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 Designed to Compare the Tolerability of an Increased Dose of Enteric-coated Mycophenolate Acid (MPA) in Renal Transplant Patients Whose Dose of Mycophenolate Mofetil (MMF) Was Reduced Due to Gastrointestinal Symptoms (NCT00658333), a randomized phase 4 study. The primary outcome is Number of Participants With Response (Yes/no).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00658333 |
| Phase | Phase 4 |
| Condition | Renal Transplantation |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 30 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
Renal transplant recipients whose mycophenolate mofetil dose had been reduced because of gastrointestinal symptoms. The primary outcome population is identified as the Intent to Treat Population. The registry record does not report further eligibility details in the information available for this analysis.
Intervention
Conversion to enteric-coated mycophenolate acid, with an increased dose assessed for tolerability. The intervention description states that 1000 mg mycophenolate mofetil corresponds to 720 mg enteric-coated mycophenolate acid as an MPA-equivalent dose. The active and placebo medications were dispensed in separate bottles.
Comparator
Mycophenolate mofetil therapy with placebo enteric-coated mycophenolate acid. The record describes active and placebo medications for both treatment groups, consistent with its double-dummy description. Further details about how treatment assignment was generated or concealed are not reported in the registry record.
Primary question
Could participants tolerate an increase of 360 mg/day in enteric-coated mycophenolate acid from baseline, maintain that dose for 4 weeks until Week 6, and have physician-assessed gastrointestinal symptoms that improved or did not change in intensity at study end? The registry record supplies this response definition but does not report the number of participants who met it in either group.
3. Trial Design
The registry describes a Phase 4, randomized, parallel-group study sponsored by Novartis Pharmaceuticals. The title identifies the study as multicenter and double blind, with a double-dummy design; the registry’s masking field says triple. The record does not identify which people were included in that masking designation, so the roles covered by masking cannot be specified. Enrollment was 30. The study began in 2008-03, had primary completion in 2009-03, and is listed as terminated. A reason for termination is not reported in the registry record.
The study compared enteric-coated mycophenolate acid with mycophenolate mofetil in renal transplant recipients whose mycophenolate mofetil dose had been reduced because of gastrointestinal symptoms. The intervention descriptions include active treatment and a matching placebo for the other formulation. For the enteric-coated mycophenolate acid group, the record describes an equimolar dose and states that 1000 mg mycophenolate mofetil equals 720 mg enteric-coated mycophenolate acid on an MPA-equivalent basis. The medications were dispensed in separate bottles identified as Bottle A and Bottle B. More detail about dose adjustment, allocation procedures, or the conduct of the trial is not reported in the registry record.
The primary outcome was a yes/no response assessed at 6 weeks. A positive response required a dose increase that was tolerated and maintained until the end of the study, along with no worsening in physician-assessed gastrointestinal symptom intensity. The record also lists average daily doses of both formulations by treatment-duration intervals as a secondary outcome. The registry record does not report the primary response counts or the results for that secondary outcome.
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: Patients were screened for eligibility. If eligible, willing to participate and provided informed consent, patients were randomized in a blinded fashion to either an equimolar dose of enteric-coated mycophenolate acid (MPA) or remained on the current dose of mycophenolate mofetil (MMF).
Overall Study
| Stage | Enteric-coated Mycophenolate Acid | Mycophenolate Mofetil |
|---|---|---|
| STARTED | 15 | 15 |
| COMPLETED | 13 | 14 |
| NOT COMPLETED | 2 | 1 |
Reasons for not completing this period:
| Reason | Enteric-coated Mycophenolate Acid | Mycophenolate Mofetil |
|---|---|---|
| Adverse Event | 2 | 1 |
Analysis population for the primary outcome, as defined in the registry: Intent to Treat Population
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 | Enteric-coated Mycophenolate Acid | Mycophenolate Mofetil | Total |
|---|---|---|---|---|
| Participants analysed | 15 | 15 | 30 | |
| Age Continuous | years | 51.3 (SD 12.54) | 49.8 (SD 12.45) | 50.5 (SD 12.30) |
| Sex: Female, Male: Female | Participants | 8 | 7 | 15 |
| Sex: Female, Male: Male | Participants | 7 | 8 | 15 |
| Region of Enrollment: United States | participants | 15 | 15 | 30 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Response (Yes/no), measured over 6 weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is a binary measure: whether a participant met the registry’s definition of response by the end of the 6-week study. The definition combines a dose-escalation requirement with a tolerability requirement. A positive response required an increase of 360 mg/day in enteric-coated mycophenolate acid from baseline, tolerated and maintained for a 4 week duration until Week 6. It also required physician-assessed gastrointestinal symptoms to have improved or remained unchanged in intensity at study end, based on the physician-administered evaluation of gastrointestinal symptomatology.
Combining these conditions makes the endpoint relevant to the stated study question: it asks whether the increased dose could be maintained while symptoms did not worsen. It is not simply a measure of dose taken, nor does the definition treat dose escalation alone as a response. Because the outcome is yes/no, the central comparison would ordinarily be the proportion of participants meeting the full definition in each treatment group. The registry record identifies the Intent to Treat Population and a 6-week timeframe, but does not report group response counts, an effect estimate, or a confidence interval. Therefore, the endpoint’s comparative result cannot be interpreted from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes the question and endpoint but does not provide the primary response results. It states that response was defined as a yes/no outcome and gives the conditions for a positive response, but no group counts or comparative statistical analysis are reported. Consequently, the posted record does not establish how many participants met the endpoint in either group or how different the response rates were. The definition alone is not evidence that the endpoint was achieved.
The study enrolled 30 participants. The safety information lists 15 participants at risk in each group. For serious adverse events, the enteric-coated mycophenolate acid group lists 2 affected participants and the mycophenolate mofetil group lists 0. For other adverse events, each group lists 12 affected participants. These counts describe the registry entries; they do not provide the primary endpoint comparison. The record also lists serious adverse event terms with percentages, but does not assign those terms to a treatment group in the available information.
A confidence interval, when reported, describes the statistical uncertainty around an estimate under the analysis used. Its width helps readers judge the precision of the estimate; it does not remove limitations in the underlying study or establish clinical importance by itself. No primary-outcome confidence interval is reported in the registry record. No p-value or analysis estimate for the primary comparison is reported either. Without those results, there is no basis in the registry record to describe the size or precision of a treatment-group difference.
The study status is terminated, but the reason is not reported in the registry record. That status alone does not explain whether termination was related to recruitment, conduct, safety, or another issue. Likewise, the absence of posted primary results does not show that the endpoint was negative or positive; it means the comparative result is unavailable in the record. Interpretation should remain limited to the documented endpoint definition, study design, and posted safety counts.
9. Statistical Methods Explained
Randomization is a method for assigning participants to treatment groups using a chance-based process. In general, it can reduce systematic differences between groups at enrollment, though it does not guarantee that groups will be identical, especially in a small study. This registry record identifies the study as randomized, but does not report the sequence-generation method, allocation concealment procedures, or any factors used to balance assignments.
What does the parallel-group design mean?
In a parallel-group design, participants are assigned to a treatment group and assessed while receiving that assigned regimen. The record identifies enteric-coated mycophenolate acid and mycophenolate mofetil groups. It also describes placebo versions of the two formulations and separate dispensing bottles. The official title calls the study double blind and double dummy, while the registry masking field says triple. These labels indicate masking was part of the design, but the record does not state which roles were masked or explain the difference in labeling.
How should the primary endpoint be understood?
The primary endpoint is binary: each participant either met the stated response definition or did not. In general, a binary endpoint can be summarized as the number or proportion of participants meeting the criterion in each group, followed by a comparison between groups. Here, response required both a specified dose increase that was maintained and acceptable gastrointestinal symptom assessment at study end. The combined definition matters because a participant who met the dose condition but not the symptom condition would not meet the complete response definition. The registry record does not report how the components were handled if information about either was missing.
What does a treatment-effect estimate show?
In general, an effect estimate describes the observed contrast between treatment groups on an outcome. A confidence interval gives a range of values compatible with the data and the analysis assumptions, and conveys precision. A p-value, when used, measures how unusual the data would be under a specified null hypothesis and statistical model; it is not a measure of effect size or clinical importance. The registry record reports no primary comparison estimate, confidence interval, or p-value, so these concepts cannot be applied to a numerical primary result for this study.
Why can small studies produce uncertain estimates?
In general, a study with limited enrollment may yield imprecise estimates, particularly for outcomes that occur in relatively few participants. Randomization remains useful, but chance imbalances can be more consequential when the study is small. The enrollment listed in this record is 30; without the primary outcome counts, an estimate and its precision cannot be described. Safety counts should also be read as descriptive registry results rather than as proof of a group difference, especially when the record does not provide an inferential analysis.
What does over-dispersion mean in general?
For count outcomes, over-dispersion means the observed variability is greater than a chosen statistical model expects. If it is ignored, standard errors and uncertainty intervals can be too small, making results appear more precise than they are. This is a general issue for count-data analyses, not a reported finding for this trial. The primary endpoint is binary, and the registry record does not report an analysis model or diagnostics for over-dispersion.
How do planning calculations differ from trial results?
In general, sample-size calculations are planning tools that estimate the enrollment needed to detect a specified effect under chosen assumptions. They are not evidence that the effect occurred, and calculations based on an observed effect are retrospective illustrations rather than the trial’s original design justification. The registry record does not report the trial’s sample-size justification or a statistical plan. It also does not report primary endpoint results from which a trial-specific precision assessment could be made. A planning calculation should therefore not be interpreted as an observed treatment effect or as observed power.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists the primary response outcome and a secondary outcome of average daily doses of enteric-coated mycophenolate acid and mycophenolate mofetil by treatment-duration intervals. It states that there are two outcome measures, but does not report statistical analyses. A plan for handling multiplicity across outcomes, time intervals, or other comparisons is not reported in the registry record. In general, multiplicity matters because testing multiple hypotheses can increase the chance of finding an apparently notable result by chance. Whether or how that issue was addressed in this study cannot be determined from the record.
The primary outcome population is identified as the Intent to Treat Population. In general, an intent-to-treat approach analyzes participants in the groups to which they were randomized, regardless of later treatment changes, according to the prespecified rules. The registry record does not describe those rules in detail or state how participants with missing endpoint information were handled. The number of participants with evaluable primary endpoint data is not reported in the registry record.
Missing-data methods can affect estimates when outcome status is unavailable for some participants. General approaches may rely on assumptions about why information is missing; the appropriateness of an approach depends on trial conduct and the missingness pattern. Neither the amount of missing primary outcome data nor an imputation or sensitivity-analysis method is reported in the registry record. The record also does not report a statistical analysis plan, interim analyses, or the reason for termination. These omissions limit assessment of how completely the posted outcome definition was applied and how robust any estimated treatment comparison would be.
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 |
|---|---|---|---|
| Enteric-coated Mycophenolate Acid | 2 | 15 | 13.3% |
| Mycophenolate Mofetil | 0 | 15 | 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 |
|---|---|
| Enteric-coated Mycophenolate Acid | 12 of 15 |
| Mycophenolate Mofetil | 12 of 15 |
Most frequent serious adverse event terms
| Event term | Organ system | Enteric-coated Mycophenolate Acid | Mycophenolate Mofetil |
|---|---|---|---|
| Cardiac failure congestive | Cardiac disorders | 1 of 15 | 0 of 15 |
| Blood creatinine increased | Investigations | 1 of 15 | 0 of 15 |
| Renal failure acute | Renal and urinary disorders | 1 of 15 | 0 of 15 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Enteric-coated Mycophenolate Acid | Mycophenolate Mofetil |
|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 4 of 15 | 4 of 15 |
| Flatulence | Gastrointestinal disorders | 3 of 15 | 4 of 15 |
| Eructation | Gastrointestinal disorders | 2 of 15 | 3 of 15 |
| Abdominal distension | Gastrointestinal disorders | 0 of 15 | 4 of 15 |
| Constipation | Gastrointestinal disorders | 1 of 15 | 3 of 15 |
| Dyspepsia | Gastrointestinal disorders | 0 of 15 | 4 of 15 |
| Gastrointestinal disorder | Gastrointestinal disorders | 3 of 15 | 1 of 15 |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | 0 of 15 | 4 of 15 |
| Abdominal pain lower | Gastrointestinal disorders | 1 of 15 | 2 of 15 |
| Abdominal pain upper | Gastrointestinal disorders | 1 of 15 | 1 of 15 |
Serious events with the highest arm-level rate: cardiac failure congestive (6.7%), blood creatinine increased (6.7%), renal failure acute (6.7%).
The registry safety entries list participants at risk and participants affected for serious and other adverse events. For enteric-coated mycophenolate acid, 15 participants are listed at risk, with 2 affected by serious adverse events and 12 affected by other adverse events. For mycophenolate mofetil, 15 are listed at risk, with 0 affected by serious adverse events and 12 affected by other adverse events. These are descriptive counts, not an adjusted comparison or a test of statistical significance.
The serious adverse event terms listed are Cardiac failure congestive, Blood creatinine increased, and Renal failure acute, each with 6.7%. The registry information does not identify the treatment group for each listed term or provide further event-level detail. Death counts are not reported in the registry record. The entries should not be read as showing that every affected participant experienced the same event, or that the listed terms account for all adverse events. The record does not report exposure-adjusted rates or an inferential safety analysis, so differences in the listed counts should be interpreted cautiously.
12. What the Result Does, and Does Not, Mean
The record establishes that a randomized, parallel-group study was undertaken to assess whether an increased dose of enteric-coated mycophenolate acid could be tolerated after conversion from mycophenolate mofetil in renal transplant recipients with gastrointestinal symptoms that had led to dose reduction. It also supplies a specific binary response definition, a 6-week timeframe, and safety counts for the two groups. These details clarify what the study intended to assess and what safety information was posted.
The registry record does not report the number of participants meeting the primary response definition in either group, a treatment-effect estimate, or an uncertainty interval. It therefore does not show the magnitude or precision of any primary-outcome difference. The safety counts are not a substitute for the primary endpoint results and do not by themselves establish a treatment effect or a causal safety difference. The listed serious adverse event terms are not assigned to a treatment group in the available information.
These limitations do not mean that there was no effect, that an effect was present, or that the study failed to collect the information. They mean the posted registry information does not allow the primary comparison to be evaluated. The study is listed as terminated, but a reason is not reported in the registry record. No conclusion about why it ended or how termination affected results can be drawn from that status alone. The appropriate reading is therefore descriptive: the intended question, design features, endpoint definition, and posted safety counts are documented, while the comparative primary outcome and its statistical uncertainty remain unavailable.
13. Why This Trial Matters Statistically
This trial raises a statistical issue that is important in studies of treatment tolerability: the endpoint combines whether a participant maintained an increased dose with whether symptoms improved or did not worsen. The definition is more informative than a dose measure alone because it requires both a dosing condition and a symptom assessment. It also makes clear why outcome definitions should be examined before interpreting a reported response rate: each component must be satisfied for a participant to count as a responder.
The design includes randomization and masking, features intended in general to reduce bias in treatment comparison and outcome assessment. At the same time, enrollment was 30, and the registry record does not report primary response counts or an analysis estimate. Without those results, readers cannot assess the observed group contrast or its precision. This illustrates the distinction between a clearly stated research question and an interpretable statistical result: the former is present in the record, while the latter is not.
The safety data also illustrate why event counts need context. Counts by group are descriptive, and the record does not provide a statistical comparison, exposure-adjusted rates, or group assignments for the listed serious event terms. For researchers, the case emphasizes the value of reporting outcome results, missing-data handling, analysis methods, and the reason for trial termination alongside the endpoint definition. Those details are necessary to assess not only what was intended, but how much can be inferred from the observed data.
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 that the registry record does not report primary endpoint results. Although the response definition and analysis population are stated, the numbers meeting the definition by group, a comparative estimate, and its precision are unavailable. The secondary outcome is described, but its results are not reported in the registry information.
The record identifies the study as terminated but does not report the reason. It does not state how many participants completed the study or had evaluable primary outcome data, how missing data were handled, or whether any participants changed or discontinued treatment. These details are important when interpreting a short-term response outcome that requires maintaining a dose through study end.
The registry identifies randomization and masking, but does not report the randomization procedures, allocation concealment, the roles masked, or the statistical analysis plan. There is also no reported account of multiplicity control or interim analyses. The official title describes double blinding and double-dummy control, whereas the registry masking field says triple; the roles involved are not specified, so the difference cannot be resolved from the record.
The safety information is limited to participant counts and selected serious adverse event terms. Death counts are not reported in the registry record, and the record does not supply event-level detail, exposure-adjusted rates, or an inferential comparison. With these omissions, the safety entries can be described but not used to make a detailed comparative assessment. Together, these limitations mean that the documented study question and design cannot be matched to a reported primary treatment-effect result.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study Designed to Compare the Tolerability of an Increased Dose of Enteric-coated Mycophenolate Acid (MPA) in Renal Transplant Patients Whose Dose of Mycophenolate Mofetil (MMF) Was Reduced Due to Gastrointestinal Symptoms — NCT00658333.
- Registry record last updated 2012-08-07; status last verified 2012-07.
- Results first posted 2011-03-11.
- 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
NCT00658333 is a randomized, parallel-group Phase 4 study in renal transplant recipients whose mycophenolate mofetil dose was reduced because of gastrointestinal symptoms. The study compared enteric-coated mycophenolate acid with mycophenolate mofetil and is listed as terminated, with enrollment of 30. Its primary endpoint was a yes/no response at 6 weeks, requiring a tolerated and maintained increase in enteric-coated mycophenolate acid dose and gastrointestinal symptoms that improved or did not worsen.
The registry record lists serious adverse event counts of 2 affected participants among 15 at risk in the enteric-coated mycophenolate acid group and 0 among 15 in the mycophenolate mofetil group. Other adverse event counts are 12 among 15 in each group. Primary endpoint results, statistical analyses, the reason for termination, and details of missing-data handling are not reported in the registry record. The record therefore documents the study question and selected safety information but does not permit interpretation of the primary comparative result.