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 Buprenorphine Disposition and CYP3A (NCT01576575), a registered na study. The primary outcome is Plasma Cmax of Buprenorphine.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01576575 |
| Phase | NA |
| Condition | Healthy |
| Allocation | Not Stated |
| Design model | Sequential |
| Masking | None (open label) |
| Enrollment | 21 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Washington University School of Medicine |
| Results posted | Yes |
2. Clinical Question
Population
The registry describes healthy males and non-pregnant females. The study record reports enrollment of 21, but the primary outcome description says 0 participants were analyzed. The findings therefore cannot characterize a measured response in this population.
Intervention
The study concerns intravenous or sublingual buprenorphine under different CYP3A modulation conditions. Listed regimens include buprenorphine with rifampin, grapefruit juice, or ketoconazole, as well as buprenorphine control without pretreatment. The registry describes sessions using intravenous buprenorphine at 0.025-0.2 mg infused over 1 hr and sublingual buprenorphine at 2-4 mg, with 1-3 week washout between sessions.
Comparator
The listed control is buprenorphine without pretreatment. The registry identifies a sequential model, and allocation is not stated. It also notes that the arms are not a like-for-like control comparison. The control should therefore not be read as evidence of a randomized comparison with each modulation condition.
Primary question
The stated aim is to evaluate the role of CYP3A in buprenorphine disposition and effect. The named primary outcome is plasma Cmax of buprenorphine, with a timeframe of 96 hr. Cmax is the peak plasma concentration. Because the registry reports no study data and 0 participants analyzed for this outcome, the record does not show whether or how Cmax differed among conditions.
3. Trial Design
The registry identifies this as a sequential study with no masking. Its phase is listed as NA, and its status is completed. The record lists Washington University School of Medicine as sponsor, a start date of 2010-06, and a primary completion date of 2014-03-29. Enrollment is reported as 21. The listed population is healthy males and non-pregnant females.
The interventions include buprenorphine control, buprenorphine with rifampin, buprenorphine with grapefruit juice, and buprenorphine with ketoconazole. The arm descriptions identify control without pretreatment and name conditions for liver and gut CYP3A induction, gut-only CYP3A inhibition, and liver and gut CYP3A inhibition. The study description says participants would be studied during a maximum of seven occasions. Sessions included intravenous buprenorphine infused over 1 hr and sublingual buprenorphine, with 1-3 week washout between sessions. The registry does not give a complete sequence of all sessions in the available arm description.
Allocation is not stated. The record explicitly cautions that the arms are not a like-for-like control comparison, so the listed conditions should not be interpreted as randomized parallel groups. The primary outcome is plasma Cmax of buprenorphine over 96 hr. Although the study status is completed, the primary outcome record says that 0 participants were analyzed, that no study data are available, and that the PI had left the institution after unsuccessful efforts to make contact. The registry records 0 analyses.
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.
Buprenorphine Control
| Stage | Healthy Volunteers |
|---|---|
| STARTED | 21 |
| COMPLETED | 18 |
| NOT COMPLETED | 3 |
Reasons for not completing this period:
| Reason | Healthy Volunteers |
|---|---|
| Withdrawal by Subject | 3 |
Buprenorphine + Rifampin
| Stage | Healthy Volunteers |
|---|---|
| STARTED | 18 |
| COMPLETED | 15 |
| NOT COMPLETED | 3 |
Reasons for not completing this period:
| Reason | Healthy Volunteers |
|---|---|
| Withdrawal by Subject | 3 |
Buprenorphine + Grapefruit
| Stage | Healthy Volunteers |
|---|---|
| STARTED | 15 |
| COMPLETED | 14 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | Healthy Volunteers |
|---|---|
| Withdrawal by Subject | 1 |
Buprenorphine + Ketoconazole
| Stage | Healthy Volunteers |
|---|---|
| STARTED | 14 |
| COMPLETED | 14 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: 0 participants analyzed. The PI has left the institution. Sincere efforts were made to contact the PI but were unsuccessful. No study data are available.
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 | Healthy Volunteers |
|---|---|---|
| Participants analysed | 21 | |
| Age, Continuous | years | 27 (SD 8) |
| Sex: Female, Male: Female | Participants | 8 |
| Sex: Female, Male: Male | Participants | 13 |
6. Primary Endpoint
The registry lists the primary outcome as Plasma Cmax of Buprenorphine, measured over 96 hr.
| 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 is plasma Cmax of buprenorphine, with a stated timeframe of 96 hr. Cmax means the highest concentration of a drug measured in plasma during the specified observation period. It describes a peak in measured concentration; it is not, by itself, a complete description of drug exposure over time or of a clinical effect.
As a general statistical and pharmacological concept, peak concentration can be useful when a question concerns how high measured plasma levels rise under different conditions. It can be compared across conditions when the study has analyzable observations and a defined approach to estimation. In this record, the endpoint title is present, but its unit, parameter, dispersion, and description are not reported in the registry record. More importantly, the outcome entry states that 0 participants were analyzed and that no study data are available. There is consequently no posted Cmax estimate, comparison, or measure of its precision to interpret.
The stated timeframe identifies the observation window associated with the endpoint, but it does not supply a concentration value or explain the timing of individual measurements. The record therefore supports identifying what outcome was intended, not determining what peak concentrations were observed or how they related to clinical effects.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry establishes that the study was completed and that it was designed to examine CYP3A modulation in relation to buprenorphine disposition and clinical effects. It does not establish an observed effect on the primary endpoint. The primary outcome description states that 0 participants were analyzed and that no study data are available. No Cmax values, treatment contrasts, uncertainty intervals, or analysis results are posted in the record.
This distinction matters: enrollment describes the planned or recorded study enrollment, whereas an analyzed population is the set of participants whose data contribute to an outcome analysis. The record gives enrollment of 21 but reports 0 analyzed for the primary outcome. Those entries do not support treating enrollment as an outcome sample size or inferring that enrolled participants contributed usable endpoint measurements.
The study's sequential model and the registry's warning that the arms are not a like-for-like control comparison also limit interpretation of the named conditions as direct treatment contrasts. Allocation is not stated. Without an analysis and details about how observations across occasions were handled, the record does not support attributing any hypothetical difference to rifampin, grapefruit juice, or ketoconazole. There is no posted estimate whose magnitude or precision could be assessed.
As a general statistical principle, an estimate is more informative when accompanied by a measure of uncertainty, such as a confidence interval. A confidence interval describes a range of values compatible with the data under the specified method; it does not replace the estimate or resolve design limitations. No interval is reported for this outcome, and there are no data from which to evaluate one in the registry record.
The adverse-event entries are separate from the primary endpoint and do not provide evidence about Cmax. They report serious adverse events and other adverse-event counts by listed group. Those counts can be described as registry entries, but they do not substitute for the absent outcome analysis or establish a causal comparison. Overall, the posted record documents a study question, design labels, and some safety counts, but not an analyzable result on buprenorphine disposition.
9. Statistical Methods Explained
The registry describes a sequential model and states that masking was absent. It does not report an allocation method. The record also warns that the arms are not a like-for-like control comparison. These features are important when interpreting comparisons: a sequential study examines conditions across occasions, while a randomized parallel comparison would assign participants to distinct groups. The available record does not support treating these arms as randomized groups or assuming that any contrast was adjusted for the order or timing of conditions.
What does the primary measure represent?
As a general concept, Cmax is the maximum measured plasma concentration during a specified observation period. It is a summary of the peak rather than the full concentration-time profile. The registry names plasma Cmax and gives a timeframe of 96 hr, but the endpoint unit, parameter, dispersion, and description are not reported. The record also contains no participant-level concentration results or group-level Cmax summaries. Thus, the intended measure can be identified, but its observed distribution cannot be described.
What can be inferred from the study structure?
The record lists intravenous and sublingual buprenorphine, several CYP3A modulation conditions, and a control without pretreatment. It describes a maximum of seven occasions and a washout of 1-3 week between sessions. These details indicate that the study involved repeated study occasions, but the complete occasion sequence and analysis approach are not reported in the registry record. General statistical practice for repeated observations may account for their dependence within a participant; the registry does not say whether or how such dependence was handled. No model specification or treatment contrast is reported.
The registry's note that the arms are not a like-for-like control comparison is especially relevant. In general, a causal interpretation requires a design and analysis that address alternative explanations for differences between conditions. With allocation not stated, no posted analysis, and no outcome data, it is not possible to assess balance, ordering effects, or other sources of bias for this study.
What is known about statistical testing?
The registry records 0 analyses. It does not report a statistical analysis plan, a test used for the primary endpoint, a significance threshold for the trial's outcome analysis, or an uncertainty estimate. These items are not reported in the registry record. Their absence means readers cannot evaluate how the study intended to estimate or test a Cmax contrast. It would be inappropriate to infer a test or model from the endpoint name or design label alone.
The record includes assumptions for a planning illustration: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not evidence that the trial used this method for its own analysis. The observed effect and numeric planning results are not reported in the registry record. Any sample-size figures associated with such planning are illustrations, not observed power. The assumptions do not repair the lack of outcome data and do not establish the trial's original design justification.
Why does the missing outcome result matter?
Statistical interpretation requires an estimate based on observed measurements and a description of the population contributing those measurements. Here, the primary outcome entry explicitly reports 0 participants analyzed and no available study data. There is therefore no estimate to interpret, no variation to quantify, and no basis for recalculating a result from summary statistics. General explanations of confidence intervals, hypothesis tests, or model assumptions cannot create information absent from the record.
In general, over-dispersion matters when observed variability exceeds what a chosen statistical model expects; that can affect standard errors and inference. The registry does not provide outcome data or a model that would allow assessment of dispersion for this trial. It is therefore not possible to say whether over-dispersion occurred or whether it influenced any analysis. The appropriate statistical conclusion is limited: the registry describes an intended Cmax outcome and a sequential study, but no primary endpoint result is available for evaluation.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 1 outcome measure and 0 analyses. The named primary outcome is plasma Cmax of buprenorphine. A prespecified multiplicity strategy, including whether multiple comparisons were planned and how they would be handled, is not reported in the registry record. The different intervention conditions alone do not establish which contrasts were planned or whether any adjustment was intended.
The primary outcome entry says that 0 participants were analyzed and that no study data are available. This is a statement about the outcome analysis, not a finding of zero Cmax or zero change. The registry does not describe the reasons individual observations might be missing, how missing measurements would have been handled, or whether any sensitivity analysis was planned. Missing-data methods are not reported in the registry record.
The record gives enrollment of 21, but it does not report an analyzed population for the primary endpoint beyond the explicit statement of 0 participants analyzed. No flow of participants through the sequential occasions, endpoint-specific exclusions, or analysis population definitions is reported. It is therefore not possible to determine how many participants completed each condition or which data would have been included in a particular analysis.
As a general matter, multiplicity and missing-data decisions can affect how estimates and uncertainty are interpreted. With no outcome analysis and no reported analysis plan, neither issue can be evaluated for this study. The registry's planning assumptions do not supply a multiplicity approach or missing-data method.
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 |
|---|---|---|---|
| Control (no Pretreatment) | 0 | 21 | 0.0% |
| Liver and Gut CYP3A Induction | 0 | 18 | 0.0% |
| Gut Only CYP3A Inhibition | 0 | 14 | 0.0% |
| Liver and Gut CYP3A Inhibition | 0 | 13 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Control (no Pretreatment) | 0 of 21 |
| Liver and Gut CYP3A Induction | 0 of 18 |
| Gut Only CYP3A Inhibition | 0 of 14 |
| Liver and Gut CYP3A Inhibition | 0 of 13 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Control (no Pretreatment) | 21 of 21 |
| Liver and Gut CYP3A Induction | 15 of 18 |
| Gut Only CYP3A Inhibition | 14 of 14 |
| Liver and Gut CYP3A Inhibition | 13 of 13 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Control (no Pretreatment) | Liver and Gut CYP3A Induction | Gut Only CYP3A Inhibition | Liver and Gut CYP3A Inhibition |
|---|---|---|---|---|---|
| nausea | Gastrointestinal disorders | 12 of 21 | 13 of 18 | 11 of 14 | 12 of 13 |
| itch | General disorders | 14 of 21 | 10 of 18 | 11 of 14 | 8 of 13 |
| Headache | Nervous system disorders | 4 of 21 | 2 of 18 | 3 of 14 | 5 of 13 |
| Dizzyness | Nervous system disorders | 4 of 21 | 3 of 18 | 1 of 14 | 1 of 13 |
The registry separates serious adverse events from other adverse events. In the control group, the serious adverse-event count is 0 among 21 at risk, while the other adverse-event count is 21 among 21 at risk. For liver and gut CYP3A induction, the serious adverse-event count is 0 among 18 at risk, and the other adverse-event count is 15 among 18 at risk. For gut-only CYP3A inhibition, the serious adverse-event count is 0 among 14 at risk, and the other adverse-event count is 14 among 14 at risk. For liver and gut CYP3A inhibition, the serious adverse-event count is 0 among 13 at risk, and the other adverse-event count is 13 among 13 at risk. The recorded death count is 0 in each group.
These are descriptive counts as entered in the registry. The record does not provide event terms for serious events, and the serious-event count is zero in every listed group. It does not provide enough information to establish whether other events were caused by a study drug, when they occurred, or how event severity was classified. Because the study is sequential and the record cautions that the groups are not like-for-like control comparisons, the counts should not be read as a randomized safety contrast. They also do not replace the missing primary endpoint data.
12. What the Result Does, and Does Not, Mean
The record documents a completed study intended to evaluate CYP3A's role in buprenorphine disposition and effect. It identifies plasma Cmax as the primary endpoint and lists control and CYP3A modulation conditions. It also reports some adverse-event counts by group. These registry entries describe the study's purpose and selected registry entries, but they do not establish a result for the primary question.
The registry explicitly reports 0 participants analyzed for the primary outcome and says no study data are available. There is no posted Cmax value, effect estimate, statistical test, or uncertainty interval. Consequently, the record cannot show whether peak buprenorphine concentration differed across conditions, by how much it might have differed, or how precise any estimate would be. It also cannot support a conclusion about clinical effects from the primary endpoint.
The existence of a completed study does not mean its results are available in this record. Likewise, enrollment of 21 is not evidence that 21 participants contributed data to the Cmax analysis. The sequential design, unstated allocation, and registry warning against treating the arms as like-for-like comparisons further constrain interpretation.
As a general point, absence of an analyzable result is not evidence that conditions had equal effects, nor is it evidence that they differed. It means the posted registry record does not permit that question to be answered. The other adverse-event counts provide descriptive safety reporting but do not fill this evidentiary gap. The most defensible reading is that the research question and intended endpoint are documented, while the primary outcome result is unavailable.
13. Why This Trial Matters Statistically
This study raises a useful statistical distinction between a registered research question and an interpretable result. The record identifies CYP3A modulation, buprenorphine disposition, and plasma Cmax as the focus, but it reports no analyzable primary outcome data. A clearly named endpoint does not, on its own, provide an estimate or allow readers to evaluate uncertainty.
The sequential structure also highlights the importance of understanding the unit and sequence of analysis. When conditions are studied on separate occasions, the handling of within-participant observations and order can matter. General statistical methods can account for repeated measurements when appropriate, but the registry does not report the analysis method used or a primary analysis result. A design label cannot replace those details.
The record is also a reminder that safety counts and efficacy or disposition outcomes answer different questions. The listed other adverse-event counts describe reported events by group; they do not provide a concentration estimate. Conversely, the absent Cmax result does not alter the adverse-event counts recorded. Keeping endpoint types distinct avoids treating one kind of information as a substitute for another.
Finally, the entry makes the difference between planning and observation important. The registry describes assumptions for a sample-size planning illustration, but it gives no observed effect or numeric planning result in the available record. Planning calculations are not findings and are not observed power. For statistical interpretation, access to analyzable results, an analysis description, and uncertainty estimates would be necessary; they are not reported for the primary endpoint.
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 is that the registry reports no study data for the primary outcome and 0 participants analyzed. Without observed Cmax values or an analysis result, the intended comparison cannot be evaluated. The endpoint's unit, parameter, dispersion, and description are also not reported in the registry record.
The design information is incomplete for assessing comparisons. The study is labeled sequential and unmasked, allocation is not stated, and the record cautions that the arms are not a like-for-like control comparison. The available arm description does not set out the complete sequence of occasions. The registry does not report how repeated observations, condition order, or washout periods were addressed in an analysis.
The statistical analysis plan, missing-data approach, endpoint analysis population, and multiplicity handling are not reported in the registry record. Although planning assumptions are listed, the observed effect and numeric planning outputs are not reported there. The planning assumptions should not be taken as proof of the trial's original sample-size justification or of an analysis conducted on observed data.
The safety entries are also limited: serious-event counts are zero in each listed group, while other adverse-event counts are recorded, but event terms and causal assessments are not posted in the registry record. The sequential design and warning about unlike-for-like groups prevent treating those counts as a randomized comparative safety analysis. Together, these limitations leave the study question identifiable but the primary result unavailable.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Buprenorphine Disposition and CYP3A — NCT01576575.
- Registry record last updated 2020-01-22; status last verified 2020-01.
- Results first posted 2020-01-22.
- 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
The registry record describes a completed, unmasked sequential study sponsored by Washington University School of Medicine. It lists healthy males and non-pregnant females, enrollment of 21, and interventions involving buprenorphine alone or with rifampin, grapefruit juice, or ketoconazole. The stated primary endpoint is plasma Cmax of buprenorphine over 96 hr.
The primary outcome entry reports 0 participants analyzed and says no study data are available. The registry lists 0 analyses and cautions that the arms are not a like-for-like control comparison; allocation is not stated. Serious adverse-event counts and deaths are recorded as 0 in each listed group, alongside counts for other adverse events. The record documents the research question and selected design and safety information, but it does not provide an analyzable primary endpoint result.