Glucose Response of G-Pen (Glucagon Injection) in Pediatric T1D Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Glucose Response of G-Pen (Glucagon Injection) in Pediatric T1D Patients (NCT03091673), a non-randomized phase 3 study. The primary outcome is Change in Plasma Glucose.

2. Clinical Question

3. Trial Design

This is a phase 3, sequential study of glucagon injection in pediatric patients with type 1 diabetes. The registry lists enrollment of 31 and classifies allocation as non-randomized, masking as none, and the model as sequential. The study status is completed. The registry record gives the study start as 2017-03-27 and primary completion as 2017-09-07.

The study summary describes an efficacy and safety evaluation. Participants were to receive insulin to induce a low normal glycemic state, then receive an age-appropriate dose of G-Pen in a clinical research center or comparable setting. The arm descriptions specify one subcutaneous injection, at either 0.5 mg or 1.0 mg. The record does not explain how the dose was selected for each participant, whether the dose arms were enrolled in a particular sequence, or whether other design features governed the sequence.

Because allocation was non-randomized and masking was absent, the dose arms are not a randomized comparison. Differences between them, if reported elsewhere, would not by themselves isolate a dose effect from other differences between the groups. There is no placebo or untreated comparator described in the registry record. The listed primary endpoint concerns change in plasma glucose after treatment, rather than a comparison against a control condition.

Enrollment, design labels, and completion status describe the planned or recorded study structure; they do not supply the outcome results. The registry record does not report the actual number analyzed for the primary endpoint, participant flow, reasons for any exclusions, or details of the analysis plan.

4. Participant Flow and Accounting

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

First Dose

Second Dose

Analysis population for the primary outcome, as defined in the registry: All enrolled subjects.

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 Change in Plasma Glucose, measured over 0-30 minutes.

The primary endpoint is change in plasma glucose, measured in mg/dL over 0-30 minutes. The record emphasizes the increase from baseline to 30 minutes after dosing and identifies the measure as a mean with standard deviation. Its stated population is all enrolled subjects.

Plasma glucose is the direct measure named by the study's primary question: after insulin induces a low normal glycemic state, the endpoint describes how the measured glucose level changes following G-Pen administration. A change-from-baseline measure focuses on movement from each participant's starting value rather than only on a post-dose value. The 30-minute point provides a defined time for the emphasized increase, while the stated 0-30 minute timeframe indicates the endpoint's broader observation window.

General statistical context: a mean summarizes the average change, while a standard deviation describes how spread out individual changes are around that average. Neither statistic is reported numerically in the registry record. The record also does not provide a confidence interval, a test statistic, or a p-value for the primary endpoint. Consequently, the endpoint definition can be explained, but its observed magnitude and precision cannot be assessed from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous measure: change in plasma glucose, expressed in mg/dL. The registry identifies the summary measure as a mean and the dispersion measure as a standard deviation. These choices describe different features of the data. The mean represents the average change in the analyzed group, whereas the standard deviation represents the spread of individual changes around that average. The registry record names these statistics but does not report their observed values.

What does a change from baseline represent?

A change score describes the difference between a participant's measurement at a starting point and a later measurement. In general, this can make the endpoint directly reflect movement after treatment, rather than relying on the later measurement alone. Here, the endpoint description emphasizes the increase from baseline to 30 minutes post-dosing and gives the timeframe as 0-30 minutes. The record does not specify the detailed measurement schedule within that window or how baseline was operationally defined beyond the endpoint description.

How should the mean and standard deviation be read?

General explanation: a mean is sensitive to the size of all values and can summarize the average response, but it does not show whether individual responses were similar or widely dispersed. The standard deviation gives a measure of that dispersion; it is not itself a measure of uncertainty in the estimated mean. A confidence interval is commonly used to express uncertainty in an estimate. No confidence interval is reported for the primary endpoint in the registry record, so precision cannot be judged from the endpoint summary named there.

The analysis population is described as all enrolled subjects. This is a population description in the endpoint record, not a report of how many participants contributed usable measurements. The number analyzed, completeness of endpoint measurements, and handling of missing measurements are not reported in the registry record. Without those details, it is not possible to assess whether the analysis followed the stated population definition in practice.

What does the design imply for comparisons?

General explanation: random allocation can help balance measured and unmeasured characteristics between treatment groups, while masking can reduce some sources of measurement or care-related bias. This study is listed as non-randomized and unmasked. Its sequential model and lack of a described control arm mean that a between-dose contrast, even if results were available, would not have the same interpretation as a randomized controlled comparison. The record does not describe the assignment procedure, the order of enrollment by dose, or an adjustment strategy.

The registry lists the primary outcome and four secondary outcome topics: time for plasma glucose to increase by at least 25 mg/dL, plasma glucagon area under the curve, plasma glucagon Cmax, and plasma glucagon Tmax. Multiple outcomes can raise questions about how inferential findings are selected and how the chance of false-positive findings is managed. The registry record does not report a multiplicity procedure or explain how confirmatory and exploratory analyses were distinguished.

How should planning estimates be interpreted?

General explanation: a sample-size calculation estimates the number of participants needed under stated assumptions to detect a specified effect with a chosen statistical power and significance level. It is a planning exercise, not evidence that an observed result had that power. The planning illustration associated with this study uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it considers effects expressed as fractions of the observed effect. Such illustrations should be read as hypothetical planning scenarios rather than as the trial's original design justification. The registry record does not report the trial's own sample-size justification.

The study summary gives an enrollment of 31, but the record does not provide numerical primary-outcome results or the underlying estimates needed to evaluate the planning scenarios. In general, a planning calculation based on an observed effect is conditional on that effect estimate and its assumptions; it does not establish that the original study was adequately powered, nor does it substitute for an uncertainty interval around the observed endpoint.

10. Confidence Intervals for Each Arm

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

R code and output

arm <- c("Subjects 2 to <6 Years of Age", "Subjects 6 to <12 Years of Age", "Subjects 12 to <18 Years of Age")
n   <- c(7, 13, 11)
m   <- c(81.4, 84.2, 54)
sp  <- c(18.3, 25.3, 27.3)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Subjects 2 to <6 Years of Age  7  81.400  18.300  64.475  98.325
CARM  Subjects 6 to <12 Years of Age  13  84.200  25.300  68.911  99.489
CARM  Subjects 12 to <18 Years of Age  11  54.000  27.300  35.660  72.340

11. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary endpoint and secondary outcome measures, including a glucose-threshold timing measure and several plasma glucagon measures. Considering multiple outcomes can create a multiplicity issue: when several statistical tests are performed, the chance of at least one apparently positive result can increase if no adjustment or prespecified testing strategy is used. General statistical practice may address this through an adjustment, a hierarchy of tests, or a distinction between confirmatory and exploratory outcomes. The registry record does not report whether any such approach was planned or used.

The record states that the primary endpoint population is all enrolled subjects, but it does not report the number included in the endpoint analysis or how missing measurements were handled. It does not describe reasons for missing data, exclusions, imputation, or sensitivity analyses. These omissions matter because incomplete follow-up or exclusions can affect both the estimated mean change and how representative it is of the enrolled population.

The record lists one analysis, but does not describe its statistical procedure, covariates, model assumptions, or treatment of repeated measurements. It does not report an analysis population beyond the endpoint's stated population, nor does it identify a per-protocol or other analysis set. The registry record also does not report interim analyses. These details should not be inferred from the study's phase, design labels, or endpoint definition.

12. 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 2% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious and other adverse-event figures separately for three age groups. For subjects 2 to <6 years of age, the serious-event count affected is 0 among 7 at risk, and the other adverse-event count affected is 5 among 7 at risk. For subjects 6 to <12 years of age, the corresponding figures are 0 among 13 for serious events and 12 among 13 for other events. For subjects 12 to <18 years of age, they are 0 among 11 for serious events and 8 among 11 for other events. Deaths are listed as 0 in each group.

These are descriptive counts reported by age group. The record does not list serious-event terms, and it does not provide further descriptions or severity details for the other adverse events. The figures should not be interpreted as a comparison with an untreated group: no such control group is described, and allocation was non-randomized. The registry record also does not give additional context about event timing, duration, or attribution. These safety counts are distinct from the unreported primary glucose-response results.

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

The registry record establishes that the study evaluated glucose change after G-Pen administration in pediatric patients with type 1 diabetes following insulin-induced low normal glycemia. It describes the primary endpoint, the dose arms, and safety counts by age group. It does not report the numerical primary-endpoint result, the standard deviation, or an uncertainty interval. As a result, the magnitude and precision of the glucose change cannot be determined from the posted results in this record.

The design labels are also important to interpretation. This was non-randomized, unmasked, and sequential, with no control arm described. The record therefore does not support treating the dose arms as randomized groups or using any hypothetical difference between them as an unconfounded dose effect. It also does not establish a comparison with no treatment or another intervention.

General statistical context: an observed change over time can describe what happened within a study group, but without a control condition it cannot by itself separate the intervention's contribution from other influences. That distinction is especially relevant when the endpoint is measured after a deliberately induced glycemic state. The record does not report enough outcome detail to evaluate the size of the change, its variability, or how it differed across doses.

The listed safety counts describe reported events in the age groups, including zero serious events affected and zero deaths listed in each. They do not establish that no unreported or unrecorded events occurred, and they do not provide a comparative safety estimate. The appropriate reading is therefore limited to what the registry records: a study design and endpoint definition, plus descriptive adverse-event counts, without numerical primary efficacy results or a controlled comparison.

14. Why This Trial Matters Statistically

This trial raises several useful statistical issues for clinical researchers. First, the endpoint is a continuous change measure with a named summary, mean, and dispersion statistic, standard deviation. Those measures answer different questions: the mean describes average change, while the standard deviation describes variation among individual changes. Because the registry record does not report their values, it illustrates why an endpoint definition alone is not enough to assess the size or precision of a finding.

Second, the design is non-randomized, unmasked, and sequential. Such features affect how dose-group comparisons should be interpreted. A numerical contrast between arms would not automatically have the causal meaning of a randomized comparison, particularly when the record does not describe the assignment process or a control condition.

Third, the study includes multiple outcome measures, but the registry record does not describe a multiplicity strategy, missing-data handling, or the statistical model. These omissions make it difficult to reconstruct how the analysis was conducted or how strongly any reported result would support a confirmatory claim. The record also makes clear why planning illustrations should remain distinct from observed evidence: a sample-size calculation is conditional on assumptions and is not observed power.

The study is therefore useful as an example of separating what a registry record establishes about design from what it establishes about outcomes. Here, the design and endpoint are described, while numerical primary results are not reported.

15. Limitations

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

The main limitation for statistical interpretation is that the registry record does not report a numerical result for the primary endpoint. The mean change, standard deviation, confidence interval, and inferential test are not reported in the record. Without them, neither the magnitude nor the precision of the primary glucose response can be evaluated.

The study is non-randomized and unmasked, and no control arm is described. The record does not explain how participants were assigned to the two dose arms or provide information that would support a controlled estimate of a dose effect. The sequential design label is reported, but the operational sequence and its implications for analysis are not described.

The endpoint population is identified as all enrolled subjects, but the number contributing measurements and the handling of incomplete data are not reported. The record does not provide participant flow, reasons for missingness or exclusion, or sensitivity analyses. The statistical model, multiplicity approach, and interim-analysis procedures are also not reported in the registry record.

Safety reporting is limited to counts by age group. Serious-event terms are not listed, and further descriptions of other adverse events are not reported. The record also does not provide a control-group safety comparison. These limits mean that the posted information supports a description of the study and its recorded counts, but not a complete appraisal of outcome precision, comparative effects, or detailed safety patterns.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Glucose Response of G-Pen (Glucagon Injection) in Pediatric T1D Patients — NCT03091673.
• Registry record last updated 2018-12-11; status last verified 2018-11.
• Results first posted 2018-11-16.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT03091673 is a completed phase 3, non-randomized, unmasked, sequential study of G-Pen glucagon injection in pediatric patients with type 1 diabetes. The registry lists enrollment of 31 and describes single subcutaneous doses of 0.5 mg and 1.0 mg after insulin was used to induce a low normal glycemic state.

The primary endpoint is mean change in plasma glucose over 0-30 minutes, emphasizing the increase from baseline to 30 minutes. The registry record does not report numerical results for this endpoint. It lists serious and other adverse-event counts by age group, with 0 serious events affected and 0 deaths listed in each group. The record does not describe a control arm, the statistical analysis in detail, or the handling of missing data.