EC PK in Women With Normal and Obese BMI: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for EC PK in Women With Normal and Obese BMI (NCT02689804), a randomized phase 4 study. The primary outcome is Area Under the Curve From Time 0 to 24 Hours of Serum LNG Concentration.

2. Clinical Question

3. Trial Design

The registry describes a completed, randomized, unmasked, phase 4 crossover study sponsored by Columbia University. It lists enrollment of 34 and gives the study dates as 2015-07-10 to 2015-12-29 for the start and primary completion. The primary-result description identifies 16 normal-BMI and 16 obese-BMI participants. It states that participants received both drugs in random order. How the enrollment figure relates to the primary-result population is not reported in the registry record.

In each BMI group, participants received a first emergency-contraception dose, completed pharmacokinetic assessments, and returned after at least 8 days to receive the second study drug and repeat the assessments. The crossover structure means each participant was exposed to LNG-EC and ulipristal acetate emergency contraception; the comparison of interest for the primary endpoint, however, is between BMI groups for serum levonorgestrel exposure. The registry does not provide a sequence-specific account of the treatment order or further details about the period structure.

The primary endpoint is the area under the curve for serum levonorgestrel concentration from time 0 to 24 hours. The registry lists mean as the summary measure and interquartile range as the dispersion measure. It also lists secondary pharmacokinetic outcomes covering elimination half-life, clearance, maximum concentration, and time to maximum concentration for both drugs. The study is classified as addressing contraception, but the posted primary result is a pharmacokinetic measurement rather than a clinical effectiveness outcome.

Masking is listed as none. The registry record does not report additional details about allocation procedures, sequence generation, concealment, period effects, or how the crossover data were modeled. Those details should not be inferred from the design label alone.

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: No significant events in the study that occur after participant enrollment, but prior to assignment of participants to an arm or group.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Cross-over study: 16 normal-BMI and 16 obese-BMI enrolled and each participant received both drugs in random order.

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: This is a cross-over study with the same 32 participants receiving each study drug. 34 participants were enrolled into this study but 2 participants discontinued. The final sample includes a total of 16 normal-BMI women and 16 obese-BMI women.

6. Primary Endpoint

The registry lists the primary outcome as Area Under the Curve From Time 0 to 24 Hours of Serum LNG Concentration, measured over Up to 24 hours.

The area under the serum concentration curve from time 0 to 24 hours summarizes levonorgestrel exposure across the measurement period. Rather than describing concentration at a single sampling time, the area-under-the-curve measure incorporates concentration over time. In pharmacokinetic research, this is used to describe overall drug exposure during a specified interval. It does not by itself measure a clinical outcome such as emergency-contraception failure.

The registry specifies a mean as the summary measure and an interquartile range as the dispersion measure. It gives group means of 208.5 ng*h/mL for the normal-BMI group and 100.8 ng*h/mL for the obese-BMI group. Bounds of 171.4 to 245.6 and 82.9 to 118.7 are also reported for the respective groups, but the type of interval represented by those bounds is not stated. Numerical interquartile ranges are not reported in the registry record.

Because the endpoint concerns serum levonorgestrel, it addresses exposure after LNG-EC, not exposure after ulipristal acetate. Its relevance is to the study’s pharmacokinetic question: whether measured levonorgestrel exposure differs between BMI groups. It cannot establish why any exposure difference occurs, nor does it establish how a pharmacokinetic difference relates to clinical outcomes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Pharmacokinetic outcomes describe the concentration of a drug in the body over time. The study’s primary outcome is area under the serum levonorgestrel concentration curve from time 0 to 24 hours. This measure combines information across the specified interval and is used to characterize exposure. It is distinct from a clinical endpoint: a concentration measure does not directly count treatment failures or other health outcomes.

What does the reported mean describe?

A mean gives a central summary of the observed values in a group. The registry identifies the primary outcome’s summary measure as a mean and its dispersion measure as an interquartile range. An interquartile range describes the middle portion of a distribution and can help show how observations vary around the center. The numerical interquartile ranges are not reported in the registry record, so the degree of within-group spread cannot be read from that measure. The record gives separate bounds for each group, but does not identify what kind of interval they represent. They should therefore be treated as reported bounds, not automatically labeled confidence intervals.

What does the p-value say?

The registry reports a two-sided t-test and p <0.01 for the primary comparison. In general, a p-value describes how compatible the observed data are with a specified null hypothesis under the assumptions of the statistical test. A small p-value is not the probability that the null hypothesis is true, and it does not quantify the size or clinical importance of an effect. A two-sided test allows evidence in either direction to count against the null hypothesis. The registry does not report a numeric primary contrast estimate or a confidence interval for that contrast, so the magnitude and precision of the between-group difference are not fully expressed by the p-value alone.

Why does the crossover design matter?

In a crossover study, participants receive more than one treatment, often in different orders. Here, the registry states that each participant received LNG-EC and ulipristal acetate in random order, with a return after at least 8 days before the second drug and repeat assessments. This design makes measurements from the same participant relevant to comparisons between treatments. However, the primary question compares BMI groups for levonorgestrel exposure, and the registry does not describe the statistical model used for this group comparison or how within-participant correlation, treatment order, or period was handled. The reported test name alone does not resolve those details.

Randomized treatment order can help distribute order effects across the treatment sequences, but the registry record does not give the sequence-generation or allocation-concealment procedures. It also does not report whether the interval between doses was considered adequate for all pharmacokinetic purposes or whether carryover was assessed. These are not conclusions about what happened; they are items for which details are not reported in the registry record.

How should uncertainty be read?

A confidence interval, in general, gives a range of values compatible with the data and a stated statistical procedure, and its width indicates precision. The primary record’s interval type is not identified, so the listed bounds cannot be interpreted as confidence limits on that basis. The sponsor’s p-value indicates evidence against the null under the reported test, but without a named interval for the between-group contrast, the precision of that contrast is not directly available. Greater precision would ordinarily mean a narrower interval, while wider intervals leave more uncertainty about the possible effect size.

For the two secondary time-to-maximum-concentration outcomes with recalculated comparisons, the posted unadjusted estimates include intervals that cross zero. In general, an interval for a difference that crosses zero is compatible with no difference as well as differences in either direction, given the method used. These are simple unadjusted recalculations from posted summary statistics, not sponsor-reported analyses. They do not replace the sponsor’s primary analysis and should be interpreted as exploratory context.

What are the planning illustrations?

Planning illustrations translate an assumed effect into an approximate number of participants per arm for a chosen power under stated assumptions. The posted illustrations use a two-sided significance level of 0.05, equal allocation, and a normal approximation; they consider fractions of the observed effect. The assumptions describe a planning exercise based on the observed effect, not the trial’s original design. The resulting sample sizes are planning illustrations, not observed power and not evidence that the trial had a particular probability of detecting an effect.

In general, power depends on the effect size, variability, analysis method, and planned sample size. A planning calculation based on an observed effect is especially uncertain because the observed effect itself may be imprecise. Smaller assumed effects require more participants per arm to reach the same target power under the calculation’s assumptions. These calculations do not account for unreported features of the trial, such as missing data, crossover correlation, or any multiplicity strategy.

Multiplicity arises when many outcomes or comparisons are tested. In general, testing more hypotheses without an adjustment increases the chance of at least one apparently unusual result under null effects. The registry lists several secondary pharmacokinetic outcomes, but a multiplicity procedure is not reported in the registry record. Consequently, unadjusted secondary p-values should be treated as exploratory rather than as confirmatory evidence. The primary result and secondary results also address different pharmacokinetic measures, so they should not be collapsed into a single claim.

10. Analyses Reported by the Sponsor

The sponsor’s reported primary analysis is a two-sided t-test with p <0.01 for the comparison of serum levonorgestrel area under the curve between the normal-BMI and obese-BMI groups. The group means are 208.5 ng*h/mL and 100.8 ng*h/mL, respectively. No recalculated primary contrast or interval is posted in the registry record. The sponsor’s stated analysis therefore remains the relevant inferential result for this endpoint; a recalculation should not be presented as an alternative primary finding.

Simple unadjusted recalculations are available for the two posted secondary time-to-maximum-concentration outcomes. They use the posted summary statistics and are not sponsor-reported analyses. They address different endpoints from the primary area-under-the-curve outcome, so they neither reproduce nor independently validate the primary test. The registry does not report a sponsor analysis for those secondary comparisons.

The recalculations are useful as descriptive checks on secondary summary data, but they are not a substitute for a fully specified analysis of the crossover design. The registry record does not provide enough information to assess whether the primary test accounts for the crossover structure or other design features. The sponsor’s reported test and its p-value should be distinguished from the exploratory recalculations, and neither should be interpreted as a clinical effectiveness result.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary pharmacokinetic outcome and several secondary outcomes covering both study drugs. It does not report a multiplicity procedure, a hierarchy of hypotheses, or whether the secondary outcomes were intended to support confirmatory claims. Without that information, the secondary comparisons should be treated cautiously. In general, when multiple statistical tests are conducted, the chance of at least one result appearing notable by chance can rise unless the testing strategy accounts for multiplicity. No adjustment should be assumed when it is not reported.

Information about missing data is also limited. The registry does not report whether any endpoint measurements were missing, how missing observations were handled, or whether any participants were excluded from particular analyses. The enrollment figure is 34, while the primary-result description identifies 16 normal-BMI and 16 obese-BMI participants. The record does not explain the relationship between these figures or provide participant flow that would clarify the analysis population. It is therefore not possible to determine from the registry record whether the primary analysis included every enrolled participant.

Although the study is described as a crossover, the registry does not report whether the analysis population was defined by assigned sequence, received treatment, or complete measurements, nor does it describe the handling of participants who did not complete both treatment periods. Details about the treatment sequence, period effects, carryover, and within-participant correlation are not reported in the registry record. These details matter to assessment of the analytic approach, but their absence should not be filled by assumptions.

The record identifies a two-sided t-test for the primary result but does not give a full statistical analysis plan, missing-data strategy, or interim-analysis information. Those items are not reported in the registry record. As a result, the reported primary p-value can be cited as the sponsor’s stated analysis, while the reproducibility and sensitivity of that analysis cannot be fully evaluated from the registry information alone.

12. 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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse events as zero in each listed safety group: normal-BMI on LNG, normal-BMI on UPA, obese-BMI on LNG, and obese-BMI on UPA. Each group lists 8 participants at risk for serious events. These are the figures recorded for the listed groups, and they should not be treated as proof that serious harms cannot occur.

Other adverse events are listed for each group, with counts of 4, 3, 4, and 2 in the order; each group lists 8 participants at risk for other events. The registry does not provide further event detail in the record excerpt, so the nature, timing, severity, and relationship of these events to study drugs are not established by these counts. No deaths are reported in the listed groups.

The safety figures use group sizes that differ from the primary-result population descriptions. The registry does not explain the safety population or its relationship to the pharmacokinetic analysis population. The counts should therefore be read as posted safety summaries for the named groups, not as a complete account of all possible adverse events or of comparative safety.

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

The primary result concerns serum levonorgestrel exposure over time in women in the normal-BMI and obese-BMI groups. The sponsor reports a two-sided test with p <0.01, alongside group means of 208.5 ng*h/mL and 100.8 ng*h/mL. This supports a statistical difference in the measured primary pharmacokinetic endpoint under the reported analysis. It does not determine the clinical importance of that difference.

The study does not directly test emergency-contraception failure rates or pregnancy outcomes in the posted primary result. A pharmacokinetic measurement is not a clinical outcome, and the registry does not establish that a difference in serum exposure causes a difference in effectiveness or safety. The investigators’ proposed hypothesis concerned pharmacokinetic parameters; the posted primary result addresses one of those parameters for levonorgestrel.

The result should also be kept within the study’s scope. It compares BMI groups in a crossover pharmacokinetic study, with each participant described as receiving both drugs in random order. It does not establish that every pharmacokinetic measure differs, that the same pattern applies to ulipristal acetate, or that the result generalizes beyond the studied participants. The registry record does not report enough information about participant disposition, missing observations, or analytic handling of crossover features to resolve those questions.

Statistical significance is not a measure of certainty about every aspect of a result. The reported p-value does not give a direct estimate of the between-group difference or its precision, and the type of the reported group bounds is not stated. Accordingly, the result can be described as evidence of a difference in the reported endpoint, but not as a complete account of its magnitude, mechanism, or clinical consequence.

14. Why This Trial Matters Statistically

This trial illustrates why the outcome being measured matters to interpretation. The primary endpoint is an area-under-the-curve measure of serum levonorgestrel concentration, which characterizes exposure over a defined period. It addresses a biological and pharmacokinetic question, not directly whether emergency contraception prevents pregnancy. Keeping those questions separate prevents a statistical finding on drug concentration from being overstated as a clinical outcome.

The crossover design is another important statistical feature. Each participant received both study drugs in random order, while the primary comparison is between BMI groups for levonorgestrel exposure. A crossover can make within-participant information relevant, but the registry reports only a t-test for the primary analysis and does not describe how the design was reflected in the model. Readers can identify the design from the record while also recognizing that the analysis details needed to evaluate it fully are not reported.

The record also highlights the distinction between a group-level significance test and a precise effect estimate. The sponsor reports p <0.01, but the primary between-group contrast and its interval are not reported. The group means and bounds offer descriptive information, yet the bound type is unspecified and the stated interquartile-range values are absent. This limits how fully the result’s size and precision can be assessed.

Finally, multiple secondary pharmacokinetic outcomes invite careful interpretation. Unadjusted secondary recalculations can be informative as exploratory context, but they do not carry the same weight as a prespecified primary analysis when a multiplicity plan is not reported. The record therefore supports a focused reading of the primary pharmacokinetic result while making clear that secondary patterns, missing-data handling, and analysis details remain incompletely documented.

15. 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 registry record does not explain the difference between enrollment of 34 and the primary-result description of 16 participants in each BMI group. Participant flow, exclusions, and the analysis population are not reported in the registry record. This prevents a clear assessment of how enrollment translated into the population contributing to the primary endpoint.

The primary outcome is identified as a mean with interquartile-range dispersion, but numerical interquartile ranges are not reported. The record gives bounds for each group without identifying the interval type, and it does not report a direct primary contrast estimate with an uncertainty interval. These omissions limit assessment of the primary result’s precision and the distribution of measurements.

The study is described as randomized and crossover, but details about sequence generation, allocation concealment, period effects, carryover, and the statistical handling of within-participant data are not reported in the registry record. The primary analysis is named as a two-sided t-test, without a fuller model description. Missing-data procedures, interim analyses, and a complete statistical analysis plan are also not reported in the registry record.

The primary result concerns one pharmacokinetic measure for levonorgestrel; it does not report a clinical effectiveness outcome. The secondary outcomes cover multiple pharmacokinetic measures, but a multiplicity strategy is not reported. Some outcomes lack values estimable for a two-arm comparison, and the secondary recalculations available are unadjusted. These limitations constrain both the breadth of conclusions and the strength of secondary inferences.

Safety summaries are reported for groups with 8 participants at risk, but the relationship of those groups to the primary analysis population is not explained. The record gives counts without detailed event descriptions or attribution. These limitations leave the safety summaries descriptive rather than a comprehensive evaluation of comparative risk.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: EC PK in Women With Normal and Obese BMI — NCT02689804.
• Registry record last updated 2017-07-07; status last verified 2017-06.
• Results first posted 2017-07-07.
• 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.

19. Record Summary

The registry describes a completed, randomized, unmasked, phase 4 crossover pharmacokinetics study sponsored by Columbia University. It compares women in normal-BMI and obese-BMI groups, with participants receiving LNG-EC and ulipristal acetate in random order. The primary endpoint is serum levonorgestrel area under the curve from time 0 to 24 hours.

The primary group means are 208.5 ng*h/mL for normal-BMI and 100.8 ng*h/mL for obese-BMI. The sponsor reports a two-sided t-test with p <0.01. The type of the group-level bounds is not identified, and a direct contrast estimate and interval are not reported in the registry record. The result is pharmacokinetic, not a direct clinical effectiveness finding.

Secondary outcomes cover additional pharmacokinetic measures for both drugs. Recalculated secondary comparisons are unadjusted, while multiplicity handling, missing-data procedures, and fuller crossover-model details are not reported in the registry record.