Global Study to Evaluate the Long-Term Safety and Efficacy of Elagolix in Women With Moderate to Severe Endometriosis-associated Pain: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Global Study to Evaluate the Long-Term Safety and Efficacy of Elagolix in Women With Moderate to Severe Endometriosis-associated Pain (NCT02143713), a randomized phase 3 study. The primary outcome is Percentage of Participants With a Response for Dysmenorrhea at Month 6 Based on Daily Assessment.

2. Clinical Question

This was an extension study, not a comparison of elagolix with placebo throughout the full study period. The registry describes the study as randomized and quadruple-masked, but all four extension groups received elagolix. The comparison therefore concerns response proportions across treatment sequences and extension doses. It does not isolate a placebo-controlled effect during the extension.

The primary outcome required both a reduction in dysmenorrhea from baseline and no increase in rescue analgesic use under the endpoint definition. That joint criterion is important: a participant had to satisfy both parts to count as a responder. The registry defines the endpoint population by treatment exposure and availability of baseline and Month 6 data; broader details about how missing endpoint data were handled are not reported in the registry record.

3. Trial Design

The registry describes NCT02143713 as a Phase 3, randomized, quadruple-masked, parallel-group study. It was sponsored by AbbVie and marked completed. Enrollment was 496. Its stated purpose was to evaluate continued safety and efficacy of elagolix among adult pre-menopausal women with moderate to severe endometriosis-associated pain who had completed six months of treatment in pivotal Study M12-671.

Four treatment-sequence groups appear in the primary results: Placebo/Elagolix 150 mg QD, Placebo/Elagolix 200 mg BID, Elagolix/Elagolix 150 mg QD, and Elagolix/Elagolix 200 mg BID. The extension descriptions specify elagolix tablets once a day or twice a day for six months. The sequence labels indicate that participants had received placebo or elagolix in the pivotal study before entering the elagolix extension. The registry record does not provide further detail about allocation procedures or how masking was maintained across the sequence.

The primary endpoint was assessed at Month 6. Its baseline could refer to baseline in pivotal Study M12-671 for participants who had received elagolix in that study, or baseline in extension Study M12-821 for participants who had received placebo in the pivotal study. Thus the reported comparison combines response data from participants with differing prior treatment histories and baseline reference points.

The registry lists 18 outcome measures and 16 posted secondary outcomes. It records no reported analyses for the secondary measure with detailed results in the available record. The protocol’s original sample-size rationale, planned interim analyses, and full statistical analysis plan are not reported in the registry record. The primary results include unadjusted comparisons, but a broader adjustment strategy for multiple comparisons is not reported 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: The study consisted of a 6-month Treatment Period and a Post-treatment Follow-up (PTFU) of up to 12 months. Participants who received elagolix in the pivotal study continued to receive the same dose for a further 6 months; participants on placebo in the pivotal study were randomized 1:1 to either elagolix 150 mg once daily or 200 mg twice daily.

Treatment Period (6 Months)

Reasons for not completing this period:

Post-treatment Follow-up (12 Months)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants who received at least 1 dose of double-blind study drug in this extension study with available baseline and month 6 data.

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.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With a Response for Dysmenorrhea at Month 6 Based on Daily Assessment, measured over Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and Month 6.

The primary endpoint is the percentage of participants who were classified as responders for dysmenorrhea at Month 6 based on daily assessment. Dysmenorrhea means pain during menstruation. A responder had to meet both parts of the definition: a reduction of -0.85 or more from baseline in dysmenorrhea, and no increase in rescue analgesic use beyond the stated allowance. The rescue-use condition was defined as a < 15% increase in average rescue analgesic pill count and no additional analgesic. The registry says this response threshold was determined in pivotal Study M12-671 and represents a clinically meaningful response.

Participants recorded rescue analgesic use daily and recorded dysmenorrhea and its impact on daily activities each day of their period in an electronic diary. Pain was rated on a scale from no discomfort through severe pain that made usual activities difficult. Pain scores and analgesic use were averaged over the 35 days before each visit. These repeated daily records were therefore condensed into a participant-level response status for the Month 6 comparison.

A responder endpoint can be easier to interpret as the share of participants meeting a defined criterion than as a change in an average score. However, converting continuous symptom and medication-use information into responder status makes the result depend on the chosen threshold. The registry’s record supports interpretation of the specified response definition, not conclusions about every possible level of pain change or medication use.

7. Results Posted in the Registry

• Placebo/Elagolix 200 mg BID: 57.1% (56/98) versus 37.0% (30/81) on control; risk difference 20.1 percentage points (95% CI 5.7 to 34.5), risk ratio 1.54 (1.11–2.15); unadjusted two-proportion z-test p = 0.007.
• Elagolix/Elagolix 150 mg QD: 50.8% (62/122) versus 37.0% (30/81) on control; risk difference 13.8 percentage points (95% CI 0.0 to 27.5), risk ratio 1.37 (0.98–1.91); unadjusted two-proportion z-test p = 0.053.
• Elagolix/Elagolix 200 mg BID: 75.9% (88/116) versus 37.0% (30/81) on control; risk difference 38.8 percentage points (95% CI 25.7 to 51.9), risk ratio 2.05 (1.51–2.77); unadjusted two-proportion z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Number of Participants With Non-study Health Visits During the Treatment Period

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Placebo Elagolix 200 mg BID: 58.6% (65/111) versus 47.1% (48/102) on control; risk difference 11.5 percentage points (95% CI -1.8 to 24.8), risk ratio 1.24 (0.96–1.61); unadjusted two-proportion z-test p = 0.093.
  • Elagolix/Elagolix 150 mg QD: 53.5% (76/142) versus 47.1% (48/102) on control; risk difference 6.5 percentage points (95% CI -6.2 to 19.2), risk ratio 1.14 (0.88–1.47); unadjusted two-proportion z-test p = 0.319.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Placebo Elagolix 200 mg BID and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Elagolix/Elagolix 150 mg QD and the control. The interval gives the range of effects that remain compatible with the data.

The registered outcome set spans several kinds of information: monthly response percentages for dysmenorrhea, non-menstrual pelvic pain, and dyspareunia; changes in those pain domains; and changes in rescue analgesic use, including NSAID use. The posted record also includes a measure of non-study health visits during the six-month treatment period. This breadth gives context beyond the primary dysmenorrhea response measure, but the outcomes are not interchangeable: they address different pain domains, time patterns, or health-service use.

The secondary results in the registry record do not support a single reliable statement about an overall direction across all these domains. The detailed data available for a secondary outcome concern non-study health visits, while the record lists no reported analyses for that measure. The set of posted secondary outcomes is broader than the results for which a comparison is available in the record. Without the full outcome-level estimates and analysis details, it is not possible to establish whether the secondary outcomes consistently reinforce, qualify, or differ from the primary result.

Secondary measures can help assess whether a primary finding fits with other aspects of the clinical picture, but they should not be treated as independent confirmation without considering their definitions, missingness, and analysis plan. Some are measured repeatedly, and several are related pain outcomes. Their results may be correlated rather than representing separate, independent pieces of evidence.

The primary endpoint has a specific status and definition, whereas secondary outcomes generally provide additional context. The registry record does not report a multiplicity adjustment for secondary testing. When numerous endpoints or time points are evaluated without adjustment, individual unadjusted results carry less weight as confirmatory evidence because chance findings become more likely across the set. The available record therefore supports cautious description of the secondary outcome domains, not a broad conclusion based on a complete pattern of secondary effects.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Percentage of Participants With a Response for Dysmenorrhea at Each Month Based on Daily Assessment
• Percentage of Participants With a Response for Non-menstrual Pelvic Pain at Each Month Based on Daily Assessment
• Percentage of Participants With a Response for Dyspareunia at Each Month Based on Daily Assessment
• Percent Change From Baseline in Dysmenorrhea Based on Daily Assessment
• Percent Change From Baseline in Non-menstrual Pelvic Pain Based on Daily Assessment
• Percent Change From Baseline in Dyspareunia Based on Daily Assessment
• Change From Baseline in Any Rescue Analgesic Use
• Change From Baseline in NSAID Rescue Analgesic Use

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary at the participant level: a person either met the response definition at Month 6 or did not. The posted percentages summarize the number meeting that definition in each group relative to the number in the endpoint population. For example, the reference group had 30 responders among 81 participants with endpoint data, and the Placebo/Elagolix 200 mg BID group had 56 among 98. The corresponding counts for the other two groups were 62 among 122 and 88 among 116. These endpoint denominators differ from the overall enrollment and should be used when interpreting the primary response percentages.

The reported effect measure is the risk difference, meaning the difference between the two group response proportions. A positive risk difference in these comparisons indicates a higher observed response proportion in the named group than in the reference group. The reported estimates are 0.201, 0.138, and 0.388 for the three comparisons. These are unadjusted comparisons; the registry record does not describe covariate adjustment for the primary contrasts.

A confidence interval describes a range of estimates compatible with the data under the method’s assumptions. Its width conveys precision: narrower intervals indicate greater precision, while wider intervals leave more uncertainty about the size of the contrast. An interval that includes zero is compatible with no risk difference under the interval procedure; an interval entirely above zero is compatible with a positive risk difference under that procedure. This interpretation does not account for the possibility of multiple testing unless an adjustment is specified.

The posted p-values are labeled unadjusted. A p-value assesses how surprising data at least as incompatible with a null hypothesis would be if that hypothesis and the test assumptions held. It is not the probability that the null hypothesis is true, nor a measure of clinical importance. The registry record does not give enough detail to identify the exact test procedure or to establish whether the posted p-values reproduce a prespecified analysis.

The endpoint combines pain-score change with rescue-analgesic use. This protects against counting a pain reduction as a response when it is accompanied by a disallowed increase in rescue medication. It also means that the result is sensitive to the operational definition: participants near either threshold can be classified differently even when their underlying symptom experiences are similar. As a general statistical point, dichotomizing information into responder/non-responder status can simplify interpretation while discarding detail about the magnitude and distribution of changes. The registry does not report a complementary continuous primary analysis in the posted results.

Daily diary data were averaged over the 35 days before each visit. Averaging repeated measurements can reduce the influence of day-to-day variation, but the registry excerpt does not describe the precise diary-completeness requirements or the statistical handling of incomplete daily records. The endpoint population required available baseline and Month 6 data, so the reported estimates pertain to that population rather than automatically to every enrolled participant.

General statistical context: comparisons across several groups and outcomes create opportunities for chance findings. When many hypotheses are examined, the chance of at least one apparently unusual result can increase unless the analysis accounts for multiplicity or clearly treats results as exploratory. The registry record reports unadjusted p-values and does not report a multiplicity procedure. Consequently, the p-values should not be read as if they were necessarily adjusted for the full set of comparisons.

The parallel-group label means the study assigned participants to groups rather than describing a crossover comparison within each participant. The randomized and quadruple-masked design descriptors are useful characteristics, but the record does not state the randomization sequence, allocation concealment procedures, or which participant and study personnel roles were included in the masking description. Those implementation details are not reported in the registry record.

The registry’s analysis population definition matters for generalizability. Participants needed at least one dose of extension study drug and baseline and Month 6 data to contribute to the primary endpoint. The record does not report how many enrolled participants lacked endpoint data, whether missing outcomes were imputed, or whether sensitivity analyses assessed alternative missing-data assumptions. Without those details, the effect of missing data on the estimated response proportions cannot be assessed from the registry record alone.

11. Confidence Intervals and Precision

The primary confidence intervals give a sense of the uncertainty around each risk-difference estimate. For Placebo/Elagolix 200 mg BID versus the reference group, the estimate was 0.201, with a confidence interval from 0.057 to 0.345. For Elagolix/Elagolix 150 mg QD, the estimate was 0.138, with an interval from < 0.001 to 0.275. For Elagolix/Elagolix 200 mg BID, the estimate was 0.388, with an interval from 0.257 to 0.519. The first and third intervals lie above zero; the second has a lower limit close to zero.

All three intervals cover a range of plausible risk differences, rather than a single known value. The intervals overlap one another, and the comparisons each use the same reference group. The estimates therefore should not be treated as precise rankings of the treatment sequences or as direct statistical comparisons between the three non-reference groups. Pairwise comparisons among those groups are not reported in the registry record.

Group sizes for the primary endpoint ranged from 81 to 122 participants. The degree of precision is shaped by both group size and the distribution of responses; the interval is not determined by the point estimate alone. As a general matter, a wider interval signals greater uncertainty in the effect size, while a narrower interval signals more precision. Neither interval width nor a p-value establishes clinical importance.

Confidence intervals describe uncertainty under the method used to calculate them. The registry record does not identify the interval method, its assumptions, or any adjustment for multiple comparisons. The intervals should therefore be read as posted, unadjusted estimates rather than as guaranteed ranges that account for every analysis or source of uncertainty.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are illustrations for future study planning, not a report of the original trial’s design calculation. They are listed as participants per arm for 80% power and participants per arm for 90% power. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to a stated fraction of the observed effect. The trial’s own original sample-size assumptions are not reported in the registry record.

In plain language, the 80% power column estimates the number of participants per arm under which a study would have an 80% chance of detecting the chosen effect under the planning assumptions, if that effect and those assumptions were true. The 90% power column uses a higher target chance of detection and consequently calls for more participants per arm for the same effect scenario. These are planning concepts, not guarantees about the result of a future study.

The rows for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect illustrate how the required enrollment changes when the target effect is smaller than the one observed. Smaller effects need more participants to distinguish them from random variation with the same target power. The displayed planning values differ by contrast because the observed effects differ.

These calculations are not observed power. They do not describe the probability that this completed study detected an effect, and they do not replace the confidence intervals for the trial’s actual estimates. They are conditional planning illustrations based on the stated assumptions and observed effect scenarios.

The planning display concerns two-arm comparisons. It does not establish that the original four-group extension was designed using these assumptions, nor does it provide a new sample-size recommendation for every endpoint. The registry does not report the original design rationale, so the planning illustrations should not be used to infer what enrollment the investigators intended or whether the completed study met a prespecified power target.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.370; treatment proportion p₁ = 0.571; average p̄ = 0.471.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.7059 = 1.3836.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6914 = 0.5819.
4. n = (1.3836 + 0.5819)² / (0.2011)² = 95.6, rounded up to 96 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.37037037037037                          # control proportion
p1 <- 0.571428571428571                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(2143713)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 96 (80% power), 128 (90% power)
 75% of observed effect: n per arm = 170 (80% power), 227 (90% power)
 50% of observed effect: n per arm = 378 (80% power), 505 (90% power)
power.prop.test: 95.6 
Simulated power at n = 96 per arm: 0.806 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several statistical comparisons are made, such as comparisons across treatment groups, endpoints, or assessment times. Even if each individual test uses a conventional threshold, considering many tests can increase the chance that at least one result appears unusual by chance. Statistical plans may address this through prespecified testing sequences, adjusted thresholds, or other procedures. Whether any such approach was planned for this trial is not reported in the registry record.

The primary results include three comparisons against the Placebo/Elagolix 150 mg QD group, with p-values explicitly described as unadjusted. The registry lists 18 outcome measures and includes repeated monthly outcomes in its secondary outcome descriptions. The full planned testing family and any hierarchy among outcomes or doses are not reported in the registry record. It is therefore not possible to interpret the posted p-values as multiplicity-adjusted evidence.

Missing-data handling is also important because the primary endpoint population required at least one dose of extension study drug and available baseline and Month 6 data. The record does not report the number of participants excluded from the endpoint analysis for missing data, the reasons for missingness, or the assumptions used to handle incomplete records. It does not report imputation procedures or sensitivity analyses that would show whether conclusions change under alternative assumptions about participants without Month 6 data.

These omissions limit assessment of both the robustness of the estimated response proportions and the degree to which results apply to all enrolled participants. Missing outcomes can be consequential if the chance of having observed data is related to response or treatment experience. That is a general statistical concern, not evidence that missingness affected the result in this trial.

The registry defines the primary endpoint population but does not provide further analysis-population details, such as whether a separate intention-to-treat analysis was conducted. It also does not report interim analyses, the complete statistical analysis plan, or a detailed prespecification of outcome analyses. These items are not reported in the registry record, so they cannot be used to resolve questions about multiplicity or missing-data sensitivity.

15. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: abdominal pain (2.0%), abortion induced (1.4%), incisional hernia (1.0%), arthralgia (1.0%), irritable bowel syndrome (0.9%).

The safety record reports serious adverse events and other adverse events by treatment-sequence group. For serious adverse events, the number affected and the number at risk were 4 of 102 in Placebo/Elagolix 150 mg QD, 8 of 111 in Placebo/Elagolix 200 mg BID, 7 of 142 in Elagolix/Elagolix 150 mg QD, and 8 of 140 in Elagolix/Elagolix 200 mg BID. The record reports zero deaths in each group.

For other adverse events, the corresponding affected counts and numbers at risk were 49 of 102, 74 of 111, 65 of 142, and 70 of 140. These are counts within the registry’s safety groups, not comparisons adjusted for treatment sequence or duration. The registry record does not provide an inferential comparison of safety-event rates between groups, and event counts alone do not establish a causal relationship to study drug.

The record lists the most frequent serious adverse event terms with percentages, including abdominal pain at 2.0% and abortion induced at 1.4%; the other listed terms were incisional hernia and arthralgia at 1.0%, and irritable bowel syndrome and diverticulitis at 0.9%. These entries describe reported event terms. They do not by themselves indicate how an individual event was judged to be related to treatment or provide a complete clinical account of safety.

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

The primary result describes the proportion of participants with baseline and Month 6 data who met a defined dysmenorrhea response criterion during a six-month elagolix extension. Response required both a specified decrease in pain and limits on increased rescue analgesic use. The proportions varied across the four treatment-sequence groups, and the risk-difference estimates quantify the observed contrasts against the Placebo/Elagolix 150 mg QD group.

These results do not represent a continuous placebo-controlled comparison during the extension, because the extension groups received elagolix. The group labels also encode whether participants had received placebo or elagolix in the pivotal study. The contrasts therefore should be interpreted as differences across the recorded sequences, not as a clean estimate of the effect of starting elagolix versus placebo in the extension.

The response definition is one particular way to summarize symptoms and medication use. A participant who did not meet the threshold might still have had some improvement, while someone who met it is classified as a responder regardless of how far beyond the threshold their change was. The endpoint does not represent all dimensions of endometriosis-associated pain or all patient experiences.

The confidence intervals express uncertainty around the group contrasts, and the registry reports unadjusted p-values. Neither a p-value nor a confidence interval alone determines clinical importance. The registry record does not report the complete statistical plan, multiplicity handling, or missing-data sensitivity analyses, which limits how firmly the results can be interpreted as confirmatory across the full set of outcomes.

Safety counts provide a separate description of events recorded during the trial. They do not establish that the events were caused by treatment, and the registry does not report adjusted safety comparisons. The findings should therefore be understood as trial-specific summaries of response and recorded events, rather than as comprehensive evidence about every possible benefit, risk, population, or duration of use.

17. Why This Trial Matters Statistically

This trial illustrates a recurring challenge in extension studies: the comparison groups may carry forward different treatment histories from an earlier study. The sequence labels are essential for interpreting the primary contrast. A result from participants who continued an earlier elagolix assignment cannot be treated as equivalent to one from participants who moved from placebo to elagolix, even though both groups received elagolix in the extension.

The endpoint also illustrates how a clinical outcome can combine symptom change and medication use into a single responder measure. That approach can make a result more interpretable than a score alone, but the chosen thresholds determine who is counted as a responder. Statistical interpretation therefore depends on understanding the operational definition and the data collection interval, not just the group percentages.

Precision matters alongside the estimated direction. The confidence intervals show that the comparisons have different levels of uncertainty and that one lower bound is close to zero. Reading the intervals alongside the unadjusted p-values gives more information than treating each result as a binary declaration. The results also demonstrate why multiple comparisons and repeated outcome assessments deserve attention when the full statistical plan is unavailable.

Finally, the record shows the value and limits of registry reporting. It supplies the endpoint definition, analysis population, group summaries, and safety counts, but does not report all analysis details needed to judge multiplicity, missing data, or the original sample-size rationale. Such distinctions help readers separate what the posted estimates directly describe from the broader questions that remain unanswered.

18. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The study addresses continuation of treatment after completion of a pivotal study, so its population is selected by having completed that earlier treatment period. Results may not automatically apply to people who did not complete the pivotal study or to people entering treatment without that history. The registry describes participants as adult pre-menopausal women with moderate to severe endometriosis-associated pain, but provides no further demographic or clinical breakdown in the record used for these results.

Interpretation of the four groups is complicated by treatment sequence. The placebo-labeled groups received placebo in the pivotal study and elagolix in the extension, while the elagolix-labeled groups received elagolix in both study periods. In addition, the primary endpoint baseline reference differs according to prior pivotal treatment. This design context means the observed contrasts should not be reduced to dose-only comparisons.

The primary analysis population requires baseline and Month 6 data. The registry does not report how many otherwise eligible participants were missing endpoint data, how missing diaries were handled, or whether sensitivity analyses were performed. That leaves uncertainty about the influence of incomplete follow-up on the reported percentages.

The record reports unadjusted comparisons and does not describe multiplicity procedures, detailed model specifications, or the original sample-size justification. It also does not report pairwise tests between the non-reference groups. Secondary outcomes cover multiple pain and medication-use domains, but complete analysis results are not available in the record. These limitations restrict assessment of confirmatory evidence and the consistency of findings across outcomes.

Safety summaries list affected counts and selected serious-event terms but do not provide adjusted comparisons or establish causality. As with any finite trial, the recorded events do not represent every possible safety outcome or longer-term experience beyond the period summarized.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Global Study to Evaluate the Long-Term Safety and Efficacy of Elagolix in Women With Moderate to Severe Endometriosis-associated Pain — NCT02143713.
• Registry record last updated 2021-07-13; status last verified 2021-07.
• Results first posted 2018-09-07.
• 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.

22. Record Summary

NCT02143713 is a completed Phase 3 randomized, quadruple-masked, parallel-group extension study sponsored by AbbVie, with enrollment of 496. It evaluated six months of elagolix in adult pre-menopausal women with moderate to severe endometriosis-associated pain who had completed treatment in pivotal Study M12-671.

The primary endpoint was the percentage of participants with a Month 6 dysmenorrhea response based on daily assessment and a rescue-analgesic-use condition. Response percentages ranged from 37.0% in Placebo/Elagolix 150 mg QD to 75.9% in Elagolix/Elagolix 200 mg BID. Reported contrasts are unadjusted comparisons against the Placebo/Elagolix 150 mg QD group.

The record also reports serious and other adverse-event counts, with zero deaths in each safety group. Details about the original sample-size rationale, missing-data procedures, multiplicity adjustment, and complete statistical analysis plan are not reported in the registry record.