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 A Study to Evaluate the Effectiveness of Ezetimibe/Atorvastatin 10 mg/20 mg Combination Tablet Compared to Marketed Ezetimibe 10 mg and Atorvastatin 20 mg Tablets in Participants With High Cholesterol (MK-0653C-185 AM1) (NCT01370590), a randomized phase 3 study. The primary outcome is Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) After 6 Weeks of Treatment.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01370590 |
| Phase | Phase 3 |
| Condition | Hypercholesterolemia |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Double |
| Enrollment | 406 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Organon and Co |
| Results posted | Yes |
2. Clinical Question
The clinical question is whether the change in LDL-C after six weeks of treatment differs between a fixed-dose tablet containing ezetimibe/atorvastatin 10 mg/20 mg and the co-administration of ezetimibe 10 mg and atorvastatin 20 mg. The registry describes the objective as evaluating whether the two treatment formulations are equivalent in lowering LDL-C. The reported comparison concerns the measured endpoint and the statistical analysis; it does not, by itself, establish equivalence without the relevant decision criteria.
The trial enrolled participants with high cholesterol, and its official title specifies primary hypercholesterolemia. Participants were assigned in a randomized, double-blind crossover study to compare the formulations. The posted primary efficacy results are from the Per-Protocol Population and report least-squares mean percent change from baseline in LDL-C for each formulation, along with a comparative estimate.
Population
Participants with primary hypercholesterolemia, described in the registry as having high cholesterol. The primary efficacy results use the Per-Protocol Population, which excluded participants for important protocol deviations that may have substantially affected the primary endpoint.
Intervention
Ezetimibe/atorvastatin 10 mg/20 mg fixed-dose combination tablet, administered daily. The arm description specifies a double-dummy regimen with placebo tablets to match the separate-tablet treatment.
Comparator
Daily co-administration of ezetimibe 10 mg and atorvastatin 20 mg. The arm description also specifies a double-dummy regimen, including a placebo to the fixed-dose combination.
Primary question
How did LDL-C percent change from baseline after six weeks in each treatment period, and what was the reported difference between the formulations?
The registry record does not report an equivalence margin or the criteria used to decide whether the formulations met an equivalence objective. The comparative confidence interval and the sponsor-reported analysis are therefore important to interpret, but the numerical estimate alone should not be treated as a definitive equivalence decision.
3. Trial Design
This was a Phase 3, randomized, double-blind, active-controlled, multicenter crossover study. The registry reports an enrollment of 406 participants and a completed study. The recorded start was 2011-09, and primary completion was 2012-04. The study compared a fixed-dose ezetimibe/atorvastatin tablet with marketed ezetimibe and atorvastatin tablets taken together.
A crossover design compares treatments across treatment periods, so the study evaluated both formulations within a two-period framework. The endpoint description specifies measurements at baseline and after six weeks in each of the two treatment periods. A crossover can account for differences between participants by comparing treatment responses within participants, but the registry record does not describe the treatment sequence, any washout, or the details of the crossover analysis model. Those details should not be inferred from the design label alone.
Blinding was double, and both treatment descriptions specify a double-dummy approach. In the fixed-dose arm, participants took the combination tablet with placebo to ezetimibe and placebo to atorvastatin. In the separate-tablet arm, participants took ezetimibe and atorvastatin with placebo to the fixed-dose combination. This arrangement is intended to keep the treatment-taking experience similar while concealing which formulation is being taken.
The primary outcome was continuous: percent change from baseline in LDL-C after six weeks. The registry reports least-squares means for each formulation in the Per-Protocol Population. The arm-specific analyzed counts were 353 for the fixed-dose formulation and 346 for co-administration. These are analysis counts reported by formulation and should not be read as a count of distinct participants across the whole crossover study.
The registry lists five secondary outcomes: percent change from baseline in total cholesterol, HDL-C, non-HDL-C, apolipoprotein B, and triglycerides, each after six weeks of treatment. It records six outcome measures and six analyses overall. Details of randomization procedures, the allocation sequence, specific model terms, the planned analysis population beyond the posted primary population, and the protocol's sample-size justification are 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.
Period 1
| Stage | Coadministered/Combination Sequence | Combination/Coadministered Sequence |
|---|---|---|
| STARTED | 203 | 203 |
| COMPLETED | 187 | 192 |
| NOT COMPLETED | 16 | 11 |
Reasons for not completing this period:
| Reason | Coadministered/Combination Sequence | Combination/Coadministered Sequence |
|---|---|---|
| Adverse Event | 8 | 4 |
| Lost to Follow-up | 2 | 2 |
| Protocol Violation | 2 | 2 |
| Withdrawal by Subject | 4 | 2 |
| Could not access randomization system | 0 | 1 |
Crossover Washout Period
| Stage | Coadministered/Combination Sequence | Combination/Coadministered Sequence |
|---|---|---|
| STARTED | 187 | 192 |
| COMPLETED | 181 | 186 |
| NOT COMPLETED | 6 | 6 |
Reasons for not completing this period:
| Reason | Coadministered/Combination Sequence | Combination/Coadministered Sequence |
|---|---|---|
| Adverse Event | 1 | 4 |
| Lost to Follow-up | 2 | 0 |
| Non-compliance with Study Drug | 1 | 0 |
| Withdrawal by Subject | 2 | 2 |
Period 2
| Stage | Coadministered/Combination Sequence | Combination/Coadministered Sequence |
|---|---|---|
| STARTED | 181 | 186 |
| COMPLETED | 180 | 184 |
| NOT COMPLETED | 1 | 2 |
Reasons for not completing this period:
| Reason | Coadministered/Combination Sequence | Combination/Coadministered Sequence |
|---|---|---|
| Adverse Event | 0 | 1 |
| Withdrawal by Subject | 1 | 1 |
Analysis population for the primary outcome, as defined in the registry: Per-Protocol Population, which excluded participants due to important deviations from the protocol that may have substantially affected the results of the primary efficacy endpoint(s). A participant could be excluded from 1 or more of the analyses. Results are reported by treatment formulation and not by sequence.
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 | Coadministered/Combination Sequence | Combination/Coadministered Sequence | Total |
|---|---|---|---|---|
| Participants analysed | 203 | 203 | 406 | |
| Age, Customized: 30 to 39 years | Participants | 14 | 10 | 24 |
| Age, Customized: 40 to 49 years | Participants | 35 | 28 | 63 |
| Age, Customized: 50 to 59 years | Participants | 78 | 81 | 159 |
| Age, Customized: 60 to 64 years | Participants | 40 | 51 | 91 |
| Age, Customized: ≥65 years | Participants | 36 | 33 | 69 |
| Sex: Female, Male: Female | Participants | 126 | 122 | 248 |
| Sex: Female, Male: Male | Participants | 77 | 81 | 158 |
6. Primary Endpoint
The registry lists the primary outcome as Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) After 6 Weeks of Treatment, measured over Baseline and Week 6.
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | Percentage Change |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was percent change from baseline in serum LDL-C after six weeks of treatment. LDL-C was calculated using the Friedewald formula at baseline and after six weeks in each treatment period. The result is expressed as a percentage change, and the registry reports a least-squares mean for each formulation with a 95% confidence interval.
LDL-C is the specific cholesterol measure named in the study objective. The endpoint therefore directly addresses the registry's question about lowering LDL-C with the fixed-dose tablet compared with taking ezetimibe and atorvastatin separately. Measuring change from baseline relates the treatment-period value to the participant's starting measurement, rather than presenting only an endpoint value. Percent change expresses that change relative to baseline; the registry does not provide additional detail on how values were transformed or on any additional endpoint-processing rules.
Least-squares means are model-based estimates rather than necessarily simple arithmetic averages. They can express estimated treatment responses while accounting for terms included in a statistical model. The registry identifies the sponsor's comparative method as ANCOVA, but the model's covariates and other terms are not reported in the registry record. The endpoint's confidence intervals communicate uncertainty around the estimated treatment responses; they do not describe the range of individual participant responses.
Six weeks is the stated endpoint time within each treatment period. The results address the measured LDL-C change over that interval. They do not, on their own, answer questions about longer-term outcomes or other effects that were not assessed as the primary endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
In the Per-Protocol Population, the reported least-squares mean percent change in LDL-C was -54.0 for the fixed-dose combination, with a 95% confidence interval from -55.8 to -52.2. For co-administration, the reported mean was -53.8, with a 95% confidence interval from -55.7 to -52.0. These are estimates of average percent change from baseline after six weeks in each treatment period, not descriptions of every participant's response.
The registry also reports an ANCOVA comparison as a difference in least-squares means. The estimate is -0.2, with a 97.5% confidence interval from -1.7 to 3.3. The registry does not state a p-value for this comparison. It also does not report the equivalence margin or other decision threshold needed to interpret the result as meeting a formal equivalence criterion. The point estimate and interval should therefore be read as the reported comparison and its uncertainty, not as a standalone proof of equivalence.
A confidence interval describes a range of values compatible with the data and the assumptions of the analysis. A narrower interval indicates greater precision than a wider interval, while neither interval describes the distribution of individual outcomes. The arm-specific intervals are 95% confidence intervals; the comparative interval is reported at 97.5%. Because these intervals refer to different estimates and confidence levels, they should not be treated as interchangeable or used as a substitute for the sponsor's comparative analysis.
The direction and definition of the difference should be understood as recorded: the registry labels it a difference in least-squares means and gives the estimate and interval. The registry does not spell out the subtraction order in the posted analysis description. No direction-specific claim about which formulation had the larger estimated response should be based on an assumed order of subtraction. The arm-specific means are both negative, indicating decreases in LDL-C from baseline on the reported percentage-change scale; no further clinical judgment follows from that statistical description alone.
The analysis population matters. The primary results use a Per-Protocol Population that excluded participants for important protocol deviations that may have substantially affected the primary efficacy endpoint. The registry notes that a participant could be excluded from one or more analyses. The arm counts are 353 and 346 by formulation; the registry does not provide a complete account of all exclusions or missing endpoint observations. These results consequently describe the posted per-protocol analysis, not necessarily every randomized participant.
The available results support a precise description of the posted estimates and their stated uncertainty. They do not report the full protocol, the margin for equivalence, a p-value, or enough detail to reconstruct the model. Accordingly, the estimate should be considered alongside those reporting gaps rather than converted into a broader claim about equivalence or other outcomes.
9. Statistical Methods Explained
The primary outcome is continuous, meaning it is measured on a numerical scale rather than counted as a yes-or-no event. Here the outcome is percent change in LDL-C from baseline. For a continuous outcome, investigators commonly summarize treatment responses using a mean or a model-based mean, then quantify uncertainty around the estimate. The registry reports least-squares means and confidence intervals for the two formulations.
What does a least-squares mean represent?
A least-squares mean is an estimate from a statistical model. In contrast with a simple mean calculated directly from observed values, a model-based mean can account for specified factors included in that model. The registry identifies ANCOVA for the sponsor's comparison, but the specific covariates, factors, coding choices, and handling of the crossover periods are not reported in the registry record. It is therefore possible to explain the general role of a model-based estimate, but not to reconstruct the exact adjusted analysis.
ANCOVA is a general method for comparing a continuous outcome across groups while incorporating covariates into a model. Covariate adjustment can improve precision or account for measured differences when the model is suitably specified. That general description does not establish which variables were included in this trial's model. In a crossover study, period and treatment sequence can be relevant considerations; whether and how they were handled in this analysis is not reported in the registry record.
How should the confidence intervals be read?
A confidence interval gives a range around an estimate that reflects sampling uncertainty under the analysis assumptions. In repeated use of the same method under its assumptions, intervals at a stated confidence level would cover the target parameter at that level over the long run. For a single trial, the interval is not a probability statement about the fixed parameter, and it is not a range expected to contain a specified proportion of participant results.
The fixed-dose arm's mean is -54.0 with a 95% confidence interval from -55.8 to -52.2; the co-administration arm's mean is -53.8 with a 95% confidence interval from -55.7 to -52.0. The comparative estimate is -0.2 with a 97.5% confidence interval from -1.7 to 3.3. These intervals belong to different estimates and, for the comparison, a different stated confidence level. Comparing overlap between the two arm-specific intervals is not a replacement for interpreting the direct comparative estimate and its interval.
What does the crossover design change?
In a crossover design, participants receive treatments in separate periods, which can allow each participant's response under one treatment to be compared with that participant's response under another. This can reduce the effect of stable differences between participants. The design also requires attention to period effects, treatment order, and possible carryover from one period to another. General statistical practice recognizes these issues, but the registry does not report the sequence, washout arrangements, or model terms used to address them. No conclusion about those design features should be inferred from the word crossover alone.
The endpoint description says LDL-C was measured at baseline and after six weeks in each of two treatment periods. The primary analysis results are described as being reported by treatment formulation and count. The registry does not provide participant-level data or enough model details to verify whether each participant contributed measurements to both treatment estimates in the analysis or how any incomplete crossover data were handled.
What does an equivalence analysis require?
Equivalence is a claim that the treatment difference is sufficiently close to zero according to a prespecified margin. A confidence interval is judged against that margin; the estimate alone is not enough. The registry describes the study objective as equivalence and labels the comparative analysis as a legacy non-inferiority-or-equivalence analysis. However, the margin and the exact decision rule are not reported in the registry record. The reported interval can be described, but its relationship to an equivalence boundary cannot be assessed from the available record.
The comparative confidence interval is reported at 97.5%, whereas each arm-specific mean has a 95% confidence interval. The confidence level used for the comparison is part of the posted analysis description. It should not be silently changed or treated as if it were one of the arm-specific intervals. The registry reports no p-value for the comparison.
How should planning calculations be interpreted?
A sample-size planning illustration uses assumptions to show how many participants per arm might be needed under a stated design and target effect. The stated assumptions for the illustration are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a fraction of the observed effect. Such a calculation is not the trial's original sample-size justification, and it is not observed power. The protocol's own sample-size justification is not reported in the registry record. Planning estimates depend on their assumptions and should not be confused with the trial's enrollment or analyzed counts.
For a continuous outcome, variability affects the precision of an estimate and the sample size required to detect a specified effect. Greater variability generally makes a given difference harder to estimate precisely. The posted registry summaries do not give an arm-specific standard deviation for this endpoint; the arm results instead report confidence intervals. No additional variability estimate or sample-size figure should be inferred from those summaries.
Finally, statistical significance, equivalence, precision, and clinical importance are distinct concepts. A p-value, when reported, addresses a test under a particular null hypothesis; a confidence interval gives a range of uncertainty; equivalence requires a justified margin; and clinical importance requires context beyond a statistical estimate. The registry record supplies an estimate and interval for the comparison but does not report all information needed to make each of those judgments.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| ANCOVA | Difference in Least-square Means -0.2 | -1.7 to 3.3 | not reported |
The registry reports the sponsor's primary comparison as an ANCOVA estimate of the difference in least-squares means: -0.2, with a 97.5% confidence interval from -1.7 to 3.3. The arm-specific least-squares means and their 95% confidence intervals are also posted. No p-value is reported for the comparative analysis, and the equivalence margin is not reported in the registry record.
The posted summary does not include a separate recalculated two-arm comparison for this continuous endpoint. The registry indicates that values were missing or not estimable for that recalculation. Consequently, there is no independent recalculated estimate to place alongside the sponsor's ANCOVA result. The sponsor's reported analysis remains the available direct comparison in the registry record.
The treatment-specific means are descriptive model-based estimates, while the sponsor's ANCOVA result is the stated comparative analysis. Those are different summaries and should not be conflated. The registry does not provide enough model detail to reproduce the ANCOVA, verify its covariate adjustment, or determine how all crossover-specific features were handled. Nor does it provide the margin required to assess formal equivalence. The comparison can therefore be quoted and interpreted in terms of its estimate and reported interval, while recognizing these limits.
11. Multiplicity, Missing Data and Analysis Populations
The registry lists five secondary outcomes: percent change from baseline after six weeks in total cholesterol, HDL-C, non-HDL-C, apolipoprotein B, and triglycerides. Along with the primary LDL-C outcome, the record lists six outcome measures and six analyses. These outcomes address different cholesterol-related measurements, but their presence does not establish how the study controlled the chance of false-positive findings across multiple comparisons.
A multiplicity plan specifies how inference is handled when several outcomes, comparisons, time points, or subgroups are assessed. Without such a plan, interpreting each result as if it were the only test can overstate the strength of a collection of findings. The registry record does not report a multiplicity adjustment, a testing hierarchy, or how secondary outcomes were to affect the primary conclusion. No multiplicity-adjusted interpretation can be reconstructed from the posted primary result.
The primary outcome is reported for the Per-Protocol Population. The registry describes this population as excluding participants because of important protocol deviations that may have substantially affected the primary efficacy endpoint, and notes that a participant could be excluded from one or more analyses. The arm-specific analysis counts are 353 for the fixed-dose formulation and 346 for co-administration. The registry does not provide a complete participant flow or a detailed accounting of exclusions for each analysis in the information summarized.
Missing-data handling is also not reported in the registry record. The available information does not describe the extent or pattern of missing endpoint values, any imputation method, or sensitivity analyses for missing data. Nor does it state whether an intention-to-treat or other analysis population was used for the primary comparison. These omissions limit assessment of how departures from the planned treatment periods or incomplete measurements might have affected the result. The per-protocol estimates should be understood as the posted analysis population, without assuming that they represent every randomized participant.
These reporting gaps do not invalidate the numerical summaries, but they restrict what can be concluded about robustness and multiplicity. The estimates and intervals should be interpreted with the population definition and missing details in view.
12. 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 |
|---|---|---|---|
| Ezetimibe/Atorva Fixed Dose Combination | 2 | 383 | 0.5% |
| Co-Administration Ezetimibe and Atorvastin | 4 | 388 | 1.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Ezetimibe/Atorva Fixed Dose Combination | 0 of 383 |
| Co-Administration Ezetimibe and Atorvastin | 0 of 388 |
Most frequent serious adverse event terms
| Event term | Organ system | Ezetimibe/Atorva Fixed Dose Combination | Co-Administration Ezetimibe and Atorvastin |
|---|---|---|---|
| Myocardial infarction | Cardiac disorders | 1 of 383 | 0 of 388 |
| Stress cardiomyopathy | Cardiac disorders | 0 of 383 | 1 of 388 |
| Ventricular extrasystoles | Cardiac disorders | 0 of 383 | 1 of 388 |
| Colitis ischaemic | Gastrointestinal disorders | 0 of 383 | 1 of 388 |
| Hypokalaemia | Metabolism and nutrition disorders | 1 of 383 | 0 of 388 |
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 383 | 1 of 388 |
Serious events with the highest arm-level rate: myocardial infarction (0.3%), hypokalaemia (0.3%), stress cardiomyopathy (0.3%), ventricular extrasystoles (0.3%), colitis ischaemic (0.3%).
The registry reports serious adverse events for 383 participants at risk in the fixed-dose combination group, with 2 participants affected, and for 388 participants at risk in the co-administration group, with 4 participants affected. Other adverse events are recorded as 0 affected in each group: 383 at risk for the fixed-dose group and 388 at risk for co-administration. The record does not report death counts.
The serious-event figures are participant counts, not measures of event severity beyond the registry's serious-adverse-event category. The at-risk counts differ from the primary efficacy analysis counts because the safety and efficacy summaries use their respective reported populations. The registry does not provide further detail in these figures about event timing, treatment-period exposure, relatedness, or whether an event occurred during one or both treatment periods. These details should not be inferred.
The registry lists myocardial infarction, hypokalaemia, stress cardiomyopathy, ventricular extrasystoles, ischaemic colitis, and basal cell carcinoma among the serious-event terms, each reported as 0.3%. The record does not assign those listed terms to a treatment group in this summary. The percentages should therefore not be read as arm-specific comparisons. Small counts and the absence of detailed exposure and attribution information also limit interpretation. These data describe the serious adverse events recorded in the registry; they do not establish a comparative safety conclusion.
13. What the Result Does, and Does Not, Mean
The results describe a comparison of two formulations of ezetimibe and atorvastatin for percent change in LDL-C after six weeks in each treatment period. In the posted Per-Protocol analysis, the least-squares mean changes were -54.0 for the fixed-dose combination and -53.8 for co-administration. The sponsor-reported difference in least-squares means was -0.2, with a 97.5% confidence interval from -1.7 to 3.3. These statistics summarize the trial's reported estimates and their uncertainty.
The registry's stated objective was to evaluate equivalence, but a formal equivalence conclusion depends on a prespecified margin and a decision rule. The margin is not reported in the registry record. The point estimate being close to zero is not, by itself, enough to establish equivalence, and the comparative confidence interval cannot be assessed against an unreported margin. The data should not be described as proving equivalence on the basis of the summary alone.
The results are specific to the posted primary outcome, analysis population, and treatment period duration. They do not establish effects on outcomes beyond the measured LDL-C change, including the listed secondary outcomes for which no results are included in the registry record. They also do not answer questions about longer-term outcomes. The analysis population excluded certain important protocol deviations, and the registry does not provide full information about missing data or alternative analysis populations.
Statistical precision is not the same as clinical importance. Confidence intervals express uncertainty in estimates under the analysis assumptions; deciding what size of difference matters requires a prespecified context and a relevant margin or other clinical standard. That context is not available in the registry record. Similarly, safety counts are limited summaries and do not establish that the formulations have identical safety profiles.
The most defensible reading is therefore descriptive: the registry reports similar treatment-specific least-squares mean percent changes and a sponsor ANCOVA comparison with its stated interval. The limitations in analysis detail and the absent equivalence margin prevent a stronger claim about the formal study objective.
14. Why This Trial Matters Statistically
This trial is statistically instructive because its randomized crossover design compares two formulations across treatment periods, while its primary outcome is a continuous measure summarized by model-based means. The design highlights why analysis details matter: treatment, period, order, and possible carryover can all be relevant in crossover studies. The registry identifies the design but does not report enough model detail to establish how those features were addressed.
It also illustrates the distinction between treatment-specific summaries and a direct treatment comparison. The two least-squares means describe estimated change under each formulation. The ANCOVA estimate and its confidence interval address the comparative question more directly. Their interpretation depends on the model and, for the stated equivalence objective, on a decision margin. The registry gives the comparison interval but not the margin, so the objective cannot be judged from the interval alone.
Analysis populations are another important consideration. The primary endpoint results use a Per-Protocol Population that excludes participants with specified important deviations. This can be relevant for interpreting a treatment-formulation comparison, but the registry's note that participants could be excluded from one or more analyses and its lack of a full accounting make population-level interpretation less complete. The safety counts are reported separately and should not be treated as if they were the primary efficacy counts.
Finally, the record demonstrates why reporting uncertainty and methods alongside estimates is essential. Confidence intervals convey precision, while missing information about multiplicity, missing data, model terms, and the equivalence margin limits wider conclusions. These are general interpretive lessons; the trial's posted estimates remain tied to the specific outcome, population, and analysis described in the registry.
15. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The registry provides the principal endpoint summaries and the sponsor's comparative estimate, but it does not report the equivalence margin. Without that margin, the stated equivalence objective cannot be evaluated using the comparison interval. The exact decision rule and the rationale for the selected confidence level are also not reported in the registry record.
Several details of the statistical model are absent. The registry identifies ANCOVA but does not list the model covariates or specify how treatment period, treatment sequence, or possible carryover were addressed. The crossover design is described, and the endpoint is measured in each of two treatment periods, but the treatment order and any washout arrangement are not reported. These omissions prevent independent reconstruction of the sponsor's analysis.
The primary results are from a Per-Protocol Population, with exclusions for important protocol deviations that may have substantially affected the primary efficacy endpoint. The registry notes that a participant could be excluded from one or more analyses, but does not provide a full accounting of all participants by analysis or a detailed explanation of each exclusion. Missing-data methods, sensitivity analyses, and results from other analysis populations are not reported.
The record lists secondary outcomes but does not provide their numerical results in the registry record for this analysis. It does not report how multiplicity was handled, whether analyses were prespecified in a hierarchy, or whether the secondary outcomes were intended to support the primary objective. The protocol's own sample-size justification and details of interim analyses are not reported in the registry record.
Safety reporting is also limited in the available summary. Death counts are not reported, and the listed serious-event terms are not assigned to treatment groups in the information available. Event timing, exposure-adjusted summaries, and attribution details are not included. These limitations define the scope of interpretation; they do not change the values that the registry reports.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: A Study to Evaluate the Effectiveness of Ezetimibe/Atorvastatin 10 mg/20 mg Combination Tablet Compared to Marketed Ezetimibe 10 mg and Atorvastatin 20 mg Tablets in Participants With High Cholesterol (MK-0653C-185 AM1) — NCT01370590.
- Registry record last updated 2022-02-09; status last verified 2022-02.
- Results first posted 2013-08-05.
- 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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19. Record Summary
NCT01370590 is a completed Phase 3 randomized, double-blind, active-controlled, multicenter crossover study sponsored by Organon and Co. It enrolled 406 participants with high cholesterol and compared ezetimibe/atorvastatin 10 mg/20 mg as a fixed-dose tablet with ezetimibe 10 mg and atorvastatin 20 mg taken together.
The primary endpoint was percent change from baseline in LDL-C after six weeks in each treatment period. In the Per-Protocol Population, the reported least-squares means were -54.0 for the fixed-dose combination and -53.8 for co-administration. The sponsor-reported ANCOVA difference was -0.2, with a 97.5% confidence interval from -1.7 to 3.3. The registry does not report an equivalence margin, a p-value for that comparison, or detailed model terms.
The registry also lists five secondary outcomes and reports serious adverse-event counts by treatment group. Important limitations include missing information on the equivalence decision criteria, multiplicity, missing-data handling, and crossover analysis details.