A Study of Eliglustat Tartrate (Genz-112638) in Patients With Gaucher Disease Who Have Reached Therapeutic Goals With Enzyme Replacement Therapy (ENCORE): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Eliglustat Tartrate (Genz-112638) in Patients With Gaucher Disease Who Have Reached Therapeutic Goals With Enzyme Replacement Therapy (ENCORE) (NCT00943111), a randomized phase 3 study. The primary outcome is Percentage of Participants Who Remained Stable for 52 Weeks During the Primary Analysis Period.

2. Clinical Question

The primary endpoint combines stability across hematological measures and organ volumes. It therefore asks whether participants stayed within the protocol’s specified limits across the relevant measures, rather than whether a single laboratory value or organ measurement changed. Spleen volume was considered when applicable; liver volume was included in the stability definition.

The registry reports the percentage stable in each treatment group and a sponsor analysis of the difference in percentages. A separate unadjusted comparison can describe the observed difference and its uncertainty, but it is not a substitute for the sponsor’s analysis. The registry record does not report enough detail to determine the sponsor’s full statistical method or the margin used for any non-inferiority interpretation.

3. Trial Design

This was a Phase 3, randomized, parallel-group, open-label, active-comparator study. Its official title describes a multi-center, multi-national trial. The study compared eliglustat tartrate with imiglucerase in participants with Gaucher disease type 1 who had reached therapeutic goals with enzyme replacement therapy. The recorded enrollment was 160.

Participants were assigned to one of two treatment arms, but the registry record does not report the allocation ratio or the procedures used to generate and conceal the randomization sequence. Masking was listed as none, so the trial was open-label. That feature is relevant when considering outcomes involving clinical decisions or subjective judgments, although the primary endpoint is defined using specified hematological and organ-volume thresholds.

The primary endpoint covered baseline through Week 52. Its analysis used a per-protocol population rather than simply including every randomized participant. For this population, participants had to meet the stated adherence requirement during the primary analysis period, have no major protocol deviations, and not have a hematological decline attributed to medically determined causes other than Gaucher disease. The endpoint analysis included 99 participants in the eliglustat group and 47 in the imiglucerase group.

The registry lists bone mineral density, hemoglobin, platelet counts, and spleen volume among secondary outcomes. It records 17 outcome measures and 15 posted secondary outcomes. The posted results include only a subset of secondary analyses in the available statistical record. Detailed information about treatment dosing, follow-up procedures beyond the stated endpoint timeframe, and the original statistical plan is 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: All enrolled participants received eliglustat or imiglucerase in 52 week primary analysis period (PAP). After 52-weeks PAP, all participants who remained on-study, received eliglustat in the long-term treatment period (LTTP) for up to 5 years.

52-Weeks Primary Analysis Period

Reasons for not completing this period:

5 Years Long-term Treatment Period

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Per protocol population for PAP included participants who were at least 80% compliant with treatment during PAP, had no major protocol deviations, and did not exhibit hematological decline as a result of medically determined etiologies other than Gaucher disease.

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: Full analysis set (FAS) for PAP: included all participants who signed informed consent and received at least 1 dose of study drug (Imiglucerase or eliglustat).

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Who Remained Stable for 52 Weeks During the Primary Analysis Period, measured over Baseline up to Week 52.

The primary endpoint is the percentage of participants who remained stable for 52 weeks during the primary analysis period. Stability required meeting criteria in hematological parameters and organ volumes. Hemoglobin could not decrease by more than 1.5 g/dL from baseline, and platelet count could not decrease by more than 25%. Spleen volume, when applicable, could not increase by more than 25%, and liver volume could not increase by more than 20% from baseline. A participant had to satisfy the relevant criteria to be classified as stable.

A composite endpoint of this kind is used to represent stability across several clinically relevant domains rather than relying on one measure alone. It can make a broad outcome easier to summarize, but it also means that the overall percentage does not reveal which component was most influential for any participant. The registry record does not report component-level primary results.

The endpoint was assessed in a per-protocol population with specified adherence and protocol-deviation requirements. Consequently, its percentage describes participants meeting those analysis-population rules; it is not simply a percentage of all randomized participants. The record does not report the full handling of missing component measurements or the detailed statistical procedure for the sponsor’s primary comparison.

7. Results Posted in the Registry

• Imiglucerase: PAP: 93.6% (44/47) versus 84.8% (84/99) on control; risk difference 8.8 percentage points (95% CI -1.2 to 18.7), risk ratio 1.10 (0.99–1.23); unadjusted two-proportion z-test p = 0.132.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Hemoglobin Level

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Imiglucerase: PAP: mean 13.80 versus 13.59 on control; difference 0.21 (95% CI -0.22 to 0.63), standardized effect d = 0.17; z-test p = 0.348.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Imiglucerase: PAP and the control. The interval gives the range of effects that remain compatible with the data.

Absolute Change From Baseline in Hemoglobin Levels at Week 52

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Imiglucerase: PAP: mean 0.05 versus -0.22 on control; difference 0.27 (95% CI 0.03 to 0.51), standardized effect d = 0.39; z-test p = 0.027.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Imiglucerase: PAP than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Percent Change From Baseline in Platelet Counts at Week 52

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Imiglucerase: PAP: mean 2.63 versus 3.93 on control; difference -1.30 (95% CI -7.19 to 4.59), standardized effect d = -0.08; z-test p = 0.665.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Imiglucerase: PAP and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes cover several domains, including bone mineral density, hemoglobin, platelet counts, and spleen volume. The posted numerical secondary analyses are limited compared with the number of outcomes recorded. Their overall pattern is not a uniform shift in favor of one treatment across every measure: the estimated direction varies by outcome, and the intervals do not all provide the same degree of information.

These findings add context to the primary stability result because hemoglobin, platelet counts, and organ volume are among the domains represented in the composite endpoint. However, secondary summaries are not a substitute for the primary endpoint. They may use different populations, timepoints, outcome definitions, or statistical models; the registry record does not report enough detail to establish that all secondary analyses align exactly with the primary population and method.

The secondary results should carry less weight than the primary result when interpreting the trial’s main question. The registry does not report a multiplicity adjustment or a hierarchy for testing secondary outcomes. If many outcomes are examined separately, a result that appears notable by chance becomes more likely. Unadjusted secondary p-values should therefore be interpreted cautiously and in the context of the full outcome set, rather than as independent confirmation of a treatment difference.

The available secondary results can describe the measured outcomes, but they do not resolve the uncertainty in the primary comparison or establish a consistent treatment effect across all domains. The registry record also does not report all numerical secondary results needed to assess the full pattern across the complete outcome inventory.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Total T-Scores for Bone Mineral Density
• Absolute Change From Baseline in Total T-Scores for Bone Mineral Density at Week 52
• Total Z-Scores for Bone Mineral Density
• Absolute Change From Baseline in Total Z-Scores for Bone Mineral Density at Week 52
• Hemoglobin Level
• Absolute Change From Baseline in Hemoglobin Levels at Week 52
• Percent Change From Baseline in Platelet Counts at Week 52
• Percent Change From Baseline in Spleen Volume (MN) at Week 52

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary at the participant level: each participant is classified as stable or not stable according to the endpoint criteria. A group percentage therefore estimates the proportion classified as stable in that analysis population. The registry reports the group percentages with 95% confidence intervals. A confidence interval expresses the uncertainty around an estimate under the assumptions of the analysis; it is not a range that guarantees the true value lies within it.

What does the difference in percentages represent?

A risk difference compares the proportion with the outcome in one group with the proportion in another. The recalculated comparison uses imiglucerase relative to eliglustat, so a positive value corresponds to a higher observed stable proportion in the imiglucerase group. Reversing the order reverses the sign but does not change the underlying contrast. This orientation matters when comparing the recalculation with the sponsor’s reported difference, which is listed for the groups in the registry’s other ordering.

The recalculated risk difference is unadjusted: it uses the posted group counts and denominators without modeling covariates or applying the sponsor’s possibly different analysis procedure. The posted counts are 84 stable participants out of 99 in the eliglustat analysis population and 44 out of 47 in the imiglucerase analysis population. The recalculated comparison reports an unadjusted p-value of 0.132. A p-value measures how compatible the observed data are with a specified null model, assuming that model and the analysis assumptions hold. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of a difference.

How should the interval and p-value be read together?

The recalculated confidence interval includes zero, as does the sponsor-reported interval for the difference in percentage stable. A zero difference corresponds to equal percentages under the contrast being used. An interval that includes zero indicates that the data do not rule out zero difference at the confidence level used; it does not show that the true difference is zero. The sponsor’s reported analysis is described as a non-inferiority or equivalence analysis, but the registry record does not report its margin or full decision rule. A conventional difference test and a non-inferiority test address different questions, so a general p-value or interval should not be treated as a substitute for the prespecified non-inferiority assessment.

The sponsor analysis and the recalculation need not match exactly. The sponsor’s analysis may use procedures, analysis-population handling, or assumptions not reproduced by a comparison of summary counts. The statistical method for the sponsor’s estimate is not reported in the registry record. The recalculated result is therefore useful as a transparent, simple check on the posted summaries, but it is not a reconstruction of the trial’s complete analysis.

Why does the analysis population matter?

Randomization is intended to make treatment groups comparable at assignment. A per-protocol analysis selects participants using post-assignment features such as adherence and protocol deviations. Such selection can affect comparability because inclusion in the analysis may be related to participant characteristics or outcomes. The registry’s stated criteria define who was included, but the record does not report enough information to quantify the effect of this selection or to compare the primary result with an intention-to-treat analysis.

The primary population contained 99 participants in the eliglustat group and 47 in the imiglucerase group. Those analysis denominators are not the same as the safety denominators, which were 106 and 53, respectively. Each denominator belongs to a particular analysis and should not be interchanged with the others. Details about missing outcome measurements, exclusions after randomization, and any imputation method are not reported in the registry record.

What can be learned from the secondary continuous outcomes?

For continuous outcomes, a group mean or least-squares mean describes a location estimate, while a standard deviation describes variation among observations and a standard error describes uncertainty in an estimated mean. These quantities are not interchangeable. The baseline hemoglobin result is reported as a mean with standard deviation. The changes in hemoglobin and platelet counts are reported as least-squares means with standard errors. The registry does not report the full model specification that produced the least-squares means.

The secondary comparisons include mean differences and confidence intervals. Their recalculated p-values are unadjusted, and the registry record does not report a multiplicity correction. When several outcomes are examined, the chance of at least one apparently notable result can rise if each is assessed separately without an adjustment or an explicitly hierarchical plan. Secondary findings are therefore best treated as supportive or exploratory unless the trial’s prespecified testing strategy is available.

Overall, the main statistical distinction is between the registry’s sponsor-reported analysis and a simple unadjusted recalculation from posted summaries. The former is the trial’s reported result; the latter makes a limited comparison using the available counts. Neither the recalculation nor the observed percentages supply missing details about the original design, the margin for non-inferiority, or the handling of incomplete data.

11. Confidence Intervals and Precision

Precision is conveyed by the confidence intervals as well as by the point estimates. For the primary endpoint, the 95% confidence interval is 76.2% to 91.3% for eliglustat and 82.5% to 98.7% for imiglucerase. These intervals show substantial uncertainty around each group percentage. The imiglucerase estimate is based on 47 participants in the primary analysis population, compared with 99 in the eliglustat population, so the group estimates are not equally supported by the number of analyzed participants.

The sponsor-reported difference is -8.8, with a 95% confidence interval from -17.6 to 4.2. This interval includes zero and spans values on either side of no difference. The recalculated unadjusted difference interval also includes zero. Neither interval identifies a single precise value for the treatment contrast. In particular, an interval that includes zero does not prove equality, and a point estimate alone should not be read as the exact underlying effect.

Confidence intervals quantify uncertainty under the method and assumptions used to construct them. The registry record does not report the sponsor’s statistical method or the margin relevant to the non-inferiority or equivalence label. That limits how completely the sponsor interval can be assessed. The recalculated interval is based on a simple unadjusted comparison and likewise does not incorporate any unreported modeling or design features.

Overlap between separate group confidence intervals is not itself a formal test of the difference. The comparison interval is the more direct summary of uncertainty about the contrast. Even so, the available difference intervals leave a broad range of plausible values, so the results do not pin down the size of any difference with high precision.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm for this binary primary outcome. They are not total event counts. The registry’s planning illustration assumes a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It uses the observed effect as a reference and considers planning for 100%, 75%, or 50% of that observed effect. These assumptions describe the illustration, not the original trial design; the trial’s own sample-size assumptions are not reported in the registry record.

For planning at 100% of the observed effect, the illustration gives 195 participants per arm for 80% power and 261 participants per arm for 90% power. For planning at 75% of the observed effect, it gives 379 participants per arm for 80% power and 506 participants per arm for 90% power. For planning at 50% of the observed effect, it gives 921 participants per arm for 80% power and 1,232 participants per arm for 90% power.

In plain terms, the 80% power column describes the planning sample size associated with an 80% chance of detecting the stated effect under the illustration’s assumptions, if that effect and those assumptions were true. The 90% power column uses a higher target chance of detection and consequently requires a larger planned sample size. Smaller effects are harder to distinguish from random variation, so planning to detect a smaller fraction of the observed effect requires more participants per arm.

These are planning illustrations based on the observed effect, not observed power. They should not be read as evidence about the probability that the completed trial produced a reliable result, and they do not establish what sample size the investigators originally planned.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.848; treatment proportion p₁ = 0.936; average p̄ = 0.892.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.4384 = 0.8592.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.4340 = 0.3652.
4. n = (0.8592 + 0.3652)² / (0.0877)² = 195.0, rounded up to 195 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.848484848484849                          # control proportion
p1 <- 0.936170212765957                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(943111)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 195 (80% power), 261 (90% power)
 75% of observed effect: n per arm = 379 (80% power), 506 (90% power)
 50% of observed effect: n per arm = 921 (80% power), 1,232 (90% power)
power.prop.test: 195 
Simulated power at n = 195 per arm: 0.808 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry reports a sponsor analysis of the difference in percentage stable as -8.8, with a 95% confidence interval from -17.6 to 4.2. It labels this result as a non-inferiority or equivalence analysis. The record does not give a p-value for this analysis, the statistical method, or the non-inferiority margin and decision rule. Without those details, the label and interval do not establish whether the trial met a prespecified non-inferiority criterion.

The recalculation is a simple, unadjusted risk-difference comparison derived from the posted group summaries. It contrasts imiglucerase with eliglustat, whereas the sponsor result is listed for the groups in the other order. The sign therefore has to be interpreted in light of the contrast direction. The recalculated interval includes zero, and its unadjusted p-value is 0.132.

The sponsor analysis is the registry’s reported trial analysis; the recalculation is a limited check using summary data and does not reproduce an unavailable analysis plan. Any differences in statistical procedures or population handling cannot be resolved from the registry record. The two presentations are best read as related but not interchangeable descriptions of the comparison.

15. Multiplicity, Missing Data and Analysis Populations

The registry record lists 17 outcome measures and 15 posted secondary outcomes, alongside the primary endpoint. It does not report whether the original analysis plan controlled the family-wise error rate, used a hierarchy for testing, or applied another multiplicity strategy. The recalculated secondary p-values are unadjusted. As a general statistical matter, conducting multiple tests without adjustment increases the chance that at least one result appears statistically notable even when there is no corresponding underlying effect. This makes isolated secondary findings less conclusive.

The primary endpoint population is described as per protocol. The record states that participants had to meet the compliance criterion, have no major protocol deviations, and not have hematological decline due to medically determined etiologies other than Gaucher disease. It does not report an intention-to-treat primary analysis alongside this result, nor does it provide enough detail to assess how exclusions affected the randomized comparison.

Missing-data procedures are not reported in the registry record. In particular, the record does not explain how missing laboratory values, organ-volume measurements, or incomplete follow-up were handled in classifying stability. It does not state whether values were imputed, whether missingness was treated as failure, or whether sensitivity analyses were performed. These choices can affect a binary composite endpoint, especially when every relevant component must satisfy a stability criterion.

The sponsor’s statistical method, the non-inferiority margin, and the original sample-size justification are also not reported in the registry record. Interim analyses and stopping rules are not reported in the registry record. These omissions limit the ability to evaluate the prespecified analysis strategy and its safeguards against selective interpretation. They do not invalidate the posted summaries, but they constrain how far those summaries can support conclusions beyond the descriptive comparison.

16. 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: syncope (2.8%), polycythaemia (1.9%), acute myocardial infarction (1.9%), myocardial infarction (1.9%), injury (1.9%).

The registry reports serious adverse events for safety populations of 106 participants receiving eliglustat and 53 receiving imiglucerase. Serious adverse events affected 18 participants in the eliglustat group and 7 in the imiglucerase group. Other adverse events affected 91 participants in the eliglustat group and 38 in the imiglucerase group. These are counts of participants affected, not event rates calculated for a common follow-up period.

The registry lists serious adverse-event terms including syncope (2.8%), polycythaemia (1.9%), acute myocardial infarction (1.9%), myocardial infarction (1.9%), injury (1.9%), and benign ovarian tumour (1.9%). The record does not provide enough detail in these summaries to use the listed terms as a complete account of severity, timing, relatedness, or differences between treatment groups. Deaths are not reported in the registry record.

Because the safety groups have different denominators and the registry summary does not provide adjusted comparisons or further exposure detail, the counts should be read descriptively. They do not by themselves establish a comparative safety profile.

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

The posted results describe the proportion of participants in the specified per-protocol populations who met a composite definition of stability through Week 52. The observed stable percentages were 84.8% for eliglustat and 93.6% for imiglucerase. The sponsor-reported interval for the difference includes zero, and the simple recalculated comparison also has an interval that includes zero. This means the posted comparison does not precisely identify a difference between the groups.

The result does not show that the treatments are identical. Failure to establish a difference is not proof of equality, and a non-inferiority conclusion requires a prespecified margin and analysis rule. Although the registry labels the sponsor analysis as non-inferiority or equivalence, the margin and decision rule are not reported in the registry record. The available information is therefore insufficient to independently determine whether a non-inferiority criterion was met.

The finding also does not describe every randomized participant. The primary analysis used a per-protocol population with stated adherence and exclusion criteria, while the safety summaries use different denominators. Nor does the composite percentage reveal the separate contribution of hemoglobin, platelet counts, spleen volume, or liver volume. Component-level primary results are not reported in the registry record.

Finally, the endpoint concerns the stated baseline-to-Week-52 period. It does not answer questions about longer-term outcomes, all possible measures of disease status, or the experience of people outside the study population. These results are statistical descriptions of the registry record and are not medical advice or a treatment recommendation.

18. Why This Trial Matters Statistically

This trial raises a statistical question that is common in active-comparator studies: how to interpret a comparison when the scientific objective is to show that a treatment preserves a specified level of outcome rather than to show superiority. A non-inferiority conclusion depends on a prespecified margin, a suitable analysis strategy, and careful attention to the analysis population. The registry identifies the sponsor analysis as non-inferiority or equivalence, but the margin and decision rule are not reported in the registry record.

The endpoint also illustrates the trade-off involved in composite outcomes. Combining hematological and organ-volume thresholds yields one summary of stability across multiple domains. At the same time, a single percentage can conceal which component drove a participant’s classification and whether the components behave similarly between groups. The registry’s primary result is therefore best read as a summary of the defined composite, not as a separate conclusion about each measure.

Finally, the difference between the per-protocol primary population and the larger safety denominators matters. Randomization supports fair comparisons at assignment, while selection into a per-protocol analysis can alter comparability. Transparent reporting of both analysis populations, missing-data handling, and the prespecified testing strategy would help readers judge how robust the result is. The posted record supplies some of this context, but not enough to reconstruct the complete analysis plan.

19. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The primary endpoint is based on a per-protocol population rather than a reported analysis of all randomized participants. Its eligibility rules depend on adherence, protocol deviations, and medically determined causes of hematological decline. Those post-assignment criteria can affect group comparability. The registry record does not report a parallel intention-to-treat result or sensitivity analyses that would show how the population definition influenced the comparison.

The trial was open-label, with no masking. The primary outcome uses specified laboratory and organ-volume thresholds, which can limit some forms of subjective judgment, but the registry record does not describe how measurements were obtained, reviewed, or adjudicated. It also does not provide component-level results for the composite endpoint.

The sponsor’s reported analysis is labeled as non-inferiority or equivalence, but its statistical method, margin, and decision rule are not reported in the registry record. The original sample-size justification, missing-data procedures, and interim-analysis plan are also not reported. As a result, the sponsor’s inferential framework cannot be fully checked against the registry summary.

The primary analysis populations include 99 participants in the eliglustat group and 47 in the imiglucerase group. The unequal group sizes and the smaller comparator analysis population contribute to uncertainty. The posted primary interval is broad, and the study endpoint covers only the stated period through Week 52. The registry also lists more outcomes than it provides numerical secondary results for, and it does not report a multiplicity strategy. These features limit the strength and scope of conclusions that can be drawn from the posted summaries.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Study of Eliglustat Tartrate (Genz-112638) in Patients With Gaucher Disease Who Have Reached Therapeutic Goals With Enzyme Replacement Therapy (ENCORE) — NCT00943111.
• Registry record last updated 2016-11-25; status last verified 2016-10.
• Results first posted 2014-09-04.
• 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.

23. Record Summary

NCT00943111 is a completed Phase 3 randomized, parallel-group, open-label study comparing eliglustat tartrate with imiglucerase in participants with Gaucher disease type 1 who had reached therapeutic goals with enzyme replacement therapy. The recorded enrollment was 160. The primary endpoint was the percentage remaining stable from baseline through Week 52, assessed in a per-protocol population.

The posted stable percentages were 84.8% for eliglustat and 93.6% for imiglucerase. The sponsor-reported difference was -8.8, with a 95% confidence interval from -17.6 to 4.2. The unadjusted recalculated comparison also has an interval including zero. The registry record does not report the non-inferiority margin, full statistical method, missing-data procedure, or multiplicity strategy, limiting independent assessment of the sponsor’s inferential conclusion.