Safety, Tolerability and Drug- Drug Interaction Study of Ubrogepant With Erenumab or Galcanezumab in Participants With Migraine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety, Tolerability and Drug- Drug Interaction Study of Ubrogepant With Erenumab or Galcanezumab in Participants With Migraine (NCT04179474), a randomized phase 1 study. The primary outcome is Part 1: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Time t (AUC0-t) for Ubrogepant Alone and in Combination With Erenumab.

2. Clinical Question

3. Trial Design

This was a Phase 1b, open-label study with randomized allocation and a parallel model. The registry record describes it as a two-part, fixed-sequence study of ubrogepant with erenumab or galcanezumab in participants with migraine. Enrollment was 40, and the study is listed as completed. The recorded start date was 2019-09-26 and the primary completion date was 2019-12-23.

Both parts began with a single oral dose of ubrogepant 100 mg on Day 1 under fasted conditions. In Part 1, participants then received a single subcutaneous injection of erenumab 140 mg on Day 8. In Part 2, they received two subcutaneous injections of galcanezumab 120 mg on Day 8. In both parts, the sequence continued with ubrogepant 100 mg orally once daily on Days 12, 13, 14 and 15 under fasted conditions.

The primary endpoint is specific to Part 1 and compares ubrogepant alone with ubrogepant in combination with erenumab. The registry also lists secondary pharmacokinetic outcomes for both antibody combinations. Allocation is recorded as randomized, but the registry record does not report the randomization procedure or the sequence-allocation details. Masking is recorded as none, so this was an open-label study.

The primary pharmacokinetic population included participants with evaluable ubrogepant plasma pharmacokinetic parameters for both ubrogepant alone and ubrogepant in combination with erenumab or galcanezumab. The primary analysis lists 20 participants for ubrogepant alone and 19 for the erenumab combination. Reasons for the difference in evaluable counts are not reported in the registry record. The protocol’s original statistical design assumptions, including any original sample-size justification, are 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.

Treatment Period 1 (First Intervention)

Treatment Period 2 (Second Intervention)

Treatment Period 3 (Third Intervention)

Analysis population for the primary outcome, as defined in the registry: Pharmacokinetic 1 (PK1) population included all participants who had evaluable plasma PK parameters of ubrogepant for both ubrogepant alone and ubrogepant in combination with erenumab or galcanezumab.

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 population included all participants who received/took at least 1 administration of study intervention in Part 1 or Part 2.

6. Primary Endpoint

The registry lists the primary outcome as Part 1: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Time t (AUC0-t) for Ubrogepant Alone and in Combination With Erenumab, measured over Day 1 (Treatment Period 1): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose; Day 12 (Day 1 of Treatment Period 3): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose.

The primary endpoint is the area under the plasma concentration-versus-time curve from time 0 to time t, abbreviated AUC0-t, for ubrogepant alone and in combination with erenumab. It is reported in nanogram*hour/milliliter (ng*h/mL), as a mean with a standard deviation. Sampling was scheduled on Day 1 and Day 12 at predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose.

General statistical explanation: an area under a concentration-time curve combines concentration measurements across a period of time. It is used in pharmacokinetic studies as a measure of overall drug exposure during that period, rather than as a single concentration at one sampling time. A mean describes the average endpoint value in a group; the standard deviation describes the spread of individual values around that average. The endpoint therefore addresses whether the measured ubrogepant exposure differed between the two treatment conditions. It does not, by itself, measure a clinical migraine outcome.

The registry record identifies the primary pharmacokinetic population as participants with evaluable plasma pharmacokinetic parameters for ubrogepant both alone and in combination with erenumab or galcanezumab. It does not report a fuller account of how missing or unevaluable pharmacokinetic measurements were handled.

7. Results Posted in the Registry

• Part 1: Ubrogepant in Combination With Erenumab: mean 1,960 versus 1,841 on control; difference 118.54 (95% CI -240.40 to 477.48), standardized effect d = 0.21; z-test p = 0.517.

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.

Part 1: Terminal Elimination Rate Constant (λz) for Ubrogepant Alone and in Combination With Erenumab

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Part 1: Ubrogepant in Combination With Erenumab: mean 0.16 versus 0.14 on control; difference 0.02 (95% CI 0.00 to 0.04), standardized effect d = 0.67; z-test p = 0.037.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Part 1: Ubrogepant in Combination With Erenumab than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Part 2: λz for Ubrogepant Alone and in Combination With Galcanezumab

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Part 2: Ubrogepant in Combination With Galcanezumab: mean 0.17 versus 0.15 on control; difference 0.02 (95% CI -0.02 to 0.05), standardized effect d = 0.28; z-test p = 0.391.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Part 2: Ubrogepant in Combination With Galcanezumab and the control. The interval gives the range of effects that remain compatible with the data.

Part 1: Terminal Elimination Half-life (T½) for Ubrogepant Alone and in Combination With Erenumab

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Part 1: Ubrogepant in Combination With Erenumab: mean 4.62 versus 5.26 on control; difference -0.64 (95% CI -1.25 to -0.03), standardized effect d = -0.66; z-test p = 0.039.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Part 1: Ubrogepant in Combination With Erenumab than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary pharmacokinetic outcomes broaden the description beyond the primary AUC0-t comparison. The available estimates cover measures of elimination and include both antibody-combination parts. Across the numerical secondary comparisons that are posted, the pattern is mixed: some confidence intervals include zero and some do not. Taken together, these outcomes do not give a single uniform signal that can be treated as a substitute for the primary result.

The secondary measures relate to different features of the ubrogepant concentration-time profile. They may help describe whether the observed exposure comparison is accompanied by differences in timing or elimination measures, but they are not interchangeable with the primary exposure endpoint. Nor do secondary pharmacokinetic measures answer a clinical outcome question.

Unadjusted secondary results carry less weight when multiple outcomes are examined because the chance of finding at least one apparently notable result can increase across repeated tests. General statistical explanation: multiplicity procedures are used in some analyses to control that risk, but the registry record does not report such an adjustment for these outcomes. The reported secondary estimates should therefore be regarded as exploratory evidence and interpreted with their intervals, the number of outcomes, and the lack of a reported multiplicity plan in mind.

The registry lists 15 posted secondary outcomes, but numerical details for all of them are not reported in the registry record. This limits any synthesis across the full intended secondary outcome set. The available secondary data can inform the pharmacokinetic description, but they do not establish a broader pattern beyond the measures actually reported.

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

• Part 1: Time of Maximum Plasma Drug Concentration (Tmax) for Ubrogepant Alone and in Combination With Erenumab
• Part 2: Tmax for Ubrogepant Alone and in Combination With Galcanezumab
• Part 1: Terminal Elimination Rate Constant (λz) for Ubrogepant Alone and in Combination With Erenumab
• Part 2: λz for Ubrogepant Alone and in Combination With Galcanezumab
• Part 1: Terminal Elimination Half-life (T½) for Ubrogepant Alone and in Combination With Erenumab
• Part 2: T½ for Ubrogepant Alone and in Combination With Galcanezumab
• Part 1: Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F) for Ubrogepant Alone and in Combination With Erenumab
• Part 2: CL/F for Ubrogepant Alone and in Combination With Galcanezumab

9. Statistical Interpretation

10. Statistical Methods Explained

General statistical explanation: a continuous endpoint is measured on a numerical scale. The primary endpoint, AUC0-t, is summarized with a mean and standard deviation for each treatment condition. The mean gives a group’s average value, while the standard deviation describes how dispersed the observed values are around that mean. A standard deviation is not the same as the uncertainty in the estimated mean or in the between-condition difference.

What does the mean difference represent?

The recalculated mean difference expresses the estimated contrast between the two arithmetic means on the original AUC0-t scale. Its confidence interval gives a range of values compatible with the observed data under the calculation’s assumptions. A difference of zero would represent no difference on that scale. Because the primary interval extends across zero, it does not identify a clear direction of difference. The registry record does not state the exact statistical method used for its own primary analysis.

How does the sponsor analysis differ?

The registry’s reported analysis is a ratio of geometric mean percentages, not a difference between arithmetic means. A ratio compares values on a relative scale, whereas a mean difference compares them on the original measurement scale. Those summaries can answer related but non-identical questions and should not be treated as interchangeable. The registry record gives the sponsor’s ratio and 90% confidence interval, but does not identify the analysis method or state a decision margin for equivalence.

What do confidence intervals and p-values convey?

General statistical explanation: a confidence interval communicates the uncertainty around an estimated quantity; it is not a guarantee that the true value lies inside the particular interval. The unadjusted p-value measures how inconsistent the observed data are with a specified null hypothesis under the assumptions of the test. It is not the probability that the null hypothesis is true, and it does not measure clinical importance. The posted p-value is explicitly unadjusted, and the registry record does not report a multiplicity procedure for the outcomes.

The recalculations use posted group summary statistics and are simple unadjusted comparisons. They are not the same as a complete participant-level analysis. The registry’s sponsor analysis is the relevant posted analysis from the trial record; the recalculated contrast offers a separate description on the arithmetic-mean scale. No discrepancy between the posted analysis and the recalculation is flagged in the registry record.

Why can spread affect interpretation?

General statistical explanation: when individual measurements vary substantially, group averages are estimated with less precision unless the available sample is large enough to offset that variability. The primary groups contain 20 and 19 participants, and the reported standard deviations are substantial relative to the precision sought from a group comparison. The confidence interval is a direct way to see that uncertainty in the estimated contrast. It should not be replaced by a judgment based on whether the group means look numerically different.

General statistical explanation: over-dispersion matters most for outcome models that assume a particular variance structure, especially count outcomes. The primary endpoint is continuous and is summarized as a mean and standard deviation; the registry record does not report an over-dispersion model for it. The main issue visible in the posted primary summary is uncertainty around the mean difference, not evidence that a particular variance model was used.

The listed secondary pharmacokinetic outcomes include time of maximum plasma concentration, terminal elimination rate constant, terminal elimination half-life, and apparent total body clearance. These are distinct characteristics of the concentration-time profile. A change in one measure does not automatically establish a change in another, and each outcome has its own estimate and uncertainty. Only some secondary estimates and comparisons are reported with numerical results in the registry record; other endpoint details are not reported in the registry record.

The registry record identifies the primary analysis population by evaluability of pharmacokinetic parameters. It does not report the full statistical analysis plan, the exact procedures for handling missing observations, the rationale for the analysis population, or whether any interim analyses were conducted. Those details therefore cannot be used to clarify how the estimates were selected or how uncertainty was handled beyond what is posted.

11. Confidence Intervals and Precision

The recalculated 95% confidence interval for the primary mean difference runs from -240.4 to 477.5 ng*h/mL. Its span across zero means the result is not precise enough to distinguish a positive difference from a negative difference at that interval level. The interval also covers values that could represent materially different magnitudes on the AUC0-t scale. The estimate of 118.5 ng*h/mL is therefore best read together with its interval, not as a stand-alone indication of a stable effect size.

The sponsor-reported ratio of geometric means is 105.55%, with a 90% confidence interval from 96.21% to 115.79%. This interval describes uncertainty on the ratio scale and is not directly interchangeable with the interval for the arithmetic mean difference. The registry record does not report equivalence bounds, so the interval alone cannot establish that a prespecified equivalence criterion was met.

General statistical explanation: confidence intervals are influenced by sample size and variability. A narrower interval indicates greater precision for the particular estimate and scale; a wider interval leaves more uncertainty about the possible values. The primary comparison has evaluable groups of 20 and 19 participants. The group standard deviations are 490.2 and 639.5 ng*h/mL, respectively. These summaries help contextualize why the estimate should not be read as exact.

The interval addresses sampling uncertainty under the calculation’s assumptions. It does not account for every possible limitation, such as missing-data handling, the open-label design, or an unreported analysis choice. The registry record does not provide enough detail to quantify those sources 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 sample-size figures are planning illustrations based on the observed effect, not the study’s original design calculations. For these continuous outcomes, the figures are participants per arm, rather than total events. The assumptions listed for the illustrations are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The target effect is set at the stated fraction of the observed effect: 100%, 75%, or 50%.

The 80% power column gives the estimated participants per arm for a hypothetical study to have an 80% chance of detecting the specified effect under those assumptions, if that effect were the true one. The 90% power column gives the corresponding planning figure for a 90% chance. These are planning concepts, not probabilities that the observed result is correct and not descriptions of what happened in this completed study.

The illustrations use the observed effect as their reference, then consider smaller fractions of that effect. Smaller effects are harder to distinguish from random variation, so they require more participants under the same assumptions. The displayed figures can therefore change substantially across the effect scenarios. They should be interpreted as conditional planning examples rather than as a recommended design or as a reconstruction of the trial’s own sample-size justification.

The trial’s original statistical design assumptions and original sample-size justification are not reported in the registry record. This is not observed power: observed power is not an appropriate substitute for interpreting the uncertainty in the confidence interval, and these planning calculations do not describe the achieved evidential strength of the completed study.

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, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 118.540; pooled standard deviation σ = 567.750.
2. n = 2 × (1.96 + 0.842)² × 567.750² / 118.540² = 360.1, rounded up to 361 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
delta <- 118.54                      # observed difference in means
sigma <- 567.749960926844                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^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 (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(4179474)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 361 (80% power), 483 (90% power)
 75% of observed effect: n per arm = 641 (80% power), 858 (90% power)
 50% of observed effect: n per arm = 1,441 (80% power), 1,929 (90% power)
power.t.test: 361.1 
Simulated power at n = 361 per arm: 0.805 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-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. Analyses Reported by the Sponsor

The registry’s own primary analysis reports a ratio of geometric mean percentage of 105.55%, with a 90% confidence interval from 96.21% to 115.79%. The separate recalculation uses the posted arithmetic means and standard deviations to estimate a mean difference of 118.5 ng*h/mL, with a 95% confidence interval from -240.4 to 477.5. One result is expressed as a ratio and the other as an absolute difference, so their numerical values are not directly comparable.

The recalculated comparison is unadjusted and based on posted summary statistics. It does not replace the sponsor’s analysis. The registry record does not identify the sponsor analysis method, and it does not report equivalence margins or a formal equivalence decision rule. The sponsor’s estimate and its confidence interval should therefore be distinguished from the recalculation, rather than combined into a single conclusion. No discrepancy between the two is flagged in the registry record.

General statistical explanation: different scales can make a result easier to interpret for different questions, but the scale and method must be stated. A ratio conveys a relative comparison, while a difference remains in the endpoint’s measurement units. Neither is inherently a complete account of uncertainty without its interval and the assumptions of its analysis.

15. Multiplicity, Missing Data and Analysis Populations

The study lists a primary endpoint and a set of secondary pharmacokinetic outcomes across two parts. When many outcomes are examined, separate unadjusted tests can increase the chance of at least one result appearing unusual by chance alone. General statistical explanation: multiplicity methods may adjust the interpretation of several tests, or investigators may specify a hierarchy for the outcomes. The registry record does not report a multiplicity adjustment, testing hierarchy, or other strategy for controlling multiple comparisons.

The posted recalculated p-values are unadjusted. They should not be read as if they account for the number of outcomes or comparisons considered. The primary endpoint is distinct from the secondary outcomes, but the registry record does not state whether the study’s analysis plan protected the primary comparison from other inferential decisions or how secondary tests were intended to be interpreted.

The primary pharmacokinetic population required evaluable ubrogepant parameters under both treatment conditions. The record lists 20 participants for ubrogepant alone and 19 for the erenumab combination in the primary comparison. It does not report why evaluable counts differ, how missing samples or incomplete concentration-time profiles were handled, or whether participants with incomplete data were excluded according to a prespecified rule.

The registry record does not report the full statistical analysis plan, the trial’s original sample-size justification, interim analyses, or details of the randomization procedure. It also does not report how the analysis addressed any departures from the assumed distribution or whether sensitivity analyses were undertaken. These gaps limit assessment of whether all analysis decisions were prespecified and how robust the reported estimates are to alternative choices.

These are limits on what can be inferred from the registry record, not evidence that any particular procedure was or was not carried out. Without the missing details, the most defensible reading stays close to the posted estimates, their intervals, the stated analysis population, and the stated outcome definitions.

16. 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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports zero serious adverse events in each of the six listed intervention groups and zero deaths. The listed groups cover ubrogepant and antibody treatment periods in Part 1 and Part 2. The group sizes at risk range from 19 to 20 participants, as recorded for the separate intervention periods.

These counts describe the serious adverse event entries in the registry record. They do not show that serious events are impossible or that the treatments are free of risk. Small groups provide limited information about uncommon events, and the registry record does not provide additional detail on event definitions or follow-up beyond the listed intervention groups.

Other adverse events are also recorded, with affected-participant counts varying by intervention group. Those counts are not serious adverse event counts and should not be conflated with them. No serious adverse event terms are listed in the registry record. The safety counts are descriptive; this study’s primary question was pharmacokinetic, and these entries do not establish a comparative safety conclusion.

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

The primary result estimates ubrogepant exposure with and without erenumab using AUC0-t. The recalculated mean difference is uncertain: its 95% confidence interval includes zero and spans both negative and positive values. The sponsor’s geometric-mean ratio provides a second description on a relative scale, with its own 90% confidence interval. These statistics describe the data recorded for the study’s pharmacokinetic population; neither establishes a clinical outcome.

The study does not establish whether either antibody combination changes migraine symptoms or clinical outcomes. The registry record presents pharmacokinetic endpoints and adverse event counts, not a comparison of migraine frequency, severity, or treatment response. It would therefore be inappropriate to translate a pharmacokinetic estimate directly into a claim about clinical benefit or lack of benefit.

The results also do not prove that there is no difference. A confidence interval that includes zero is compatible with values on either side of zero, and the limited evaluable group sizes leave uncertainty. Similarly, the sponsor-reported ratio should not be treated as proof of equivalence because the registry record does not report equivalence bounds or a decision rule.

The secondary pharmacokinetic findings do not resolve these limitations. They concern additional aspects of drug disposition and include a mixed pattern of uncertainty. Unadjusted secondary comparisons are also harder to interpret as definitive evidence when the registry does not report a multiplicity strategy.

The serious adverse event entries report no serious events in the listed groups, but these counts do not rule out uncommon events or establish a general safety profile. Overall, the record offers a small-study pharmacokinetic comparison with descriptive safety information, rather than a clinical effectiveness evaluation or a definitive safety assessment.

18. Why This Trial Matters Statistically

This study is statistically informative because it separates a pharmacokinetic question from a clinical outcome question. AUC0-t summarizes exposure across a sampling period, while the secondary outcomes address other features of the drug concentration-time profile. Keeping those measures distinct helps prevent a pharmacokinetic result from being overstated as evidence about clinical response.

The record also illustrates why effect estimates and confidence intervals should be read together. The primary mean difference is accompanied by an interval that includes values in both directions. The point estimate alone cannot convey that uncertainty. The sponsor’s geometric-mean ratio uses a different scale, showing why analysts should identify whether a comparison is an absolute difference or a relative ratio before interpreting its magnitude.

The design includes two antibody combinations and sequential dosing, but the posted primary endpoint is specific to Part 1 and erenumab. Part 2 contributes secondary pharmacokinetic information, rather than a parallel posted primary AUC comparison. That distinction matters when summarizing what the study directly tests and what the available estimates can support.

Finally, the registry record demonstrates the importance of reporting analytic details. The evaluable population is described, but missing-data handling, multiplicity methods, the original sample-size rationale, and other design assumptions are not reported. Without those details, readers can interpret the posted estimates and uncertainty but cannot fully assess the intended inferential framework. The statistical value lies in describing the observed pharmacokinetic data precisely and respecting the boundaries of what those data answer.

19. Limitations

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

The primary comparison has 20 participants in the ubrogepant-alone group and 19 in the combination group, leaving limited precision for a continuous endpoint with the reported spread. The interval around the recalculated mean difference is broad and includes zero, so the estimate does not tightly identify the direction or magnitude of the difference.

The primary result concerns Part 1 and erenumab. The posted primary endpoint does not provide a corresponding AUC0-t comparison for Part 2 and galcanezumab. The secondary results cannot be treated as if they were that missing primary comparison, because they measure different pharmacokinetic characteristics.

The study is open-label. The primary endpoint is a laboratory-based pharmacokinetic measure, but open-label status remains part of the design context, and the registry record does not provide further information about procedures that might mitigate possible sources of bias. The design is described as randomized and fixed-sequence, but the randomization procedure and allocation details are not reported.

The registry record does not report the original sample-size justification, full statistical analysis plan, missing-data handling, multiplicity strategy, or interim analyses. The sponsor analysis method and any equivalence decision limits are also not reported. These omissions make it difficult to determine how closely the posted analyses align with prespecified decision rules or how secondary findings were intended to be interpreted.

Only some numerical secondary results are available in the registry record. This restricts evaluation of the complete secondary outcome set. The safety entries are counts from small intervention groups and do not provide a comprehensive characterization of less common events. These limitations constrain inference; they do not establish that unreported procedures or events were absent.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Safety, Tolerability and Drug- Drug Interaction Study of Ubrogepant With Erenumab or Galcanezumab in Participants With Migraine — NCT04179474.
• Registry record last updated 2021-03-10; status last verified 2021-02.
• Results first posted 2021-03-10.
• 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.

23. Record Summary

NCT04179474 is a completed Phase 1b, open-label study with randomized allocation and a parallel model. It enrolled 40 participants with migraine and assessed ubrogepant alone and in combination with erenumab or galcanezumab using fixed treatment sequences.

The primary endpoint was Part 1 AUC0-t for ubrogepant alone versus ubrogepant with erenumab. The recalculated mean difference was 118.5 ng*h/mL, with a 95% confidence interval from -240.4 to 477.5 and an unadjusted p-value of 0.517. The sponsor analysis reported a geometric-mean percentage ratio of 105.55% with a 90% confidence interval from 96.21% to 115.79%.

The record also includes secondary pharmacokinetic outcomes and descriptive adverse event counts. It reports zero serious adverse events and zero deaths in the listed intervention groups. The available results address pharmacokinetics and recorded safety events, not clinical migraine outcomes.