Study to Investigate the Effect of Rifampin and Itraconazole on the Action of Pamiparib in Participants With Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Investigate the Effect of Rifampin and Itraconazole on the Action of Pamiparib in Participants With Cancer (NCT03994211), a non-randomized phase 1 study. The primary outcome is Maximum Observed Concentration (Cmax) of Pamiparib in Plasma for Part A.

2. Clinical Question

3. Trial Design

This Phase 1 study was open-label, non-randomized, and parallel-group, with a fixed sequence of study treatments. The registry lists enrollment of 25 and describes the study as completed. Its stated focus was pharmacokinetics: Part A investigated CYP3A induction by rifampin, while Part B investigated CYP3A inhibition by itraconazole. The record does not describe this as an efficacy comparison.

The core phase included Part A and Part B. In Part A, participants received pamiparib 60 mg orally on Days 1 and 10 in the fasted state, with rifampin 600 mg once a day from days 3 to 11. In Part B, participants received a single 20 mg oral dose of pamiparib on days 1 and 7 in the fasted state, with itraconazole 200 mg once a day from Day 3 to day 8. The record gives meal and pre-dose instructions for these treatments. Participants were offered an extension phase in which they received pamiparib 60 mg orally twice a day in 28-day cycles until progression of disease, unacceptable toxicity, withdrawal of consent, or another reason for discontinuation.

Because allocation was not randomized and the arms used different concomitant drugs and pamiparib regimens, the arms should not be read as interchangeable treatment groups. The extension phase also differed from the core phase in purpose and duration. These design features matter when interpreting any apparent differences between groups or phases: they do not by themselves isolate a causal effect of one drug interaction from all other differences.

The study start was 2019-05-29, and primary completion was 2019-10-25. The registry record does not report a detailed statistical analysis plan or a justification for the enrollment target.

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: The screening period consisted of Days -28 to -1.

Core Phase

Reasons for not completing this period:

Extension Phase

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The pharmacokinetic (PK) population includes all participants who received at least 1 dose of pamiparib and have evaluable PK data. A participant was to be excluded from the PK summary statistics and statistical analysis if the participant had an adverse event (AE) of vomiting that occurred at or before 2 x median tmax.

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.

Population: The safety population included all participants who received at least 1 dose of pamiparib

6. Primary Endpoint

The registry lists the primary outcome as Maximum Observed Concentration (Cmax) of Pamiparib in Plasma for Part A, measured over Part A: from Day -1 (admission) to Day 12 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12, 24, and 48 hours post-dose.

Cmax is the highest observed concentration of a drug in plasma during a defined sampling period. It describes peak measured exposure, rather than the total amount of drug exposure over time or the time taken to reach a peak. In a pharmacokinetic interaction study, comparing Cmax under different concomitant-drug conditions can help characterize whether peak pamiparib concentrations differ when CYP3A activity is altered. That is a general explanation of the endpoint, not a statement about the findings of this study.

The listed primary endpoint is the median Cmax of pamiparib in plasma for Part A, with dispersion described as the full range. The timeframe runs from Day -1 (admission) to Day 12 (discharge), with sampling 30 min pre-dose and at 0.5, 1, 2, 4, 6, 9, 12, 24, and 48 hours post-dose. A median gives a central value that is less affected by unusually high or low observations than a mean; the full range conveys the observed extremes but can be sensitive to them. The numeric Cmax result and full range are not reported in the registry record, so the endpoint’s magnitude and precision cannot be assessed from the information recorded.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does Cmax represent?

Cmax is the maximum observed plasma concentration over a specified observation period. It is one aspect of pharmacokinetics, which describes how drug concentrations change over time. In general, peak concentration can answer a different question from measures that summarize exposure across the entire concentration-time profile. Cmax alone does not describe the full profile, and it should not be treated as a measure of clinical benefit or harm by itself.

The registry identifies the primary endpoint as median Cmax for Part A and describes dispersion using the full range. A median is the middle value after observations are ordered. It is often useful when a distribution is skewed or contains extreme values, because an extreme observation has less influence on the median than on the mean. The full range reports the lowest and highest observations, making the spread visible in a simple way. In general, however, a range depends heavily on the most extreme observations and does not show how values are distributed between those extremes. The registry does not report the actual median or range.

Why does the sampling schedule matter?

The endpoint depends on observed concentrations, so the timing of blood sampling determines which portions of the concentration-time profile can be measured. Part A’s listed schedule includes a pre-dose sample and several post-dose time points through 48 hours. In general, more frequent sampling around a concentration peak can better characterize its timing and height, while sparse sampling can miss a peak between measurements. The registry gives the planned sampling times but does not report the individual concentration profiles or the observed time of peak concentration. It is therefore not possible to assess from the registry whether the measured maximum coincided with the true peak between samples.

What does the fixed-sequence design mean?

In general, a fixed-sequence design specifies an order for treatments rather than assigning treatment order at random. This can make the sequence of dosing and measurement clear, but it does not provide the protection against allocation-related differences that randomization is designed to offer. Here, the registry describes a non-randomized parallel-group study with fixed sequences, and it gives treatment schedules for Part A and Part B. It does not report enough detail to infer additional design features or the exact analysis used to compare pharmacokinetic measurements. In particular, the two core parts should not be treated as randomized arms: they differ in concomitant drug and pamiparib dose.

What statistical summaries or tests were used?

The registry specifies a median and full range for the primary endpoint, but does not report a statistical test, confidence interval, adjusted model, or a formal comparison estimate for Cmax. In general, a confidence interval describes a range of values compatible with an estimate under the method’s assumptions. Its width can communicate precision, while the estimate’s direction and size communicate the observed pattern. No confidence interval for the primary endpoint is reported in the registry record, so neither its precision nor a formal contrast can be evaluated from this information.

The record lists 20 outcome measures and 6 analyses, but those counts do not identify the methods used for each measure. The statistical analysis plan, handling of values below quantification limits, approach to outliers, and any model covariates are not reported in the registry record. These are general issues that can affect pharmacokinetic analyses; their handling in this trial should not be assumed.

How should the planning illustrations be understood?

The sample-size assumptions describe planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. Those are assumptions for an illustration, not a report of the trial’s own design rationale. The registry does not report a sample-size justification for the study. Planning illustrations are not observed power, and they do not establish that the study had adequate precision for its primary endpoint. The record does not provide the numeric observed effect or the associated planning outputs in the information available for interpretation.

Why does over-dispersion matter in general?

When data vary more than a statistical model expects, standard errors based on that model can be too small, making uncertainty appear narrower than it is. This is called over-dispersion in settings where the model specifies a particular variance pattern. It is a general statistical concern, not a reported feature of this study. The registry record does not describe a model for the primary endpoint or report a variance assessment, so no claim about over-dispersion or its handling can be made.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 20 outcome measures and 6 analyses. The available record identifies median Cmax of pamiparib in Part A as the primary endpoint, and it lists safety outcomes including treatment-emergent adverse events, serious adverse events, and clinically significant abnormalities in laboratory assessments, vital signs, ECG parameters, and physical examinations. The record does not specify which analyses correspond to which outcomes, or whether all listed outcomes were analyzed according to a prespecified hierarchy.

When a study examines multiple outcomes or performs multiple tests, the chance of at least one apparently unusual result can increase. Statistical approaches can address this in different ways, for example by controlling a family-wise error rate or by defining a primary endpoint and treating other results as exploratory. This is a general explanation; the registry record does not report a multiplicity adjustment, testing hierarchy, or other procedure for interpreting multiple analyses. No claim should be made that multiplicity was or was not controlled in the trial’s actual analysis.

The pharmacokinetic population is described as participants who received at least one dose of pamiparib and had evaluable pharmacokinetic data. The record also begins to describe exclusion from PK summary statistics and analysis for a participant with vomiting, but the criterion is truncated. The complete exclusion rule is not reported in the registry record. The record does not specify how missing concentration measurements, incomplete profiles, or other nonevaluable PK data were handled.

Other analysis populations, the number of participants included in each endpoint analysis, and the methods for missing safety or clinical measurements are not reported in the registry record. Enrollment is listed as 25, but enrollment does not by itself establish how many participants contributed to each analysis. Without analysis-population counts and missing-data methods, the completeness of endpoint-specific data cannot be assessed.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 3% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: anaemia (8.3%), vomiting (8.3%), intestinal obstruction (7.7%).

The registry reports participants with serious adverse events as counts by group: 0 of 12 in Core Phase Arm A, Pamiparib + Rifampin; 1 of 13 in Core Phase Arm B, Pamiparib + Itraconazole; and 2 of 24 in the Extension Phase. It reports 0 deaths in each group. These counts describe what was recorded for the listed groups; they are not estimates of comparative risk and should not be converted into a treatment ranking.

The registry separately lists other adverse-event counts of 5 of 12, 6 of 13, and 18 of 24, respectively. The detailed definitions and event-level results are not reported in the registry record. Listed serious-event terms include Anaemia at 8.3%, Vomiting at 8.3%, and Intestinal obstruction at 7.7%. The record does not clarify those terms’ group attribution in the information used here, so they should not be assigned to a particular group.

These descriptive safety figures do not establish causation. The study was non-randomized, the groups had different treatment contexts, and the extension phase differed from the core phase. The figures also do not show how long participants were observed or how exposure duration varied. They should be read as registry counts, not as proof that a treatment caused or prevented an event.

12. What the Result Does, and Does Not, Mean

The record describes a Phase 1 investigation of pamiparib pharmacokinetics in the presence of rifampin, a CYP3A inducer, and itraconazole, a CYP3A inhibitor. It identifies maximum observed plasma concentration in Part A as the primary endpoint and gives the sampling schedule and summary type. This establishes the kind of pharmacokinetic question the study set out to address; it does not supply the numeric primary endpoint result.

Because the Cmax median and full range are not reported in the registry record, the magnitude, direction, and variability of the primary result cannot be described. The record also does not report an inferential estimate or confidence interval for that endpoint. As a result, the available information cannot establish how precisely a pharmacokinetic difference was estimated or whether any observed difference met a statistical criterion.

The treatment groups are not randomized like-for-like comparators. Their concomitant drugs and pamiparib doses differ, and the extension phase has a distinct treatment purpose. These features mean that simple differences between group-level observations would not, on their own, isolate the effect of one concomitant drug. The listed safety counts are descriptive and do not show that treatment caused an event.

In general, a pharmacokinetic result can inform understanding of drug exposure, but Cmax is only one concentration measure. It does not by itself establish clinical benefit, clinical harm, or an appropriate treatment decision. No medical advice or treatment recommendation follows from the information in this record. The registry does not report the complete statistical analysis plan, endpoint-specific analysis populations, or missing-data methods, so the robustness and precision of the results cannot be fully judged.

The appropriate reading is therefore bounded: the study design and intended pharmacokinetic question are described, and safety counts are listed, but the primary Cmax findings and key analysis details are not reported in the registry record. Those absences prevent a quantitative interpretation of the main endpoint, rather than demonstrating that there was no effect or no analysis.

13. Why This Trial Matters Statistically

This study is statistically relevant because its question concerns drug exposure under conditions intended to alter CYP3A activity. Pharmacokinetic endpoints such as Cmax describe a specific feature of a concentration-time profile, and their interpretation depends on sampling, the summary measure, and the analysis population. The registry identifies these elements for Part A, including median Cmax, full-range dispersion, and scheduled sampling through 48 hours.

The design also illustrates why a stated study objective and a valid comparative interpretation are not the same thing. The record is non-randomized, and the two core parts use different concomitant drugs and pamiparib doses. That structure does not support treating the groups as interchangeable control arms. Recognizing this distinction helps avoid attributing every difference between groups to the concomitant drug alone.

The safety information offers another statistical lesson: counts by treatment group are descriptive evidence, not automatically causal comparisons. Exposure context, duration of observation, and analysis methods matter, and those details are not fully reported in the record. Similarly, a listed outcome measure does not convey its result unless the estimate and its uncertainty are available.

Finally, the record distinguishes trial enrollment from analysis populations and provides a planning-illustration assumption set without reporting the study’s own sample-size justification. These details matter when assessing precision and the scope of inference. The study is therefore useful as an example of how pharmacokinetic aims, design structure, endpoint summaries, and completeness of reporting jointly shape statistical interpretation, even when the primary numerical result is unavailable.

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 interpreting the main endpoint is that the registry record does not report the numeric Cmax median or full range. It also does not report a confidence interval, formal comparison estimate, or detailed statistical test for that endpoint. The available information consequently does not permit assessment of the size or precision of the primary pharmacokinetic finding.

The non-randomized design and differing core regimens limit direct comparisons between Part A and Part B. The record describes different pamiparib doses and different concomitant drugs, so the parts are not like-for-like control groups. The extension phase has a distinct treatment course and should not be treated as equivalent to either core part.

The registry lists enrollment of 25, but does not report how many participants contributed to each endpoint analysis or how many had evaluable data. The PK population definition is given, but the description of an exclusion related to vomiting is incomplete. Handling of missing samples, incomplete concentration profiles, and other nonevaluable data is not reported in the registry record.

Further limitations include the absence of a detailed statistical analysis plan, a reported multiplicity procedure, and a sample-size justification. Safety counts are provided, but the record does not give the exposure duration or the full context needed to compare groups. These limitations are specific to the available registry record and restrict interpretation; they do not establish that relevant analyses or procedures were absent from the study itself.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study to Investigate the Effect of Rifampin and Itraconazole on the Action of Pamiparib in Participants With Cancer — NCT03994211.
• Registry record last updated 2024-10-26; status last verified 2024-10.
• Results first posted 2023-05-23.
• 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.

18. Record Summary

The registry describes NCT03994211, a completed Phase 1, open-label, non-randomized, parallel-group study with a fixed sequence. Enrollment was 25, and the study start and primary completion dates were 2019-05-29 and 2019-10-25. The study investigated the effect of rifampin and itraconazole on pamiparib pharmacokinetics in cancer patients with solid tumors.

The core phase comprised Part A, which investigated rifampin, and Part B, which investigated itraconazole. Participants were offered an extension phase with continued pamiparib. The primary endpoint was median Cmax in plasma for Part A, with full-range dispersion and a stated sampling timeframe. The numeric primary endpoint result, detailed statistical analysis plan, multiplicity procedure, and endpoint-specific analysis counts are not reported in the registry record.

Safety counts are listed for serious and other adverse events and for deaths by group. These figures are descriptive and do not establish causal treatment effects. The non-randomized design and differing treatment regimens limit direct comparisons across groups.