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 Pharmacokinetic Effect of SCH 503034 (Boceprevir) on Methadone or Buprenorphine/Naloxone Plasma Concentrations (P08123) (NCT01396005), a non-randomized phase 1 study. The primary outcome is Area Under the Concentration Versus Time Curve (AUC) at Steady State of Methadone Enantiomers When Administered With or Without Boceprevir.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01396005 |
| Phase | Phase 1 |
| Condition | Hepatitis C Virus |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 21 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Merck Sharp & Dohme LLC |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled patients receiving maintenance therapy with methadone or buprenorphine/naloxone. The registry lists Hepatitis C Virus as the condition and records enrollment of 21 participants. The primary endpoint population is described as all participants receiving standard methadone maintenance therapy with boceprevir.
Intervention
Boceprevir was administered alongside the participant’s maintenance therapy. In the methadone arm, participants received their standard methadone therapy on Days 1 through 8 and boceprevir on Days 2 through 7. In the buprenorphine/naloxone arm, participants received standard buprenorphine/naloxone therapy on Days 1 through 8 and boceprevir on Days 2 through 7.
Comparator
The primary question concerns methadone exposure without boceprevir versus methadone exposure with boceprevir, measured at different study periods. The study also included a buprenorphine/naloxone maintenance arm, but the record does not describe a randomized, like-for-like control comparison between the arms.
Primary question
For participants receiving methadone maintenance therapy, how did the area under the concentration-versus-time curve for methadone enantiomers differ when methadone was administered with boceprevir compared with without boceprevir? AUC represents drug exposure over time. The registry describes the measurement schedule and endpoint but does not report the numerical comparison or its statistical uncertainty.
3. Trial Design
This was a Phase 1, open-label, nonrandomized, parallel study, recorded as completed. The registry lists a start in 2011-09 and primary completion in 2011-12. Enrollment was 21. Because allocation was nonrandomized and the arms were not designed as a like-for-like control comparison, the study should be read as a pharmacokinetic investigation rather than a randomized comparison of treatment groups.
The two regimens were methadone plus boceprevir and buprenorphine/naloxone plus boceprevir. In the methadone arm, standard maintenance therapy was 20-150 mg in tablet, liquid, or disket form, orally once per day on Days 1 through 8. Boceprevir was 800 mg, given as 4 x 200 mg capsules orally every 8 hours on Days 2 through 7. In the other arm, standard buprenorphine/naloxone maintenance therapy was 8/2-24/6 mg in sublingual tablets once per day on Days 1 through 8, with the same boceprevir regimen on Days 2 through 7.
The primary endpoint focused on methadone enantiomer AUC at steady state, with samples collected on Day 1 without boceprevir and on Day 7 with boceprevir. Predose samples on Days 5-6 were intended to check steady state during co-administration. Secondary outcomes named in the registry concern naloxone AUC and maximum concentration, each at steady state with or without boceprevir. The registry describes six outcome measures overall, but numerical results 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.
Overall Study
| Stage | Methadone + Boceprevir | Buprenorphine/Naloxone + Boceprevir |
|---|---|---|
| STARTED | 10 | 11 |
| COMPLETED | 10 | 9 |
| NOT COMPLETED | 0 | 2 |
Reasons for not completing this period:
| Reason | Methadone + Boceprevir | Buprenorphine/Naloxone + Boceprevir |
|---|---|---|
| Withdrawal by Subject | 0 | 1 |
| Non-compliance with protocol | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: All participants receiving standard methadone maintenance therapy + boceprevir
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 | Methadone + Boceprevir | Buprenorphine/Naloxone + Boceprevir | Total |
|---|---|---|---|---|
| Participants analysed | 10 | 11 | 21 | |
| Age, Continuous | years | 34.2 (SD 10.2) | 33.2 (SD 29.0) | 33.7 (SD 10.1) |
| Sex: Female, Male: Female | Participants | 2 | 2 | 4 |
| Sex: Female, Male: Male | Participants | 8 | 9 | 17 |
6. Primary Endpoint
The registry lists the primary outcome as Area Under the Concentration Versus Time Curve (AUC) at Steady State of Methadone Enantiomers When Administered With or Without Boceprevir, measured over Methadone samples collected Day 1, 0 (predose) through 24 hours post-dose (Day 2). Boceprevir and methadone samples collected Day 7, 0 (predose) through 24 hours post-dose (Day 8). Predose samples also collected on Days 5-6..
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Geometric Coefficient of Variation |
| Unit | (ng.hr/mL)/mg |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is area under the concentration-versus-time curve (AUC) at steady state for methadone enantiomers when administered with or without boceprevir. Its unit is (ng.hr/mL)/mg. AUC represents the amount of drug in the blood over time, so it characterizes overall exposure across the sampling interval rather than a concentration at a single moment. The endpoint is reported as a geometric mean, with geometric coefficient of variation as the stated measure of dispersion.
The registry describes methadone samples collected on Day 1 from predose through 24 hours post-dose, before boceprevir co-administration. Methadone and boceprevir samples were collected on Day 7 from predose through 24 hours post-dose, during co-administration. Predose samples on Days 5-6 were intended to check whether methadone plus boceprevir had reached steady state. The record defines steady state as the point at which the amount eliminated by the body is in equilibrium with the amount taken in.
Comparing AUC across these periods is intended to assess whether measured methadone exposure differed with co-administration. The registry does not report the resulting AUC estimates, the size or direction of any difference, or uncertainty around an estimate. Therefore the endpoint definition and sampling schedule can be described, but the magnitude and precision of the observed pharmacokinetic comparison cannot be judged from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the study question, treatment schedules, sampling periods, and planned pharmacokinetic measures. It does not report numerical primary-outcome estimates. In particular, it contains no reported geometric mean AUC values for the methadone enantiomers, no estimate of the comparison between periods, and no confidence interval or p-value. The direction, magnitude, and precision of the primary comparison are therefore not reported in the registry record.
The primary endpoint is a within-participant, period-based comparison: methadone was measured without boceprevir on Day 1 and with boceprevir on Day 7. This differs from a randomized parallel comparison in which different participants are assigned to intervention and control groups. The study is open-label and nonrandomized, and the registry explicitly notes that its arms are not a like-for-like control comparison. Those design features limit what can be attributed to boceprevir solely from differences between the two arms. The primary endpoint, however, is described as the comparison of methadone measurements across the periods, not as a direct comparison of the two maintenance-therapy arms.
The other named outcomes concern naloxone AUC and Cmax at steady state with or without boceprevir. Cmax refers to the maximum measured concentration, while AUC represents exposure over time. The record does not provide numerical results for these outcomes either. It lists six outcome measures but no analyses. Without outcome estimates and their uncertainty, the posted information cannot establish how large or consistent any pharmacokinetic change was.
The adverse-event counts are separate from the primary pharmacokinetic endpoint. The record lists no participants with serious adverse events in either arm, while it reports other adverse events in both arms. These counts describe the posted safety record but do not substitute for the missing endpoint results or provide a randomized comparison. The deaths field is not reported in the registry record.
Overall, the registry record supports a description of the study’s design and intended measurements, not a conclusion about the numerical effect of boceprevir on methadone or buprenorphine/naloxone concentrations. Estimates, uncertainty intervals, analysis details, and result-level interpretation are not reported in the registry record.
9. Statistical Methods Explained
The registry names the primary measure as a geometric mean AUC and identifies geometric coefficient of variation as its dispersion measure. It does not provide numerical estimates or describe a full statistical analysis plan. The explanations below give general statistical context; they should not be taken as claims about analyses performed in this study beyond what the registry record states.
What AUC measures
General: concentration measurements taken at multiple times can be used to describe exposure over a period. AUC summarizes the area under the concentration-versus-time profile. It is useful when a single concentration measurement would not capture the overall pattern of drug exposure. The endpoint is expressed per mg and uses the unit (ng.hr/mL)/mg. The registry describes measurements from predose through 24 hours post-dose on the specified sampling days.
AUC is not the same as Cmax. AUC characterizes exposure across the sampling interval, whereas Cmax identifies the maximum measured concentration. The registry names naloxone AUC and Cmax among secondary outcomes, but numerical findings for either are not reported in the registry record.
Geometric means and variation
General: geometric summaries are often used for measurements that are positive and whose variation is better described proportionally than as a fixed additive amount. A geometric coefficient of variation describes relative spread on a multiplicative scale. It is distinct from a confidence interval: a coefficient of variation describes dispersion among observations, while a confidence interval describes uncertainty in an estimated quantity. The registry specifies geometric mean and geometric coefficient of variation for the primary endpoint but does not report their values or confidence intervals.
Interpreting the sampling-period comparison
The registry describes methadone sampling on Day 1 without boceprevir and on Day 7 with boceprevir. This makes the endpoint a comparison across study periods for the methadone regimen. General: measurements from the same participant across periods can help account for stable differences between participants, but a period comparison may still depend on the design, measurement conditions, and analysis choices. The registry record does not describe the statistical model, any adjustment, or how repeated measurements were handled. It also does not report whether all planned samples were available for each participant.
The Days 5-6 predose samples were described as checks for steady state during methadone plus boceprevir. General: steady state matters in pharmacokinetic interpretation because exposure during a dosing regimen can differ while drug amounts are still accumulating or otherwise changing. The registry gives the purpose of those samples but does not report their results or state how they affected inclusion in an analysis.
Uncertainty and hypothesis tests
General: a confidence interval conveys a range of values compatible with an estimate under a statistical model and makes precision visible. A p-value, when used, summarizes how compatible observed data are with a specified null hypothesis under the model; it does not measure the size or clinical importance of an effect. Neither a confidence interval nor a p-value for the primary comparison is reported in the registry record. Since the registry lists zero analyses, no inferential result can be reviewed there.
Planning assumptions
The record describes sample-size illustrations as planning illustrations based on the observed effect, not as the trial’s own design. It states assumptions of a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect defined as a stated fraction of the observed effect. For non-time-to-event outcomes, such illustrations are expressed as participants per arm for a specified power; time-to-event illustrations use total events. These assumptions do not establish that the trial was designed using that calculation, and the sample-size justification is not reported in the registry record. Such planning illustrations are not observed power and do not replace estimates of the actual effect or its uncertainty.
The registry record does not describe the model used for the primary endpoint, an analysis population, handling of missing pharmacokinetic measurements, or an interim analysis. Those details should not be inferred from the endpoint definition or sample schedule.
10. Multiplicity, Missing Data and Analysis Populations
The registry names six outcome measures and identifies a primary methadone AUC outcome, as well as secondary outcomes involving naloxone AUC and Cmax. It does not report a multiplicity strategy, such as an adjustment to account for testing several outcomes. The statistical plan for defining or prioritizing analyses beyond the primary endpoint is not reported in the registry record. As a result, the record does not establish how any multiple comparisons were intended to be interpreted.
The registry lists zero analyses and gives no numerical primary or secondary outcome results. It also does not report confidence intervals, p-values, or other measures of uncertainty. Thus, no assessment can be made from this record about statistical significance or precision, even for the designated primary endpoint.
The record does not describe the analysis populations, the number of participants contributing data to each pharmacokinetic outcome, or how missing samples or incomplete profiles were handled. It states the primary endpoint population as all participants receiving standard methadone maintenance therapy plus boceprevir, but does not define a more detailed analysis set or say whether exclusions occurred. The handling of missing data is not reported in the registry record.
The registry also does not describe interim analyses, stopping rules, or a formal sample-size justification. The stated sample-size assumptions are identified as planning illustrations rather than the trial’s own design. Without a protocol-level statistical plan and posted outcome analyses, it is not possible to determine whether any unreported analysis choices affected the results.
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 |
|---|---|---|---|
| Methadone + Boceprevir | 0 | 10 | 0.0% |
| Buprenorphine/Naloxone + Boceprevir | 0 | 11 | 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 |
|---|---|
| Methadone + Boceprevir | 10 of 10 |
| Buprenorphine/Naloxone + Boceprevir | 9 of 11 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Methadone + Boceprevir | Buprenorphine/Naloxone + Boceprevir |
|---|---|---|---|
| Dysgeusia | Nervous system disorders | 2 of 10 | 5 of 11 |
| Headache | Nervous system disorders | 3 of 10 | 3 of 11 |
| Nausea | Gastrointestinal disorders | 3 of 10 | 2 of 11 |
| Pollakiuria | Renal and urinary disorders | 2 of 10 | 2 of 11 |
| Dry mouth | Gastrointestinal disorders | 2 of 10 | 1 of 11 |
| Product taste abnormal | General disorders | 2 of 10 | 1 of 11 |
| Somnolence | Nervous system disorders | 3 of 10 | 0 of 11 |
| Vomiting | Gastrointestinal disorders | 2 of 10 | 0 of 11 |
| Abdominal pain upper | Gastrointestinal disorders | 1 of 10 | 0 of 11 |
| Flatulence | Gastrointestinal disorders | 1 of 10 | 0 of 11 |
The registry lists serious adverse events for each treatment group. In the Methadone + Boceprevir group, 10 participants were at risk and 0 were affected by serious adverse events. In the Buprenorphine/Naloxone + Boceprevir group, 11 participants were at risk and 0 were affected by serious adverse events. The record lists no top serious adverse-event terms.
For other adverse events, the registry records 10 participants at risk and 10 affected in the methadone group, and 11 at risk and 9 affected in the buprenorphine/naloxone group. These are counts within the posted groups, not evidence from a randomized, like-for-like control comparison. They do not describe event severity, timing, duration, or causal attribution beyond the registry’s category labels.
The death fields are null, so death counts are not reported in the registry record; they should not be read as zero. The safety counts are descriptive and do not provide an estimate of comparative risk or replace the pharmacokinetic outcomes. The record does not provide further detail on the listed other adverse events in the registry record for this summary.
12. What the Result Does, and Does Not, Mean
This record describes a Phase 1 pharmacokinetic study of boceprevir administered with maintenance methadone or buprenorphine/naloxone. Its primary question concerns methadone enantiomer AUC with and without boceprevir. The sampling schedule identifies when those measurements were intended to be collected, and the registry explains that predose measurements during co-administration were intended to check steady state.
What the record does not provide is the numerical answer to that primary question. Geometric mean AUC estimates, the comparison between sampling periods, and uncertainty measures are not reported in the registry record. Nor are numerical results reported for the named naloxone AUC and Cmax outcomes. Consequently, no magnitude or direction of a pharmacokinetic difference can be described from this record, and its precision cannot be assessed.
The design also shapes interpretation. The study was open-label and nonrandomized, with parallel maintenance-therapy groups that the registry says are not a like-for-like control comparison. The primary endpoint compares methadone sampling periods, rather than presenting a randomized comparison between methadone and buprenorphine/naloxone groups. The design details therefore do not justify treating the two arms as direct controls for each other.
The safety record reports zero participants affected by serious adverse events in each group, and reports other adverse events in both groups. The death counts are not reported in the registry record. These counts are descriptive and should not be interpreted as a controlled estimate of comparative safety.
The appropriate reading is limited to the stated question, design, planned measurements, and posted event counts. The record does not establish a treatment effect, provide evidence about clinical outcomes, or support conclusions about the size or certainty of any pharmacokinetic change.
13. Why This Trial Matters Statistically
This study illustrates why the design and the target estimand matter in clinical pharmacology. The main question is not simply whether participants in two maintenance-therapy groups differed. It is whether methadone exposure, summarized by AUC, differed between a period without boceprevir and a period with boceprevir. The registry’s sampling schedule and endpoint description clarify that distinction.
It also shows why outcome definitions and result reporting are both needed. AUC, Cmax, geometric means, and geometric coefficients of variation describe different features of concentration data. Knowing which measure was planned helps readers understand the intended question, but without the numerical estimates and uncertainty, readers cannot judge the size or precision of the observed result. In this record, analyses and numerical outcome results are not reported in the registry record.
The nonrandomized, open-label design is another important statistical feature. The registry explicitly warns that the two treatment arms are not a like-for-like control comparison. That caveat prevents an overly simple interpretation of between-arm counts or measurements and directs attention to the specified within-period methadone comparison.
Finally, planning calculations must be kept distinct from observed evidence. The registry characterizes sample-size illustrations as planning exercises based on the observed effect, not as the trial’s design or as observed power. That distinction is important because sample-size planning cannot substitute for reporting the actual endpoint estimate and its uncertainty. Taken together, this record is informative about how a pharmacokinetic question was framed, while leaving the numerical answer and much of the analysis approach unreported.
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 central limitation for statistical interpretation is that numerical primary-outcome results are not reported in the registry record. The geometric mean AUC values, their comparison, and the geometric coefficients of variation are absent. Confidence intervals and p-values are also not reported, so the magnitude and precision of the primary pharmacokinetic result cannot be assessed.
The registry lists zero analyses. It does not describe the model or estimator used, how repeated measurements were handled, or whether any adjustments were made. It identifies the primary endpoint population broadly but does not define detailed analysis populations or report how many participants contributed data to each outcome.
Although the sampling schedule is described, the registry does not report whether all samples were collected or how incomplete sampling profiles and missing measurements were handled. It states that predose samples on Days 5-6 were intended to check steady state but does not provide those results or explain how they were used in analysis.
The open-label, nonrandomized design and the registry’s warning that the arms are not a like-for-like control comparison limit interpretation of between-arm contrasts. The sample-size justification and statistical plan are not reported in the registry record. A multiplicity approach, interim analyses, and stopping rules are also not reported. The safety fields include null death counts, so deaths cannot be interpreted as zero. These limitations leave key analysis and result details unavailable for evaluation.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Evaluate the Pharmacokinetic Effect of SCH 503034 (Boceprevir) on Methadone or Buprenorphine/Naloxone Plasma Concentrations (P08123) — NCT01396005.
- Registry record last updated 2017-04-07; status last verified 2017-03.
- Results first posted 2013-03-11.
- 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
The registry record describes a completed Phase 1, open-label, nonrandomized, parallel study with enrollment of 21 participants. It examined boceprevir given with methadone or buprenorphine/naloxone maintenance therapy. The primary endpoint was steady-state AUC for methadone enantiomers with or without boceprevir, reported in the registry as a geometric mean with geometric coefficient of variation.
The record specifies the dosing schedules and sampling periods and names naloxone AUC and Cmax as secondary outcomes. It lists six outcome measures and zero analyses. Numerical pharmacokinetic results, uncertainty estimates, a detailed statistical plan, analysis populations, and missing-data methods are not reported in the registry record. Serious adverse events affected 0 participants in each group; other adverse events were recorded in both groups. Death counts are not reported in the registry record.