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 Ezetimibe-Ursodiol Combination Therapy on Biomarkers of Liver Function and Sterol Balance in Subjects With NAFLD (NCT02244944), a na phase 2 study. The primary outcome is Reduction in Serum Alanine Transaminase (ALT).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02244944 |
| Phase | Phase 2 |
| Condition | Nonalcoholic Fatty Liver Disease (NAFLD) |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 2 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Gregory Graf, PhD |
| Results posted | Yes |
2. Clinical Question
Population
Subjects with nonalcoholic fatty liver disease (NAFLD). The registry record lists an enrollment of 2. It does not report further eligibility details or a description of the participants enrolled.
Intervention
EZ-Urso combination therapy: ursodiol (URSO Forte) 13-15 mg per kg (250-500 mg b.i.d. or t.i.d depending on body weight) combined with Ezetimibe (Zetia) 10 mg o.p.d. The study sought information about sterol balance and biomarkers of liver function during combination therapy.
Comparator
No comparator group is described. The registry identifies a single-group model and allocation as NA. The record therefore does not describe a randomized, like-for-like comparison with a control arm.
Primary question
The primary outcome was reduction in serum alanine transaminase (ALT) over 6 months. The stated purpose was to determine whether the combination therapy improved liver function tests, as assessed by ALT. The registry says the trial was terminated early and no data were collected to analyze this primary outcome.
This question combines a specific laboratory measure with a proposed treatment exposure, but the registered design does not include a separate comparison group. Without primary-outcome observations, the record cannot describe an observed change in ALT during the study. It also cannot estimate how any change would compare with the change that might occur without the combination therapy.
The registry lists an increase in plasma lathosterol and a reduction in hepatic fat fraction as secondary outcomes. It does not report results for those outcomes. The clinical question is therefore identifiable from the stated aims, but the record does not provide outcome evidence to answer it.
3. Trial Design
This is a phase 2, single-group study of EZ-Urso combination therapy in subjects with NAFLD. The registry lists an enrollment of 2 and identifies the study as terminated. The listed start is 2014-09, and the primary completion is listed as 2015-09. Allocation is recorded as NA, masking as none, and the model as single group.
The intervention combines ursodiol with ezetimibe. The registry describes ursodiol (URSO Forte) 13-15 mg per kg (250-500 mg b.i.d. or t.i.d depending on body weight) and Ezetimibe (Zetia) 10 mg o.p.d. It does not describe a separate control regimen. In a single-group design, observations from participants receiving the intervention are not a direct randomized comparison against another group. Changes over time, if recorded, would not by themselves distinguish treatment effects from other explanations for change.
The primary outcome was reduction in serum ALT, with a timeframe of 6 months. The listed secondary outcomes are increase in plasma lathosterol and reduction in hepatic fat fraction. The registry states that the trial was terminated early and that no data were collected to analyze the primary outcome. It lists no analyses, and the registry record does not report results for the secondary outcomes.
The record does not report the reason for termination, the timing of termination relative to participant follow-up, or a detailed statistical analysis plan. It also does not describe the intended analysis population, procedures for outcome measurement, or a sample-size justification. These details cannot be inferred from the small enrollment or from the stated outcomes. The design details that are available define a limited, uncontrolled study, while the absence of primary outcome data prevents a treatment-effect estimate from this 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.
Overall Study
| Stage | EZ-URSO Combination Therapy |
|---|---|
| STARTED | 2 |
| COMPLETED | 0 |
| NOT COMPLETED | 2 |
Reasons for not completing this period:
| Reason | EZ-URSO Combination Therapy |
|---|---|
| Withdrawal by Subject | 1 |
| Study Terminated | 1 |
Analysis population for the primary outcome, as defined in the registry: The trial was terminated early. No data was collected to analyze the primary outcome measure.
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 | EZ-URSO Combination Therapy |
|---|---|---|
| Participants analysed | 2 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 2 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age, Continuous | years | 43.5 (33 to 54) |
| Sex: Female, Male: Female | Participants | 2 |
| Sex: Female, Male: Male | Participants | 0 |
| Region of Enrollment: United States | participants | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Reduction in Serum Alanine Transaminase (ALT), measured over 6 months.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was reduction in serum alanine transaminase (ALT), with a stated timeframe of 6 months. ALT is a liver enzyme measured in blood and is used as a laboratory marker in assessments of liver function. A change in ALT is a measurable endpoint, but it is not a complete description of liver health or disease status. Its interpretation depends on the measurement context and on what other clinical and laboratory information is available.
The registry’s objective was to determine whether ezetimibe-ursodiol combination therapy improved liver function tests, assessed through ALT. The endpoint is therefore a biomarker outcome rather than a reported clinical event or patient-reported outcome. The registry record does not specify the precise endpoint definition beyond reduction in serum ALT, such as whether the intended measure was a change from baseline, a comparison at a particular visit, or another summary.
Most importantly, the registry states that the trial was terminated early and no data were collected to analyze the primary outcome. There is consequently no reported ALT estimate, measure of variability, or inferential result in this record. The planned endpoint describes what the study intended to evaluate; it does not constitute evidence that an ALT reduction was observed.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the study’s aim and design but does not supply an analyzable result for its primary question. The primary outcome was reduction in serum ALT over 6 months. The record explicitly says the trial was terminated early and that no data were collected to analyze this outcome. As a result, there is no reported estimate of ALT change, no uncertainty interval, and no statistical test result for the primary endpoint. The treatment effect on ALT cannot be estimated from the registry record.
The study enrolled 2 participants, but enrollment is not the same as an analyzable primary-outcome sample. In this case, the record states that no primary-outcome data were collected for analysis. It would be misleading to treat enrollment alone as evidence of follow-up measurements or as a basis for estimating change. The record does not report a reason for early termination or clarify whether any participants had partial follow-up.
The design is single-group, with allocation recorded as NA and masking recorded as none. There is no registered comparator group. A single-group observation can describe outcomes among participants if measurements are available, but it cannot provide the same causal contrast as a randomized comparison. Even if an outcome change had been recorded, changes over time could reflect factors other than the intervention. Here, the absence of primary-outcome data means even a within-group description is unavailable for ALT.
The registry lists plasma lathosterol increase and hepatic fat fraction reduction as secondary outcomes, but it reports no analyses and no results for these measures. Their presence in the outcome list indicates planned areas of interest, not observed findings. The registry record does not report whether data were collected for either secondary outcome, so no conclusion about their measurement or results is warranted.
The safety record lists 2 participants at risk in the EZ-URSO combination therapy group, 0 with serious adverse events, and 1 with other adverse events. These are descriptive counts in a very small group, with no listed serious adverse event terms. The counts do not establish the absence of risk; they describe only what is recorded for this study. Deaths are not reported in the registry record.
In statistical terms, the main limitation is not an imprecise estimate but the absence of an estimate. No confidence interval can characterize uncertainty around the primary outcome because there is no reported primary-outcome result. The small enrollment and single-group design would also limit what could be learned from any observed changes, especially about comparative effects. The registry record therefore documents a research question and a terminated study, rather than evidence that answers the question.
9. Statistical Methods Explained
What does a single-group design estimate?
In general, a single-group design follows participants receiving an intervention without a separate comparison group. If outcomes are measured before and after treatment, a within-group change may be described. That change is not, by itself, a direct estimate of what would have happened to the same participants without treatment. Time trends, co-interventions, measurement variation, and other influences can contribute to observed changes. A randomized comparator helps address this problem by establishing a concurrent contrast between groups, although its validity also depends on design and conduct.
For this study, the registry identifies a single-group model and lists allocation as NA. No comparator arm is described. More importantly, the registry says that no data were collected to analyze the primary outcome. Thus, there is no reported within-group ALT change to describe and no comparative effect to estimate. The design and the lack of outcome data are distinct limitations: a single-group result could have been descriptive, but the record does not report such a primary-outcome result.
What would an effect estimate and confidence interval mean?
In general, an effect estimate is a numerical summary of the difference or change being studied. A confidence interval describes the uncertainty around an estimate under the assumptions of the statistical method. A narrower interval generally indicates greater precision, while a wider interval indicates less precision. Neither the estimate nor its interval automatically establishes clinical importance; interpretation also depends on the outcome, the design, and the context.
No ALT estimate or confidence interval is reported in the registry record. Because the primary outcome has no reported analysis, there is no numerical result whose precision can be assessed. The absence of an interval should not be read as a precise result, a null result, or evidence that the treatment and outcome are unrelated. It reflects the absence of an analyzed primary-outcome estimate.
What can a p-value establish?
In general, a p-value measures how incompatible observed data are with a specified null model, assuming the model and analysis are appropriate. It does not give the probability that a treatment works, the probability that the null hypothesis is true, or the size of an effect. A small p-value does not replace an effect estimate and its uncertainty, and a larger p-value does not demonstrate equivalence or absence of an effect.
The registry record lists no analyses and no p-value for the primary outcome. There is therefore no inferential result to interpret. The study’s termination and lack of primary-outcome data preclude a statistical test of ALT reduction in the posted record.
Why do sample size and precision matter?
In general, the amount of information in a study influences the precision of its estimates. A very small sample can yield unstable estimates and limited ability to distinguish a real pattern from random variation. A sample-size calculation is a planning exercise based on assumptions about the effect to detect, variability, significance level, and design. It is not a result from participants, and it is not “observed power.” Planning illustrations cannot restore information that was not collected or replace an observed estimate.
The registry lists enrollment of 2. It does not report a sample-size justification or the assumptions used to plan enrollment. The record does not provide the outcome variability needed to assess precision for ALT. The sample-size assumptions accompanying any planning illustration are not the trial’s documented design rationale and should not be interpreted as evidence about the participants or the treatment effect.
Why does the comparator matter?
In general, an intervention’s effect is a contrast between outcomes under different treatment conditions. Random assignment can make groups comparable, on average, with respect to both measured and unmeasured factors, subject to the trial’s conduct and the role of chance. Without a comparator, a change after treatment cannot be separated cleanly from other changes occurring over the same period.
This record describes no randomized comparison and flags that the arms are not a like-for-like control comparison. The registry’s single-group design does not support a controlled treatment contrast. Since no primary-outcome data were collected for analysis, the record also does not support a descriptive ALT change.
In general, over-dispersion matters when count data vary more than a chosen statistical model assumes. Ignoring that extra variation can make uncertainty appear too small. The registry record does not report an analysis of counts for the primary endpoint, and it does not report a statistical model or evidence about over-dispersion. This concept therefore explains a general modeling issue, not a feature established for this trial.
10. Multiplicity, Missing Data and Analysis Populations
Multiplicity arises when a study assesses several outcomes, time points, subgroups, or statistical tests. In general, the more hypotheses examined, the greater the chance of obtaining at least one apparently unusual result by chance if no adjustment or prespecified interpretation strategy is used. Possible approaches include defining a primary outcome in advance, using a hierarchy for testing, or adjusting inferential thresholds. The appropriate approach depends on the analysis plan and the study objectives.
The registry identifies serum ALT reduction as the primary outcome and lists increase in plasma lathosterol and reduction in hepatic fat fraction as secondary outcomes. It does not report a multiplicity strategy, statistical testing hierarchy, or adjustment procedure. It is therefore not possible to determine from the registry record how multiple outcomes were intended to be handled. The record lists no analyses, so there are no reported outcome tests for which multiplicity adjustment can be assessed.
Missing-data handling is also not reported. For the primary outcome, the registry states that the trial was terminated early and no data were collected to analyze the measure. This is not a reported analysis of missing primary-outcome values; it is an explicit statement that there were no data for that analysis. The registry record does not describe partial measurements, imputation, sensitivity analyses, or the reasons for termination.
The analysis population is not reported in the registry record. It does not specify whether an intention-to-treat, per-protocol, or other population was intended. With no primary-outcome analysis, there is no analysis population to characterize from posted results. These omissions limit assessment of the planned statistical procedures, but they do not justify guessing what methods might have been intended.
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 |
|---|---|---|---|
| EZ-URSO Combination Therapy | 0 | 2 | 0.0% |
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 |
|---|---|
| EZ-URSO Combination Therapy | 1 of 2 |
Most frequent non-serious adverse event terms
| Event term | Organ system | EZ-URSO Combination Therapy |
|---|---|---|
| diarrhea | Gastrointestinal disorders | 1 of 2 |
The registry lists the EZ-URSO combination therapy group with 2 participants at risk for serious adverse events and 0 participants with serious adverse events. For other adverse events, it lists 2 participants at risk and 1 affected. No serious adverse event terms are listed. Deaths are not reported in the registry record.
These are descriptive counts, not comparative safety estimates. The study has a single group and no registered control arm, so the figures do not show how event occurrence compares with another treatment or with no intervention. The record does not provide event descriptions for the other adverse events, their timing, severity, or attribution to treatment. It also does not state in the adverse-event entry whether all participants had complete safety follow-up.
The absence of a recorded serious adverse event in this small enrolled group does not establish that serious events cannot occur or that the intervention is safe. A small group provides limited information about uncommon events, and the early termination further limits the scope of what can be learned. The counts should be read as the events recorded for this study, not as proof of a general safety profile.
12. What the Result Does, and Does Not, Mean
The registry record shows that investigators planned to study ezetimibe-ursodiol combination therapy in subjects with NAFLD, with reduction in serum ALT as the primary outcome. It also identifies plasma lathosterol and hepatic fat fraction as secondary outcomes. The record reports enrollment of 2 and states that the trial was terminated early. Most consequentially, it says no data were collected to analyze the primary outcome.
These registry entries do not show whether ALT decreased, increased, or remained unchanged. There is no reported primary-outcome estimate and no uncertainty interval. The record also does not report results for the secondary outcomes. A listed endpoint is not a result, and a study objective is not evidence that an outcome changed.
The record does not establish whether the combination therapy caused any change. The design is single group, with no comparator described, so even a reported before-and-after difference would not by itself isolate the effect of treatment from other influences. In this case, the primary-outcome data needed for even that within-group description are absent.
The recorded safety counts describe a very small group and cannot support broad conclusions about risk. The absence of listed serious adverse events should not be interpreted as proof that serious adverse events do not occur. Likewise, the one recorded other adverse event does not establish that treatment caused it; the record does not report attribution or event details.
The appropriate statistical reading is that the registry documents an unanswered research question and a terminated study without analyzable primary-outcome data. It does not support a conclusion for or against a treatment effect, nor does it supply a basis for judging the precision of an effect estimate. Any stronger claim would go beyond the results reported in the registry record.
13. Why This Trial Matters Statistically
This trial matters statistically because it illustrates the difference between a registered research question and an answer supported by analyzed data. The registry defines a primary outcome—reduction in serum ALT—and a timeframe of 6 months. But it also states that the study was terminated early and that no data were collected to analyze the primary outcome. A clear endpoint does not generate an estimate when the relevant measurements are absent.
The record also shows why study design and outcome availability must be considered together. The model is single group, allocation is NA, and no control group is described. Such a design cannot provide a randomized treatment contrast. Here, the lack of primary-outcome data means that neither a comparative estimate nor a reported within-group ALT change is available.
Enrollment of 2 gives important context for the scale of the study but does not resolve the missing-outcome problem. Enrollment is not a substitute for an analyzed endpoint, and planning calculations do not create evidence about participants. Statistical interpretation must remain anchored to observed results, not to the objective, the intervention description, or hypothetical planning assumptions.
The record further distinguishes safety counts from a full safety assessment. It lists event counts but no serious adverse event terms and does not provide details for the other adverse event. These entries are informative as registry reporting, yet they cannot support broad inferences from a small, uncontrolled study.
For clinical researchers and statisticians, the central lesson is to separate what a study intended to measure, what its design could estimate, and what results are actually reported. In this case, the intended primary question is clear, but the registry record does not contain the outcome data needed to answer it.
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 primary limitation is that no data were collected to analyze the primary outcome. The registry explicitly reports early termination and no primary-outcome analysis. Consequently, it supplies no ALT result, estimate of change, measure of variability, or confidence interval. Results for the listed secondary outcomes are also not reported.
The study is described as single group, with allocation recorded as NA and masking as none. No comparator is described, so the design does not provide a randomized treatment contrast. Any change observed in a single group, if it had been reported, would require cautious interpretation because other influences over time could not be ruled out by a concurrent control group.
The registry lists enrollment of 2. It does not report a sample-size justification, the reason for termination, details of participant follow-up, or the intended analysis population. It also does not report a statistical analysis plan, missing-data procedures, or a multiplicity strategy. These are limitations of what can be evaluated from the registry record; their absence does not establish what the investigators did or did not do outside the record.
Safety reporting is limited to counts of participants with serious and other adverse events. No serious adverse event terms are listed, deaths are not reported, and the record does not describe the other adverse event or its attribution. The small group and lack of a comparator restrict interpretation of these counts. Together, the design and reporting limitations mean that the registry supports a description of the study’s aims and status, but not an estimate of efficacy or a broad safety conclusion.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Ezetimibe-Ursodiol Combination Therapy on Biomarkers of Liver Function and Sterol Balance in Subjects With NAFLD — NCT02244944.
- Registry record last updated 2018-02-07; status last verified 2018-01.
- Results first posted 2018-02-07.
- 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
NCT02244944 is a phase 2, single-group study of ezetimibe-ursodiol combination therapy in subjects with NAFLD. The registry lists enrollment of 2, masking as none, and study status as terminated. The primary outcome was reduction in serum ALT over 6 months. Secondary outcomes were increase in plasma lathosterol and reduction in hepatic fat fraction.
The registry states that the trial was terminated early and no data were collected to analyze the primary outcome. It lists no analyses and reports no results for the secondary outcomes. The record does not describe a comparator group, a sample-size justification, or a statistical analysis plan.
Safety entries list 0 participants with serious adverse events and 1 with other adverse events among 2 at risk. No serious event terms are listed; deaths are not reported in the registry record. The study therefore documents a planned investigation but provides no analyzable primary-outcome result.