G-Pen™ for Hypoglycemia Rescue in T1D Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for G-Pen™ for Hypoglycemia Rescue in T1D Patients (NCT02423980), a na phase 2 study. The primary outcome is Number of Subjects With Plasma Glucose > 70 mg/dL at 30 Minutes Post-treatment.

2. Clinical Question

The study addressed a short-term physiological question in a controlled research setting: whether plasma glucose crossed a specified threshold after glucagon was administered for induced hypoglycemia. It also listed time to plasma glucose > 70 mg/dL and time to resolution of induced hypoglycemia symptoms as secondary outcomes. These are distinct questions: one concerns the proportion meeting a threshold by a fixed time, while the secondary outcomes concern how long the measured glucose or symptoms took to reach a specified state.

The registry describes an exploratory pilot, not a randomized comparison. Its stated design therefore does not support interpreting the listed doses as treatment and control groups. The available record also does not provide the primary response count, individual observations, or secondary-outcome results. Accordingly, it identifies what the investigators intended to measure, but it does not allow readers to quantify the observed response or assess its precision.

3. Trial Design

This was a Phase 2, open-label, single-group, exploratory pilot study sponsored by Xeris Pharmaceuticals. The registry record lists enrollment of 7 and a completed status. The study was conducted in adults with T1D, with induced hypoglycemia as the clinical condition under study. Its stated setting involved two daytime clinical research center visits, 7-14 days apart. The brief summary says participants would receive a single injection of G-Pen™ at each visit.

The intervention is listed as glucagon. The dose description says “1 mg G-Pen™ (glucagon injection) first, followed by 0.5 mg.” This wording indicates an order but does not fully explain how dose assignment or the relationship between the two visits was handled. The registry record does not report a randomized allocation method, and the allocation entry is NA. It also identifies the model as single group and masking as none. Thus, the listed dose descriptions should not be treated as evidence of randomized, concurrent treatment arms or a controlled dose comparison.

The primary endpoint was the number of subjects with plasma glucose > 70 mg/dL at 30 minutes after treatment. Glucose was measured every 5 minutes for 90 minutes following treatment, according to the endpoint description. The record also lists two secondary outcomes: time to plasma glucose > 70 mg/dL and time to resolution of induced hypoglycemia symptoms. It reports three outcome measures but does not give results for these outcomes.

The registry lists a study start of 2015-04 and primary completion of 2015-05. Its status is completed. A detailed protocol, participant flow, eligibility criteria beyond the adult T1D population, or the full rationale for the dose sequence is not reported in the registry record. The listed enrollment is small, and the record does not describe a control group. These design features constrain the questions that can be answered from the posted information: the record can describe the planned measurements and safety counts, but it does not provide a reported primary efficacy estimate or a controlled estimate of a dose effect.

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: One subject was given the 1 mg dose of glucagon at both treatment visits, so only 6 subjects received the 0.5 mg dose.

Overall Study

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

Population: All enrolled subjects

6. Primary Endpoint

The registry lists the primary outcome as Number of Subjects With Plasma Glucose > 70 mg/dL at 30 Minutes Post-treatment, measured over 0-90 minutes.

The primary endpoint counts subjects whose plasma glucose was greater than 70 mg/dL at 30 minutes after treatment. In the registry wording, an increase to plasma glucose > 70 mg/dL within 30 minutes is considered a positive response. Glucose was measured every 5 minutes for 90 minutes following treatment, and the outcome population is described as all treated subjects.

This threshold-based outcome converts repeated glucose measurements into a binary response: each treated subject either met the stated criterion within the specified interval or did not. The threshold and time limit make the endpoint clinically interpretable as a short-term physiological milestone, while repeated measurements allow assessment of when that milestone is reached. The secondary outcomes extend the timing question to time to glucose above the threshold and time to resolution of induced hypoglycemia symptoms.

General statistical context: a binary endpoint can be reported as a count of responders, with the number assessed needed to understand its denominator. A confidence interval, when reported, would describe the statistical uncertainty around an estimated response rate; it would not correct for limitations in study design or make a small uncontrolled study comparable to a randomized trial.

The registry record does not report the number of positive responses or a denominator for the primary endpoint result. It therefore does not permit a calculation or interpretation of the observed response rate, nor does it show how precisely that response was estimated. The definition is available; the primary result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary endpoint count?

The primary endpoint is a binary outcome: it counts subjects whose plasma glucose was above the stated threshold within the specified period after treatment. For this trial, the record defines a positive response as plasma glucose > 70 mg/dL within 30 minutes. It describes glucose measurement every 5 minutes for 90 minutes after treatment. The endpoint title refers to the 30-minute result, while the measurement schedule and outcome description include follow-up over 90 minutes.

General statistical context: binary endpoints are often presented as the number meeting a criterion and the number assessed. A proportion summarizes the share meeting that criterion, and an interval estimate can communicate uncertainty around that proportion. Neither the response count nor an interval estimate is reported in the registry record. The endpoint definition alone cannot show how many participants met the criterion.

What does the design permit?

The trial is listed as single group, with allocation recorded as NA and masking as none. It is described as open-label and exploratory. The registry record does not describe a randomized control group. The adverse-event entries use separate dose labels, but the record does not say these are randomized comparative arms. The wording about 1 mg first and 0.5 mg afterward, together with two visits and one injection at each visit, does not fully specify how the doses map onto participants and visits.

General statistical context: randomization can help balance known and unknown participant characteristics across comparison groups. Without a suitable concurrent control and a design supporting comparison, differences between groups can reflect factors other than the dose. The listed adverse-event counts should therefore be read descriptively rather than as a causal comparison. The registry record does not report an adjusted or unadjusted comparative analysis.

How should repeated measurements be understood?

The described schedule measures plasma glucose every 5 minutes for 90 minutes following treatment. Repeated measurements can capture changes over time and identify when a threshold is crossed. The primary endpoint reduces this trajectory to whether the threshold was reached within 30 minutes. The secondary outcome “Time to Plasma Glucose > 70 mg/dL” focuses more directly on timing, while “Time to Resolution of Induced Hypoglycemia Symptoms” concerns symptom resolution.

General statistical context: time-to-event analyses typically account for both the timing of an event and the possibility that the event was not observed before follow-up ended. The registry record does not report the event-time results, analytic method, censoring rules, or participant-level data for these secondary outcomes. It is not possible to determine from the record how such details were handled.

What is and is not reported about the analysis?

The record lists three outcome measures and zero analyses. It does not report a statistical analysis plan, tests, model specifications, confidence intervals, or missing-data methods. It also does not report whether any interim analyses were conducted. These details are not reported in the registry record and should not be inferred from the study’s Phase 2 designation or completed status.

General statistical context: a prespecified analysis plan can clarify which outcomes and methods were intended before results were known. The registry information available for this study does not supply that detail. It also does not provide enough outcome data to independently reconstruct the primary response estimate. Consequently, no inferential conclusion can be drawn from a test statistic or uncertainty interval because neither is posted for the primary endpoint.

What does the planning illustration mean?

The registry’s planning assumptions describe an illustration based on an observed effect, not the trial’s own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event outcomes, the assumptions specify total events using the Schoenfeld method; for other outcomes, they specify participants per arm.

General statistical context: such calculations explore how a hypothetical future study’s size depends on assumptions about the effect, design, and error rates. They are planning illustrations, not observed power and not evidence that the original pilot was designed to achieve a particular power. No numerical sample-size estimates are included in the registry entries, and the record does not report the assumptions or justification used for the trial’s enrollment. The illustration should not be read as the trial’s protocol or as a substitute for a reported outcome analysis.

Overall, the statistical methods that can be described are limited to the endpoint definition, measurement schedule, design labels, and planning assumptions. The analysis methods actually used for primary or secondary outcomes are not reported in the registry record. Any further detail about tests, models, adjustment, multiplicity handling, or treatment of missing observations would be speculation.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Glucagon 1 mg", "Glucagon 0.5 mg")
n      <- c(7, 6)
events <- c(7, 6)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Glucagon 1 mg  7  7  100.0  59.0  100.0  64.6  100.0  63.1  99.7
ARM  Glucagon 0.5 mg  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists three outcome measures: the primary count of subjects with plasma glucose > 70 mg/dL at 30 minutes, time to plasma glucose > 70 mg/dL, and time to resolution of induced hypoglycemia symptoms. It does not report how these outcomes were prioritized analytically beyond identifying the first as primary. A multiplicity adjustment or strategy for interpreting multiple outcomes is not reported in the registry record.

General statistical context: when several outcomes or statistical tests are considered, the chance of at least one apparently notable result can increase unless the analysis plan accounts for the family of tests. The appropriate approach depends on the study’s aims and prespecified analysis plan. No such plan or adjustment method is described in the registry record, so it is not possible to say whether multiplicity was addressed.

The primary outcome population is described as all treated subjects, but the registry does not report the number with evaluable primary outcome data or how missing measurements were handled. It also does not report missing-data methods for the secondary outcomes. The adverse-event denominators are listed separately by dose label, but they do not establish the analysis population for the primary endpoint.

General statistical context: missing outcome data can affect an estimate when the availability of measurements is related to participants’ responses or other characteristics. Reporting the number assessed and the reasons data are missing helps readers judge this possibility. Those details are not reported in the registry record. The analysis population definitions beyond “All treated subjects” for the primary measure, and any handling of deviations from the intended treatment sequence, are also not reported.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: vasovagal syncope (14.3%).

The registry lists serious and other adverse-event counts under two dose labels. For Glucagon 1 mg, the serious adverse-event count is 1 among 7 at risk, and the other adverse-event count is 3 among 7 at risk. For Glucagon 0.5 mg, the serious adverse-event count is 0 among 6 at risk, and the other adverse-event count is 2 among 6 at risk. These entries are descriptive counts of participants with events as presented in the record.

Vasovagal syncope is listed among the top serious event terms, with 14.3% reported. The registry record does not provide further detail on the event’s timing, severity beyond its serious-event classification, outcome, or relationship to treatment. Death counts are listed as null, which is not a reported numeric count and should not be interpreted as a confirmed count of zero.

The denominators differ across the dose labels, and the study is described as single group rather than a randomized control comparison. The entries therefore do not establish a like-for-like safety comparison between doses. General statistical context: adverse-event counts in small groups are descriptive and can be imprecise; they do not by themselves establish causation. The registry record does not report a detailed safety analysis or an explanation of how the two dose groups relate to the two study visits.

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

The registry record establishes that this was a completed, open-label exploratory pilot in adults with T1D and induced hypoglycemia. It describes two daytime clinical research center visits 7-14 days apart and a single injection at each visit. The primary endpoint was whether plasma glucose rose above 70 mg/dL within 30 minutes after treatment, with measurements described every 5 minutes for 90 minutes.

Those details explain the clinical question and measurement strategy, but they do not state the primary result. The number of treated subjects who met the primary criterion is not reported in the registry record. Neither the secondary outcome results nor inferential estimates are reported. Therefore, the posted information does not show the magnitude or precision of any observed glucose response or symptom-resolution time.

The adverse-event entries provide counts by dose label and identify vasovagal syncope as a serious-event term. These counts are not a controlled comparison. The single-group design, lack of randomized allocation, and unclear mapping of dose labels to participants or visits limit any comparative interpretation. A count in one labeled group cannot establish that one dose caused more or fewer events than another.

General statistical context: an outcome definition, a study design, and an observed estimate answer different questions. A definition says what was measured; design affects which comparisons are credible; and an estimate with its uncertainty describes the observed data. The record gives the first, some design details, and limited safety counts, but not the primary efficacy estimate or its uncertainty.

Consequently, the registry material supports a description of what the pilot set out to measure and some reported safety figures. It does not support a conclusion that glucagon did or did not produce a particular response, nor does it establish comparative effectiveness or safety between the listed doses. The absence of a posted primary result is not evidence of no response; it means the result is not reported in the registry record.

14. Why This Trial Matters Statistically

This study illustrates the distinction between an outcome definition and an outcome result. The registry gives a specific threshold, time window, and measurement schedule for its primary endpoint: plasma glucose > 70 mg/dL within 30 minutes, with measurements every 5 minutes over 90 minutes. Yet the number of participants meeting the criterion is not reported. Readers can understand what the endpoint means without being able to estimate the observed response.

It also highlights why design labels matter when interpreting dose-specific counts. The study is listed as a single group with allocation recorded as NA and no masking. Although adverse-event entries are presented under 1 mg and 0.5 mg labels, the record does not describe randomized allocation or a like-for-like control comparison. The figures can be read as descriptive counts, not as evidence of a dose effect.

The small pilot enrollment and incomplete outcome reporting also make uncertainty central. General statistical context: small studies can be useful for exploratory measurement and feasibility questions, but estimates from small groups may be unstable. Reporting counts alongside denominators, analysis populations, and uncertainty intervals helps readers judge precision. The primary outcome’s result and uncertainty are not reported in the registry record.

The planning assumptions further show the difference between a prospective design question and an observed trial result. An illustration based on an observed effect may inform hypothetical future study planning, but it is not the original trial’s sample-size rationale and is not observed power. The record does not report the original sample-size justification or the analyses used. Statistically, the most important reading is therefore disciplined: distinguish the defined question, the design that could address it, and the results actually posted.

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 registry record does not report the primary endpoint count, its denominator, or an uncertainty estimate. It also does not report results for either secondary outcome. The lack of these outcome results prevents quantifying the glucose response or timing of symptom resolution from the posted information.

Enrollment was 7, and the study is described as an exploratory pilot. The record does not provide participant-level observations or a detailed account of evaluable participants. Although the primary population is described as all treated subjects, it is not reported how many had complete measurements or whether any observations were missing.

The design is listed as single group, open-label, and without randomized allocation. The registry does not describe a concurrent control group. The dose wording and two-visit schedule do not fully clarify how the dose labels relate to individual participants or visits. This limits interpretation of the separate adverse-event group counts and prevents treating them as a controlled dose comparison.

Further information about eligibility criteria, protocol procedures, analysis methods, multiplicity, missing-data handling, interim analyses, and the trial’s own sample-size justification is not reported in the registry record. The posted safety information also lacks detail about event timing, outcomes, and attribution. These limitations are specific to the available record; they do not establish what may or may not appear in other study documents.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: G-Pen™ for Hypoglycemia Rescue in T1D Patients — NCT02423980.
• Registry record last updated 2017-07-07; status last verified 2017-06.
• Results first posted 2017-04-24.
• 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

NCT02423980 is a completed Phase 2, open-label, exploratory pilot sponsored by Xeris Pharmaceuticals. It studied glucagon injection for induced hypoglycemia rescue in adults with T1D. Enrollment was 7; the study start is listed as 2015-04 and primary completion as 2015-05.

The primary endpoint was the number of treated subjects with plasma glucose > 70 mg/dL within 30 minutes after treatment. Glucose was described as measured every 5 minutes for 90 minutes. The primary outcome count and secondary outcome results are not reported in the registry record. Safety counts are listed for dose-labeled groups, with 1 serious and 3 other adverse events among 7 at risk for Glucagon 1 mg, and 0 serious and 2 other adverse events among 6 at risk for Glucagon 0.5 mg. The record does not establish a randomized comparison between these labels.