This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Combined Effects of Non-statin Treatments on Apolipoprotein A-I Up-Regulation (CENTAUR): A Feasibility Study (NCT00728910), a non-randomized phase 2 study. The primary outcome is The Apolipoprotein A-I Fractional Catabolic Rate (FCR).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00728910 |
| Phase | Phase 2 |
| Condition | Dyslipidemia |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 25 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Pennsylvania |
| Results posted | Yes |
2. Clinical Question
Population
People with dyslipidemia were enrolled. The planned enrollment was 25 participants. For the primary endpoint, the stated analysis population was participants who completed any of the three phases and had kinetic study data available for any phase of treatment.
Intervention
The regimen involved atorvastatin, ABT335 and extended-release niacin. The registry describes atorvastatin at 10 mg/day for 4 weeks; ABT335 at 135 mg/day added to atorvastatin for at least 8 weeks; and extended-release niacin titrated up to 2 g/day, with aspirin 325 mg/day, added to atorvastatin and ABT335 for 10 weeks.
Comparator
The record describes a non-randomized, single-group study, not a like-for-like comparison between treatment arms. Changes across the listed time points can be considered within the treatment sequence, but the registry does not describe a concurrent control group.
Primary question
The primary endpoint was apolipoprotein A-I fractional catabolic rate, measured in pools/day. The registry lists assessment at 4 weeks, 12 weeks and 22 weeks. It does not report the endpoint estimates, confidence intervals, or the statistical comparisons between these time points.
The study’s stated aim was to investigate whether combining medications with atorvastatin could add to changes in cholesterol-related risk factors, including HDL cholesterol, and to assess safety and side effects. The primary endpoint focused specifically on the rate of irreversible loss of labeled leucine from a modeled plasma compartment associated with apoA-I. That kinetic measure is distinct from a direct clinical outcome such as cardiovascular events.
The treatment description presents three components in a sequence: atorvastatin, then ABT335 added to atorvastatin, then extended-release niacin and aspirin added to the preceding medications. The study is identified as a feasibility study, and its registry design is single-group and non-randomized. It therefore addresses measurements during combination treatment rather than a randomized estimate of the combination’s effect relative to a control regimen.
3. Trial Design
This completed phase 2 study enrolled 25 participants with dyslipidemia. The registry lists a start date of 2008-06 and primary completion in 2009-08. The sponsor was the University of Pennsylvania. Allocation was non-randomized, masking was none, and the model was single-group. These design features mean the record does not describe random assignment to competing treatment groups or a blinded comparison.
The treatment descriptions specify atorvastatin 10 mg/day by mouth for a total duration of 4 weeks. ABT335 135 mg/day by mouth was added to atorvastatin for a total duration of at least 8 weeks. Extended-release niacin was titrated up to 2 g/day, with aspirin 325 mg/day, and added to atorvastatin and ABT335 for 10 weeks. The registry lists primary endpoint time points at 4 weeks, 12 weeks and 22 weeks. The record does not provide additional detail about visit timing, adherence, dose changes, or the sequence of measurements beyond these descriptions.
The endpoint population is described as participants who completed any of the three phases and for whom kinetic study data were available for any phase of treatment. This definition is not identical to a statement that every enrolled participant contributed data at every time point. The number with endpoint data at each time point is not reported in the registry record.
The record lists 3 outcome measures and 4 analyses. It does not report a statistical analysis plan, a sample-size justification, or the handling of interim analyses. The design should therefore be read from the registry’s explicit entries: a small, single-group feasibility study with repeated treatment-period assessments, rather than a randomized efficacy comparison. The treatment sequence and endpoint schedule make within-study changes relevant, but do not by themselves isolate the effects of individual drugs from time, sequence, or other influences.
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: Subjects washed out of current lipid lowering medications
Atorvastatin
| Stage | Atorvastatin/ABT335/Niaspan |
|---|---|
| STARTED | 25 |
| COMPLETED | 22 |
| NOT COMPLETED | 3 |
Atorvastatin+ABT335
| Stage | Atorvastatin/ABT335/Niaspan |
|---|---|
| STARTED | 22 |
| COMPLETED | 22 |
| NOT COMPLETED | 0 |
Atorvastatin+ABT335+ER Niacin
| Stage | Atorvastatin/ABT335/Niaspan |
|---|---|
| STARTED | 22 |
| COMPLETED | 22 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: Patients who completed any of the three phases for whom the kinetic study data was available for any phase of treatment
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.
| Characteristic | Unit | Group 1 |
|---|---|---|
| Participants analysed | 25 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 25 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age, Continuous | years | 47 (SD 10.74) |
| Sex: Female, Male: Female | Participants | 13 |
| Sex: Female, Male: Male | Participants | 12 |
| Region of Enrollment: United States | participants | 25 |
6. Primary Endpoint
The registry lists the primary outcome as The Apolipoprotein A-I Fractional Catabolic Rate (FCR), measured over 4 weeks, 12 weeks and 22 weeks.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | pools/day |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was the apolipoprotein A-I fractional catabolic rate (FCR), expressed in pools/day, with the mean and a 95% confidence interval specified as the summary. FCR is a kinetic measure of apoA-I turnover: it represents the rate of irreversible loss of leucine pools from the modeled plasma compartment. It is not a direct count of cardiovascular events and is not itself a measure of HDL cholesterol concentration.
The registry describes a tracer study. Participants received small, identical meals over 20 hours, beginning at 0600 hrs, and took study medications at 0800 hrs. Five hours after the first meal, labeled leucine was administered intravenously, followed by a primed-constant infusion over 15 hrs, with 14 blood samples collected. The registry says isotopic enrichment of leucine in the apoA1 band was calculated. A compartment model was then used, assuming steady-state apo A-I metabolism, to represent precursor, intracellular synthesis and assembly, and dispositional kinetics, including a plasma pool.
General: kinetic endpoints can help characterize how quickly a biological component is produced, distributed, or removed. The FCR is used to describe one aspect of apoA-I metabolism; interpretation depends on the tracer measurements and model assumptions as well as the observed data. The registry lists assessments at 4 weeks, 12 weeks and 22 weeks, but does not report the resulting means or confidence intervals. The magnitude and precision of the endpoint estimates therefore cannot be evaluated from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the primary endpoint, its units, summary measure, assessment times, and a description of the kinetic method. It does not report numerical results for the mean apolipoprotein A-I FCR at 4 weeks, 12 weeks or 22 weeks, nor does it give confidence intervals or tests comparing measurements. Consequently, the direction, magnitude and precision of any change in FCR are not reported in the registry record. No conclusion about an increase or decrease can be drawn from the endpoint description alone.
The treatment sequence included atorvastatin, ABT335 added to atorvastatin, and extended-release niacin with aspirin added to the preceding medications. Because the study is described as a single group with non-randomized allocation and no masking, it does not supply a randomized comparison separating the effects of these treatment components. Measurements at different time points could reflect treatment exposure and other changes over time; the registry record does not provide a design feature that would establish which component caused a measured change.
General: a confidence interval describes statistical uncertainty around an estimate under the analysis assumptions. Its width is informative about precision, but it does not resolve design limitations such as lack of a concurrent randomized control group. In this record, the confidence-interval format is specified, but the actual intervals are not reported. Precision cannot therefore be assessed from the registry entries.
The stated primary analysis population includes participants who completed any of the three phases and had kinetic data available for any treatment phase. That wording allows data to be available for a subset of phases rather than necessarily all phases for every participant. The registry does not report the number contributing endpoint data at each time point, the number excluded from each analysis, or how incomplete measurements were handled. Those omissions limit assessment of whether estimates at different time points were based on comparable groups of participants.
The record lists 3 outcome measures and 4 analyses, but does not state which analysis was primary beyond the named primary endpoint, how the analyses related to one another, or whether multiplicity was addressed. The statistical analysis plan is not reported in the registry record. Without the numerical results and analysis details, neither statistical significance nor the robustness of any apparent pattern can be judged. The enrollment of 25 is a design fact, not evidence by itself that an effect was or was not detectable.
Overall, the registry describes what was measured and how the tracer-based endpoint was intended to be derived, but does not provide the outcome estimates needed to characterize the posted result. The available information supports describing the study design and endpoint methodology, not quantifying treatment-associated changes or attributing them to a specific medication.
9. Statistical Methods Explained
What does the endpoint summary represent?
The primary outcome is continuous: the registry specifies a mean FCR, in pools/day, with a 95% confidence interval. A mean describes the average endpoint value in the analyzed participants. A confidence interval communicates uncertainty around that estimated mean, conditional on the data and statistical assumptions used to calculate it. The registry record names this summary format but does not report its numerical values, so neither the estimated means nor their precision can be interpreted.
General: continuous outcomes can take a range of numerical values, rather than representing only counts or categories. For a continuous endpoint, a mean is one way to summarize a group’s measurements. It does not show the full spread of individual values, and it may not describe every participant’s response. The record does not report additional distribution summaries for FCR.
How was FCR measured?
The registry describes a stable-isotope tracer procedure and a compartment-model analysis. Participants received a controlled sequence of small meals over 20 hours, took medication at 0800 hrs, and were given intravenous labeled leucine five hours after the first meal. A primed-constant infusion continued for 15 hrs, with 14 blood samples collected. Isotopic enrichment in leucine from the apoA1 band was calculated, and the model represented precursor leucine, an intracellular compartment for apoA1 synthesis and lipoprotein assembly, and compartments for subfraction disposition, including a plasma pool.
The endpoint is defined as the rate of irreversible loss of leucine pools from Compartment 3. The registry states that the model assumed steady-state apo A-I metabolism. General: a compartment model is a mathematical representation of flows among connected pools. Model-derived rates are not direct observations in the same way as a laboratory concentration; their interpretation depends on the measurements and the model structure and assumptions. The registry gives a description of the compartments but does not report model diagnostics, sensitivity analyses, or alternative-model results.
What does a confidence interval add?
General: a confidence interval is a range calculated from sample data to express uncertainty about an estimated quantity. A narrower interval usually indicates greater statistical precision under the chosen method, while a wider interval indicates less precision. The interval does not automatically account for bias from study design, missing measurements, or an incorrect model. No interval bounds are reported for the endpoint in the registry record, so this study’s precision cannot be assessed from those entries.
What can repeated time points establish?
The primary endpoint timeframe lists 4 weeks, 12 weeks and 22 weeks. Repeated measurements can describe how an outcome varies over time in the participants measured. General: when the same people contribute measurements at several times, the observations are related, and an analysis may need to account for that relationship. The record does not report the statistical method used for repeated measurements, whether all time points were analyzed jointly, or whether comparisons were made between particular time points.
The single-group, non-randomized design matters to interpretation. General: a change over time in one group does not, on its own, distinguish an effect of treatment from other time-related influences. A randomized concurrent comparison can help address some alternative explanations, but the registry describes no such control group for this study. It also does not report a masking procedure.
What is the role of sample-size planning?
The planning description refers to an illustration based on a fraction of an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It specifies that non-time-to-event planning entries are participants per arm. These are planning assumptions, not the study’s observed enrollment results or evidence of observed power. The registry does not report the study’s own sample-size justification, and the numerical planning estimates are not reported in the registry record. Because the actual study is described as a single group, the illustration’s equal-allocation assumption does not describe the enrolled trial design.
General: a sample-size calculation estimates how many observations a hypothetical design might require to detect a specified effect under stated assumptions. It does not establish that an effect exists, and a post hoc calculation based on an observed effect should not be called observed power. Any planning illustration must be interpreted separately from the trial’s actual design and outcome estimates.
What cannot be reconstructed from the registry entries?
The record does not report the inferential test, model specification for outcome comparisons, covariate adjustment, confidence-interval calculation method, or handling of repeated observations. It does not report diagnostics for the kinetic model, missing-data procedures, or a correction for multiple analyses. These details are necessary to reproduce the statistical analysis or to assess whether modeling choices affected its conclusions. The endpoint description offers methodological context, but it is not a substitute for a complete analysis plan or numerical results.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 3 outcome measures and 4 analyses. It identifies FCR as the primary endpoint, but does not report how the other outcomes and analyses were ranked, which comparisons were prespecified, or whether the analysis accounted for multiple testing. A multiplicity plan is not reported in the registry record.
General: when several outcomes or comparisons are examined, the chance of at least one apparently unusual result can increase if each is interpreted separately without accounting for the set of analyses. Adjustment methods and prespecified outcome hierarchies are possible approaches, but the registry does not state that any particular approach was used. The absence of a reported plan does not establish that no adjustment occurred; it means the record does not describe one.
The stated primary endpoint population comprised participants who completed any of the three phases and had kinetic study data available for any phase of treatment. The number of participants with usable data at each time point is not reported in the registry record. Nor are reasons for missing data, withdrawals, exclusions, or the extent of incomplete measurement reported. The record does not describe imputation, a complete-case analysis, or another missing-data procedure.
General: missingness can affect interpretation when participants without measurements differ from those with measurements, or when missingness is related to outcomes. Without counts and reasons for unavailable data, it is not possible to determine whether the analyzed participants represent all enrolled participants at each assessment. The registry’s population wording also does not establish that every participant contributed measurements at every listed time point.
The statistical analysis plan, treatment of incomplete repeated measurements, and definition of analysis sets beyond the stated endpoint population are not reported in the registry record. These gaps limit reproducibility and make it difficult to judge the sensitivity of any reported estimates to missing data or multiple analyses.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Atorvastatin/ABT335/Niaspan | 1 | 25 | 4.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 4% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Atorvastatin/ABT335/Niaspan | 1 of 25 |
Most frequent serious adverse event terms
| Event term | Organ system | Atorvastatin/ABT335/Niaspan |
|---|---|---|
| ulcer | Gastrointestinal disorders | 1 of 25 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Atorvastatin/ABT335/Niaspan |
|---|---|---|
| headache | Nervous system disorders | 1 of 25 |
Serious events with the highest arm-level rate: ulcer (4.0%).
The registry lists one treatment group, titled atorvastatin/ABT335/Niaspan, with 25 participants at risk for serious adverse events and 1 affected. For other adverse events, it also lists 25 participants at risk and 1 affected. The record identifies ulcer as the top serious adverse event term, at 4.0%. Deaths are not reported in the registry record.
These are descriptive safety counts for the listed group. The registry entry does not specify whether the participant recorded for serious adverse events was also the participant recorded for other adverse events, so the entries should not be added to infer a number of distinct participants. The listed ulcer percentage is a reported term-level figure; the record does not give additional event-level descriptions, timing, severity grading, or causal assessments in the registry record presented.
General: adverse-event counts describe events recorded under the study’s collection and reporting procedures. They do not establish that a medication caused an event, and a small group’s counts cannot characterize uncommon risks precisely. The record does not describe a control group for comparing event rates. Safety interpretation is therefore limited to the reported counts and term, rather than a comparative estimate of treatment-related risk.
12. What the Result Does, and Does Not, Mean
This record documents a phase 2 feasibility study of a medication sequence involving atorvastatin, ABT335 and extended-release niacin with aspirin. Its primary endpoint was a kinetic measure of apoA-I turnover, assessed at 4 weeks, 12 weeks and 22 weeks. The registry gives a detailed description of the tracer procedure and compartment model, and specifies a mean with a 95% confidence interval as the endpoint summary.
However, the endpoint estimates and confidence intervals are not reported in the registry record. The record therefore does not establish the direction or size of any FCR change, or how precisely it was estimated. It also does not report the statistical comparisons between time points. No treatment-effect claim can be supported from the endpoint description alone.
The study’s single-group, non-randomized design is important. Even if changes were reported, a before-and-after pattern in one group would not by itself show that the medication combination caused those changes. The design does not provide a randomized concurrent control for separating treatment effects from other influences over time, and the sequence does not isolate the contribution of each medication.
The registry lists safety counts, including one participant affected by a serious adverse event and one by another adverse event in the group of 25 at risk for each category. It identifies ulcer as the top serious term at 4.0%. These entries are descriptive and do not provide a controlled comparison or establish causation. Deaths are not reported in the registry record.
General: a feasibility study can contribute information about whether a study approach and measurements are practicable, but the label alone does not establish which feasibility criteria were met. The registry does not report specific feasibility thresholds or a sample-size justification. The enrolled total of 25 should not be interpreted as evidence of adequate power for a treatment-effect claim. The posted registry information supports a description of the design and measurement methods, but not a conclusion that the combination improved a clinical outcome or that it did not.
13. Why This Trial Matters Statistically
This study is statistically notable for using a tracer-based kinetic endpoint rather than relying only on a conventional concentration measurement. The registry explains how labeled leucine enrichment was measured and how a compartment model was used to estimate apoA-I FCR. That distinction matters: a model-derived turnover rate answers a different biological question from a single circulating lipid value.
The design also illustrates why the interpretation of repeated measurements depends on comparison structure. Assessments are listed at 4 weeks, 12 weeks and 22 weeks while medications were introduced in a treatment sequence. Such measurements can describe patterns over time, but a single-group, non-randomized design does not by itself attribute a pattern to a specific treatment component. A concurrent randomized control would address a different question from the one described in this registry record.
The registry’s analysis population is defined by completion of any phase and availability of kinetic data for any treatment phase. That wording makes participant flow and time-specific availability important for understanding the estimates. The record does not report the number analyzed at each time point or how missing measurements were handled, so the extent to which the analyzed groups align across time cannot be assessed.
Finally, the primary endpoint results and confidence intervals are not reported in the registry record. This makes a useful statistical distinction visible: a clear methods description does not substitute for outcome estimates. Without estimates and uncertainty intervals, readers cannot judge the observed magnitude or precision. The record supports examining the design and measurement strategy, while leaving the principal numerical result unavailable for interpretation.
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 principal limitation for interpreting the primary outcome is that the registry record does not report the FCR means or 95% confidence intervals at the listed assessments. Without those estimates, the outcome’s direction, magnitude and precision are unavailable. The statistical tests or comparisons between time points are also not reported.
The design is single-group and non-randomized, with no masking. Thus, the record does not describe a randomized concurrent control comparison. The treatment sequence includes multiple medications introduced over time, so a within-group pattern would not by itself distinguish the effects of each component or separate treatment-associated change from other changes over time.
The analysis population requires completion of any phase and available kinetic data for any phase, but the number of participants contributing data at each time point is not reported. Reasons for missing measurements, withdrawals, exclusions, and missing-data methods are not reported in the registry record. This prevents assessment of how complete the longitudinal data were and whether the analysis population changed across time.
The registry describes a compartment model and its steady-state assumption, but does not report model diagnostics, sensitivity analyses, or the statistical methods used to estimate and compare FCR. The statistical analysis plan, multiplicity handling, and sample-size justification are not reported. The study’s enrollment of 25 participants is stated, but the registry provides no basis for judging the planned precision of the primary endpoint.
Safety information is limited to the counts and serious-event term reported for the group. The record does not provide a comparative safety analysis, detailed event timing, or attribution information in the registry record presented. These limitations apply to what can be inferred from the registry record and do not determine what may have appeared in other study materials.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Combined Effects of Non-statin Treatments on Apolipoprotein A-I Up-Regulation (CENTAUR): A Feasibility Study — NCT00728910.
- Registry record last updated 2016-02-29; status last verified 2016-01.
- Results first posted 2016-02-29.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT00728910 is a completed phase 2 feasibility study sponsored by the University of Pennsylvania, with 25 participants and a single-group, non-randomized design. The study addressed dyslipidemia and examined a sequence involving atorvastatin, ABT335 and extended-release niacin with aspirin.
The primary endpoint was mean apolipoprotein A-I fractional catabolic rate in pools/day, with a 95% confidence interval, at 4 weeks, 12 weeks and 22 weeks. The registry describes a labeled-leucine infusion and compartment-model method. The endpoint population was participants who completed any phase and had kinetic data available for any treatment phase.
The record lists one serious adverse event affected participant and one participant affected by another adverse event among 25 at risk in each category; ulcer is the top serious event term at 4.0%. Numerical primary endpoint results, confidence intervals, analysis details, missing-data procedures, and the statistical analysis plan are not reported in the registry record.