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 Effects of Cladribine Tablets on the PK of Microgynon® (NCT03745144), a randomized phase 1 study. The primary outcome is Area Under the Plasma Concentration-Time Curve From Zero to Tau at Steady State (AUCt,ss) of Ethinyl Estradiol and Levonorgestrel.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03745144 |
| Phase | Phase 1 |
| Condition | Relapsing Multiple Sclerosis (RMS) |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Double |
| Enrollment | 28 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Merck KGaA, Darmstadt, Germany |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned pre-menopausal women with relapsing multiple sclerosis (RMS). The registry record lists an enrollment of 28. The primary pharmacokinetic analysis set was defined as participants in the Safety Set without clinically important protocol deviations or violations and without factors or events likely to affect pharmacokinetics. The number included in that analysis set is not reported in the registry record.
Intervention
Participants received cladribine tablets along with Microgynon® during the relevant treatment period. The record describes once-daily cladribine for 5 days, at 10 to 20 milligram depending on body weight, and Microgynon® administration. The study used two treatment sequences, so the order of cladribine and placebo differed between sequences.
Comparator
The comparison of interest was Microgynon® used with cladribine versus Microgynon® used with placebo or alone, as specified across the study periods. Participants were randomized to a sequence in a crossover design. The registry record does not report a single numerical contrast that compares these conditions.
Primary question
The primary endpoint was the area under the plasma concentration-time curve from zero to tau at steady state (AUCt,ss) for ethinyl estradiol (EE) and levonorgestrel (LNG). The question was whether the presence of cladribine was associated with a difference in exposure to these Microgynon® constituents. Numerical endpoint estimates and a comparative effect estimate are not reported in the registry record, so the direction and precision of any observed difference cannot be described.
3. Trial Design
This was a randomized, double-blind, 2-period, 2-sequence crossover Phase I study. Its official title describes a 1 Month run-in period and identifies the study population as pre-menopausal women with RMS. Enrollment was 28. The registry record lists the study as completed, with a start date of 2019-01-17 and primary completion on 2022-09-02.
The two sequences differed in the order of cladribine and placebo. Sequence 1 is identified as cladribine first, then placebo; Sequence 2 is identified as placebo first, then cladribine. Both sequences included Microgynon®. The descriptions indicate daily Microgynon® administration and once-daily cladribine or matched placebo during specified periods. The record also states that Microgynon® was received for 21 days, starting on the first day of the menstrual cycle. Some sequence descriptions are incomplete in the registry record, so a complete reconstruction of each period’s schedule is not possible.
In a crossover design, participants receive conditions in a sequence, so the same participant may contribute observations under more than one condition. General explanation: this can make within-participant comparisons informative because each participant can serve as their own reference, but interpretation depends on the study’s actual sequence, timing, and analysis. Whether the analysis explicitly accounted for the crossover structure is not reported in the registry record.
The stated primary outcome was pharmacokinetic rather than a clinical efficacy outcome. Safety outcomes were also listed, including treatment-emergent adverse events and clinically relevant changes in laboratory values, electrocardiograms, and vital signs. The registry record does not report a sample-size justification, a washout schedule, or a detailed statistical plan.
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 37 participants were screened, out of which 28 participants enrolled in the study.
Run-in-Period (Day 0 to Day 28)
| Stage | Microgynon® | Sequence 1: First Cladribine, Then Placebo | Sequence 2: First Placebo, Then Cladribine |
|---|---|---|---|
| STARTED | 28 | 0 | 0 |
| Safety Analysis Set | 28 | 0 | 0 |
| Pharmacokinetic Analysis Set | 21 | 0 | 0 |
| COMPLETED | 24 | 0 | 0 |
| NOT COMPLETED | 4 | 0 | 0 |
Reasons for not completing this period:
| Reason | Microgynon® | Sequence 1: First Cladribine, Then Placebo | Sequence 2: First Placebo, Then Cladribine |
|---|---|---|---|
| Other | 4 | 0 | 0 |
Period 1
| Stage | Microgynon® | Sequence 1: First Cladribine, Then Placebo | Sequence 2: First Placebo, Then Cladribine |
|---|---|---|---|
| STARTED | 0 | 13 | 11 |
| COMPLETED | 0 | 13 | 10 |
| NOT COMPLETED | 0 | 0 | 1 |
Reasons for not completing this period:
| Reason | Microgynon® | Sequence 1: First Cladribine, Then Placebo | Sequence 2: First Placebo, Then Cladribine |
|---|---|---|---|
| Other | 0 | 0 | 1 |
Period 2
| Stage | Microgynon® | Sequence 1: First Cladribine, Then Placebo | Sequence 2: First Placebo, Then Cladribine |
|---|---|---|---|
| STARTED | 0 | 13 | 10 |
| COMPLETED | 0 | 13 | 10 |
| NOT COMPLETED | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Pharmacokinetic Analysis Set included all participants in the Safety Set without clinically important protocol deviations/violations and absence of factors/events likely to affect Pharmacokinetics (PK).
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: Safety Analysis Set included all participants who were administered any dose of the trial medication.
| Characteristic | Unit | All Participants |
|---|---|---|
| Participants analysed | 28 | |
| Age, Continuous | Years | 34 (SD 6.3) |
| Sex: Female, Male: Female | Participants | 28 |
| Sex: Female, Male: Male | Participants | 0 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 28 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 28 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Area Under the Plasma Concentration-Time Curve From Zero to Tau at Steady State (AUCt,ss) of Ethinyl Estradiol and Levonorgestrel, measured over Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Geometric Coefficient of Variation |
| Unit | hour*picograms per millilitre(h*pg/ml) |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was AUCt,ss for ethinyl estradiol and levonorgestrel. AUC represents the area under a concentration-time curve: it combines concentration measurements across a specified time interval and is used as a measure of drug exposure. The endpoint’s stated unit is hour*picograms per millilitre (h*pg/ml). The measurement interval was described as zero to tau at steady state.
The registry record lists plasma sampling at pre-dose and 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14. These measurements are intended to describe concentrations over time rather than a single concentration at one sampling point. General explanation: exposure measures can help characterize how much of a substance is present in the circulation over a dosing interval. They do not, by themselves, establish a clinical outcome.
The listed summary parameter was the geometric mean, with geometric coefficient of variation as the dispersion measure. The endpoint description says the values were reported using descriptive statistics. Numerical geometric means, variability estimates, and a direct comparison between treatment conditions are not reported in the registry record. As a result, the endpoint definition can be described, but the magnitude and precision of the posted pharmacokinetic results cannot be assessed from the record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a focused pharmacokinetic question: the potential effect of cladribine on exposure to the ethinyl estradiol and levonorgestrel components of Microgynon®. It specifies AUCt,ss as the primary endpoint and gives the sampling schedule and summary approach. It does not include numerical AUC results, treatment-condition estimates, or a contrast between conditions. The size, direction, and precision of the primary result are therefore not reported in the registry record.
The primary outcome is described as being calculated with descriptive statistics. Descriptive summaries can characterize observed values, but they do not by themselves show how uncertain a treatment comparison is. No confidence interval or inferential test for the primary endpoint is listed in the registry record. The record lists 0 analyses, and the primary outcome has several categories or time points and is not reduced to one comparison. Consequently, there is no posted inferential result from which to assess evidence for a difference or compatibility with no difference.
General explanation: a confidence interval expresses the precision of an estimate under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval, while an interval that includes values representing no difference can leave a range of interpretations open. Without estimates and intervals, readers cannot assess either the uncertainty around the endpoint or whether effects of practical interest remain compatible with the data.
The crossover structure makes the choice of analysis important. General explanation: comparisons in crossover trials often use the fact that each participant contributes measurements under different conditions. Such analyses may need to account for within-participant association and treatment sequence. The statistical model, handling of period or sequence effects, and method used for any treatment comparison are not reported in the registry record. It would be inappropriate to infer those methods from the design label alone.
The enrollment of 28 gives the recorded enrollment, not the number of participants with evaluable data for each endpoint or treatment period. The size of the pharmacokinetic analysis set is not reported in the registry record. The record’s definition of that set excludes participants with specified protocol deviations or factors likely to affect pharmacokinetics, but it does not give the resulting count or describe how excluded or missing measurements were handled.
Safety summaries list participants at risk and participants affected by serious or other adverse events for each recorded period and sequence. No serious adverse events or deaths are listed in those groups. These counts are period-specific and are not a substitute for the missing pharmacokinetic estimates. They also do not establish whether any event was caused by a particular treatment. Overall, the registry record supports describing the trial’s question, design, endpoint, and posted safety counts, but not a numerical conclusion about the primary pharmacokinetic effect.
9. Statistical Methods Explained
The registry record identifies AUCt,ss as the primary pharmacokinetic measure and states that descriptive statistics were used. It does not report a treatment-effect estimate, confidence interval, hypothesis test, or detailed analysis model. The points below explain the statistical concepts relevant to the stated endpoint and design; they should not be read as a description of analyses that the registry record does not specify.
What does the AUC endpoint represent?
General explanation: a concentration-time curve traces measured plasma concentration over time. The area under that curve summarizes exposure across the chosen interval, combining information from multiple measurements rather than relying on a single concentration. AUCt,ss refers to the area from zero to tau at steady state. The registry record identifies ethinyl estradiol and levonorgestrel as the analytes and gives the unit as hour*picograms per millilitre (h*pg/ml).
The sampling schedule listed for this endpoint is pre-dose and 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14. General explanation: sampling at multiple times allows a concentration-time profile to be characterized over the specified interval. The registry record does not provide the measured concentrations or the resulting AUC values, so the values cannot be independently interpreted from the posted information.
Why use geometric summaries?
The stated summary parameter is the geometric mean, accompanied by a geometric coefficient of variation. General explanation: geometric summaries are commonly used for positive measurements that may be skewed, and they describe values on a multiplicative rather than an additive scale. The geometric coefficient of variation describes relative variability on that scale. It is not the same as a confidence interval and does not, by itself, show the precision of a comparison between treatments.
The record says the endpoint was calculated using descriptive statistics. A descriptive summary can report the distribution or central tendency of observed values for each condition. A comparative analysis would additionally quantify the difference or ratio between conditions and, if inferential methods were used, its uncertainty. No comparative estimate or uncertainty measure is reported in the registry record. Thus, the listed geometric summary approach should not be mistaken for evidence that a particular treatment contrast was statistically tested.
What does the crossover design imply?
The study is described as randomized, double-blind, and a 2-period, 2-sequence crossover. Sequence 1 is identified as cladribine first, then placebo; Sequence 2 is identified as placebo first, then cladribine. General explanation: a crossover design can compare conditions within the same participant, which can account for stable differences between participants. The repeated measurements are usually correlated, however, and an analysis should reflect that structure.
Methods for accounting for treatment, period, sequence, and within-participant variation are not reported in the registry record. Nor is a washout schedule reported. Because the sequence descriptions are incomplete, the full timing and transitions between conditions cannot be reconstructed from the available record. It is not possible to determine from the design label alone how these issues were addressed in the analysis.
How should uncertainty be considered?
General explanation: an estimate is a numerical summary of an effect, while its standard error or confidence interval communicates uncertainty. A p-value, when reported, addresses compatibility between data and a specified statistical model and null hypothesis; it does not measure the size or clinical importance of an effect. Here, numerical primary endpoint estimates, confidence intervals, and p-values are not reported in the registry record. No claim about statistical significance or precision can be made from the endpoint description alone.
The registry record lists 0 analyses and indicates that the primary outcome, which has several categories or time points, was not reduced to one comparison. This means the posted record does not offer a single analysis result to interpret. It does not establish whether other analyses were performed outside the registry record. The protocol-level statistical plan, including any prespecified contrast or model, is not reported in the registry record.
Why can over-dispersion matter in other settings?
General explanation: over-dispersion occurs when observed variability is greater than a statistical model assumes. If a model underestimates variability, standard errors and uncertainty intervals can be too small, making results appear more precise than the data warrant. This concept is relevant to selecting models for some outcome types, but the primary outcome is a continuous pharmacokinetic measure summarized geometrically. The registry record does not state that over-dispersion was assessed or that a model requiring such an assessment was used.
The record’s descriptive approach and missing inferential details limit what can be evaluated. The endpoint definition and sampling times clarify what was intended to be measured, but they do not reveal the observed exposure values, the treatment contrast, or uncertainty. A complete statistical interpretation would require the numerical results and the analysis methods, which are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 13 outcome measures, including the primary pharmacokinetic outcome and secondary safety and pharmacokinetic outcomes. The secondary outcomes include treatment-emergent adverse events; clinically relevant changes from baseline in laboratory values, electrocardiogram, and vital signs; and cladribine maximum plasma concentration and time to maximum observed concentration. The primary outcome includes results for ethinyl estradiol and levonorgestrel and is not reduced to one comparison in the posted record.
No multiplicity adjustment, hierarchy of tests, or other strategy for interpreting multiple endpoints is reported in the registry record. General explanation: when several outcomes or comparisons are examined, the chance of observing an apparently unusual result can depend on how many analyses are considered and how they are selected. A prespecified plan can clarify which findings are confirmatory and how multiplicity is handled. The registry record does not give such a plan, and it lists 0 analyses.
Missing-data methods are not reported in the registry record. The number of participants with available primary endpoint measurements, the amount or pattern of missing pharmacokinetic data, and the handling of incomplete profiles are not reported. The number in the pharmacokinetic analysis set is also not reported. The stated analysis-set definition refers to members of the Safety Set without clinically important protocol deviations or violations and without factors or events likely to affect pharmacokinetics, but the record does not state how those determinations were applied in practice.
The record does not report an intention-to-treat approach, a per-protocol analysis, sensitivity analyses, or a sample-size justification. These omissions prevent assessment of how exclusions, missing measurements, or multiple outcomes may have influenced interpretation. They should be treated as information not reported in the registry record, not as evidence that a particular method was or was not used outside the record.
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 |
|---|---|---|---|
| Run-in Period: Microgynon (Day -28 to -1) | 0 | 28 | 0.0% |
| Sequence 1 Period 1: Microgynon Alone (Day 1-8) | 0 | 13 | 0.0% |
| Sequence 1 Period 1: Microgynon + Cladribine (Day 9-28) | 0 | 13 | 0.0% |
| Sequence 1 Period 2: Microgynon Alone (Day 1-8) | 0 | 13 | 0.0% |
| Sequence 1 Period 2: Microgynon + Placebo (Day 9-14) | 0 | 13 | 0.0% |
| Sequence 1 Period 2: Microgynon + Cladribine (Day 15-28) | 0 | 13 | 0.0% |
| Sequence 2 Period 1: Microgynon Alone (Day 1-8) | 0 | 11 | 0.0% |
| Sequence 2 Period 1: Microgynon + Placebo (Day 9-28) | 0 | 10 | 0.0% |
| Sequence 2 Period 2: Microgynon Alone (Day 1-8) | 0 | 10 | 0.0% |
| Sequence 2 Period 2: Microgynon + Cladribine (Day 9-28) | 0 | 10 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Run-in Period: Microgynon (Day -28 to -1) | 0 of 28 |
| Sequence 1 Period 1: Microgynon Alone (Day 1-8) | 0 of 13 |
| Sequence 1 Period 1: Microgynon + Cladribine (Day 9-28) | 0 of 13 |
| Sequence 1 Period 2: Microgynon Alone (Day 1-8) | 0 of 13 |
| Sequence 1 Period 2: Microgynon + Placebo (Day 9-14) | 0 of 13 |
| Sequence 1 Period 2: Microgynon + Cladribine (Day 15-28) | 0 of 13 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Run-in Period: Microgynon (Day -28 to -1) | 7 of 28 |
| Sequence 1 Period 1: Microgynon Alone (Day 1-8) | 3 of 13 |
| Sequence 1 Period 1: Microgynon + Cladribine (Day 9-28) | 9 of 13 |
| Sequence 1 Period 2: Microgynon Alone (Day 1-8) | 5 of 13 |
| Sequence 1 Period 2: Microgynon + Placebo (Day 9-14) | 5 of 13 |
| Sequence 1 Period 2: Microgynon + Cladribine (Day 15-28) | 4 of 13 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Run-in Period: Microgynon (Day -28 to -1) | Sequence 1 Period 1: Microgynon Alone (Day 1-8) | Sequence 1 Period 1: Microgynon + Cladribine (Day 9-28) | Sequence 1 Period 2: Microgynon Alone (Day 1-8) | Sequence 1 Period 2: Microgynon + Placebo (Day 9-14) | Sequence 1 Period 2: Microgynon + Cladribine (Day 15-28) |
|---|---|---|---|---|---|---|---|
| Headache | Nervous system disorders | 3 of 28 | 1 of 13 | 6 of 13 | 3 of 13 | 2 of 13 | 3 of 13 |
| Fatigue | General disorders | 1 of 28 | 0 of 13 | 1 of 13 | 0 of 13 | 2 of 13 | 1 of 13 |
| Intermenstrual Bleeding | Reproductive system and breast disorders | 2 of 28 | 0 of 13 | 1 of 13 | 0 of 13 | 0 of 13 | 0 of 13 |
| Urinary Tract Infection | Infections and infestations | 1 of 28 | 0 of 13 | 0 of 13 | 0 of 13 | 1 of 13 | 0 of 13 |
| Chills | General disorders | 0 of 28 | 0 of 13 | 0 of 13 | 0 of 13 | 1 of 13 | 1 of 13 |
| Nasopharyngitis | Infections and infestations | 0 of 28 | 1 of 13 | 0 of 13 | 1 of 13 | 0 of 13 | 0 of 13 |
| Decreased Appetite | Metabolism and nutrition disorders | 0 of 28 | 0 of 13 | 1 of 13 | 0 of 13 | 1 of 13 | 0 of 13 |
| Leukocytosis | Blood and lymphatic system disorders | 1 of 28 | 0 of 13 | 0 of 13 | 0 of 13 | 0 of 13 | 0 of 13 |
| Lymphocytosis | Blood and lymphatic system disorders | 1 of 28 | 0 of 13 | 0 of 13 | 0 of 13 | 0 of 13 | 0 of 13 |
| Tonsilitis | Infections and infestations | 1 of 28 | 0 of 13 | 0 of 13 | 0 of 13 | 0 of 13 | 0 of 13 |
The registry record lists serious adverse events and other adverse events separately for the run-in period and for each recorded sequence and period. The serious adverse event count is 0 in every listed group, and the death count is 0 in every listed group. The number at risk differs across groups: it is 28 in the run-in period, 13 in the listed Sequence 1 groups, 11 for Sequence 2 Period 1 Microgynon alone, and 10 in the other listed Sequence 2 groups. The affected counts for other adverse events are period-specific and should be read alongside each group’s own at-risk count.
These figures are counts of participants affected within the named group, not event rates or a treatment-effect estimate. The groups represent different periods and treatment combinations, and the same person may contribute to more than one period in a crossover study. The counts should therefore not be added together to infer a total number of unique participants affected. The record does not provide a comparative statistical analysis of these safety counts or establish whether an event was caused by a particular treatment.
General explanation: observing zero serious events in a group does not prove that the underlying risk is zero. The amount of uncertainty depends in part on the number of participants observed and the follow-up context. No confidence intervals for the serious-event counts are reported in the registry record. The posted figures describe the recorded observations; they do not alone establish safety beyond the groups and periods documented.
12. What the Result Does, and Does Not, Mean
The record documents a randomized, double-blind crossover study designed to investigate whether cladribine affects the pharmacokinetics of the ethinyl estradiol and levonorgestrel constituents of Microgynon®. It identifies AUCt,ss as the primary endpoint, gives the plasma sampling schedule, and describes geometric means and geometric coefficients of variation as the summary approach. It also records safety outcomes by sequence and period.
Those details explain what the study set out to measure, but the numerical primary endpoint results are not reported in the registry record. There is no posted estimate of exposure under the respective conditions, no treatment contrast, and no confidence interval or p-value. The size and direction of any difference, and how precisely it was estimated, therefore cannot be stated. The safety record lists no serious adverse events and no deaths in the displayed groups, while also showing other adverse event counts. Those observations are limited to the recorded groups and periods.
The trial’s stated purpose was pharmacokinetic. It does not, in the listed primary outcome, measure contraceptive effectiveness or pregnancy outcomes. The registry record also does not provide numerical results for the primary endpoint from which to infer how cladribine may have affected exposure. A pharmacokinetic endpoint is not itself a direct measure of a clinical outcome.
General explanation: statistical evidence is best interpreted by considering both the estimated effect and its uncertainty, alongside the design and outcome being studied. Without the numerical estimates and analysis details, the record does not support a conclusion about the magnitude or precision of the primary comparison. It also does not justify a broader conclusion about outcomes or populations beyond those described in the record.
13. Why This Trial Matters Statistically
This study illustrates why design and analysis details matter in pharmacokinetic research. A crossover arrangement can make within-participant comparisons possible, while the sequence and period structure creates analytical features that need to be addressed. The registry record identifies randomization, double masking, two periods, and two treatment sequences, but it does not report the statistical model or explain how within-participant variation and period or sequence effects were handled.
The endpoint is also clearly defined: AUCt,ss for ethinyl estradiol and levonorgestrel, with plasma samples taken at specified times on Day 14. That definition helps readers understand the target of measurement. The registry record’s description of geometric means and geometric coefficients of variation communicates the intended descriptive summaries, but the absence of numerical values means neither the size of the observed exposure nor its uncertainty can be evaluated.
The record additionally illustrates the distinction between safety counts and treatment comparisons. Period-specific counts of participants with events provide a descriptive account, but participants can appear across periods in a crossover trial. Without an analysis plan and comparative estimates, those counts cannot establish a treatment-related difference.
For statistical interpretation, a trial’s design, endpoint, analysis population, missing-data handling, and uncertainty estimates work together. Here, the endpoint and broad design are documented, while the numerical primary results and several analysis details are not reported in the registry record. Keeping those boundaries clear prevents a study’s stated question from being mistaken for a demonstrated result.
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 main limitation for interpreting the primary endpoint is that numerical results are not reported in the registry record. Although the endpoint, units, sampling schedule, summary parameter, and dispersion measure are identified, the actual estimates for ethinyl estradiol and levonorgestrel are absent. A comparative estimate and a measure of uncertainty are also not reported. This prevents assessment of the direction, magnitude, and precision of the pharmacokinetic findings.
The analysis details are limited. The registry record lists 0 analyses and does not report the model, treatment contrast, handling of period or sequence, or treatment of within-participant correlation. It does not describe missing-data methods, the number with evaluable primary endpoint data, or the number included in the pharmacokinetic analysis set. A sample-size justification and protocol-level statistical plan are not reported in the registry record.
The primary endpoint is described across more than one analyte, and the record indicates that the outcome was not reduced to one comparison. No multiplicity approach is reported. The sequence descriptions are incomplete, so the full period schedule cannot be reconstructed from the registry record. A washout schedule is not reported.
The safety summaries provide counts by treatment period and sequence, but they do not provide comparative estimates or uncertainty intervals. Because a participant may contribute data in more than one period, these counts are not a tally of unique participants across all groups. The recorded enrollment does not establish the number contributing to each endpoint. These limitations concern what can be interpreted from the registry record; they do not establish whether additional results or methods exist elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Effects of Cladribine Tablets on the PK of Microgynon® — NCT03745144.
- Registry record last updated 2024-03-15; status last verified 2023-08.
- Results first posted 2024-03-15.
- 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 NCT03745144, a completed randomized, double-blind, Phase I, 2-period, 2-sequence crossover study in pre-menopausal women with relapsing multiple sclerosis. Enrollment was 28. The study investigated the potential effect of cladribine on the pharmacokinetics of ethinyl estradiol and levonorgestrel in Microgynon®.
The primary endpoint was AUCt,ss for both constituents, measured using samples scheduled through 24 hours post-dose on Day 14. The record states that descriptive statistics were used, with geometric means and geometric coefficients of variation. Numerical primary endpoint results and a comparative estimate are not reported in the registry record. The safety listings show no serious adverse events and no deaths in the recorded groups. The statistical plan, analysis details, missing-data methods, and sample-size justification are not reported in the registry record.