A Multiple Ascending Dose Trial Investigating Safety, Tolerability and Pharmacokinetics of NNC0361-0041: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Multiple Ascending Dose Trial Investigating Safety, Tolerability and Pharmacokinetics of NNC0361-0041 (NCT04279613), a randomized phase 1 study. The primary outcome is Adverse Events.

2. Clinical Question

Statistically, this is a safety-focused question rather than an efficacy comparison. The registry reports event counts for each dose group and placebo, as well as separate summaries of participants with serious and other adverse events. These summaries describe what was recorded in the trial; they do not, by themselves, establish whether a treatment caused an event or how the groups would compare under a different study design.

The secondary outcome listed is change in the area under the plasma C-peptide concentration-time curve across the 2-hour test period. The registry record does not report results for that outcome in the information available for this trial. It also does not report a numerical effect estimate or a statistical test comparing an NNC0361-0041 dose with placebo for the primary event-count outcome.

3. Trial Design

This was a randomized, placebo-controlled phase 1 trial with a sequential, multiple-ascending-dose design. The registry describes masking as triple and says that the trial was double-blinded within cohorts. The record does not specify which roles were included in triple masking or provide further detail about how the masking was implemented.

The NNC0361-0041 groups received subcutaneous injections once weekly on site. The dose levels were 1 mg, 5 mg, 12.5 mg and 25 mg, assigned in cohorts 1 through 4, respectively. Placebo was also administered subcutaneously once weekly on site. The study's sequential structure means the dose groups were organized as cohorts rather than as a single parallel comparison across all dose levels. Further operational details about cohort progression are not reported in the registry record.

The registry lists enrollment of 47, a start date of 2020-11-23, primary completion on 2023-08-31, and a completed status. The posted arm-level primary outcome counts are 230 adverse events among 9 participants in the 1 mg group, 217 among 9 participants in the 5 mg group, 215 among 9 participants in the 12.5 mg group, 169 among 8 participants in the 25 mg group, and 240 among 12 participants receiving placebo. These are event counts, not counts of participants experiencing at least one event.

The listed primary outcome timeframe is 16 weeks. Its description defines the on-treatment period as extending from first treatment through visit 15, or 5 weeks after the last treatment for participants who did not receive all injections. The registry record does not report further details of the randomization procedure, the sequence of cohort decisions, or the statistical plan for comparing groups.

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.

Cohort 1: Dose Level 1 mg

Reasons for not completing this period:

Cohort 2: Dose Level 5 mg

Reasons for not completing this period:

Cohort 3: Dose Level 12.5 mg

Reasons for not completing this period:

Cohort 4: Dose Level 25 mg

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The safety analysis set contained all participants who recieved at least one dose of study treatment.

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 Adverse Events, measured over 16 Weeks.

The primary endpoint is the number of adverse events recorded during the on-treatment period. The registry identifies the timeframe as 16 weeks and defines the observation period as from first treatment through visit 15, or 5 weeks after the last treatment for participants not receiving all injections. The safety analysis set includes participants who received at least one dose of study treatment.

An event count captures the total number of recorded events in a group. It is different from a participant count: one participant may have more than one event, so the number of events does not reveal how many people experienced an event. The registry separately reports participant-level summaries for serious and other adverse events, which answer a different descriptive question.

In general, event counts can help describe the volume of adverse-event reports during a defined period and can be useful in early-phase safety assessment. They need careful interpretation because group counts can reflect both the number of participants observed and the number of events experienced by each participant. Counts alone do not describe event severity, timing, duration, or causal relationship to treatment.

The posted primary counts are 230, 217, 215, 169 and 240 for the 1 mg, 5 mg, 12.5 mg, 25 mg and placebo groups, respectively. The registry record does not report an uncertainty interval, a model-based estimate, or a formal statistical comparison for these counts. Accordingly, the values describe the recorded event totals, without quantifying the precision of a treatment contrast.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does an event count represent?

For the primary outcome, the reported value is the total number of adverse events recorded in each group during the stated on-treatment period. It is not a binary outcome that simply classifies each participant as having or not having an event. A participant can contribute multiple events, so event totals and affected-participant counts answer different questions.

In general, event-count data are often analyzed using statistical methods designed for counts. A simple model may assume that variation in counts follows a particular distribution, but real event data can vary more than that model expects. This is called over-dispersion. It can arise, for example, when events cluster within some participants rather than occurring at a similar rate for everyone. General statistical methods can allow for over-dispersion, but the registry record does not report a model, an over-dispersion assessment, or an adjusted treatment estimate for this endpoint.

What does the trial design imply for comparisons?

The registry describes a randomized, placebo-controlled, sequential trial with multiple ascending doses and double-blinding within cohorts. In general, randomization can reduce systematic differences between assigned groups, while placebo can provide a concurrent reference condition. A sequential cohort design organizes dose administration in stages. These features provide design context, but they do not replace the statistical analysis needed to estimate a treatment contrast or its uncertainty.

The information reported does not specify the randomization procedure, the method used to allocate participants within cohorts, or how any cohort-level decisions were made. The registry does not describe whether dose groups were intended to be compared separately with placebo or whether a trend across dose levels was planned. Such analysis details are not reported in the registry record and should not be inferred from the group summaries.

Why are the reported totals not a comparison estimate?

Each arm has a raw event total and an arm size, but a comparison requires a defined estimand and an analysis method. For count data, the method may need to account for group size, observation time, repeated events within participants, and any distributional features of the counts. Depending on the analysis, results could be expressed in different ways, such as a difference in mean counts or a relative rate. The registry record does not report such a comparison or identify an approach used to estimate one.

In general, a confidence interval for a comparison communicates statistical uncertainty, while a p-value assesses compatibility with a specified null hypothesis under a model. Neither is reported for this primary outcome in the registry record. The group totals therefore cannot be treated as if they were a tested or adjusted comparison. No recalculated comparison is reported for this count-other endpoint, and the registry record does not provide the details needed to assess the precision of a contrast.

How should the participant-level safety summaries be read?

The adverse-event summary separates serious events from other events and reports how many participants were at risk and how many were affected. In general, those summaries use participants, rather than event episodes, as the unit of description. The serious-event summary records one affected participant in the 12.5 mg group and none in the other groups. The other-event summary records affected participants in every group. These summaries complement the primary event totals but do not explain the number of episodes per affected participant.

The terms adrenal insufficiency and dizziness are listed as top serious-event terms, each at 11.1%. The registry information does not provide further detail about the timing, duration, clinical course, or attribution of those terms. The record also reports no deaths in the groups. This is a descriptive accounting of reported safety information, not a statistical test of whether serious events differ across treatments.

What is and is not available for the secondary outcome?

The record lists change in the area under the plasma C-peptide concentration-time curve across the 2-hour test period as a secondary outcome. It reports one secondary outcome as posted, but the registry information for this trial does not include a result for that measure. No estimate, uncertainty interval, or group comparison for C-peptide is available in the record.

In general, a prespecified analysis plan clarifies outcome definitions, comparison methods, handling of repeated measurements, and how uncertainty will be reported. The registry record does not report the statistical analysis plan for this trial. It also does not report whether analyses were adjusted for baseline measurements or other covariates, or whether exploratory analyses were conducted. No specific statistical method should therefore be attributed to the trial beyond what is explicitly described in the record.

The endpoint information includes no spread measure or interval around the arm-level event totals. A point total alone cannot show how variable counts were across participants. Nor can it show how sensitive a group comparison might be to a small number of participants with many events. These are general considerations for interpreting count outcomes; the participant-level count distribution is not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists one secondary outcome: change in the area under the plasma C-peptide concentration-time curve across the 2-hour test period. Although the record identifies a secondary outcome, it does not report its result in the information available for this trial. It also does not report a statistical analysis plan describing how primary and secondary outcomes were to be tested or interpreted.

In general, testing several outcomes or several treatment contrasts creates a multiplicity issue: the chance of at least one apparently unusual result can increase when many tests are considered. Statistical plans may address this by defining a hierarchy, adjusting significance thresholds, or treating some analyses as exploratory. Whether any such approach was planned or used is not reported in the registry record. No multiplicity adjustment should be assumed.

The safety analysis set is described as including all participants who received at least one dose of study treatment. The primary outcome has a defined on-treatment observation period, including a stated alternative endpoint for participants who did not receive all injections. However, the record does not report the number of participants with incomplete follow-up for this outcome, how missing event information was handled, or whether any imputation was used.

In general, missing-data methods depend on why information is missing and on the outcome being analyzed. A complete-case approach, imputation, or a sensitivity analysis would each rely on assumptions that need to be stated. The registry record does not report which approach, if any, was applied. It also does not provide a separate intention-to-treat analysis population or describe how participants who did not receive treatment were handled.

The record reports no posted analysis results for the count endpoint comparison, and values are described as missing or not estimable for a two-arm comparison of this count-other outcome. The reason for this specific non-estimability is not reported in the registry record. Consequently, neither a multiplicity procedure nor a missing-data strategy can be evaluated from the posted information.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: adrenal insufficiency (11.1%), dizziness (11.1%).

The serious adverse-event summary reports participants at risk and participants affected in each group. There were no serious adverse events reported among 9 participants at risk in the 1 mg group, among 9 in the 5 mg group, among 8 in the 25 mg group, or among 12 receiving placebo. In the 12.5 mg group, 1 of 9 participants at risk was reported with a serious adverse event. No deaths were reported in any group.

Adrenal insufficiency and dizziness are listed as the top serious-event terms, each reported at 11.1%. Those terms describe event categories, not separate treatment-effect estimates. The registry record does not provide further details about the event course, timing, relatedness to treatment, or whether a participant could contribute more than one serious-event term.

In general, serious-event counts in a trial of this size are descriptive and can be imprecise. A lack of reported serious events in a group does not establish that the underlying risk is absent, and a reported event does not by itself establish that treatment caused it. The record does not report a formal statistical comparison of serious adverse events across groups, so these figures should be read as observed safety summaries rather than evidence of comparative risk.

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

The posted results describe adverse events observed during the trial's on-treatment period. The primary endpoint is an event total, and the registry reports a separate participant-level summary of serious and other adverse events. Together, these offer descriptive information about recorded events in the dose groups and placebo group.

They do not establish whether NNC0361-0041 caused an event, whether a particular dose changed the underlying event rate, or whether one group had a statistically distinguishable safety profile from another. The record does not report a formal comparison, an uncertainty interval, or a model-based estimate for the primary event counts. The event totals also do not reveal how many participants contributed multiple events or how the events were distributed within each group.

The serious-event summary reports one affected participant in the 12.5 mg group and none in the other groups, with no deaths reported. This is useful as a factual account of the registry's posted safety information, but it is not a precise estimate of uncommon risks. In general, a small number of observed events can leave substantial uncertainty about how often similar events might occur in a larger or different population.

The trial is phase 1 and uses sequential ascending-dose cohorts. Its design and reported arm sizes mean the findings are best interpreted as early clinical safety and tolerability observations. The registry record does not report results for the listed C-peptide secondary outcome, and it does not provide details that would permit evaluation of the planned statistical analyses, missing-data handling, or multiplicity procedures.

Accordingly, the posted results can be used to understand what the registry records for this completed trial, but they do not establish a treatment benefit or rule out potential harms. They should not be generalized beyond the trial participants without evidence from additional studies and analyses.

13. Why This Trial Matters Statistically

Early-phase trials often focus on safety and tolerability while evaluating dose levels in a staged manner. This trial's sequential, multiple-ascending-dose design makes the structure of the evidence important: each dose group is part of a cohort-based study, and the registry does not describe a single pooled comparison as the primary analysis.

The primary endpoint also illustrates a key statistical distinction. An event count totals reported episodes, while a participant-level adverse-event summary records how many people were affected. Those quantities can tell different stories if some participants experience repeated events. Reading them separately prevents an event total from being mistaken for a number of participants.

The posted counts vary across the dose groups and placebo, but there is no reported inferential comparison or uncertainty estimate for those totals. Statistically, that limits what can be concluded from differences in the raw numbers. In general, a comparison of event counts needs a clearly specified estimand and an analysis that accounts for the number of participants, observation time, and possible clustering of events within participants. The registry record does not report such an analysis.

The trial also has a listed C-peptide outcome, but no result for it is reported in the available registry information. This highlights why a registered outcome and a posted outcome result are not the same thing: the presence of an outcome listing does not provide an estimate or evidence of an effect.

For biostatisticians and clinical researchers, the record underscores the value of transparent reporting of analysis populations, event definitions, comparison methods, uncertainty, missing-data decisions, and multiplicity handling. Those details allow readers to distinguish a descriptive safety record from an estimate designed to support a treatment comparison.

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 posted primary outcome consists of arm-level event totals without a reported uncertainty interval or formal treatment comparison. Because the outcome counts events rather than affected participants, the totals do not show whether many participants had a small number of events or fewer participants had repeated events. Participant-level distributions for the primary endpoint are not reported in the registry record.

The trial used sequential ascending-dose cohorts, but the record does not provide details of cohort progression or explain how the sequence influenced comparisons. Randomization is reported, but the randomization procedure and allocation details are not. Masking is described as triple, and the study is also described as double-blinded within cohorts; the record does not specify which parties were masked or how the two descriptions relate operationally.

The registry lists a 16-week timeframe and defines the on-treatment period, including a different endpoint for participants who did not receive all injections. It does not report the amount of follow-up available for each participant, the handling of missing event information, or whether observation time differed among participants. The safety analysis set includes participants who received at least one dose, but other analysis populations are not described in the reported information.

The serious-event summary gives affected-participant counts and two top serious-event terms, but not event timing, duration, attribution, or clinical course. The record does not report a formal comparison of serious events across groups. The listed secondary C-peptide outcome has no result reported in the information for this trial, and the statistical analysis plan, multiplicity approach, and missing-data methods are not reported in the registry record.

These limitations constrain the interpretation to descriptive summaries of the reported trial observations. They do not imply that unreported analyses or procedures were absent; their details are simply not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Multiple Ascending Dose Trial Investigating Safety, Tolerability and Pharmacokinetics of NNC0361-0041 — NCT04279613.
• Registry record last updated 2025-05-20; status last verified 2025-05.
• Results first posted 2025-05-20.
• 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.

18. Record Summary

NCT04279613 is a completed phase 1, randomized, placebo-controlled, sequential multiple-ascending-dose trial of NNC0361-0041 in patients with type 1 diabetes. The trial administered subcutaneous weekly doses of 1 mg, 5 mg, 12.5 mg or 25 mg in cohorts, with subcutaneous placebo as comparator.

The primary outcome was the number of adverse events recorded during the on-treatment period, with a stated timeframe of 16 weeks. The registry reports event totals by group and separate summaries of serious and other adverse events. One serious adverse event was reported in the 12.5 mg group; none were reported in the other groups, and no deaths were reported.

The registry lists change in the area under the plasma C-peptide concentration-time curve across the 2-hour test period as a secondary outcome, but no result for it is reported in the information available. A formal comparison and uncertainty estimate for the primary event-count outcome are also not reported in the registry record.