Equivalence of A Stable Liquid Glucagon Formulation With Freshly Reconstituted Lyophilized Glucagon: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Equivalence of A Stable Liquid Glucagon Formulation With Freshly Reconstituted Lyophilized Glucagon (NCT02018627), a randomized phase 2, phase 3 study. The primary outcome is Tmax.

2. Clinical Question

3. Trial Design

This completed phase 2 and phase 3 study was randomized, open-label, and used a crossover model. In a crossover study, participants receive more than one treatment, so each participant can contribute observations under both conditions. The primary endpoint description states that all 13 subjects received both glucagon injections. It also reports that 7 subjects were randomized to receive Xeris first and 6 to receive Lilly first. The registry record does not report further details about the sequence allocation process, the interval between doses, or any washout procedures.

The two interventions were Xeris glucagon, 50 micrograms by subcutaneous injection, and Lilly glucagon, 30 micrograms by subcutaneous injection. The study summary frames the comparison as a test of whether Xeris glucagon would be non-inferior by pharmacokinetic and pharmacodynamic criteria. The primary endpoint was Tmax. Measures of glucose infusion rate and additional pharmacokinetic or tolerability outcomes were also listed as secondary outcomes.

The registry record lists an enrollment of 20. The primary endpoint description says 13 subjects completed the study following a consistent protocol, and the reported endpoint summaries each have 13 subjects in each treatment group. Those figures describe different stages or aspects of the record: enrollment is not the same as the number of subjects included in the posted endpoint summaries. The reason the endpoint description includes 13 completed subjects rather than all enrolled participants is not reported in the registry record.

The study began in 2014-04, had a primary completion date of 2018-08-02, and is marked completed. The record does not report the trial's original sample-size justification, the planned analysis model for its crossover structure, or the full protocol. No masking was used. These features matter when interpreting the estimates: the small number of completed subjects, the open-label design, and the unreported analysis details limit how much can be inferred from the descriptive summaries alone.

4. Participant Flow and Accounting

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

Before assignment: 20 subjects were enrolled in this study. One was ineligible after enrollment. 4 were enrolled and eligible, but were not able to schedule their study visit. 2 participated in "test run" experiments as we adjusted glucagon doses to account for concentration differences. 13 subjects completed experiments using the same protocol.

Overall Study

Analysis population for the primary outcome, as defined in the registry: 13 subjects completed the study following a consistent protocol using the glucagon doses described in the arm/group description. 7 subjects were randomized to get Xeris glucagon first, 6 subjects were randomized to get Lilly glucagon first. All 13 subjects received both glucagon injections, and the data is reported for each drug.

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 Tmax, measured over every 2 minutes for 1 hour post-dose of each glucagon.

Tmax is the time from dosing to the maximum measured concentration. In this study, the registry record describes measurement every 2 minutes for 1 hour after each glucagon dose. It is a pharmacokinetic endpoint: it concerns the timing of the measured concentration peak, rather than directly describing a clinical outcome.

The registry record identifies the primary comparison as Tmax for Xeris versus Lilly glucagon and describes the study's broader hypothesis in terms of non-inferiority by pharmacokinetic and pharmacodynamic criteria. A time-to-maximum measure can be useful in a comparison because it gives a defined summary of when the maximum concentration is reached. The group summaries report mean Tmax and standard deviation for each glucagon, while the comparison gives a mean difference and confidence interval.

For this endpoint, the reported mean was 23.8 minutes for Xeris glucagon and 15.7 minutes for Lilly glucagon. The displayed mean difference is defined in the comparison as Lilly minus Xeris and is -8.1 minutes, with a 95% confidence interval from -13.41 to -2.788. These figures describe the observed endpoint summaries. A non-inferiority conclusion requires comparison against a prespecified margin; that margin and a corresponding registry-recorded analysis are not reported in the registry record. The endpoint results therefore should be read as estimates of timing and their uncertainty, not as a stand-alone determination that the study met its stated hypothesis.

7. Results Posted in the Registry

• Lilly Glucagon: mean 15.70 versus 23.80 on control; difference -8.10 (95% CI -13.41 to -2.79), standardized effect d = -1.17; z-test p = 0.003.

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.

AOCGIR

• 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:
  • Lilly Glucagon: mean 132.20 versus 201.10 on control; difference -68.90 (95% CI -226.10 to 88.30), standardized effect d = -0.34; z-test p = 0.390.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Lilly Glucagon and the control. The interval gives the range of effects that remain compatible with the data.

GIRmin

• 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:
  • Lilly Glucagon: mean 2.90 versus 2.90 on control; difference 0.00 (95% CI -1.55 to 1.55), standardized effect d = 0.00; z-test p = 1.000.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Lilly Glucagon and the control. The interval gives the range of effects that remain compatible with the data.

t½Max

• 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:
  • Lilly Glucagon: mean 5.90 versus 11.30 on control; difference -5.40 (95% CI -7.44 to -3.36), standardized effect d = -2.04; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Lilly Glucagon than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The posted secondary results cover a pharmacodynamic measure of glucose infusion rate, a minimum glucose infusion rate measure, and the time to maximum effect. The overall pattern is mixed: some estimates are centered near zero, while others show differences in their posted mean summaries. The corresponding confidence intervals also vary in width and whether they span zero. The AOCGIR interval is notably broad, which means its estimate is relatively imprecise under the posted calculation.

These secondary outcomes provide additional context for the primary Tmax result, but they address different aspects of response. The primary endpoint concerns timing of maximum concentration; the secondary endpoints include measures related to glucose infusion and timing of maximum effect. Results across different endpoints need not follow the same pattern, and one endpoint cannot be substituted for another. The registry record's stated hypothesis encompasses pharmacokinetic and pharmacodynamic criteria, but it does not report a complete inferential analysis connecting the secondary outcomes to a formal non-inferiority decision.

Unadjusted secondary comparisons carry less weight as confirmatory evidence because multiple outcomes create multiple opportunities for apparently notable results. General statistical practice may address this through a prespecified hierarchy, adjustment, or other multiplicity strategy. The registry record does not report such a plan or an adjustment for these comparisons. The secondary p-values should therefore be read as unadjusted endpoint-level results, not as proof that a broader family of hypotheses was established.

The registry record lists additional secondary outcomes beyond the three with posted numerical summaries, including injection pain, injection-site erythema, maximal nausea, and dermal response measures. Numerical results for those outcomes are not reported in the registry record. The presence of an outcome in the list does not indicate the direction or frequency of its findings. Nor does a lack of a posted numerical comparison establish that no observations occurred. Overall, the secondary results are supportive descriptive context, but the number of subjects, incomplete set of numerical results, and absence of a reported multiplicity plan constrain their interpretation.

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

• AOCGIR
• GIRmin
• t½Max
• Injection Pain
• Injection Site Erythema
• Maximal Nausea
• Dermal Response (Draize Scale for Erythema and Eschar Formation)
• Dermal Response (Draize Scale Grade for Edema Formation)

9. Statistical Interpretation

10. Statistical Methods Explained

The results are continuous outcomes reported as means and standard deviations. A mean describes the central value of the observations, while a standard deviation describes how spread out those observations are around the mean. These summaries help characterize each treatment condition, but they do not show the individual observations or the within-person pairing that is relevant to a crossover study.

What does the mean difference represent?

The posted comparisons express the mean difference as the Lilly value minus the Xeris value. A negative estimate therefore indicates that the observed mean for Lilly is lower than the observed mean for Xeris; a positive estimate would indicate the reverse. For example, the primary endpoint estimate is -8.1 minutes. This direction describes the arithmetic contrast as posted, not whether one treatment is better or worse. The record does not report a clinical threshold for interpreting the size of a difference.

For general context, in a crossover design each participant receives multiple treatments, and the comparison may use the fact that observations from the same person are related. Accounting for that relationship can differ from comparing two independent groups. The registry record reports a crossover model and says all 13 subjects received both injections, but it does not report the model or calculation used to account for pairing, period effects, treatment sequence, or possible carryover. The available group-level summaries cannot reveal those details.

How should a confidence interval be understood?

A confidence interval gives a range of values compatible with the data and the method used to calculate the interval. In general, a narrower interval indicates greater precision, while a wider interval indicates more uncertainty about the estimated contrast. The interval does not give the probability that the true value lies within its endpoints. The primary Tmax interval is -13.41 to -2.788 minutes. The AOCGIR and GIRmin intervals include zero, whereas the intervals for Tmax and t½Max do not. The registry record does not report whether the posted intervals were adjusted for multiple comparisons or were derived from a crossover-specific model.

What does a p-value say?

A p-value describes how unusual results at least as inconsistent with a null hypothesis would be under that hypothesis and the assumptions of the analysis. It is not the probability that the null hypothesis is true, nor does it measure the importance of an effect. The primary unadjusted p-value is 0.003; the posted values for AOCGIR, GIRmin, and t½Max are 0.39, 1.0, and <0.001, respectively. These are unadjusted values. The registry record does not report a multiplicity adjustment or a complete statistical analysis plan, so the values should be interpreted as individual comparisons rather than as a documented family-wide testing procedure.

For general statistical context, a non-inferiority test asks whether the data rule out a loss greater than a prespecified acceptable margin. That margin defines what degree of difference is compatible with the non-inferiority claim. The study summary describes non-inferiority as the objective, but the margin, hypothesis-testing procedure, and corresponding registry-recorded analysis are not reported in the registry record. A confidence interval that excludes zero is not, by itself, evidence of non-inferiority: the interval must be considered against the chosen margin and in the specified direction.

Why might variability matter?

Standard deviations describe the observed spread, and the precision of an estimated mean difference depends on variability as well as the amount of information in the data. General statistical methods may also need to account for skewness, unusual observations, and dependence between repeated measures. The AOCGIR summaries show substantial variability relative to the reported means, and its comparison interval is wide. No distributional diagnostics or alternative analysis methods are reported in the registry record. These limitations are relevant when evaluating whether simple mean-based summaries adequately characterize the observations.

The displayed comparisons include pooled standard deviations, standard errors, confidence intervals, and unadjusted p-values. These quantities summarize the posted group statistics, but the registry record does not report the detailed procedure used for the primary analysis. No analyses are listed as reported analyses for the primary or posted secondary endpoints. It is therefore not possible to verify from the record whether the displayed comparisons reproduce a sponsor analysis, account for the crossover design, or implement the stated non-inferiority objective. No discrepancy is flagged in the posted comparison data, but that does not supply the missing analysis specification.

In general, statistical significance and precision are related but distinct. A p-value summarizes compatibility with a null hypothesis under specific assumptions; an interval gives a range of plausible contrast values under a method. Neither alone answers whether a result is clinically important or meets a non-inferiority criterion. Those interpretations require a prespecified margin, an appropriate analysis for the design, and context for the endpoint. Those elements are not reported in the registry record.

11. Confidence Intervals and Precision

The primary Tmax estimate is a mean difference of -8.1 minutes, with a 95% confidence interval from -13.41 to -2.788. This interval indicates that the estimated contrast is not exact: values across a range of several minutes are compatible with the data and the method used to calculate the interval. The interval does not establish the probability that the true difference falls within those bounds, and it does not determine whether any possible difference is clinically meaningful.

The endpoints vary in precision. AOCGIR has a mean difference of -68.9 mg*min/kg, with a 95% confidence interval from -226.1 to 88.3. That range spans values on both sides of zero and is wide relative to the point estimate. GIRmin has a mean difference of 0.0 dextrose mg/kg/min, with a 95% confidence interval from -1.545 to 1.545. The t½Max estimate is -5.4 minutes, with a 95% confidence interval from -7.435 to -3.365. These intervals describe uncertainty in different endpoint units and should not be compared as if the units or measurement scales were interchangeable.

For general context, confidence-interval width is influenced by the variability of the observations, the amount of information available, and the analysis method. Each posted endpoint summary has 13 subjects per treatment. The primary endpoint description says these were the 13 subjects who completed the study following a consistent protocol. Although every subject received both injections, the record does not report a paired estimate or explain how the relationship between each subject's measurements was incorporated. That missing detail limits assessment of the precision calculation in light of the crossover design.

The confidence intervals also cannot be used to decide non-inferiority without the margin and decision rule. The registry record describes a non-inferiority hypothesis but does not report those elements or a corresponding registry-recorded analysis. Thus, the intervals quantify uncertainty in the posted contrasts, but do not by themselves settle the trial's stated non-inferiority question.

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.

Read each planning scenario as an illustration of the number of participants per arm needed under the stated assumptions, not as the observed enrollment or completed sample. The planning scenarios vary the assumed effect: 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. For each scenario, the 80% power column gives the planned participants per arm for an analysis designed to have an 80% chance of detecting that assumed effect under the planning model, if the assumptions hold. The 90% power column describes the corresponding target at 90% power. Higher power targets and smaller assumed effects generally require more participants.

The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect. For the continuous outcomes in this record, the figures are participants per arm; the event-count convention for time-to-event outcomes does not apply to these endpoints. In the displayed planning scenarios, smaller fractions of the observed effect are associated with larger participant requirements. This is a planning illustration, not observed power.

These calculations are separate from the study's original design justification. The registry record does not report the assumptions or sample-size rationale used when the trial was designed. The record lists enrollment of 20 and endpoint results for 13 subjects per treatment, but those observed counts should not be confused with the planning figures or treated as evidence that a particular power target was achieved.

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 = -8.100; pooled standard deviation σ = 6.910.
2. n = 2 × (1.96 + 0.842)² × 6.910² / -8.100² = 11.4, rounded up to 12 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 <- -8.1                      # observed difference in means
sigma <- 6.90977568376861                     # 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(2018627)
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 = 12 (80% power), 16 (90% power)
 75% of observed effect: n per arm = 21 (80% power), 28 (90% power)
 50% of observed effect: n per arm = 46 (80% power), 62 (90% power)
power.t.test: 12.5 
Simulated power at n = 12 per arm: 0.780 (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. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several outcomes or hypotheses are examined: even if each individual test uses a conventional threshold, the chance of at least one apparently notable result across a group of tests can increase. General approaches include prespecifying a primary endpoint and testing hierarchy, adjusting significance thresholds, or treating secondary findings as exploratory. The registry record identifies Tmax as primary and lists several secondary outcomes, but it does not report a multiplicity strategy or explain how the secondary comparisons were intended to affect the main conclusion.

The posted p-values are unadjusted. The record does not report whether any adjustment was used in an analysis outside the registry record. No reported analyses are listed for the primary or secondary results. Consequently, the available information does not establish a family-wise testing procedure or a prespecified sequence for interpreting the outcomes. The secondary findings should be viewed with that uncertainty in mind rather than as independent confirmation of the primary result.

The registry record also does not report the handling of missing data, exclusions, or analysis populations beyond the primary endpoint description. That description states that 13 subjects completed the study following a consistent protocol and that all 13 received both injections. It reports 7 subjects randomized to Xeris first and 6 to Lilly first. The record lists enrollment of 20, but does not explain why the primary endpoint population includes 13 subjects or whether all enrolled participants were included in any other analysis.

For a crossover study, analysis-population definitions can matter because a participant may contribute observations under both treatments, and incomplete treatment sequences can affect which comparisons are available. General statistical methods may also address treatment sequence, period effects, and carryover. The registry record does not report how these issues were handled or whether the analysis used paired observations. The original statistical analysis plan, missing-data method, and rationale for the completed endpoint population are not reported in the registry record. These omissions limit assessment of both the intended inferential procedure and the potential effect of missing observations.

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.

The serious adverse event figures list 13 participants at risk in each treatment group and 0 participants affected by serious adverse events in each group. Deaths are listed as 0 in both groups. The other adverse event figures also list 13 participants at risk and 0 affected in each group. These counts describe the posted registry entries for the groups; they do not establish that no events of any kind occurred beyond the categories represented by those figures.

The registry record does not list top serious adverse event terms. The adverse event figures should be interpreted in light of the limited number of participants and the record's reporting scope. Counts from a small study provide limited information about uncommon events, and the registry record does not report further detail about event definitions, observation duration, or how events were attributed. The posted counts are descriptive safety information, not a basis for broader conclusions about safety.

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

The results describe observed pharmacokinetic and pharmacodynamic measurements after two glucagon injections in a randomized crossover study. The primary endpoint, Tmax, had a mean of 23.8 minutes for Xeris and 15.7 minutes for Lilly. The posted contrast is Lilly minus Xeris, with an estimate of -8.1 minutes and a 95% confidence interval from -13.41 to -2.788. These data describe the measured timing in the 13-subject endpoint population and the uncertainty represented by the posted interval.

They do not, by themselves, establish equivalence or non-inferiority. The study summary states a non-inferiority hypothesis, but the registry record does not report the required margin or a registry-recorded analysis against that margin. A difference estimate and an unadjusted p-value answer neither whether a difference is acceptably small nor whether a prespecified non-inferiority criterion has been satisfied. The statistical meaning of the result therefore depends on protocol details and analyses not reported in the registry record.

The results also do not establish what would happen in populations or circumstances beyond those represented by this study. The record reports 20 enrolled participants but 13 completed subjects for the primary endpoint. It does not report detailed participant characteristics, reasons for the difference between enrollment and completion, or a missing-data analysis. The open-label design and lack of reported crossover analysis details further constrain interpretation of the comparative estimates.

Secondary endpoints add descriptive information, but they are not a substitute for the primary endpoint or for a complete analysis plan. Only three secondary outcomes have numerical results in the registry record; numerical results for the other listed secondary outcomes are not reported in the registry record. The posted secondary comparisons are unadjusted, and no multiplicity strategy is reported. Taken together, the data support a careful reading of the estimates as endpoint-specific results from a small completed population, rather than as a broad conclusion about the treatments or the stated non-inferiority hypothesis.

17. Why This Trial Matters Statistically

This trial is statistically interesting because it uses a crossover design for a direct comparison of two glucagon formulations. In general, a crossover can allow each participant to serve as their own comparison, which may be useful when responses vary between people. That advantage depends on appropriate handling of paired measurements and design features such as sequence and period. Although the registry record states that all 13 endpoint subjects received both injections, it does not report how the analysis accounted for those features.

The study also illustrates why the stated hypothesis and the posted comparison need to be distinguished. Non-inferiority is not simply a finding that two means are similar, or that a difference is statistically significant or not significant. It requires a prespecified margin and an analysis whose confidence interval is evaluated against that margin. Neither the margin nor a corresponding registry-recorded analysis is reported. Readers therefore cannot use the displayed mean difference alone to determine whether the stated objective was achieved.

The endpoint summaries further show how point estimates and precision tell different parts of the story. The secondary outcomes include both broad and narrower intervals, and the registry record provides a limited set of numerical results compared with the listed outcomes. Unadjusted comparisons across several endpoints can be useful descriptively, but do not replace a planned approach to multiple testing.

Finally, enrollment and analyzed endpoint counts are not interchangeable. The record lists 20 enrolled participants and reports 13 completed subjects for the primary endpoint. Without reasons for the difference or details of the analysis populations, readers have less context for judging how representative the posted estimates are. These are general statistical concerns raised by the record, not evidence that a particular bias occurred.

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.

Several trial-specific limitations affect interpretation. The primary endpoint description reports 13 completed subjects, while the registry record lists enrollment of 20. Reasons for the difference, participant flow, and the handling of any missing endpoint data are not reported in the registry record. The displayed endpoint summaries are therefore based on a smaller population than the enrollment figure, with no registry-recorded explanation of how that population was defined.

The crossover design is clear, and the record says every subject in the primary endpoint population received both injections. However, the statistical method used for the comparison is not reported. In particular, the record does not explain whether the analysis accounted for paired observations, treatment sequence, period, or carryover. The group summaries alone do not show the within-person differences that a crossover comparison may use.

The study was open-label, and the registry record does not report whether any outcome assessment was blinded. The original sample-size rationale and the study's full statistical analysis plan are also not reported in the registry record. Although planning illustrations based on observed effects are listed, they do not reveal the assumptions used to design the original trial.

The stated non-inferiority objective is not accompanied in the registry record by a margin or a reported analysis testing that objective. The secondary comparisons are unadjusted, and a multiplicity approach is not reported. Numerical results are available for only three secondary endpoints; results for the other listed secondary outcomes are not reported in the registry record. Finally, the registry record does not report detailed participant characteristics or the duration and procedures for safety observation. These gaps limit assessment of generalizability, analysis choices, and the scope of the posted safety counts.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Equivalence of A Stable Liquid Glucagon Formulation With Freshly Reconstituted Lyophilized Glucagon — NCT02018627.
• Registry record last updated 2019-10-08; status last verified 2019-09.
• Results first posted 2019-10-08.
• 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

NCT02018627 is a completed randomized, open-label crossover study in type 1 diabetes, listed as phase 2 and phase 3. It compared Xeris glucagon 50 micrograms by subcutaneous injection with Lilly glucagon 30 micrograms by subcutaneous injection. The study summary describes a non-inferiority hypothesis based on pharmacokinetic and pharmacodynamic criteria.

The primary endpoint was Tmax, measured every 2 minutes for 1 hour after each dose. The record lists 20 participants enrolled; the primary endpoint description reports 13 subjects completed the study and received both injections. Numerical results are posted for the primary endpoint and three secondary endpoints. Other listed secondary outcomes do not have numerical results reported in the registry record. The record does not report the non-inferiority margin, detailed analysis plan, or rationale for the difference between enrollment and the completed endpoint population.