Japanese Phase II Study of SB-497115-GR in Hepatitis C Virus Infected Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Japanese Phase II Study of SB-497115-GR in Hepatitis C Virus Infected Patients (NCT01636778), a na phase 2 study. The primary outcome is Number of Participants Whose Platelet Count Increased From a Baseline Count of < 80 Gi/L to a Count >=100 Gi/L During Part 1.

2. Clinical Question

The study’s stated purpose extends beyond the primary platelet-count endpoint. It aimed to assess whether SB-497115-GR could raise platelet counts to a level considered desirable for starting antiviral therapy and maintain counts sufficient to minimise dose reductions of pegylated interferon and ribavirin. The record describes an expectation that fewer dose reductions or omissions could translate to a higher rate of sustained viral response. That statement gives the rationale for the study, not evidence that the expected sequence of outcomes occurred.

3. Trial Design

This was a Phase II, non-randomised, open-label, multi-centre study of SB-497115-GR. The registry classifies it as a single-group study, with allocation not applicable and no masking. It was conducted in participants with thrombocytopenia, chronic hepatitis C and compensated liver cirrhosis. The listed condition is chronic hepatitis C, and the intervention is SB-497115-GR, described as an investigational product for thrombocytopenia.

The study had distinct treatment periods. Part 1 was an eltrombopag dose-escalation period; the primary platelet-count outcome was assessed from baseline up to Week 9 in that part. Part 2 combined eltrombopag and antiviral therapy, and the record also includes a follow-up period after Part 2. Secondary outcomes address platelet counts at indicated time points, time to a platelet count >=100 Gi/L, the dose that enabled antiviral therapy to begin, and antiviral dose reductions.

The registry lists enrollment of 45. It records a study start of 2012-07, primary completion of 2014-05 and status as completed. These administrative details describe the study record; they do not establish how many participants contributed data to every endpoint or analysis. The primary analysis population is described as all participants enrolled in Part 1, while the safety entries list the participants at risk separately for each reported period.

Because there is no concurrent control group and treatment was open label, the design describes participant outcomes during treatment rather than a controlled comparison. Changes over time may be recorded, but without a control group they cannot by themselves distinguish treatment effects from other influences. The registry record does not report a statistical analysis plan, a sample-size justification or details of interim analyses.

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: The total study duration was a maximum of 88 weeks, which consisted of a Screening Period of less than or equal to 45 days, the Pre-Antiviral Treatment Period (Part 1) from 1 up to 9 weeks and the Antiviral Treatment Period (Part 2) of 48 weeks and Follow-up Period of 24 weeks.

Pre-Antiviral Treatment Period (Part 1)

Reasons for not completing this period:

Antiviral Treatment Period (Part 2)

Reasons for not completing this period:

Follow-up Period After Part 2

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set 1 (FAS1) Population: all participants enrolled in Part 1.

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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Whose Platelet Count Increased From a Baseline Count of < 80 Gi/L to a Count >=100 Gi/L During Part 1, measured over From Baseline up to Week 9 in Part 1.

The primary endpoint counts participants whose platelet count moved from a baseline value <80 Gi/L to a value >=100 Gi/L during Part 1, up to Week 9. Platelet counts were measured by blood draw. The endpoint is a threshold-based binary outcome: each participant either met the specified shift during the assessment period or did not. It is reported as a number of participants, rather than as an average platelet count.

The threshold is relevant to the study’s stated purpose of raising platelet counts to a level considered desirable for initiating antiviral therapy. A count at or above the specified threshold therefore describes an intermediate laboratory outcome linked to the treatment rationale. It does not, by itself, establish that antiviral therapy was started, that treatment could be maintained without dose reductions, or that a sustained viral response occurred.

The registry identifies the Full Analysis Set 1 as the primary population and defines it as all participants enrolled in Part 1. However, the observed number meeting the endpoint and its denominator are not reported in the registry record. Without those results, the endpoint’s observed frequency and the precision of any estimate cannot be described. Nor can the endpoint alone establish a treatment effect: the study has no separate control group against which to compare the platelet-count shift.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a threshold endpoint capture?

In general, a threshold endpoint reduces a measured quantity to whether a stated criterion was reached. That makes the outcome straightforward to interpret as a count of participants meeting the criterion during a defined period. It also discards information: participants just below the threshold and those much farther below it are both classified as not meeting it, while participants who cross the threshold may have different measured values. A threshold result therefore answers a specific question, not every question about the size or duration of a change.

For this study, the registry defines a shift from baseline platelet count <80 Gi/L to a count >=100 Gi/L during Part 1, up to Week 9. The measurement was by blood draw. The endpoint definition does not say how many participants met the criterion. That observed result, and any estimate of its uncertainty, are not reported in the registry record.

What does a confidence interval mean?

In general, a confidence interval expresses uncertainty around an estimated quantity under the assumptions of the analysis. A narrower interval indicates greater precision, while a wider interval indicates more uncertainty. It is not a guarantee that the true value lies within the interval, and it does not show whether a result is important in clinical terms. No confidence interval for the primary endpoint is reported in the registry record, so the precision of the primary estimate cannot be assessed from the posted outcome information.

How does the study design affect statistical interpretation?

A single-group study can describe outcomes among participants who receive the study intervention. A concurrent control group is needed for a direct comparison of outcomes under different assigned treatments. Here, allocation is listed as not applicable, the model is single group, and masking is none. Thus, the record does not support a randomised, like-for-like treatment contrast. A within-study change can be described, but it cannot by itself separate the intervention’s contribution from natural variation, changes over time, or other influences.

Open-label status is also relevant. In general, knowledge of treatment can influence care decisions, reporting and assessment. A platelet count obtained by blood draw is a measured laboratory outcome, but the broader treatment course and decisions about antiviral therapy or dose adjustment may still involve clinical judgement. The registry record does not describe additional procedures for blinded outcome assessment.

What do the planning calculations represent?

In general, sample-size calculations describe what a hypothetical study might require under stated assumptions; they do not indicate the strength of evidence observed in a completed study. The planning illustrations associated with this record are based on the observed effect, use a two-sided significance level of 0.05, assume equal allocation between two arms and use a normal approximation. They describe participants per arm for 80% power, with the effect to detect expressed as a stated fraction of the observed effect. Time-to-event planning illustrations use the total number of events.

Those calculations are planning illustrations, not the original trial’s design justification and not observed power. The registry record does not report the trial’s own sample-size justification. In addition, the study itself is single group, while the planning assumptions describe equal allocation between two arms. These calculations should therefore not be read as a description of the study’s actual allocation or as evidence that the study had a particular probability of detecting an effect.

Why can count outcomes need careful interpretation?

In general, a count of participants meeting a criterion is different from a continuous measurement such as platelet count at a particular visit. The count depends on a defined population, outcome rule and observation period. Comparisons across periods or studies require attention to those definitions and to who was included in each analysis. The primary population is defined as all participants enrolled in Part 1, but the observed endpoint count and its analysis details are not reported in the registry record.

The record lists 58 outcome measures and 1 analysis. Those entries alone do not establish how many statistical tests were conducted, whether the primary outcome was adjusted for other comparisons, or how the analysis handled repeated measurements. The statistical plan and multiplicity procedures are not reported in the registry record. Accordingly, no adjustment method, model or inferential procedure should be attributed to the trial based on the outcome count alone.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Eltrombopag Dose Escalation: Part 1")
n      <- c(45)
events <- c(43)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Eltrombopag Dose Escalation: Part 1  45  43  95.6  84.9  99.5  85.2  98.8  85.2  98.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 58 outcome measures and 1 analysis. The listed outcomes cover platelet counts at indicated time points, time to a target count, antiviral-treatment dose reductions and safety, among other measures. A long list of outcomes can create multiplicity concerns when many hypotheses are tested: in general, the more statistical comparisons considered, the greater the chance that some results may appear notable by chance. Methods such as prespecifying a primary outcome or adjusting for multiple tests can address this issue, but the registry record does not report whether or how such methods were used.

The record identifies the primary endpoint and names the Full Analysis Set 1 as all participants enrolled in Part 1. It does not report the observed primary endpoint count, the denominator used for that result, or how missing endpoint measurements were handled. Rules for excluding participants, imputing missing values or accounting for incomplete follow-up are not reported in the registry record. Consequently, the effect of missing data on the primary result cannot be assessed.

The safety entries give period-specific numbers at risk, but they do not explain whether participants who did not enter a later period, or who had incomplete observations, were handled in a particular way. The record also does not report a statistical analysis plan or interim-analysis procedures. The listed analysis count should not be taken as evidence about the full set of statistical tests or decisions made.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hepatocellular carcinoma (4.9%), liver injury (2.4%), myeloblast percentage increased (2.4%), thrombocytosis (2.4%), herpes zoster (2.4%).

The registry reports safety by study period. In the eltrombopag dose-escalation period in Part 1, 0 serious adverse events and 0 other adverse events are listed among 45 participants at risk. During Part 2, when eltrombopag was given with antiviral therapy, 3 participants had a serious adverse event and 41 had other adverse events among 41 participants at risk. In the follow-up period after Part 2, 4 participants had a serious adverse event and 6 had other adverse events among 41 at risk.

These are counts tied to different periods. They should not be added together to infer a count across the study, because the record does not establish whether the same participants contributed in multiple periods. Nor do the counts show that an event was caused by the study intervention. The registry also lists serious adverse-event terms and percentages: hepatocellular carcinoma, 4.9%; liver injury, 2.4%; myeloblast percentage increased, 2.4%; thrombocytosis, 2.4%; herpes zoster, 2.4%; and trigeminal neuralgia, 2.4%. Death counts are not reported in the registry record. These entries describe reported events; they do not, on their own, establish comparative risk or causality.

13. What the Result Does, and Does Not, Mean

The registry record describes a study designed to assess whether SB-497115-GR could raise platelet counts in thrombocytopenic participants with chronic hepatitis C and compensated liver cirrhosis. Its primary endpoint is a clearly defined threshold shift during Part 1. However, the observed number of participants meeting that endpoint is not reported in the registry record. Therefore, the posted information does not establish the observed frequency of reaching the target platelet count or the precision of that estimate.

The study’s stated rationale links platelet counts with the possibility of starting antiviral therapy and reducing dose modifications. Those are related but distinct outcomes. The primary platelet-count endpoint cannot establish whether antiviral therapy was initiated, whether antiviral doses were maintained, or whether participants achieved a sustained viral response. Although the registry lists secondary outcomes related to antiviral treatment and platelet counts over time, the outcome results for those measures are not reported in the registry record.

The design also limits conclusions about causation. The study is single group, non-randomised and open label, with no separate control group. Its results can describe outcomes observed during treatment, but cannot provide a controlled estimate of what would have happened under a different treatment. The listed safety counts likewise describe reported events in the stated periods; they do not determine whether events were caused by treatment or how risks compare with another approach.

Planning calculations, if considered alongside the study, are illustrations under specified assumptions rather than observed power or a report of the trial’s original design rationale. The registry record does not report a sample-size justification or the statistical plan. The most defensible interpretation is therefore limited: the record establishes the research question, design, endpoint definition and selected safety counts, but does not report the primary endpoint result or a comparative treatment effect.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of a threshold-based laboratory endpoint embedded in a single-group treatment sequence. The primary question is not simply whether platelet counts changed; it is whether participants who started below a defined level reached a specified target during a defined period. Such an endpoint can connect a laboratory measure to a treatment-planning objective, while remaining distinct from later treatment and virologic outcomes.

The design also makes clear why an endpoint and a treatment effect are not interchangeable. A single-group study can report what happened among treated participants, but it cannot estimate a controlled difference from an untreated or alternative-treatment group. This distinction is important when a study’s rationale describes a hoped-for chain from platelet counts to antiviral treatment and ultimately to sustained viral response. Each link in that chain requires its own outcome evidence.

The record further illustrates the need to read safety data by period and population at risk. Counts reported during dose escalation, antiviral treatment and follow-up are not necessarily independent observations. Treating them as if they were a single pooled count could misrepresent the information recorded. Percentages attached to serious adverse-event terms also need their stated context and denominator to support interpretation.

Finally, the gap between a detailed endpoint definition and an unreported endpoint result matters for statistical communication. A precise question does not tell readers what the observed answer was, how uncertain it was, or how missing observations were handled. Distinguishing these elements helps keep conclusions proportional to the evidence recorded.

15. 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 most important limitation for interpreting efficacy is that the registry record does not report the observed result for the primary endpoint. Although it defines the outcome, assessment period and analysis population, it does not give the number meeting the platelet-count threshold or an estimate of precision. A numerical conclusion about the primary result is therefore not possible from the record.

The single-group, non-randomised, open-label design provides no concurrent comparator. This prevents a like-for-like estimate of the effect of SB-497115-GR relative to another treatment or to no study treatment. Changes observed during the study could reflect multiple influences, and the design alone cannot separate them. Open-label conduct may also affect treatment decisions or event reporting.

The study includes dose escalation, antiviral treatment and follow-up periods, but the record does not explain how participants entered or contributed data to each period beyond the safety counts at risk and the definition of the primary population. Missing-data procedures, analysis exclusions and outcome-specific denominators are not reported in the registry record. Death counts are also not reported in the registry record.

The registry lists many outcome measures but does not report the statistical plan, multiplicity procedures or interim-analysis methods. The reason for the chosen enrollment and the trial’s own sample-size justification are not reported in the registry record. These omissions limit assessment of how the study was planned and how much confidence to place in any reported secondary findings. The safety counts should also be read as period-specific reports, not as proof of causation or comparative risk.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Japanese Phase II Study of SB-497115-GR in Hepatitis C Virus Infected Patients — NCT01636778.
• Registry record last updated 2016-03-01; status last verified 2015-09.
• Results first posted 2015-02-23.
• 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.

19. Record Summary

The registry describes NCT01636778, a completed Phase II, non-randomised, open-label, multi-centre, single-group study of SB-497115-GR. It concerns thrombocytopenic participants with chronic hepatitis C and compensated liver cirrhosis. Enrollment is listed as 45, the study start as 2012-07 and primary completion as 2014-05.

The primary endpoint counts participants whose platelet count shifted from <80 Gi/L at baseline to >=100 Gi/L during Part 1, up to Week 9. The analysis population is defined as all participants enrolled in Part 1. The observed primary result is not reported in the registry record. Period-specific safety counts are reported for Part 1, Part 2 and follow-up; death counts are not reported in the registry record.