Study to Test GSK256073 in Patients With Dyslipidemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Test GSK256073 in Patients With Dyslipidemia (NCT00903617), a randomized phase 2 study. The primary outcome is The GSK256073 Area Under Concentration-time Curve (AUC) and High Density Lipoprotein Cholesterol (HDLc) Data to Evolve the Exposure-response Pharmacokinetic/Pharmacodynamic (PK/PD) Relationship for Changes in HDLc Levels.

2. Clinical Question

The question is primarily about an exposure-response relationship: whether differences in drug exposure correspond to differences in a lipid measure. This differs from asking only whether a particular dose changes HDLc relative to placebo. The registry’s primary outcome description names both AUC and HDLc and specifies assessment at Week 2, 4, 6 and 8.

The study also planned to compare GSK256073 with Niaspan in Part B, including effects on lipids and flushing. That comparison was part of the planned design, not a completed comparison reported in the registry. The primary outcome data were not collected after the study stopped at the end of Part A.

3. Trial Design

This was a randomized, double-masked, parallel-group Phase IIa study with placebo control. It was described as multicenter and divided into Part A and Part B. Its stated purpose was to examine the safety, tolerability, and lipid effects of GSK256073 in subjects with dyslipidemia.

Part A was intended to establish a pharmacokinetic/pharmacodynamic (PK/PD) relationship between exposure and lipid effects. The planned groups received GSK256073 at 5 mg, 50 mg, or 150 mg, or placebo. The brief description gives 75 subjects as the Part A target. Part B was intended to confirm the effect using the dose or doses considered most relevant based on Part A data; the brief description gives approximately 90 subjects as its target. These are descriptions of the intended design, not counts of participants who completed each part.

Part B’s listed groups included placebo, 1500 mg Niaspan, a GSK256073 dose selected using Part A data, and an optional further GSK256073 dose. The brief description says Part A and Part B data would be combined to reduce the number of subjects needed in Part B. The registry record does not report how this planned combination would be implemented analytically.

The recorded enrollment was 80, and the study status is completed. The start date was 2009-06-15 and the primary completion date was 2010-02-16. The record describes the study as stopped for futility at the end of Part A. Consequently, the intended Part B confirmation and Niaspan comparison are not reported as completed results.

The registry record does not report the randomization procedure, allocation concealment details, masking procedures, or a protocol for dose selection in Part B. The listed design features establish the broad comparison structure but do not fill in those operational details.

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: A total of 80 participant were enrolled in the study. Participants on lipid-altering medications (prescription, over-the-counter and herbal preparations directed at lipid lowering) were washed out of their treatment for at least 6 weeks prior to randomization and 8 weeks wash out for participants on fibrate medications.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Data was not collected as the study was stopped for futility at the end of Part A due to lack of a compelling PK/PD relationship between GSK256073 and lipid effects that would predict success in achieving significant HDLc raising.

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 The GSK256073 Area Under Concentration-time Curve (AUC) and High Density Lipoprotein Cholesterol (HDLc) Data to Evolve the Exposure-response Pharmacokinetic/Pharmacodynamic (PK/PD) Relationship for Changes in HDLc Levels, measured over Week 2, 4, 6 and 8.

The primary outcome concerned the relationship between GSK256073 exposure and high-density lipoprotein cholesterol (HDLc). Exposure was represented by the area under the concentration-time curve (AUC), a summary of drug concentration over time. The registry describes plotting AUC against HDLc and refining a PK/PD model with Part A observed exposure and HDLc values. The outcome timeframe was Week 2, 4, 6 and 8.

In general, a PK/PD analysis asks whether a measured amount of drug exposure is associated with a measured pharmacological response. AUC can characterize exposure across time, while HDLc is the lipid measure specified as the response in this outcome. Examining their relationship can inform whether exposure differences track with changes in the outcome and can help guide dose selection. That is the rationale for this type of endpoint in a study designed to develop an exposure-response relationship; it does not by itself establish a treatment effect against a comparator.

The registry states that the primary outcome data were not collected because the study stopped for futility at the end of Part A. It attributes the stopping decision to a lack of a compelling PK/PD relationship between GSK256073 and lipid effects that would predict success in achieving significant HDLc raising. Thus, the registry provides the planned endpoint and the reason the study stopped, but not an observed primary outcome estimate, uncertainty interval, or formal treatment comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study’s stated primary method was to examine a pharmacokinetic/pharmacodynamic (PK/PD) relationship. Pharmacokinetics concerns drug exposure in the body, while pharmacodynamics concerns a biological response. In this study, the planned exposure measure was the area under the concentration-time curve (AUC), and the response measure was high-density lipoprotein cholesterol (HDLc). The registry says AUC values would be plotted against HDLc and that a PK/PD model would be refined with Part A observations.

What does an exposure-response relationship tell us?

In general, an exposure-response relationship describes how an outcome varies with measured exposure. It can be useful for considering whether a dose produces exposure associated with a biological change and for selecting doses to study further. A relationship between exposure and outcome is not automatically proof that exposure caused the outcome: interpretation depends on the design, data quality, analysis, and assumptions. The registry’s stated purpose was to evolve this relationship, not simply to report a single contrast between a dose and placebo.

AUC is used as an exposure summary because drug concentration changes over time. The registry does not report an AUC unit, a specific model form, model parameters, an estimation method, or an uncertainty interval. Those details are not reported in the registry record. The record gives Week 2, 4, 6 and 8 as the timeframe for the primary outcome, but does not specify how measurements across these visits would be combined in the analysis.

How does the two-part design fit the question?

In general, a dose-finding or model-development stage can inform which dose or doses merit later confirmation. Part A was intended to establish the exposure-lipid relationship using three GSK256073 doses and placebo. Part B was intended to confirm the effect using dose or doses selected from Part A, with placebo and a Niaspan group also listed. The brief description says data from both parts would be combined to reduce the number of subjects needed in Part B. The precise model, decision rule for selecting doses, and method for combining data are not reported in the registry record.

The plan was not completed as described: the registry says the study stopped for futility at the end of Part A. The outcome description explicitly says data were not collected. Therefore, the planned model refinement, confirmation, and relative comparison cannot be interpreted as completed analyses from the posted results.

What does randomization and masking contribute?

In general, randomization aims to make treatment groups comparable with respect to factors that could influence outcomes, including factors not measured by investigators. Double masking is intended to reduce the chance that knowledge of assigned treatment influences participants’ experiences or outcome assessment. These features can strengthen comparisons when outcomes are collected and analyzed as planned. They do not remove uncertainty caused by absent primary outcome data, and they do not independently establish that groups were comparable in this particular trial.

The registry identifies the study as randomized, double-masked, and parallel, but does not report the randomization method, allocation concealment, details of masking, or the analysis population. It also does not provide a primary outcome analysis. The design labels should therefore be read as descriptions of the intended trial structure rather than evidence for an estimated treatment effect.

How should uncertainty be understood?

In general, a confidence interval expresses the range of effect estimates compatible with the data and a specified statistical procedure. A narrow interval indicates greater precision than a wide interval, while an interval’s interpretation depends on the analysis assumptions and the data available. No primary outcome estimate or confidence interval is reported for this study, so precision about the AUC-HDLc relationship cannot be evaluated from the registry results.

In general, statistical significance and clinical or biological importance are distinct questions. A small p-value, if reported, would address compatibility with a null hypothesis under a model; it would not alone establish the size, relevance, or reliability of an effect. The registry provides no primary outcome p-value. Its statement about a lack of a compelling relationship is the explanation for stopping, not a reported numerical test result.

The record reports zero analyses and 23 outcome measures. This count does not disclose how many were analyzed, which measures had data, or what statistical procedures were applied. Those details are not reported in the registry record. The reported adverse-event participant counts are descriptive; no uncertainty intervals or comparative tests are presented in the record.

Why does over-dispersion matter in general?

General explanation: over-dispersion occurs when observed variability is greater than a statistical model assumes. If a model treats observations as less variable than they really are, its uncertainty estimates can be too small, making results appear more precise than warranted. Analysts may use methods that allow extra variability when the outcome and design call for it. The registry does not identify a count model, an over-dispersion adjustment, or any other inferential method for the adverse-event results, so no such method should be inferred.

Overall, the registry gives the broad PK/PD objective, the planned visits, and the reason the study stopped. It does not report the model specification, estimation procedures, statistical tests, confidence intervals, missing-data methods, or a detailed analysis plan. General principles explain what the intended approach could address, but they cannot replace the unreported analyses.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 23 outcome measures, including the primary PK/PD outcome and secondary safety, vital-sign, laboratory, and flushing outcomes. It records zero analyses. The presence of multiple outcomes creates the general possibility of multiplicity: when many statistical tests are performed, the chance of finding at least one apparently unusual result can increase. In general, investigators may address this through a prespecified hierarchy, adjustment procedures, or a distinction between confirmatory and exploratory outcomes. Which approach was planned or used is not reported in the registry record.

The primary outcome description states that its data were not collected because the study stopped at the end of Part A. The record does not explain whether any secondary outcomes were collected or analyzed, how missing measurements were handled, or whether data from participants who discontinued were included in any analysis. Those missing-data procedures and analysis populations are not reported in the registry record.

Part A and Part B were intended to contribute to dose selection and confirmation, and the brief description says data from both parts would be combined. The registry does not report a prespecified rule for using Part A information to select Part B doses, or a method for accounting for that selection in inference. Since the study stopped before Part B, the planned confirmation is not reported as completed.

In general, an analysis population defines which participants’ data contribute to a particular estimate, such as all randomized participants or those who received treatment. The registry does not state the population used for an efficacy analysis, and there is no reported primary efficacy analysis to interpret. The adverse-event counts identify participants at risk in each listed group, but do not establish a broader analysis-population definition.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse events for zero participants in each listed group: GSK256073 5 mg, GSK256073 50 mg, GSK256073 150 mg, and placebo. Recorded deaths were zero in each of those groups. Under other adverse events, the participant counts are 8 for GSK256073 5 mg, 12 for GSK256073 50 mg, 17 for GSK256073 150 mg, and 14 for placebo. These are descriptive counts, not estimates from a reported comparative safety analysis.

In general, a participant count does not indicate how many separate events occurred, how long participants were observed, or the severity and clinical context of each event. The registry lists no top serious-event terms. It does not report a formal comparison, uncertainty intervals, or detailed exposure time for these safety results. The listed number at risk is 19 for GSK256073 5 mg, 20 for GSK256073 50 mg, 20 for GSK256073 150 mg, and 21 for placebo; the record does not describe further details of the safety analysis population.

Zero recorded serious events should be read as no serious events recorded in the respective groups in this registry summary, not as proof that serious events cannot occur. The other-event counts likewise do not, on their own, establish that one group had a greater or lesser risk than another. The study stopped at the end of Part A, so the safety counts should not be read as results from the planned Part B Niaspan comparison.

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

The registry record supports a limited conclusion about the trial’s course: it was designed to investigate GSK256073’s lipid effects and exposure-response relationship, but stopped at the end of Part A. The stated reason was a lack of a compelling PK/PD relationship that would predict success in achieving significant HDLc raising. The primary outcome description says data were not collected. Thus, the central planned endpoint has no reported estimate in the registry.

This does not provide a quantitative answer about the amount of HDLc change associated with GSK256073 exposure. It also does not provide a completed estimate comparing a GSK256073 group with placebo, or a comparison with Niaspan. No primary outcome effect size, confidence interval, or p-value is reported. The stopping rationale should not be transformed into a numerical treatment-effect claim.

The posted safety information records zero serious adverse events and zero deaths in each of the four listed groups. It also gives participant counts for other adverse events. These descriptive summaries are useful as recorded events, but without reported methods and comparative analyses they do not determine whether event risks differed between groups or establish a comprehensive safety profile.

In general, a trial can be informative even when a planned efficacy endpoint is not observed: the reason for stopping may guide whether a research question merits further testing. However, a stopping statement is not a substitute for the planned endpoint data. The registry does not report the decision threshold, interim statistical procedure, or formal stopping rule, so the precise evidential basis for the futility decision cannot be independently assessed from this record.

The study’s intended Part B phase, including dose confirmation and a Niaspan arm, is not represented as a completed comparison. The record therefore does not answer whether selected doses would have confirmed an effect, or how GSK256073 would compare with Niaspan on lipids or flushing. Interpretation should remain confined to the recorded stopping rationale and the descriptive safety counts.

13. Why This Trial Matters Statistically

This trial illustrates a distinction between a planned clinical question and an observed result. Its primary objective was not simply to compare a fixed dose with placebo; it was to develop an exposure-response relationship connecting GSK256073 AUC with HDLc. Such a relationship can be relevant to dose selection, but it requires collected exposure and outcome data and a reported analysis. The registry says the primary data were not collected.

The two-part structure also highlights how early-stage studies may use an initial phase to shape a later confirmatory phase. Part A was intended to inform selection of dose or doses for Part B, and Part B was intended to confirm the effect. Yet the record says the study stopped at the end of Part A. Therefore, the planned confirmation and the intended Niaspan comparison cannot be treated as evidence available from completed results.

Statistically, the record makes clear that a design label, an endpoint definition, and a rationale for stopping are different kinds of information. Randomization and masking describe intended safeguards for comparisons. The endpoint description defines what the investigators planned to measure. The futility statement explains why the study stopped. None of those details supplies the absent primary outcome estimate or its precision.

The adverse-event counts show another important distinction: descriptive event reporting is not the same as inferential comparison. Counts can be reported even when no formal effect estimate or uncertainty measure is available. Reading them carefully avoids treating a zero count as proof of no risk, or treating differences in raw counts as evidence of a group difference.

Finally, the record demonstrates the importance of transparent reporting about what was planned, what was collected, and what remains unavailable. Here, the primary endpoint data were not collected, and analysis details such as multiplicity handling and missing-data methods are not reported. Those limits shape what can be concluded from the study more than the randomized design alone.

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 most consequential limitation for interpretation is explicit: the primary outcome data were not collected after the study stopped at the end of Part A. There is consequently no reported quantitative estimate of the AUC-HDLc relationship, no confidence interval, and no primary outcome test result. The registry’s description of a lack of a compelling relationship is a stopping rationale rather than a complete statistical result.

The planned Part B dose confirmation and Niaspan comparison are not reported as completed. Although the brief description outlines the intended arms and use of Part A information, the registry does not report how doses would have been selected, how the two parts would have been combined analytically, or whether any Part B data were collected.

The record lists 80 as enrollment and provides safety group counts, but does not report a detailed account of the participants’ analysis populations, follow-up for safety, or handling of missing observations. It also does not give the statistical analysis plan, model specification, multiplicity procedure, or a sample-size justification. These items are not reported in the registry record and should not be inferred from the planned design or enrollment.

The safety information is limited to descriptive participant counts for serious and other adverse events and recorded deaths. The registry lists no top serious-event terms, and it does not provide comparative estimates or uncertainty intervals. The available counts cannot establish comparative risks or characterize event timing and duration.

The record describes the study as randomized, double-masked, parallel, multicenter, and placebo-controlled, but does not provide operational details such as the randomization method or masking procedures. These omissions do not negate the stated design; they limit the ability to assess its implementation from the registry record alone.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study to Test GSK256073 in Patients With Dyslipidemia — NCT00903617.
• Registry record last updated 2019-12-05; status last verified 2019-11.
• Results first posted 2017-09-21.
• 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

NCT00903617, titled “Study to Test GSK256073 in Patients With Dyslipidemia,” was a randomized, double-masked, parallel-group Phase IIa study sponsored by GlaxoSmithKline. It was designed to examine safety, tolerability, and lipid effects in people with dyslipidemia. Recorded enrollment was 80. The study began on 2009-06-15, had a primary completion date of 2010-02-16, and is listed as completed.

Part A planned GSK256073 doses of 5 mg, 50 mg, and 150 mg plus placebo to develop an exposure-response relationship. Part B was intended to confirm a selected dose or doses and included placebo and 1500 mg Niaspan. The registry says the study stopped for futility at the end of Part A and that primary outcome data were not collected, citing a lack of a compelling relationship predictive of significant HDLc raising.

Serious adverse events and deaths were recorded as zero in each listed group. Other adverse-event participant counts were 8, 12, 17, and 14 across the GSK256073 5 mg, GSK256073 50 mg, GSK256073 150 mg, and placebo groups, respectively. No primary outcome analysis is reported.