension, respectively. These safety figures should not be mistaken for a complete account of the efficacy population at every visit. The outcome description says that only participants with measurements at both baseline and the relevant visit contributed to each change summary; the number included at each visit is not stated except for the note about one participant at certain visits.
Without numerical outcome estimates, no confidence interval or other uncertainty measure for the treatment contrast can be interpreted. A confidence interval, in general, describes the range of values compatible with data under a specified statistical procedure; its width communicates precision, not the probability that a particular treatment effect is true. Since such an interval is not reported for the primary outcome, precision cannot be evaluated.
The study status is terminated, but the registry does not report the reason. Termination alone does not establish whether the study stopped for administrative, operational, safety, efficacy, or other reasons. The posted record also does not explain whether the planned enrollment was reached, whether a protocol change occurred, or whether the primary analysis was completed. Those details are not reported in the registry record.
Accordingly, the record supports a description of the study question, design, outcome definition, and selected safety counts, but not a conclusion about comparative efficacy. The absence of posted efficacy estimates is not evidence of no effect, and it is not evidence that the treatments had equivalent effects.
9. Statistical Methods Explained
What does a geometric mean summarize?
For the primary outcome, the registry identifies the geometric mean as the summary measure and standard deviation as the dispersion measure. In general, a geometric mean is a way to summarize values on a multiplicative scale and is often used when measurements are strongly right-skewed or when relative changes are of interest. It is not interchangeable with an arithmetic mean: it describes a different feature of the distribution. The registry record does not explain why the geometric mean was selected for change from baseline, whether the changes were transformed before summarization, or how zero or negative changes were handled. Those details matter because the geometric mean is generally defined for positive values.
Standard deviation describes how dispersed individual observations are around a summary, in general. The registry explicitly notes that it was not applicable for some categories from Visit 14 to Visit 22 because only one participant was analyzed for a visit. With only one observation, a within-visit sample standard deviation cannot be estimated. The record does not provide the numerical summaries or a fuller account of the dispersion calculations.
What does the repeated-visit structure mean?
The primary outcome is listed at repeated visits from Day 5 and Day 8 through Week 26. Repeated measurements can show the course of an outcome over time, but measurements from the same participant are related rather than independent. General statistical approaches for repeated data account for that within-participant correlation or define separate analyses at each visit. The registry record does not state which approach was used, whether a single visit was designated as the main comparison, or how the multiple visits were combined.
When many visits or outcome categories are examined, the chance of finding at least one apparently notable result can increase if each is tested separately. General methods for addressing this issue include defining a primary time point in advance, adjusting inference for multiple testing, or using a model that estimates a trajectory. The registry record does not report a multiplicity strategy or a model for repeated measurements. Because no numerical estimates or tests are posted for this outcome, the scale of any multiplicity concern cannot be evaluated from the record.
How should missing measurements be understood?
The Full Analysis Set is described as all participants randomized into the study. However, the primary outcome description narrows each visit-specific summary to participants with non-missing measurements at both baseline and that visit. This is a complete-pair requirement for each visit: a participant may contribute to one visit’s change summary but not another if the necessary measurements are missing. In general, this can make the analyzed group vary over follow-up and can affect interpretation if missingness is related to participant characteristics or outcomes.
The record does not say how missing measurements were handled beyond excluding participants without both measurements for a particular change summary. It does not describe imputation, sensitivity analyses, reasons for missingness, or whether the visit-specific participant counts were tabulated. The note that only one participant contributed at some later visits signals limited information for those categories, but the missing-data pattern and its consequences are not reported.
What can the planning illustrations tell readers?
The sample-size illustrations are described as planning scenarios based on the observed effect, not as the trial’s own design justification. They assume a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is expressed as a stated fraction of the observed effect. In general, such calculations estimate how many participants per arm would be needed under the stated assumptions to detect an effect at a chosen power level. They are prospective illustrations, not observed power and not proof that the study was adequately or inadequately sized.
The registry record does not report a sample-size justification for the trial, and no numerical efficacy estimate is posted in the primary outcome information. The planning illustrations therefore should not be read as a substitute for a reported treatment estimate or as evidence about the trial’s actual statistical power. A planning calculation is conditional on its assumed effect, variability, allocation, significance level, and statistical model. If the observed-effect basis is unstable or imprecise, illustrations derived from it inherit that uncertainty.
The registry reports zero posted analyses for the primary outcome. It does not identify a statistical model, an adjustment set, a hypothesis-testing procedure, or confidence intervals for the treatment comparison. The statistical plan, including any interim analysis procedures, is not reported in the registry record. General explanations of these methods cannot fill in those missing trial-specific details.
10. Multiplicity, Missing Data and Analysis Populations
The endpoint is described at repeated time points, extending from Day 5 and Day 8 through Week 26. The registry record does not identify a single primary visit for inference, explain whether the visits were analyzed jointly, or describe any adjustment for multiple comparisons. In general, testing many time points can increase the chance of a chance-positive finding unless the analysis plan accounts for the multiplicity or interprets the results as exploratory. No numerical visit-level results or tests are reported, so the implications cannot be quantified.
The Full Analysis Set is defined as all randomized participants. For the change-from-baseline summaries, however, the record includes only participants with non-missing values at baseline and the relevant follow-up visit. Thus, the set contributing to a summary can vary by visit. The registry does not report the number analyzed at each visit, except for the statement that some categories from Visit 14 to Visit 22 had one analyzed participant. It also does not describe imputation, sensitivity analyses, or reasons for missing data.
The registry record does not state a statistical analysis plan, the treatment-effect model, an interim analysis plan, or the handling of multiple outcomes. It also does not provide numerical primary-outcome estimates. These omissions prevent assessment of the analysis population actually used for each comparison, the impact of missingness, and the inferential consequences of examining multiple visits.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Eltrombopag (Core Study) | 0 | 11 | 0.0% |
| Avatrombopag (Core Study) | 2 | 12 | 16.7% |
| Avatrombopag (Extension Phase) | 4 | 17 | 23.5% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Eltrombopag (Core Study) | 11 of 11 |
| Avatrombopag (Core Study) | 11 of 12 |
| Avatrombopag (Extension Phase) | 16 of 17 |
Most frequent serious adverse event terms
| Event term | Organ system | Eltrombopag (Core Study) | Avatrombopag (Core Study) | Avatrombopag (Extension Phase) |
|---|---|---|---|---|
| Idiopathic thrombocytopenic purpura | Blood and lymphatic system disorders | 0 of 11 | 1 of 12 | 1 of 17 |
| Portal vein thrombosis | Hepatobiliary disorders | 0 of 11 | 1 of 12 | 1 of 17 |
| Bronchitis Moraxella | Infections and infestations | 0 of 11 | 1 of 12 | 1 of 17 |
| Thrombophlebitis Septic | Infections and infestations | 0 of 11 | 1 of 12 | 1 of 17 |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | 0 of 11 | 1 of 12 | 1 of 17 |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | 0 of 11 | 1 of 12 | 1 of 17 |
| Influenza | Infections and infestations | 0 of 11 | 0 of 12 | 1 of 17 |
| Chronic lymphotic leukaemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 11 | 0 of 12 | 1 of 17 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Eltrombopag (Core Study) | Avatrombopag (Core Study) | Avatrombopag (Extension Phase) |
|---|---|---|---|---|
| Fatigue | General disorders | 5 of 11 | 1 of 12 | 5 of 17 |
| Headache | Nervous system disorders | 3 of 11 | 3 of 12 | 5 of 17 |
| Nasopharyngitis | Infections and infestations | 3 of 11 | 2 of 12 | 4 of 17 |
| Dizziness | Nervous system disorders | 2 of 11 | 3 of 12 | 4 of 17 |
| Nausea | Gastrointestinal disorders | 2 of 11 | 3 of 12 | 3 of 17 |
| Insomnia | Psychiatric disorders | 1 of 11 | 3 of 12 | 4 of 17 |
| Diarrhoea | Gastrointestinal disorders | 3 of 11 | 2 of 12 | 2 of 17 |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | 0 of 11 | 3 of 12 | 3 of 17 |
| Abdominal discomfort | Gastrointestinal disorders | 1 of 11 | 1 of 12 | 3 of 17 |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | 1 of 11 | 2 of 12 | 2 of 17 |
Serious events with the highest arm-level rate: idiopathic thrombocytopenic purpura (8.3%), portal vein thrombosis (8.3%), bronchitis moraxella (8.3%), thrombophlebitis septic (8.3%), chronic obstructive pulmonary disease (8.3%).
The serious adverse-event summaries report 0 affected participants among 11 at risk in the eltrombopag core-study group, 2 among 12 in the avatrombopag core-study group, and 4 among 17 in the avatrombopag extension group. These are counts within the registry’s listed groups, not adjusted comparisons. The extension is open-label and is a different study phase, so its figures should not be treated as a randomized comparison against the core-study group.
For other adverse events, the record reports 11 affected participants among 11 at risk in the eltrombopag core-study group, 11 among 12 in the avatrombopag core-study group, and 16 among 17 in the extension group. The registry lists six serious-event terms, each with a reported frequency of 8.3%: idiopathic thrombocytopenic purpura, portal vein thrombosis, bronchitis Moraxella, thrombophlebitis septic, chronic obstructive pulmonary disease, and pneumothorax. The record does not link these terms to specific groups in the listed summary.
Deaths are not reported in the registry record. The safety counts do not provide event timing, duration, severity beyond the serious classification, or a basis for causal attribution. With the limited group sizes and no detailed comparative analysis, these figures describe reported events but do not establish comparative safety.
12. What the Result Does, and Does Not, Mean
The registry record shows that investigators planned a randomized comparison of avatrombopag plus standard of care against eltrombopag plus standard of care in adults with chronic immune thrombocytopenia. It also describes an open-label extension of avatrombopag therapy. The listed primary outcome concerns change from baseline in local platelet count over the core treatment period, while the study summary describes durable platelet response as the efficacy objective.
What the record does not show is the numerical result for the primary outcome. There is no reported treatment-group estimate, treatment contrast, confidence interval, or p-value for that outcome. Readers therefore cannot determine whether platelet counts changed, how the groups compared, or how uncertain a comparison might be. The statement of an objective is not a result.
The safety section reports counts of participants with serious and other adverse events in the core and extension groups. These descriptive counts do not, by themselves, establish that an event was caused by a treatment. Nor do the core and extension counts represent directly comparable randomized groups: the extension is open-label and participants entered it under eligibility conditions described in the registry.
The record’s terminated status also requires restraint in interpretation. It does not identify why the study ended, whether termination was planned, or how termination affected follow-up and analysis. It cannot be used alone to infer a safety concern, lack of efficacy, or administrative explanation.
In general, a result can be interpreted only in relation to its estimate, uncertainty, analysis population, and design. Here, the available registry information supports a description of the intended comparison and some safety counts, but does not support a conclusion that one treatment was better, worse, or equivalent for the primary endpoint. It also does not show that there was no difference. Those conclusions require results and analysis details that are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial illustrates why a clearly stated clinical objective and a reported statistical result are different kinds of information. The core-study summary identifies durable platelet response as the efficacy question, while the listed primary outcome describes change from baseline in local platelet count across multiple visits. Without a clear mapping between those formulations and without numerical estimates, readers cannot tell how the stated objective was answered.
The repeated-visit endpoint also highlights the importance of prespecified analysis choices. In general, a study must define how repeated measurements will be compared, how within-participant correlation will be handled, and how inference across multiple visits will be interpreted. The registry record does not describe those choices. This omission matters even when the outcome is a familiar laboratory measure, because different summaries and analysis strategies answer different questions.
The missing-data description shows another important distinction: a population can be defined as all randomized participants, while a particular outcome summary uses only those with the required measurements. Since the number contributing to each visit-specific summary is not reported, the extent to which analyzed populations changed over time cannot be assessed. The note about single-participant summaries at some later visits further cautions against assuming that every listed time point contains comparable information.
Finally, planning illustrations are not a replacement for trial results or a design rationale. They depend on assumptions and cannot establish what the study actually observed. The registry’s terminated status and limited outcome reporting make it especially important to separate what was planned, what was analyzed, and what was reported. This record is a useful example of how registry descriptions can identify a study’s intended question while leaving the comparative statistical evidence unavailable.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The main trial-specific limitation is that the registry record does not report numerical results for the listed primary outcome. Without estimates for either group or a treatment contrast, efficacy magnitude and precision cannot be assessed. The record also does not report an inferential analysis for that outcome.
The outcome description spans repeated visits, but the record does not specify a primary analysis time point, a method for analyzing repeated measurements, or a multiplicity strategy. The study summary’s reference to durable platelet response is not accompanied by a definition or numerical result. The relationship between that objective and the listed change-from-baseline outcome is therefore unclear.
Although the Full Analysis Set is described as all randomized participants, each change summary requires non-missing baseline and follow-up data. Visit-specific analyzed counts are not reported, apart from the statement that one participant was analyzed for some categories from Visit 14 to Visit 22. The registry does not explain how missing data were otherwise handled or report sensitivity analyses. It also does not clarify the geometric-mean calculation for change values.
The registry describes the trial as double-blind in its title and records triple masking in its masking field, without explaining the discrepancy. It reports termination but not the reason, and does not provide a participant-flow account or statistical analysis plan. Safety summaries are descriptive, and extension-phase figures are not directly comparable with the randomized core-study groups. These limitations constrain interpretation of the available record; they do not establish what the unreported results would have shown.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Phase 3, Multicenter, Randomized, Double-blind,Active-controlled, Parallel-group Trial With an Open-labelExtension Phase to Evaluate the Efficacy and Safety of OralE5501 Versus Eltrombopag, in Adults With Chronic ImmuneThrombocytopenia (Idiopathic Thrombocytopenic Purpura) — NCT01433978.
- Registry record last updated 2018-02-06; status last verified 2018-01.
- Results first posted 2018-02-06.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
The registry record describes a phase 3, multicenter, randomized, parallel-group trial of avatrombopag versus eltrombopag, each with standard of care, in adults with chronic immune thrombocytopenia. The core treatment period was 26 weeks, followed by an open-label avatrombopag extension of up to 104 weeks for eligible participants. Enrollment was 24, and the study status is terminated.
The listed primary outcome is change from baseline in local platelet count at repeated visits. The record defines the Full Analysis Set as all randomized participants but limits each change summary to participants with baseline and relevant follow-up measurements. Numerical primary-outcome results and a statistical analysis plan are not reported in the registry record. Safety information includes counts of participants with serious and other adverse events for the core and extension groups; deaths are not reported.