This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study of Single and Repeated Doses of Glucagon Administered to Participants With Diabetes (NCT02806960), a randomized phase 1 study. The primary outcome is Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to T (AUC[0-tlast]) of Baseline Adjusted Glucagon.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02806960 |
| Phase | Phase 1 |
| Condition | Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2 |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Single |
| Enrollment | 12 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Eli Lilly and Company |
| Results posted | Yes |
2. Clinical Question
Population
Adults with type 1 or type 2 diabetes were eligible. The record lists an enrollment of 12, but reports zero participants analyzed for the primary outcome.
Intervention
Intranasal glucagon was studied in four regimens: one 3 mg dose; a second 3 mg dose in the same nostril 15 minutes later; a second 3 mg dose in the opposite nostril 15 minutes later; or a second 3 mg dose immediately in the opposite nostril.
Comparator
The four regimens are the relevant comparisons. The study was designed as a randomized, four-period crossover, but the record does not report treatment-sequence details or outcome estimates comparing regimens.
Primary question
The primary endpoint was the area under the concentration-versus-time curve for baseline-adjusted glucagon, from time zero to the last recorded time point. It was intended to characterize pharmacokinetics after each treatment. The record states that no participants were analyzed because of a limited number of samples and delivery of a potential sub-target dosing dose.
The study also concerned pharmacodynamics and safety, as reflected in its official title. Its summary describes dosing after an overnight fast and a low-carbohydrate breakfast. The registry record does not report primary-outcome results or a statistical comparison among the four regimens. Consequently, the clinical question can be described from the planned design, but cannot be answered using a primary pharmacokinetic estimate from this record.
3. Trial Design
The record identifies a phase 1, randomized, single-masked, crossover study at a single center. It planned four treatment periods involving intranasal glucagon in adults with type 1 or type 2 diabetes. Enrollment was 12. The record lists the study status as terminated; it does not report the reason for termination.
The four regimens varied in whether a second 3 mg dose was given, when it was given, and which nostril received it. Treatment 1 consisted of one 3 mg dose. Treatment 2 added a second 3 mg dose in the same nostril after 15 minutes. Treatment 3 added a second 3 mg dose in the opposite nostril after 15 minutes. Treatment 4 gave the second 3 mg dose immediately in the opposite nostril. These are the protocol descriptions; the record does not establish which regimens individual participants actually received.
In a crossover design, participants may serve as their own comparison when they receive multiple treatments in separate periods. This can reduce the influence of stable differences between participants, but interpretation depends on the conduct of the periods and the availability of measurements. The registry record does not report the randomized sequences, period-specific completion, washout details, or how these matters were handled in analysis.
The study summary describes administration after an 8-hour overnight fast and 4 hours after the start of a low-carbohydrate breakfast. It says the study was expected to last about 50 days for each participant. These are descriptions of the planned study, not evidence that every participant completed that schedule. The record gives a start date of 2014-06 and a primary completion date of 2014-06, and records the study as terminated.
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.
Period 1
| Stage | Sequence 1 (Treatment 1, 2, 3 and 4) | Sequence 2 (Treatment 2, 3, 4 and 1) | Sequence 3 (Treatment 3, 4, 1 and 2) | Sequence 4 (Treatment 4, 1, 2 and 3) |
|---|---|---|---|---|
| STARTED | 3 | 3 | 3 | 3 |
| COMPLETED | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 3 | 3 | 3 | 3 |
Reasons for not completing this period:
| Reason | Sequence 1 (Treatment 1, 2, 3 and 4) | Sequence 2 (Treatment 2, 3, 4 and 1) | Sequence 3 (Treatment 3, 4, 1 and 2) | Sequence 4 (Treatment 4, 1, 2 and 3) |
|---|---|---|---|---|
| Study Terminated (withdrawn by sponsor) | 3 | 3 | 3 | 3 |
Period 2
| Stage | Sequence 1 (Treatment 1, 2, 3 and 4) | Sequence 2 (Treatment 2, 3, 4 and 1) | Sequence 3 (Treatment 3, 4, 1 and 2) | Sequence 4 (Treatment 4, 1, 2 and 3) |
|---|---|---|---|---|
| STARTED | 0 | 0 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Period 3
| Stage | Sequence 1 (Treatment 1, 2, 3 and 4) | Sequence 2 (Treatment 2, 3, 4 and 1) | Sequence 3 (Treatment 3, 4, 1 and 2) | Sequence 4 (Treatment 4, 1, 2 and 3) |
|---|---|---|---|---|
| STARTED | 0 | 0 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Period 4
| Stage | Sequence 1 (Treatment 1, 2, 3 and 4) | Sequence 2 (Treatment 2, 3, 4 and 1) | Sequence 3 (Treatment 3, 4, 1 and 2) | Sequence 4 (Treatment 4, 1, 2 and 3) |
|---|---|---|---|---|
| STARTED | 0 | 0 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Zero participants analyzed due to the limited number of samples and the delivery of a potential sub-target dosing dose.
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 participants.
| Characteristic | Unit | All Participants |
|---|---|---|
| Participants analysed | 12 | |
| Age, Continuous | years | 41 (SD 13) |
| Sex: Female, Male: Female | Participants | 5 |
| Sex: Female, Male: Male | Participants | 7 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 2 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 9 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 1 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 11 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 1 |
| Region of Enrollment: Canada | Participants | 12 |
6. Primary Endpoint
The registry lists the primary outcome as Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to T (AUC[0-tlast]) of Baseline Adjusted Glucagon, measured over Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.33, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2, 2.5, and 3 hours post dose for each treatment.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was the area under the concentration-versus-time curve from time zero to the last recorded time point for baseline-adjusted glucagon. An area-under-the-curve measure combines concentration measurements across a defined interval into an overall measure of exposure over time. Baseline adjustment is intended to express post-dose concentrations relative to a baseline level rather than treating the baseline concentration as part of the post-dose response.
Pharmacokinetic measures are used to describe how drug concentrations change after administration. In this study, comparing this endpoint across dosing regimens could have characterized differences in glucagon exposure associated with the dose timing and nostril used. That is a general explanation of the endpoint’s role; the registry record contains no reported comparison or estimate to establish whether the regimens differed.
The listed measurement schedule covers Day 1 from -0.5 through 3 hours post dose, with several specified collection times. The registry record says zero participants were analyzed for this endpoint because of the limited number of samples and delivery of a potential sub-target dosing dose. It therefore reports no calculated area-under-the-curve values, variability estimates, confidence intervals, or treatment contrasts. The planned endpoint is identifiable, but its observed result cannot be interpreted from the record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central result in this record is an absence of primary pharmacokinetic analyses, rather than a numerical finding about glucagon exposure. The primary outcome description explicitly states that zero participants were analyzed. It attributes this to a limited number of samples and delivery of a potential sub-target dosing dose. No treatment-specific endpoint values, estimated differences, confidence intervals, or p-values are reported.
That distinction matters. A study can have a defined primary endpoint and a randomized design without producing an interpretable estimate for that endpoint. Randomization describes how treatment assignment was intended to occur; it does not itself create outcome data or establish a treatment effect. With no participants analyzed for the primary endpoint, this record cannot quantify exposure under any of the four regimens or compare the regimens statistically.
The total enrollment is 12, while the adverse-event group listings show 3 participants at risk in each treatment group. These entries describe different aspects of the record and should not be used to reconstruct the primary analysis population. The record does not report why those group counts differ from total enrollment, nor does it provide a participant flow accounting for treatment periods, samples, or exclusions.
The study was terminated, but the reason is not reported in the registry record. The endpoint description gives a reason for not analyzing the primary outcome, but it does not state that this was the reason for termination. Those statements should not be conflated.
The design would have allowed planned comparisons among dosing regimens, including differences in timing and nostril. However, the registry record reports no outcome estimates for those comparisons. The number of outcome measures is 7, while the number of analyses is 0 in the record. Thus, the listed endpoint and the presence of other outcomes do not imply that results were available or that a treatment ranking can be inferred.
Any sample-size calculation based on an observed effect would need a reported effect estimate to serve as its input. No primary effect estimate is reported. Any planning illustration should be understood as a hypothetical design aid, not as observed power or evidence about the result. Overall, the record describes the intended question and a reason the primary endpoint was not analyzed, but it does not provide evidence that permits a quantitative answer to that question.
9. Statistical Methods Explained
Randomization is a method for assigning treatments according to a chance-based process. In general, it helps limit systematic differences between treatment groups at baseline. The record identifies the study as randomized, but does not report the allocation sequence, the method used to generate it, or how allocation was concealed. It therefore supports describing the design as randomized, but not a more detailed account of the randomization procedure.
What does crossover mean?
In a crossover study, treatment periods allow comparisons within participants, rather than relying only on comparisons between separate groups of people. This can be useful when outcomes vary substantially from one person to another, because stable characteristics are shared across that person’s treatment periods. This is a general feature of crossover designs, not a claim about the quality of this study’s execution.
Period order and effects can matter in crossover studies. For example, a preceding treatment or the passage of time could influence a later measurement. Study protocols may address such issues through treatment sequencing, washout periods, or statistical modeling. The registry record does not report the sequence details, washout arrangements, or models used, so it is not possible to assess how these considerations were handled.
What does the primary measure represent?
The primary measure, area under the concentration-versus-time curve from time zero to the last time point, is a pharmacokinetic summary. Conceptually, it reflects the accumulated concentration across the measurement interval. Concentrations measured at scheduled times contribute to estimating the curve and its area. A limited number of usable samples can undermine the ability to characterize that curve, which is consistent with the reason stated for not analyzing participants. The record does not report how many samples were available or the specific shortfall.
Baseline adjustment generally accounts for the pre-dose concentration when describing changes after administration. The endpoint is explicitly described as baseline-adjusted glucagon, but the registry record does not provide the calculation method, transformation, or analysis model. It also does not report an endpoint unit, parameter estimate, or dispersion measure. These omissions preclude reconstructing the analysis from the registry record.
What can a confidence interval tell a reader?
In general, a confidence interval expresses the uncertainty around an estimated effect under a statistical method and its assumptions. A narrow interval indicates greater precision than a wide interval, while an interval spanning values compatible with different conclusions may leave the result uncertain. No confidence interval is reported for the primary endpoint because no participants were analyzed for it. Therefore, precision cannot be assessed for a primary treatment comparison.
Why might over-dispersion matter?
For count outcomes, over-dispersion means that observed variation exceeds what a simple count model would expect. In general, ignoring it can make uncertainty appear smaller than it is. That issue is not a reported finding in this study. The registry entries do not identify a count-outcome model, an over-dispersion assessment, or statistical analyses of count outcomes. It would be inappropriate to infer that such a method was used.
What do sample-size illustrations mean?
Sample-size planning asks how many participants or events a future study might need under stated assumptions about the effect to detect, the significance level, allocation, and statistical model. Such figures are design illustrations, not results from participants and not “observed power.” The planning description for this record refers to a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it also describes effects as fractions of an observed effect. It distinguishes participants per arm for non-time-to-event settings from a total event count for time-to-event settings.
These assumptions do not establish that the original trial used the same planning approach. The study’s own sample-size justification is not reported in the registry record. In addition, the record supplies no analyzed primary effect estimate from which to interpret an effect-based planning illustration. A hypothetical calculation cannot replace an absent outcome estimate or show that the completed study had a particular probability of detecting an effect.
Finally, a reported p-value would address compatibility of data with a specified statistical model and null hypothesis, not the size or practical importance of an effect by itself. No primary p-value is reported. The registry record also does not describe a complete statistical analysis plan, so unreported model choices and testing procedures should not be inferred.
10. Multiplicity, Missing Data and Analysis Populations
The record lists 7 outcome measures and 0 analyses. It does not report a multiplicity strategy, such as a hierarchy of endpoints, an adjustment across tests, or a prespecified approach for interpreting several comparisons. Because the four treatment regimens create multiple potential contrasts, multiplicity could matter in a completed inferential analysis. That is a general statistical consideration; the registry record does not say which contrasts were planned for formal testing.
Missingness is directly relevant to the primary outcome: zero participants were analyzed, with the record citing a limited number of samples and delivery of a potential sub-target dosing dose. It does not report how many participants had missing samples, whether samples were unusable or never collected, or whether any alternative endpoint calculation was attempted. The handling of missing observations is not reported in the registry record.
The registry record does not define analysis populations, such as an intention-to-treat population or a pharmacokinetic population, and does not explain eligibility for any such population. Enrollment of 12 should not be treated as the number analyzed for the primary endpoint; the endpoint description explicitly states that zero were analyzed. Nor can the group-level safety listings establish the size of the primary analysis population. A participant flow by treatment period and outcome availability is not reported.
Without the analysis population, missing-data approach, and multiplicity plan, a reader cannot reconstruct the intended inferential framework. Most importantly, no primary endpoint estimate is available to interpret regardless of those methodological details.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Treatment 1 | 0 | 3 | 0.0% |
| Treatment 2 | 0 | 3 | 0.0% |
| Treatment 3 | 0 | 3 | 0.0% |
| Treatment 4 | 0 | 3 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Treatment 1 | 2 of 3 |
| Treatment 2 | 2 of 3 |
| Treatment 3 | 3 of 3 |
| Treatment 4 | 3 of 3 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Treatment 1 | Treatment 2 | Treatment 3 | Treatment 4 |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | 1 of 3 | 0 of 3 | 3 of 3 | 2 of 3 |
| Headache | Nervous system disorders | 1 of 3 | 1 of 3 | 2 of 3 | 2 of 3 |
| Lacrimation increased | Eye disorders | 1 of 3 | 0 of 3 | 1 of 3 | 3 of 3 |
| Parosmia | Nervous system disorders | 1 of 3 | 1 of 3 | 0 of 3 | 0 of 3 |
| Sinus headache | Nervous system disorders | 0 of 3 | 0 of 3 | 2 of 3 | 0 of 3 |
| Eye pain | Eye disorders | 0 of 3 | 0 of 3 | 1 of 3 | 0 of 3 |
| Abdominal pain | Gastrointestinal disorders | 1 of 3 | 0 of 3 | 0 of 3 | 0 of 3 |
| Dry mouth | Gastrointestinal disorders | 1 of 3 | 0 of 3 | 0 of 3 | 0 of 3 |
| Vomiting | Gastrointestinal disorders | 0 of 3 | 0 of 3 | 1 of 3 | 0 of 3 |
| Asthenia | General disorders | 0 of 3 | 0 of 3 | 1 of 3 | 0 of 3 |
The serious adverse-event listings show 0 affected participants among 3 at risk for each of Treatment 1, Treatment 2, Treatment 3, and Treatment 4. These are the figures recorded for the listed treatment groups. The record does not list serious adverse-event terms.
These small group counts require cautious description. A zero count in a group does not establish that the underlying risk is zero; it means no serious adverse events were recorded among the participants listed as at risk in that group. The registry record does not provide a comparative safety analysis, uncertainty intervals, or a basis for determining whether differences between regimens are meaningful.
Other adverse events are listed for 2 of 3 at risk in Treatment 1, 2 of 3 in Treatment 2, 3 of 3 in Treatment 3, and 3 of 3 in Treatment 4. These figures concern non-serious adverse events as grouped in the record and should not be mistaken for serious events. Because this was a crossover study, the group entries should not automatically be treated as four independent sets of unique participants. The record does not explain overlap or provide event-level detail in the listed details. Death figures are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The record establishes that a randomized, single-center, four-period study of single and repeated intranasal glucagon doses was registered, with adults with type 1 or type 2 diabetes as the target population. It identifies a primary pharmacokinetic endpoint and explains why no participants were analyzed for that endpoint. Those details are informative about the intended research question and the limits of the posted results.
The record does not establish the magnitude or direction of any pharmacokinetic difference among the four regimens. It contains no analyzed primary outcome values, treatment contrasts, confidence intervals, or p-values. Therefore, it cannot quantify glucagon exposure, characterize precision, or support a statistical ranking of the regimens. The absence of an estimate is not evidence that the regimens had the same result, and it is not evidence that one regimen differed from another.
The safety counts are descriptive entries for the listed groups. They do not, on their own, establish comparative safety, particularly given the limited number at risk in each listing and the lack of a reported comparative analysis. Nor do they replace the unreported pharmacokinetic outcome.
The study status is terminated, but the reason for termination is not reported in the registry record. The primary endpoint description attributes the lack of analysis to a limited number of samples and a potential sub-target dosing dose; no further explanation is recorded. It is not possible to infer whether other operational or scientific factors contributed to termination.
In practical statistical terms, the registry record supports a description of the design, planned doses, primary measure, and the absence of primary analysis. It does not support a conclusion about treatment effects. Any interpretation beyond those documented features would require results or methodological details that are not reported in the registry record.
13. Why This Trial Matters Statistically
This study is statistically notable because its design and primary question are documented, while the primary endpoint has no analyzed participants. That contrast illustrates why a registered endpoint is not the same as an observed result. A reader needs both a defined outcome and analyzable measurements to estimate treatment differences and their uncertainty.
The crossover design also makes clear why participant counts need careful interpretation. In general, a crossover can make within-person comparisons possible, but the periods, sequences, and measurements must be sufficiently documented to understand the analysis. Here, the record identifies four periods and four dosing regimens, but does not report period-level completion or treatment-sequence information. The planned structure alone cannot establish which comparisons were actually estimable.
The stated reason for the lack of primary analysis points to the importance of data availability and dose delivery for pharmacokinetic inference. When too few measurements are available, or a dose may not meet its target, the intended concentration-time summary may not be calculable or interpretable. The record does not give enough detail to assess the extent of either issue, but it explicitly connects them to the absence of primary analyses.
Finally, the study illustrates a boundary between descriptive safety counts and inferential evidence. The listed counts document recorded events in small risk groups, but do not provide comparative estimates or uncertainty. Statistical interpretation depends not just on the design label, but on usable data, transparent analysis populations, and reported estimates. Those elements are absent for the primary outcome in this record.
14. 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 most important limitation is that zero participants were analyzed for the primary pharmacokinetic endpoint. The registry record attributes this to a limited number of samples and delivery of a potential sub-target dosing dose. With no endpoint estimates, the intended treatment comparisons cannot be quantified or assessed for precision.
The record does not report participant flow through the four periods, numbers completing each treatment, sample availability by period, or the amount of missing data. Although enrollment was 12, that number does not resolve how many participants contributed usable measurements to any particular outcome. The listed at-risk counts for adverse events do not fill this gap.
Several design and analysis details are also not reported in the registry record: treatment sequences, washout arrangements, the statistical model, the analysis population, the approach to missing observations, and the multiplicity strategy. The reason for study termination is not reported. The study’s own sample-size justification is also not reported.
For safety, the serious adverse-event listings show no affected participants in the small groups listed, but no comparative analysis or uncertainty measure is reported. The registry entries do not provide serious-event terms, and death figures are not reported in the registry record. The listed non-serious-event counts are descriptive and do not establish a comparative treatment effect.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of Single and Repeated Doses of Glucagon Administered to Participants With Diabetes — NCT02806960.
- Registry record last updated 2019-12-13; status last verified 2019-11.
- Results first posted 2019-12-13.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry record describes a phase 1, randomized, single-masked, single-center, four-period crossover study of intranasal glucagon in adults with type 1 or type 2 diabetes. Enrollment was 12, and the study status is terminated. The four planned regimens used one 3 mg dose or a second 3 mg dose delivered at different times and in either the same or opposite nostril.
The primary endpoint was baseline-adjusted glucagon area under the concentration-versus-time curve from time zero to the last time point. The record states that zero participants were analyzed because of limited samples and a potential sub-target dosing dose. No primary treatment-effect estimate is reported. Serious adverse events were listed as 0 among 3 at risk in each treatment group; the corresponding non-serious counts were also recorded. The reason for termination, detailed statistical plan, and analysis populations are not reported in the registry record.