Efficacy and Safety, Long-Term Study of NPC-01 to Treat Dysmenorrhea Associated With Endometriosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety, Long-Term Study of NPC-01 to Treat Dysmenorrhea Associated With Endometriosis (NCT00902746), a na phase 3 study. The primary outcome is Patient Response to Treatment for Dysmenorrhea, as Evaluated by Difference of Total Dysmenorrhea Score (Baseline/Pretreatment-End of Treatment).

2. Clinical Question

This is a before-and-after question within a treated group, rather than a question about the difference between two assigned treatment groups. A change over time can describe the experience of the analyzed patients, but without a concurrent comparator it cannot isolate the effect of NPC-01 from other explanations for change. For example, general statistical reasoning recognizes that symptoms may vary over time and that expectations or other care may also influence reports; whether such influences mattered in this study is not reported in the registry record.

The study is identified as phase 3 and completed. Its registry enrollment is 149, while the primary-outcome description identifies an analysis population of 112 patients with end-of-study data. These are different descriptions of enrollment and outcome availability, and should not be treated as interchangeable denominators. Reasons that end-of-study data were unavailable for other patients are not reported in the registry record.

3. Trial Design

This was a phase 3, open-label, long-term clinical trial of NPC-01 for dysmenorrhea associated with endometriosis. The official title characterizes it as NSAID-add-on. The record lists a single-group model and allocation as NA; it does not describe a randomized allocation or a separate control arm. The study is marked completed. Its recorded start is 2009-05 and its primary completion is 2012-02.

NPC-01 is identified as norethisterone and ethinyl estradiol. The record’s purpose statement is to determine whether NPC-01 is effective in treating dysmenorrhea associated with endometriosis. The primary outcome evaluates the difference in total dysmenorrhea score from baseline or pretreatment to the end of treatment, with a 52-week timeframe. A secondary outcome is the difference in the Visual Analog Scale of dysmenorrhea from baseline or pretreatment to the end of treatment.

Open-label means that the study was not masked, according to the registry entry. The record does not specify how treatment expectations were handled or whether symptom assessment was conducted by a blinded assessor. Because the design is single-group, there is no concurrent control trajectory against which to compare symptom change. That limits what the design alone can establish about whether changes were caused by treatment.

The registry lists enrollment as 149. The primary-outcome description says the analysis was carried out for 112 patients with end-of-study data on FAS. The record does not explain the relationship between the enrollment figure and the patients available for this analysis, beyond identifying the analysis population as stated. Detailed eligibility criteria, recruitment procedures, treatment adherence, dose, concomitant-care rules, and the NSAID regimen are not reported in the registry record.

The record describes a mean and standard deviation for a continuous outcome, but does not supply the observed mean change or standard deviation. It also records no analyses. Consequently, the design and outcome definitions can be described, but the registered information does not support a quantitative estimate of the primary treatment-associated change or its precision.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: This analysis was carried out for 112 patients whom end of study data was available on FAS.

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: Baseline analysis were carried out on 147 patients except 1 patients who has no available data of efficacy and safety in 148 cases that study drug administration was started.

6. Primary Endpoint

The registry lists the primary outcome as Patient Response to Treatment for Dysmenorrhea, as Evaluated by Difference of Total Dysmenorrhea Score (Baseline/Pretreatment-End of Treatment), measured over 52 weeks.

The primary endpoint is the difference in total dysmenorrhea score between baseline or pretreatment and the end of treatment, evaluated at 52 weeks. It is a continuous measure summarized as a mean with a standard deviation. The score combines a pain subscale and a drug-use subscale during a menstrual period. Each subscale ranges from 0 to 3, and their sum ranges from 0 to 6.

For pain, the recorded categories run from none to severe. The descriptions distinguish mild pain associated with some trouble at work, moderate pain requiring bed rest and/or affecting work, and severe pain involving more than 1 day in bed and inability to work. For drug use, the categories distinguish no analgesics, analgesics for 1 days, for 2 days, and for more than 3 days during a menstrual period. These components represent different aspects of dysmenorrhea: experienced pain and use of analgesics. A combined score can capture both, but a change in the total alone does not show which component changed.

Using a defined score at baseline and follow-up allows investigators to describe within-patient symptom change over the treatment period. A mean summarizes the group’s average score difference, while the standard deviation describes variation among individual scores. A lower or higher score cannot be interpreted from the endpoint title alone: the registry does not provide the direction or magnitude of the observed mean change, or the score results for either time point. The endpoint definition also does not report a threshold for a clinically important change. Whether a particular difference would be meaningful to patients is therefore not established by the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous score difference, summarized in the record as a mean and standard deviation. These statistics answer related but distinct questions. A mean difference describes the average change in the analyzed group. A standard deviation describes how widely individual observations vary around that average. Neither statistic is reported numerically for the primary outcome in the registry record.

What does a mean change represent?

For a baseline-to-follow-up outcome, an individual’s change is based on measurements at both time points. The group mean change then summarizes those individual changes. It is not the same quantity as the average baseline score or the average end-of-treatment score considered separately. The registry identifies the comparison as baseline or pretreatment versus end of treatment, but does not publish the mean change or the separate time-point means.

A mean can be useful because it condenses a set of score changes into a single summary. However, it does not show whether most patients changed by a similar amount or whether individual experiences varied substantially. The standard deviation is relevant to that spread, but it is not a measure of uncertainty in the mean. A confidence interval is commonly used to express uncertainty around an estimated mean or difference: it gives a range of values compatible with the data and analysis under the method’s assumptions. No confidence interval for the primary outcome is reported in the registry record.

What does the scale capture?

The total dysmenorrhea score sums pain and analgesic-use subscales, each scored from 0 to 3, for a total range from 0 to 6. The pain component describes symptoms and effects on work or time in bed. The drug component records the duration of analgesic use during a menstrual period. Combining components gives a compact outcome, but it also means that the same total score may arise from different component profiles. Without component-level results, the total does not reveal whether a change reflected pain, drug use, or both.

The score is bounded by its stated minimum and maximum. In general, bounded scales can have distributions that are not well represented by a symmetric bell-shaped model, especially when many observations cluster near a boundary. Whether that occurred in this trial is not reported. The registry identifies the outcome as continuous and gives mean and standard deviation, but does not report score distributions or methods for checking modeling assumptions.

Why does the single-group design matter?

A within-group comparison uses observations over time in the treated group. It can describe change, but it does not provide a separate group’s change over the same period as a counterfactual reference. Without such a concurrent comparator, ordinary time trends and other influences cannot be separated from treatment-associated change by a simple pre/post contrast. This is a general limitation of single-group before-and-after comparisons.

The study is open-label. In general, knowledge of treatment can affect subjective symptom reporting, expectations, or decisions about other care. That consideration is relevant to a patient-reported or symptom-based measure, but the registry does not state whether or how such influences were evaluated. The record also does not report whether the primary analysis was adjusted for baseline score or other variables.

What can be said about statistical significance?

A p-value, when reported, measures how incompatible the observed data are with a specified null model, given the analysis assumptions. It is not the probability that the treatment is effective, nor does it measure the clinical importance of a change. A confidence interval complements a p-value by expressing uncertainty in the estimated effect on its scale. No primary-outcome p-value or confidence interval is reported in the registry record, and no analysis is listed. Statistical significance therefore cannot be assessed from the recorded primary-outcome information.

Statistical significance would not resolve the design limitation even if a within-group test were available. A test of change from baseline addresses whether the observed group’s average change is distinguishable from a null value under its assumptions. It does not create the missing control group or establish that treatment caused the change. Interpretation requires attention to the study design as well as the numerical result.

How should planning illustrations be understood?

Any sample-size planning illustration based on an observed effect is a hypothetical planning calculation, not a result observed in a new group and not observed power. The registry’s stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a stated fraction of the observed effect. For outcomes other than time-to-event outcomes, the stated convention is participants per arm for 80% power or another displayed power level; time-to-event planning uses a total number of events.

Those assumptions describe an illustration rather than this trial’s design. This study is recorded as single-group, not as an equal-allocation two-arm comparison. The registry does not report the trial’s sample-size justification or the assumptions used to plan its enrollment. Any planning number should therefore not be read as evidence about the actual precision or power of the completed study.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("NPC-01")
n   <- c(112)
m   <- c(2.4)
sp  <- c(1.8)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  NPC-01  112  2.400  1.800  2.063  2.737

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 2 outcome measures, including the primary total dysmenorrhea score and a secondary Visual Analog Scale difference. It lists 0 analyses. The record does not report a prespecified statistical analysis plan, a hierarchy of tests, an adjustment for multiple comparisons, or whether additional outcomes were assessed but not entered as analyses. The handling of multiplicity is therefore not reported in the registry record.

Multiplicity matters when several outcomes or analyses are examined: the more opportunities there are to identify an apparently notable result, the more important it is to understand which comparisons were planned and how they were interpreted. This is a general statistical concern, not evidence that selective analysis occurred in this study. Without analysis details and numerical results, the registry does not permit assessment of how multiplicity affected interpretation.

The primary-outcome description says the analysis was carried out for 112 patients with end-of-study data on FAS. The meaning and implementation of FAS are not expanded in the record. It does not specify whether all enrolled patients were included in the intended analysis, how missing end-of-study scores were handled, whether any imputation was used, or whether sensitivity analyses were conducted. Reasons for unavailable outcome data and outcomes among patients without end-of-study data are also not reported in the registry record.

Missing data can affect a before-and-after estimate if the availability of follow-up scores is related to symptoms, tolerability, or other factors. That is a general possibility; the registry does not establish why data were unavailable or whether missingness altered the result. The enrollment figure of 149 and the stated outcome population of 112 should therefore be read as separate recorded counts, not as a basis for inferring reasons for nonavailability or the results in those not included.

12. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: haemorrhagic ovrian cyst (1.4%), depressed level of consciousness (0.7%), endometriosis (0.7%), cellulitis orbital (0.7%).

The safety entry lists one NPC-01 group. Serious adverse events are recorded for 5 among 147 at risk. Other adverse events are recorded for 147 among 147 at risk. The registry’s safety summary also lists the following serious-event terms and percentages: Haemorrhagic ovrian cyst, 1.4%; Depressed level of consciousness, 0.7%; Endometriosis, 0.7%; and Cellulitis orbital, 0.7%.

These figures describe the safety information as entered in the registry, not a comparison with an untreated group. The record does not say whether an event was judged to be caused by NPC-01. It also does not provide event timing, duration, severity details beyond the serious classification, or a breakdown of the other adverse events. The terms and percentages should not be taken as a complete clinical account of individual cases.

The safety denominator is 147 at risk, whereas the primary-outcome description refers to 112 patients with end-of-study data. These are different denominators for different recorded information. The registry does not explain the difference, and it should not be interpreted as establishing why outcome data were unavailable. Deaths are listed as null, which is not a reported numerical death count. No conclusion about comparative safety can be drawn from this single-group safety summary.

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

The registry record identifies a completed, open-label, phase 3, single-group study of NPC-01 for dysmenorrhea associated with endometriosis. It specifies a 52-week primary endpoint based on the change in a combined pain and analgesic-use score, and names a Visual Analog Scale difference as a secondary outcome. It also records the analysis population for the primary outcome and a safety summary.

Those details clarify the question the trial intended to address and the outcomes it intended to measure. They do not provide the primary numerical result. The mean score difference, its standard deviation, and any confidence interval or p-value are not reported in the registry record. As a result, the size, direction, and precision of the primary outcome cannot be determined from this information. The registry’s purpose statement is not itself evidence of an observed treatment effect.

Even a numerical change within the treated group would not, on its own, establish that NPC-01 caused that change. The single-group design has no concurrent control group to represent what might have happened without treatment. Open-label status is also relevant when outcomes involve reported pain and medication use. These are limitations on causal interpretation; they do not establish that any particular source of bias occurred.

The score combines two components, so an overall difference would not necessarily describe a uniform change in pain and analgesic use. No component-level primary results or threshold for a clinically important difference are given. The registry also does not report the secondary outcome’s numerical findings or explain how missing outcome data were handled.

The safety record reports serious and other adverse events for the NPC-01 group, but provides no comparator and no causal assessment in the recorded summary. Those counts cannot establish comparative safety. In short, the registry supplies a study framework and outcome definitions, but not the numerical efficacy findings needed to estimate symptom change or its uncertainty. It also does not support a controlled causal conclusion.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a clearly named clinical outcome and a reported result. The registry defines a combined dysmenorrhea score, its components, its range, and the 52-week assessment timeframe. Yet without the mean change and a measure of uncertainty, readers cannot quantify the observed pattern or assess its precision. Outcome definitions are necessary for interpretation, but they do not substitute for numerical estimates.

The single-group design also highlights the difference between describing change and estimating a treatment effect. Baseline-to-follow-up measurements can characterize what happened over time in the analyzed group. A concurrent comparator is generally needed to separate treatment-associated change from other explanations for change. The registry identifies no control group, so the intended before-and-after contrast should not be mistaken for a controlled treatment comparison.

The scoring approach illustrates a trade-off in composite outcomes. Adding pain and analgesic-use subscales creates one summary measure, while potentially concealing different patterns in its components. Reporting component-level estimates alongside a total can help explain what a composite change represents. Such component results are not reported in the registry record.

Finally, the primary-outcome population and safety denominators differ in the registry. Keeping each denominator tied to its stated analysis is important; neither should be substituted for the other or used to infer unreported reasons for missing outcome data. The record does not report the analysis plan, missing-data methods, or multiplicity approach. These omissions limit reproducibility and the ability to judge how robust any estimate might be, quite apart from the absent numerical outcome results.

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 main trial-specific limitation is the absence of a concurrent comparator. Because the study is recorded as single-group, the primary before-and-after contrast cannot separate change associated with treatment from change over time or other influences. The study is also open-label, and the primary outcome concerns reported symptoms and analgesic use. The registry does not report procedures that would clarify how expectations or assessment could have influenced measurement.

The record does not provide the primary outcome’s mean difference, standard deviation, confidence interval, or p-value. It therefore does not allow readers to assess the direction, magnitude, or precision of the stated endpoint. Although a secondary Visual Analog Scale difference is listed, its numerical result is not reported in the registry record. The record does not state a threshold for a clinically important score difference.

The primary analysis is described for 112 patients with end-of-study data on FAS, while enrollment is listed as 149. The registry does not report why end-of-study data were unavailable for some patients, how missing data were handled, or whether sensitivity analyses were done. It does not define the FAS in further detail. Consequently, the potential influence of missing outcomes cannot be evaluated.

Other limitations of the available record include absent details on eligibility criteria, treatment dose and adherence, the NSAID regimen, concomitant care, and the statistical analysis plan. The safety record has no comparator and does not report event causality in its summary. These limitations concern what can be inferred from the registry information; they do not establish that any specific problem occurred during trial conduct.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Efficacy and Safety, Long-Term Study of NPC-01 to Treat Dysmenorrhea Associated With Endometriosis — NCT00902746.
• Registry record last updated 2025-06-15; status last verified 2025-06.
• Results first posted 2014-06-13.
• 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

NCT00902746 is a completed phase 3, open-label, long-term, single-group study of NPC-01 for dysmenorrhea associated with endometriosis. NPC-01 is described as norethisterone and ethinyl estradiol, and the official title characterizes the trial as NSAID-add-on. Enrollment is listed as 149. The primary outcome is the difference in total dysmenorrhea score from baseline or pretreatment to the end of treatment at 52 weeks. The primary-outcome description identifies 112 patients with end-of-study data on FAS.

The record describes a secondary Visual Analog Scale outcome and lists safety information for the NPC-01 group. It does not report numerical primary or secondary efficacy results, a statistical analysis, missing-data methods, or a comparative control group. The safety summary lists serious adverse events affecting 5 among 147 at risk and other adverse events affecting 147 among 147 at risk. These data describe the registry entry but do not establish comparative efficacy or safety.