Extension to a Randomized, Double-blind, Placebo Controlled Study of LCQ908 in Subjects With Familial Chylomicronemia Syndrome.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Extension to a Randomized, Double-blind, Placebo Controlled Study of LCQ908 in Subjects With Familial Chylomicronemia Syndrome. (NCT01589237), a na phase 3 study. The primary outcome is Number of Patients With Any Adverse Events, Serious Adverse Events and Death.

2. Clinical Question

3. Trial Design

This was a Phase 3, open-label extension study of LCQ908 in subjects with Familial Chylomicronemia Syndrome (FCS) (HLP Type I). Its official title describes it as a 52-week safety and tolerability extension to a randomized, double-blind, placebo-controlled study. That description refers to the parent study; this extension itself is recorded as having no masking, no applicable allocation, and a single-group model. It should therefore not be interpreted as a randomized comparison.

The registry lists enrollment as 38. The study began in 2013-02, had primary completion in 2015-07, and has status TERMINATED. The record does not report why it was terminated, whether the planned follow-up was completed, or whether the termination changed the analysis. Those details should not be inferred from the status alone.

LCQ908 was the listed drug intervention. The regimen description states that patients began at 10 mg/day, with optional up-titration after at least 8 weeks on a dose and one permitted down titration from the highest dose attained. The adverse-event results are grouped by Part A and Part B regimen labels, including placebo, 20 mg, 40 mg, and regimens from Study A2212. The registry does not describe the allocation process connecting those groups to the extension, so the groups cannot be treated as contemporaneous randomized arms.

The stated purpose was to assess long-term safety and tolerability and continued triglyceride-lowering efficacy. The primary outcome is safety-focused; changes in triglycerides, cholesterol measures, glycerol, free fatty acids, and apolipoproteins are listed as secondary outcomes. The record names nine outcome measures, but reports zero analyses. It does not provide an efficacy estimate or an inferential analysis for these outcomes.

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: 100% patients who completed the screening phase were enrolled in the study.

Part A (52 Weeks)

Reasons for not completing this period:

Part B (Planned for 78 Week-terminated)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety set (SAF) - All subjects who received at least one dose of study drug and had at least one post-baseline safety assessment in this extension study.

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) - All subjects in the extension study who were in full analysis set in either study LCQ908A2212/NCT01146522 or LCQ908B2302/NCT01514461.

6. Primary Endpoint

The registry lists the primary outcome as Number of Patients With Any Adverse Events, Serious Adverse Events and Death, measured over 52 weeks.

The primary endpoint is the number of patients with any adverse events, serious adverse events, and deaths over 52 weeks. It is a count-based safety endpoint: it describes how many participants in the defined safety population were recorded as experiencing events, rather than estimating a change in a laboratory measurement or a time-to-event effect. The safety set includes subjects who received at least one dose of study drug and had at least one post-baseline safety assessment in the extension.

Such endpoints are used to characterize the kinds and frequency of harms recorded during treatment and follow-up. Serious adverse events are an important part of safety monitoring because their seriousness distinguishes them from the broader category of adverse events; the registry's exact event definitions and adjudication procedures are not reported. Counts alone do not indicate event severity beyond the registry's classification, duration, recurrence, timing, or relationship to treatment.

The 52-week timeframe identifies the stated outcome window. It does not establish that every participant was observed for the full period. The registry lists group-level counts for serious and other adverse events, but the death values are not reported in the registry record. It also does not provide an overall endpoint estimate, confidence interval, or comparative test. Accordingly, the endpoint supports descriptive reading of the recorded safety counts, not a causal conclusion about treatment or a comparison of regimens.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What the registered outcome captures. The primary outcome is the number of patients with any adverse events, serious adverse events, and deaths during 52 weeks. It is a count endpoint, not a continuous outcome such as a mean change in triglycerides. In general, a count endpoint can be presented as a number of participants experiencing an event and the number at risk. Those quantities provide a direct description of recorded events, but they do not by themselves account for differences in follow-up time or estimate a treatment effect. The registry record does not specify an event-rate model, an exposure-adjusted approach, or a formal comparison.

Why the design matters. Random allocation can make treatment groups more comparable on average, supporting causal comparisons when the rest of the design and analysis are appropriate. This extension is recorded as having allocation not applicable and a single-group model, with no masking. Its adverse-event group labels include placebo and dose regimens, but the record identifies Part A and Part B and includes a regimen from Study A2212. These labels alone do not establish randomized assignment within the extension. The record explicitly does not support treating the groups as like-for-like controls. Accordingly, the group counts are descriptive and should not be read as estimates of a causal contrast.

Counts, denominators, and uncertainty. The serious-event and other-event entries give a number at risk and a number affected for each listed group. In general, a denominator gives context for a count, but a count fraction is not a complete account of uncertainty or follow-up. A confidence interval, when reported, describes the range of values compatible with a specified statistical procedure and its assumptions. No confidence intervals or comparative tests are reported in the registry record. The record also does not state whether participants were followed for equal durations, how events were collected, or how repeat events were handled. Without that information, the counts should not be extended into unreported rates or adjusted comparisons.

Over-dispersion and event models. In general, count data can vary more than a simple model assumes, a property often called over-dispersion. When that matters, a suitable model may need to allow for greater variability than a basic count model. This is a general statistical consideration, not a claim about the analysis of this extension. The registry record reports zero analyses and does not identify any model, adjustment variables, variance assumptions, or inferential procedure. No conclusions about over-dispersion or model fit can therefore be drawn from the posted results.

Outcome families and multiplicity. The record lists nine outcome measures, including the primary safety outcome and secondary changes in triglycerides and several lipid-related measures. In general, testing many outcomes can increase the chance of at least one apparently notable result if no multiplicity strategy is specified. A statistical plan may define a hierarchy, adjust significance thresholds, or treat secondary outcomes as exploratory. The registry record does not report a multiplicity procedure, a hierarchy, or analyses for the listed outcomes. It would be inappropriate to assume that any particular control strategy was used.

Planning illustrations are not trial results. The accompanying sample-size calculations are described as planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect is a fraction of the observed effect. In general, such calculations ask how many participants per arm would be needed under a specified assumed effect and statistical framework. They are not observed power and do not change the extension's recorded single-group design. Because the registry does not report an inferential effect estimate for this extension, the illustrations should not be mistaken for evidence of precision or evidence that the study was designed around those assumptions.

What can be concluded statistically. The registry provides event counts by its listed groups and names serious-event terms with percentages. It does not report an analysis population for each separate group beyond the endpoint's safety-set definition, a statistical analysis plan, estimates of comparative effects, or measures of uncertainty. The record also does not report how missing observations were handled. In general, these details determine how robustly an analysis can address differences between groups and incomplete follow-up. Their absence limits interpretation to what is directly registered: descriptive safety information, without a reported inferential comparison.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists nine outcome measures. The primary outcome concerns adverse events, serious adverse events, and deaths over 52 weeks; secondary outcomes include changes from baseline in triglycerides, cholesterol measures, glycerol, free fatty acids, and apolipoproteins. It reports zero analyses. A multiplicity strategy, such as an outcome hierarchy or adjustment for testing multiple outcomes, is not reported in the registry record. Therefore, the listed endpoints do not establish which outcomes were intended to support confirmatory claims or how any multiple testing was addressed.

Missing-data procedures are also not reported in the registry record. The record does not specify how missing safety assessments, incomplete follow-up, or unavailable laboratory measurements were handled, nor does it describe imputation or sensitivity analyses. The primary outcome population is defined as subjects who received at least one dose and had at least one post-baseline safety assessment in the extension. That definition identifies who could enter the safety set, but it does not explain how missing observations within that set were treated.

In general, missingness can affect interpretation when the chance of an observation being unavailable is related to health status, treatment, or outcome. Statistical methods may describe the extent of missingness and assess the effect of plausible assumptions, but no such approach is stated. The record also does not report interim analyses, a statistical analysis plan, or endpoint-specific analysis populations. These omissions prevent assessment of whether the reported counts reflect complete follow-up or a particular missing-data strategy. They should be treated as limitations of the registry information, not filled in by assuming a standard procedure.

11. 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: pancreatitis (40.0%), pancreatitis acute (10.0%), postoperative wound infection (10.0%), anaemia (8.3%), coronary artery stenosis (8.3%).

Read the serious adverse-event figures as group-level counts: the first number is the number affected and the second is the number at risk. For example, the Part A 20 mg regimen group has 6 affected among 12 at risk, while the Part B 20 mg group has 0 among 6. These entries describe what the registry records for those labels; they are not an adjusted comparison. The “other adverse events” counts are listed separately and should not be combined with the serious-event counts.

The group names include Part A and Part B, placebo and dose regimens, and a regimen from Study A2212. Since the extension is open label, single group, and has allocation recorded as not applicable, those labels do not make the groups randomized controls. Differences in counts cannot be attributed to treatment from this record alone. The definition and adjudication rules for serious events are not reported in the registry record.

Deaths are not reported in the registry record. The serious-event term list includes percentages, but the denominators and counting rules for those percentages are not stated. The percentages therefore should be read as registered descriptive summaries, not as directly comparable group-specific risks.

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

The record contributes descriptive information about safety events in an open-label LCQ908 extension for people with Familial Chylomicronemia Syndrome (FCS) (HLP Type I). It identifies a 52-week primary safety outcome and gives serious and other adverse-event counts for several regimen-labeled groups. It also lists serious-event terms and percentages. This allows readers to see which events were recorded in those listings and how the entries are organized by Part A and Part B labels.

It does not establish that LCQ908 caused or prevented any particular event. The extension is not a randomized comparison, and the record does not report an inferential analysis, confidence intervals, or adjusted effects. The presence of placebo and dose labels in the adverse-event groups is not enough to make those groups comparable experimental arms. The group counts should therefore not be interpreted as evidence that one regimen is safer or less safe than another.

The registry also does not report deaths as numerical results, reasons for termination, completion of planned follow-up, event definitions, missing-data handling, or a statistical analysis plan. The stated safety population requires at least one dose and at least one post-baseline safety assessment, but that definition does not establish complete observation through the full timeframe for every participant.

Secondary lipid-related outcomes are named, including changes in triglycerides, but the record reports zero analyses. No efficacy result or precision estimate for those outcomes can be inferred from their listing. Overall, the posted results are a limited descriptive safety record rather than a basis for a causal treatment conclusion, a comparative safety ranking, or an estimate of efficacy.

13. Why This Trial Matters Statistically

This trial is statistically notable because its parent-study context and extension design must be kept separate. The official title describes an extension to a randomized, double-blind, placebo-controlled study, whereas the extension itself is registered as open label, with allocation not applicable and a single-group model. That distinction matters: randomization in a parent study does not automatically establish randomized comparisons within an extension.

The adverse-event results show why group labels require careful interpretation. Part A and Part B listings include placebo, dose regimens, and a group from Study A2212. The registry's counts are useful as descriptions of recorded events, but differences between those groups do not constitute a randomized estimate of relative safety. This is a general design issue: a descriptive group contrast can be influenced by differences in participant composition, treatment history, exposure, or follow-up, and the record does not report enough information to separate those possibilities.

The record also illustrates the gap between registered outcomes and reported analyses. It names nine outcome measures, including safety and lipid-related outcomes, but records zero analyses. Consequently, readers have no reported uncertainty estimates or inferential results with which to assess precision. The sample-size illustrations use stated planning assumptions, but they are not the study's observed power and do not transform the extension into a two-arm trial.

For clinical researchers and biostatisticians, the central lesson is to align interpretation with the design and the analysis actually reported. Here, the evidence supports a cautious description of registered adverse-event counts, not a causal comparison or a claim about efficacy. The missing statistical-plan and missing-data details further constrain what can be concluded.

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.

Several limitations are specific to this record. First, the extension is open label and recorded as a single-group study with allocation not applicable. Although the adverse-event listings are divided into regimen groups, the record does not establish those groups as randomized comparisons. The Part A and Part B labels and the group from Study A2212 also make direct comparison difficult to interpret without additional design details.

Second, the primary outcome is stated for 52 weeks, but the registry does not report whether each participant completed that timeframe or how differences in follow-up were handled. The safety-set definition requires at least one dose and one post-baseline safety assessment; it does not describe the completeness of observation after entry into that set. Missing-data methods are not reported.

Third, the registry lists event counts but does not report event definitions, adjudication procedures, timing, duration, recurrence rules, or treatment relatedness. Death counts are not reported in the registry record. The denominators and counting rules for the listed serious-event percentages are also not reported, limiting interpretation of those summaries.

Finally, the record reports zero analyses and does not describe an analysis plan, multiplicity strategy, interim analyses, or reasons for termination. Secondary lipid-related outcomes are named, but no analyses are reported for them. These gaps mean the record cannot support estimates of comparative effects, precision, or efficacy, and the reason for the study's terminated status should not be inferred.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Extension to a Randomized, Double-blind, Placebo Controlled Study of LCQ908 in Subjects With Familial Chylomicronemia Syndrome. — NCT01589237.
• Registry record last updated 2016-11-15; status last verified 2016-09.
• Results first posted 2016-11-15.
• 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.

18. Record Summary

This Phase 3 record concerns an open-label, 52-week safety and tolerability extension of LCQ908 in subjects with Familial Chylomicronemia Syndrome (FCS) (HLP Type I). Enrollment is listed as 38; the study began in 2013-02, had primary completion in 2015-07, and is marked TERMINATED. The primary outcome is the number of patients with any adverse events, serious adverse events, and deaths.

The registry reports group-level serious and other adverse-event counts, plus serious-event terms with percentages. Deaths are not reported in the registry record. The extension is recorded as single group, with no masking and allocation not applicable, so the regimen listings are not a randomized comparison. Nine outcome measures are listed, but zero analyses are reported. The registry does not report a statistical analysis plan, multiplicity or missing-data procedures, or a reason for termination. The results therefore support descriptive reading of the registered safety information, not causal or efficacy conclusions.