Study to Assess the Effect of BMS-790052 on the Pharmacokinetics of Ortho Tri-Cyclen® in Healthy Female Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Assess the Effect of BMS-790052 on the Pharmacokinetics of Ortho Tri-Cyclen® in Healthy Female Subjects (NCT00983957), a na phase 1 study. The primary outcome is Maximum Observed Plasma Concentration (Cmax) of Ethinyl Estradiol.

2. Clinical Question

The question is pharmacokinetic: what plasma concentration of ethinyl estradiol was observed after study drug exposure, and how might co-administration relate to that concentration? Cmax is the maximum observed concentration during the specified sampling period. The endpoint description says it was derived from plasma concentration-versus-time data using non-compartmental methods.

The record lists measurements at pre-dose and at specified post-dose times on Days 49 and 77. Those repeated time points describe the sampling schedule; they do not, by themselves, establish a comparison between the days or show a change. The registry record does not report the Cmax estimates, their geometric coefficients of variation, or an estimated treatment effect.

This was not a randomized comparison. The record does not describe an independent control group against which to distinguish the effect of BMS-790052 from other influences. Consequently, the clinical question is limited to the pharmacokinetic assessment recorded for the combination, not a comparative claim about treatment benefit or clinical outcomes.

3. Trial Design

The registry identifies NCT00983957 as a completed Phase 1 study sponsored by Bristol-Myers Squibb. It lists enrollment as 47, with a start in 2009-10 and primary completion in 2010-02. The study title and purpose describe an assessment of BMS-790052's effect on the pharmacokinetics of Ortho Tri-Cyclen® in healthy female subjects.

The design is listed as SINGLE GROUP, with allocation NA and masking NONE. The sole arm description names BMS-790052 plus Ortho Tri-Cyclen®. No randomized control arm is described, so the record does not support a like-for-like between-arm interpretation. The registry record does not report a more detailed protocol sequence or explain how study periods were assigned.

The primary outcome is maximum observed plasma concentration of ethinyl estradiol. Sampling is listed at pre-dose and at post-dose time points on Days 49 and 77. The outcome description says that ethinyl estradiol was measured in plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and that Cmax was derived from 24 hour concentration-versus-time data using non-compartmental methods.

The record lists 13 outcome measures and 6 analyses. Secondary outcomes include pharmacokinetic measures for norgestrel, serious adverse events, adverse events leading to discontinuation, deaths, laboratory abnormalities, and clinically meaningful effects in vital signs and ECG parameters. The record's safety summaries use several Ortho Tri-Cyclen time periods, including a period titled Ortho Tri-Cyclen plus Daclatasvir. The registry record does not explain the relationship between that wording and the BMS-790052 name in the study title.

The enrollment figure and the safety groups' risk sets are not the same. The record lists enrollment of 47, while the safety summaries list 20 participants at risk in the all-treated group and later list 18 for some periods. It does not explain the difference, nor does it report a fuller disposition accounting 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.

Before assignment: A total of 47 participants were enrolled; 20 were treated. Reasons 27 participants were not treated: 21 no longer met study criteria, 2 withdrew consent, and 4 other reasons.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants who received the study drug.

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: All participants who received at least one dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Maximum Observed Plasma Concentration (Cmax) of Ethinyl Estradiol, measured over Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Days 49 and 77.

The primary endpoint is maximum observed plasma concentration (Cmax) of ethinyl estradiol, measured in picograms per millilitre (pg/mL). Ethinyl estradiol is identified as an analyte of Ortho Tri-Cyclen®. Its concentration was measured in plasma using LC-MS/MS, and Cmax was derived from 24 hour plasma concentration-versus-time data using non-compartmental methods. The endpoint population is described as all participants who received the study drug.

Cmax is used in pharmacokinetic studies to characterize the highest observed concentration during a defined sampling interval. As a general statistical concept, a maximum observed value depends on the timing and density of measurements: the true peak may occur between scheduled samples. Thus, the specified sampling schedule is part of how this endpoint should be understood. The registry lists pre-dose and post-dose sampling on Days 49 and 77.

The endpoint is summarized as a geometric mean, with geometric coefficient of variation as its dispersion measure. In general, a geometric mean is a way to summarize positive measurements when values are naturally considered on a multiplicative scale. A geometric coefficient of variation describes relative variability rather than variability in the original units. Neither measure, on its own, indicates whether an observed concentration is clinically important.

The registry record does not report the numerical Cmax estimates or the geometric coefficients of variation. It also does not report a confidence interval or a quantitative contrast for this primary endpoint. Accordingly, the endpoint definition and measurement method can be described, but the magnitude and precision of the observed pharmacokinetic result cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a pharmacokinetic measure: maximum observed plasma concentration of ethinyl estradiol. The record says that concentrations were measured in plasma by LC-MS/MS, a laboratory method, and that Cmax was derived from 24 hour concentration-versus-time data using non-compartmental methods. The reported summary type is geometric mean, with geometric coefficient of variation as the measure of dispersion.

What does Cmax describe?

In general, Cmax is the highest concentration observed during the sampling interval. It is a summary of concentration measurements, not a direct measurement of a clinical outcome. The timing of samples matters because the maximum observed value can depend on whether sampling captures the period around the concentration peak. In this study, the endpoint description lists pre-dose sampling and post-dose sampling on Days 49 and 77. The record does not provide the individual concentration profiles or the numerical Cmax values.

Why report a geometric mean?

As a general statistical explanation, positive pharmacokinetic measurements are often summarized on a multiplicative scale. A geometric mean is obtained by working with logarithms of the measurements and then returning to the original scale. This can be suitable when relative changes are more meaningful than equal absolute changes. The registry record states that the endpoint is a geometric mean, but does not report the estimate itself.

The geometric coefficient of variation describes relative dispersion around measurements summarized on a geometric scale. In general, it is not the same as a standard deviation in the original concentration units. The registry record does not include its numerical value, so the observed variability cannot be quantified from the recorded result.

What does non-compartmental analysis mean?

In general, non-compartmental pharmacokinetic analysis derives summary measures from observed concentration-time data without requiring the data to be represented by a specified compartment model. The registry says this approach was used to derive Cmax from 24 hour concentration-versus-time data. It does not report additional model assumptions, software, or analysis procedures, so further methodological detail is not available.

How were measurements below quantitation handled?

The endpoint description states that pre-dose concentrations below the lower limit of quantitation and concentrations before the first quantifiable concentration that were below that limit were treated as missing. This rule applies to the described measurements. In general, a value below an assay's quantitation limit is not a measured concentration that can be interpreted as an exact zero. Treating such observations as missing is an analysis choice, and its implications depend on how often it occurs and where it occurs in the concentration-time profile. The registry record does not report the number of affected observations or any alternative handling analyses.

How should precision be assessed?

In general, a confidence interval describes a range of values compatible with the data and the statistical procedure used, with the nominal confidence level defined by that procedure. A point estimate alone does not show how precisely a quantity has been estimated. No confidence interval for the primary endpoint is reported in the registry record, and the record does not provide the Cmax estimate or its dispersion. Statistical precision therefore cannot be assessed from the available endpoint description.

The registry lists 6 analyses and 13 outcome measures, but does not describe the analysis plan in enough detail to determine which tests were applied, whether estimates were adjusted, or whether interim analyses were planned. Those matters are not reported in the registry record. The presence of multiple outcomes alone does not establish which results were considered confirmatory or how any multiplicity was handled.

Why does the design affect interpretation?

The study is listed as single-group, with no masking and allocation NA. In general, an observed concentration can describe the participants and conditions in which it was measured. A comparative causal interpretation requires a meaningful reference or comparison strategy. The registry record does not describe a randomized comparator, and its safety groups are period-based summaries rather than like-for-like randomized arms. Consequently, neither those safety summaries nor the primary endpoint definition supplies a controlled treatment contrast.

The record lists an enrollment of 47, but does not provide a sample-size justification or explain the difference between enrollment and the safety risk sets. It does not report a power calculation for the primary endpoint. A sample-size rationale, interim analysis plan, and detailed statistical plan are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The record lists 13 outcome measures and 6 analyses. Secondary outcomes cover norgestrel pharmacokinetic measures as well as safety and clinical monitoring measures. However, the registry record does not report a multiplicity strategy, such as a hierarchy among endpoints, an adjustment to account for multiple tests, or a distinction between confirmatory and exploratory analyses. The number of outcomes alone does not establish that a particular adjustment was required or used.

The record does not report interim analyses or stopping rules. It also does not provide the detailed statistical analysis plan, the tests used for the primary endpoint, or whether estimates were adjusted for any covariates. These items are not reported in the registry record and cannot be inferred from the outcome list.

The primary endpoint description gives one explicit missing-data rule: pre-dose measurements below the lower limit of quantitation, and measurements before the first quantifiable concentration that were below that limit, were treated as missing. The record does not report how many values were affected, whether missingness occurred at other time points, or how any other missing observations were handled. It does not describe an imputation method or sensitivity analysis.

The endpoint population is described as all participants who received the study drug. The record lists enrollment as 47, while safety summaries identify groups at risk of 20 or 18 participants, depending on group or period. It does not provide a participant flow or a complete account of which participants contributed to each pharmacokinetic analysis. Therefore, the analyzed population size for the primary endpoint is not reported in the registry record.

11. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent non-serious adverse event terms

The safety record reports zero participants with serious adverse events in the all-treated group, where 20 participants are listed as at risk. It also reports zero in each period-specific group. The number at risk is 20 for Ortho Tri-Cyclen Days 1-28, Days 29-46, and Days 47-56, and 18 for Days 57-67 and Ortho Tri-Cyclen plus Daclatasvir Days 68-77. These are the registry's recorded group counts.

For other adverse events, the all-treated group reports 16 participants affected among 20 at risk. The period-specific counts affected are 8, 3, 7, 5, and 12, corresponding to the listed periods. These are descriptive participant counts. The record does not establish that the period groups are independent, so the counts should not be added together or interpreted as a total number of distinct participants across periods.

The serious-event summaries do not provide detail about event types because no top serious-event terms are listed. Deaths are recorded as null rather than as a numerical count, so a death count is not reported in the registry record. These safety entries should not be read as evidence of comparative safety: the study is single-group and does not describe a randomized control group. The record also does not establish that reported events were caused by either study drug.

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

The registry record establishes that this completed Phase 1 study assessed the pharmacokinetics of Ortho Tri-Cyclen® when co-administered with BMS-790052 in healthy female subjects, as described in its title and purpose. It identifies Cmax of ethinyl estradiol as the primary endpoint, specifies how it was measured and summarized, and lists a sampling schedule. Those details explain what was intended to be measured.

They do not establish the size of the observed concentration or the precision of that estimate. The numerical primary endpoint result, its geometric coefficient of variation, and any confidence interval are not reported in the registry record. Nor does the record give a quantitative comparison against a control group. The pharmacokinetic effect therefore cannot be quantified or judged from these entries alone.

The design also limits what can be inferred. The record describes a single group, no masking, and allocation NA; it does not describe a randomized comparator. A single-group measurement may document concentrations under the study conditions, but it does not by itself separate the contribution of co-administration from other explanations. No treatment-benefit claim follows from the endpoint description.

Safety information is descriptive. The record reports zero serious adverse events in the listed safety groups and reports other adverse events in the all-treated group and across periods. These counts do not establish comparative risk, and the deaths field is null rather than a reported numerical count. The record does not establish causation for the adverse events.

In general, a registry record is useful for identifying the planned question, recorded design features, and posted outcomes. It may not provide all details needed for a full statistical appraisal. In this case, sample-size justification, a detailed statistical analysis plan, multiplicity handling, interim analyses, and a complete account of missing observations are not reported in the registry record. The appropriate interpretation is therefore bounded by the recorded methods and descriptive safety counts, without inferring unreported results.

13. Why This Trial Matters Statistically

This study illustrates why the design and the endpoint must be read together. The endpoint is a pharmacokinetic summary, Cmax of ethinyl estradiol, measured at specified times and summarized geometrically. That is a different kind of question from whether a treatment improves a clinical outcome. Concentration measurements can characterize drug exposure, but interpretation depends on the comparison strategy and on the numerical result.

The record identifies a single-group design, no masking, and allocation NA. That makes the lack of a randomized comparator central to statistical interpretation. A measured concentration can describe what was observed under the study conditions, but the design as recorded does not provide a like-for-like control comparison. This is an important distinction between describing data and attributing a difference to an intervention.

The record also demonstrates that endpoint definitions do not substitute for endpoint results. It gives the assay method, the sampling schedule, the derivation of Cmax, and the summary measure, but no numerical estimate or precision measure. Without those results, readers cannot quantify the observed endpoint or assess how precisely it was estimated.

The safety summaries offer a related lesson in reading group counts. The record includes an all-treated group and several time-period groups, with different numbers at risk in some periods. Period-specific counts are not automatically independent observations or a cumulative count of unique participants. Care is needed not to combine them without a stated rationale.

Finally, a registry's outcome list and analysis count do not reveal the full statistical plan. Multiplicity handling, sample-size justification, interim analyses, and detailed missing-data methods are not reported in the registry record. Recognizing what the record specifies—and what it leaves unreported—is essential to a restrained statistical interpretation.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary limitation for interpreting the main outcome is that its numerical result is not reported in the registry record. The Cmax estimate, geometric coefficient of variation, and confidence interval are absent. Consequently, neither the magnitude nor the precision of the primary pharmacokinetic outcome can be assessed.

The study is recorded as single-group, with allocation NA and no masking. No randomized comparator is described. This limits interpretation to a description of the study conditions and does not support a like-for-like treatment comparison. The registry record does not report additional design details that would clarify the sequence of exposure or the basis for any within-participant contrast.

The record lists enrollment as 47, while the safety summaries list 20 participants at risk in the all-treated group and 18 in some later periods. A participant flow or explanation of these differing counts is not reported in the registry record. The number included in the primary endpoint analysis is also not reported beyond the stated population description of all participants who received study drug.

The endpoint description specifies that certain below-quantitation measurements were treated as missing, but does not report how many such values occurred or whether other missing data arose. Further missing-data methods and sensitivity analyses are not reported. A detailed statistical analysis plan, multiplicity approach, interim analysis plan, and sample-size justification are likewise not reported in the registry record.

The condition field lists Chronic Hepatitis C, while the title and purpose describe healthy female subjects. The registry record does not explain this difference. Safety summaries include several periods and a group named Ortho Tri-Cyclen plus Daclatasvir; the record does not explain the naming relationship to BMS-790052. These are record-description limitations, not grounds to infer unreported study details.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study to Assess the Effect of BMS-790052 on the Pharmacokinetics of Ortho Tri-Cyclen® in Healthy Female Subjects — NCT00983957.
• Registry record last updated 2015-10-16; status last verified 2015-09.
• Results first posted 2015-09-16.
• 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

NCT00983957 is listed as a completed Phase 1 study sponsored by Bristol-Myers Squibb. Its stated purpose was to assess the effect of BMS-790052 on the pharmacokinetics of Ortho Tri-Cyclen® in healthy female subjects. The registry lists enrollment as 47 and describes a single group, with allocation NA and no masking.

The primary endpoint was maximum observed plasma concentration of ethinyl estradiol, summarized as a geometric mean with geometric coefficient of variation. Plasma measurement used LC-MS/MS, and Cmax was derived from 24 hour concentration-versus-time data using non-compartmental methods. The numerical primary result and its precision are not reported in the registry record.

Safety summaries report zero serious adverse events in the listed groups. Other adverse events are reported for 16 participants in the all-treated group, with additional period-specific counts. Deaths are not reported as a numerical count. The record does not describe a randomized comparison or provide a detailed statistical analysis plan, sample-size justification, or multiplicity approach.