A Trial to Evaluate the Effect of C21 on Endothelial Dysfunction in Subjects With Type 2 Diabetes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Trial to Evaluate the Effect of C21 on Endothelial Dysfunction in Subjects With Type 2 Diabetes (NCT05831644), a randomized phase 1 study. The primary outcome is Pharmacodynamic Effect.

2. Clinical Question

This is a short-term comparison of measurements associated with the two treatments, not a comparison of long-term clinical outcomes. The primary endpoint is a continuous score, and the posted treatment contrast is a mean difference. The reported sponsor analysis gives a mean difference of -0.124 for C21 relative to placebo, with a 90% confidence interval from -0.285 to 0.037 and p = 0.193. The interval includes zero, so the estimate is compatible with values on either side of no mean difference at that confidence level.

The trial record does not report a separate clinical outcome question such as whether participants experienced fewer complications. Its primary question concerns a measure of endothelial function within the stated timeframe of maximum 15 days after first Investigational Medical Product intake. The registry does not report a minimum clinically important difference for RHI, so the clinical importance of a given score difference cannot be established from the record alone.

3. Trial Design

The registry describes NCT05831644 as a randomized, double-blind, placebo-controlled, 2-way crossover phase 1b trial evaluating C21’s pharmacodynamic effect on endothelial dysfunction and safety in subjects with type 2 diabetes mellitus. The phase field lists PHASE1. The sponsor is Vicore Pharma AB. The record lists the study as completed, with a start date of 2023-03-31 and a primary completion date of 2023-06-16.

In a crossover design, treatment assignment concerns the order in which participants receive the study treatments. The registry describes one sequence as a single dose of C21 at visit 2 followed by a single dose of placebo at visit 3, and the other as placebo at visit 2 followed by C21 at visit 3. This design allows outcomes under both treatments to be collected within the crossover arrangement. However, the record does not report details such as the timing between visits, any washout period, or how potential period or carryover effects were handled. Those aspects should not be inferred from the design label alone.

The registry lists 11 participants enrolled and reports 11 for each treatment arm in the posted primary outcome data. Because the treatment arms describe crossover treatment conditions and sequences, these entries should not be added to produce a total participant count. The registry record does not report a detailed analysis population, the number of participants with complete paired measurements, or how missing observations were handled.

Randomization and double masking are stated in the record, as are placebo control and the crossover model. The original trial protocol’s statistical plan, sample-size justification, planned handling of crossover effects, and any interim analyses are not reported in the registry record. Consequently, the posted results can be described, but the record does not establish how every design feature was accounted for in the sponsor’s analysis.

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 Intervention

Washout Between 1st and 2nd Intervention

Second Intervention

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 Pharmacodynamic Effect, measured over Maximum 15 days after first Investigational Medical Product (IMP) intake..

The primary endpoint is the reactive hyperemia index (RHI) score measured with EndoPAT, a device that uses endothelial pulse amplitude tonometry. The registry describes RHI as a ratio comparing pulse-amplitude signals after and before occlusion in the occluded arm with the corresponding ratio in a control arm, corrected for baseline vascular tone. EndoPAT software calculates the score using a computerized, automated algorithm.

RHI is used in this trial as a measure of endothelial function. The registry lists a normal value as RHI > 1.67 and an abnormal value as RHI ≤ 1.67. It also notes that there is no theoretical minimum or maximum for the score. These reference categories give context to the measurement, but the primary comparison is a difference in mean score between C21 and placebo, not a comparison of the number of participants crossing a threshold.

The primary outcome timeframe is maximum 15 days after first Investigational Medical Product intake. The registry states that a lower RHI score following C21 compared with placebo is the desired outcome. That direction describes the trial’s stated pharmacodynamic objective; by itself, it does not define the clinical importance of a difference or establish what a change in RHI would mean for health outcomes. The registry does not report a threshold for a meaningful between-treatment difference.

Continuous measurements retain differences in score rather than reducing each observation to a category. The mean difference therefore describes the average contrast on the RHI scale, while uncertainty around that estimate indicates how precisely the contrast is estimated.

7. Results Posted in the Registry

• C21 Treatment: mean 1.79 versus 1.91 on control; difference -0.12 (95% CI -0.30 to 0.05), standardized effect d = -0.60; z-test p = 0.157.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Augmentation Index (AI) Score as Measured by EndoPAT (Endothelial Pulse Amplitude Tonometry (PAT)). The AI Score Reported is Change Between Baseline Value and Value at the Visit Where Either C21 or Placebo is Taken.

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • C21 Treatment: mean 15.94 versus 20.88 on control; difference -4.94 (95% CI -11.83 to 1.95), standardized effect d = -0.60; z-test p = 0.160.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between C21 Treatment and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary outcome is the change in Augmentation Index (AI) score from baseline at the visit when either C21 or placebo was taken. The pattern of its posted treatment summaries is directionally similar to the primary result in that the estimated C21-minus-placebo contrast is negative. Its interval also spans zero. This broad pattern does not supply independent confirmation of the primary result, because both outcomes come from the same trial and are subject to the limitations of the design and analysis record.

AI and RHI are distinct EndoPAT measures, so their numerical scales and meanings should not be treated as interchangeable. The registry describes RHI as a measure of endothelial function and lists AI as a secondary outcome; it does not report a rule for combining them into a single overall effect. The secondary result can therefore be considered alongside the primary endpoint as additional descriptive evidence, not as a replacement for the prespecified primary question.

The secondary analysis reports an unadjusted p-value and an ANOVA result, but the registry record does not report a multiplicity adjustment or a strategy for controlling the chance of false-positive findings across outcomes. When several outcomes are examined, unadjusted results carry less weight as confirmatory evidence because chance findings become more plausible across the set. That is a general statistical concern, not evidence that a particular secondary finding is false.

The record lists one secondary outcome and two outcome measures and analyses. It does not report whether additional analyses were planned but not posted, how outcome selection was determined, or whether the secondary endpoint was intended as supportive or exploratory. Interpret the overall secondary pattern cautiously and in context of the primary estimate, rather than treating a nominal result from a secondary measure as definitive evidence.

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

• Augmentation Index (AI) Score as Measured by EndoPAT (Endothelial Pulse Amplitude Tonometry (PAT)). The AI Score Reported is Change Between Baseline Value and Value at the Visit Where Either C21 or Placebo is Taken.

9. Statistical Interpretation

10. Statistical Methods Explained

What does the mean difference describe?

The primary endpoint is continuous, so the posted comparison is expressed as a mean difference. A mean is an average of measured scores; a mean difference expresses the contrast between the treatment-condition means on the original RHI scale. The reported estimate is -0.124 for C21 relative to placebo. A negative estimate means the C21 mean is lower under the reported direction of comparison. The registry states that lower RHI following C21 was the desired direction, but direction alone does not establish the importance of the difference.

The arm summaries report means and standard errors. A standard error describes uncertainty in an estimated mean, rather than the spread of individual participants’ measurements. It should not be interpreted as a range containing most participant scores. The posted standard error is 0.062 for each treatment condition. The record does not provide individual observations or a standard deviation for the observed endpoint in the arm summaries.

What does the reported ANOVA add?

The sponsor’s posted analysis is an ANOVA with the parameter described as mean difference in final values, classified as a superiority analysis. It reports a mean difference of -0.124, a 90% confidence interval from -0.285 to 0.037, and p = 0.193. ANOVA is a general framework for comparing means. The registry record does not describe the model terms, whether participant-level pairing or treatment sequence was included, or how any period or carryover effects were assessed. The word ANOVA alone does not answer those design-specific questions.

The crossover structure matters because each sequence receives C21 and placebo at different visits. A suitable analysis may need to distinguish treatment differences from visit or period differences and account for repeated observations within participants. Those are general considerations for crossover trials; the specific statistical handling in this trial is not reported in the registry record. The final-values label does not, by itself, establish whether the model made use of within-participant pairing.

How should the recalculation be understood?

The unadjusted recalculation uses posted summary statistics to estimate a mean difference and its uncertainty without reconstructing the sponsor’s full analysis model. It gives -0.124, an interval from -0.296 to 0.048, and p = 0.157. The matching point estimate is consistent with the listed treatment means, while the difference between the recalculated and sponsor intervals and p-values reflects the fact that these are not the same analysis. The recalculation is simple and unadjusted; it should not be treated as a crossover-model analysis.

A p-value describes how compatible the observed result is with a specified null model, under the assumptions of the analysis. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of the effect. The posted sponsor p-value and the recalculated unadjusted p-value are both above conventional thresholds often used for statistical significance, but that observation does not prove the absence of an effect.

What does a confidence interval communicate?

A confidence interval expresses uncertainty around an estimate under the method used to construct it. In repeated use of a valid procedure under its assumptions, intervals at a stated confidence level would cover the target value at the procedure’s stated rate. For an individual result, the interval is best read as a range of values reasonably compatible with the data and analysis assumptions, not as a range guaranteed to contain the true value.

The sponsor’s interval is explicitly reported at the 90% level. It includes zero and extends in both directions around the estimated difference. The recalculated interval also includes zero, but its confidence level is not stated in the registry record, so it should not be assigned a confidence percentage based only on the posted endpoints. Both intervals signal uncertainty, and neither narrows the plausible contrast to a single direction.

Why do crossover details matter?

In a crossover design, outcomes under different treatments can be related because the same participant contributes measurements under both conditions. This dependence is a general feature of repeated measurements. Accounting for it can affect standard errors and confidence intervals. Conversely, an analysis that treats measurements as independent when they are paired may not reflect the design correctly. The registry record does not specify the variance model or covariance structure used in the sponsor analysis, so the adequacy of that aspect cannot be assessed from the posted information.

Period effects are systematic differences between visits that are unrelated to the treatment itself. Carryover refers to an effect of an earlier treatment that persists into a later treatment period. These are general possibilities to consider in crossover studies, not findings established for this trial. The record does not report a washout interval or a specific assessment of these effects. It is therefore not appropriate to assume either that they occurred or that they were ruled out.

What can the outcome summaries establish?

The means, standard errors, estimated difference, interval, and p-value describe the posted endpoint result. They do not establish the mechanism behind any observed score pattern, the durability of a change, or effects on clinical events. The registry’s automated EndoPAT description explains how RHI is calculated, but no validation analysis or relationship between the observed difference and patient-important outcomes is reported in the registry record.

Statistical interpretation also depends on choices made before analysis, including the target population, outcome definition, analysis population, handling of missing observations, and treatment of multiple outcomes. These details are not reported in the registry record. The reported numbers can be interpreted as results of the sponsor’s stated ANOVA and as a separate unadjusted recalculation, while the limitations of unreported methods remain relevant.

11. Confidence Intervals and Precision

The sponsor’s primary estimate is a mean difference of -0.124, with a 90% confidence interval from -0.285 to 0.037. The interval includes zero and crosses from negative to positive values. This means the sponsor’s estimate is not precise enough to exclude no difference at the stated confidence level, and it leaves uncertainty about the direction of the underlying mean contrast.

The interval is not a measure of the range of individual RHI scores. It describes uncertainty about the estimated mean difference, conditional on the analysis and its assumptions. The registry does not report a clinically meaningful difference threshold, so interval endpoints cannot be classified as clinically important or unimportant on the basis of the record.

The unadjusted recalculation gives an interval from -0.296 to 0.048 around the same point estimate of -0.124. Its endpoints also span zero. The recalculation’s confidence level is not reported in the registry record; the interval should therefore be considered on its own terms and not assigned a confidence level that is absent from the record.

The sponsor’s standard error of 0.062 is reported for each treatment condition. Standard errors quantify precision of estimated means, not variability among individual observations. The registry record does not provide enough methodological detail to determine how dependence between repeated measurements was represented in the sponsor’s uncertainty estimates. This matters because the study is a crossover trial.

Overall, the posted primary estimate points toward a lower mean RHI under C21, the stated desired direction, but the interval leaves substantial uncertainty around that estimate. Precision is limited, and the result does not establish equivalence, a clinically important difference, or a particular effect in a broader population.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total event counts. The registry’s planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set as the stated fraction of the observed effect. These figures are planning illustrations computed from the observed effect, not the trial’s own original design assumptions; those original assumptions are not reported in the registry record.

The 80% power column gives the planned participants per arm under the stated assumptions for a design with an 80% chance of detecting the specified effect, if that effect and the assumptions were correct. The 90% power column gives the corresponding per-arm planning figure for a design with a 90% chance under those assumptions. Power is a property of a planned study under a specified effect and model; it is not a statement about the probability that a result is true.

The entries show planning for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. At each power target, the participant requirement grows as the assumed effect becomes smaller. Smaller effects are harder to distinguish from random variation, so more participants are needed under the same planning assumptions. The displayed calculations are based on a simple two-arm planning setup and should not be taken as a reconstruction of a crossover-specific design.

These figures are not observed power. They are not the number enrolled in this trial, and they do not show the probability that the trial’s result is correct. Their use is illustrative: they show how strongly planning requirements depend on the effect size assumed, while the actual design’s sample-size rationale is not reported in the registry record.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -0.124; pooled standard deviation σ = 0.206.
2. n = 2 × (1.96 + 0.842)² × 0.206² / -0.124² = 43.2, rounded up to 44 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -0.124                      # observed difference in means
sigma <- 0.205630737002035                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(5831644)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 44 (80% power), 58 (90% power)
 75% of observed effect: n per arm = 77 (80% power), 103 (90% power)
 50% of observed effect: n per arm = 173 (80% power), 232 (90% power)
power.t.test: 44.2 
Simulated power at n = 44 per arm: 0.795 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The sponsor’s posted primary analysis is an ANOVA of final values. It reports a mean difference of -0.124, a 90% confidence interval from -0.285 to 0.037, and p = 0.193. The unadjusted recalculation from the posted summaries gives the same point estimate, with an interval from -0.296 to 0.048 and p = 0.157.

The recalculation is a simple unadjusted comparison, whereas the sponsor reports an ANOVA. Their different intervals and p-values should not be read as a contradiction in the estimated direction: both intervals include zero, and both point estimates are -0.124. The registry does not flag a discrepancy between the recalculation and sponsor result. The sponsor’s own analysis is the trial’s reported analysis; the recalculation is supplementary and does not substitute for the sponsor’s model or establish that crossover features were handled in a particular way.

The registry record does not give enough detail about the ANOVA specification to assess its treatment of repeated measurements, sequence, or period. Accordingly, the sponsor result should be described as reported, with the model details that are absent kept explicit rather than inferred from the analysis label.

15. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a multiplicity adjustment or a prespecified strategy for handling inference across the primary and secondary outcomes. Multiplicity is the issue that arises when more than one hypothesis is tested: as the number of opportunities to find a nominally unusual result increases, the chance of at least one such result can also increase. This is a general statistical concern. It does not mean that any particular result in this trial is spurious.

The record identifies a primary endpoint and a secondary AI outcome, but it does not state whether the testing sequence was hierarchical, whether secondary tests were exploratory, or whether any adjustment was planned. Consequently, the reported p-values should be read as reported analyses, not as evidence that family-wise error or another multiplicity target was controlled.

Details about missing data are not reported in the registry record. It does not state how many outcome observations were missing, whether participants withdrew, what methods were used for missing measurements, or whether sensitivity analyses were conducted. The listed enrollment and arm outcome counts do not establish that every participant contributed complete observations in both crossover periods.

The analysis population is also not reported in sufficient detail. The registry record does not specify whether the primary analysis followed an intention-to-treat principle, included participants with complete measurements only, or used another population definition. It does not report a participant flow for the primary endpoint or explain exclusions from analysis.

These omissions limit assessment of the robustness and reproducibility of the reported inference. They do not show that missingness, multiplicity, or exclusions biased the result; they mean the record does not provide the information needed to evaluate those possibilities. The trial’s original statistical analysis plan and any interim analyses are not reported in the registry record.

16. 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 non-serious adverse event terms

The posted safety figures list zero serious adverse events for C21 treatment and zero for placebo treatment. The registry lists 11 at risk in each treatment condition. No serious adverse event terms are listed among the top serious terms. These are the serious-event figures recorded for the treatment conditions; they do not establish that serious events are impossible or that the treatments have equal safety.

The record also lists other adverse events affecting 2 under C21 treatment and 1 under placebo treatment. Those figures are separate from the serious adverse event counts and should not be conflated with them. The registry lists zero deaths in both treatment conditions.

Safety interpretation is constrained by the limited trial size and the short timeframe described for the outcomes. The record does not provide event descriptions, severity details, relatedness assessments, or a broader account of follow-up in the safety entry. Zero observed serious events in these posted figures is a description of what was recorded, not proof that risk is absent or that the groups can be compared precisely for rare harms.

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

The result establishes that the registry record contains a short-term comparison of RHI under C21 and placebo in a randomized, double-blind crossover trial involving subjects with type 2 diabetes. The posted means are 1.787 under C21 and 1.911 under placebo, and the sponsor’s estimated mean difference is -0.124. The estimate is in the direction the registry describes as desired, because it is lower under C21.

The result does not establish a clear difference between treatment conditions. The sponsor’s 90% confidence interval, from -0.285 to 0.037, includes zero, and the reported p-value is 0.193. The unadjusted recalculation also has an interval that includes zero. These results leave uncertainty about the size and direction of the underlying difference. They do not demonstrate equivalence, because no equivalence margin or analysis is reported.

The endpoint is a measure of endothelial function, not a clinical event or a direct measure of how participants feel or function. The registry does not report evidence connecting the observed RHI difference to patient-important outcomes, a threshold for a meaningful change, or persistence beyond the stated short-term timeframe. The result therefore cannot establish a long-term effect, a reduction in complications, or a change in clinical outcomes.

The study’s design and sample also constrain generalization. It is a phase 1b single-centre trial, and the registry lists 11 enrolled. The registry record does not report enough detail about the analysis population, missing data, crossover model, or period and carryover handling to fully assess the statistical analysis. The posted findings are best understood as an early, imprecise estimate from this trial, not as a definitive answer for other populations or settings.

The safety record reports zero serious adverse events in either treatment condition, alongside other adverse events in the posted counts. Such limited observations cannot establish absence of risk. In summary, the record describes an estimated short-term pharmacodynamic contrast and its uncertainty; it does not establish clinical benefit, lack of effect, equivalence, or a complete safety profile.

18. Why This Trial Matters Statistically

This trial is statistically informative as an example of how a crossover design and a continuous physiological endpoint shape interpretation. The treatment sequences expose participants to both C21 and placebo, while the primary result is expressed as a mean difference in RHI. In principle, crossover designs can use within-participant information, but valid precision depends on how that repeated-measure structure is represented. The registry reports an ANOVA but does not provide enough model detail to assess that aspect.

The result also illustrates why a point estimate should not be read in isolation. The estimated difference is in the stated desired direction, but the sponsor’s interval includes zero and extends across both negative and positive values. The estimate’s direction is therefore not the same as a conclusive finding. The distinction between the sponsor’s reported model and a simple unadjusted recalculation further demonstrates that analysis choices can affect uncertainty estimates even when the point estimate is unchanged.

Planning illustrations based on the observed effect show how sensitive participant requirements are to the assumed effect size. A smaller target effect calls for more participants under the stated planning assumptions. Those calculations are not the original rationale for this trial and are not observed power, but they make the relationship between effect size, precision, and planning explicit.

Finally, the record highlights the role of registry transparency. Details about the analysis population, missing data, multiplicity, and crossover-specific methods are not reported. Their absence does not prove an analysis was inappropriate, but it limits independent assessment. For clinical researchers and biostatisticians, separating what the results estimate from what the registry does not document is essential to a calibrated interpretation.

19. 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 gives limited detail for assessing the primary model in the context of the crossover design. Although the sponsor reports an ANOVA of final values, the record does not specify model terms or explain how participant-level pairing, treatment sequence, or visit period was handled. It also does not report a washout interval or a carryover assessment. These are design-specific uncertainties, not evidence that a problem occurred.

The primary endpoint is a short-term physiological measure, with a timeframe of maximum 15 days after first Investigational Medical Product intake. The record does not report longer-term RHI results, clinical outcomes, or a threshold defining a meaningful treatment difference. Consequently, the relationship between the estimated score contrast and patient-important effects cannot be assessed from the registry entry.

The registry lists 11 enrolled and reports 11 for each treatment condition in the primary outcome summaries, but it does not provide a detailed participant flow or explain whether all observations were paired. Missing-data methods and the analysis population are not reported in the registry record. These omissions limit evaluation of attrition and analytic exclusions.

The trial is described as single-centre and phase 1b. Its findings may not represent other settings or populations, but the registry does not provide evidence to quantify generalizability. The record also does not report a clinically meaningful difference threshold, a sample-size justification, or the original statistical analysis plan. The planning illustrations based on the observed effect cannot fill those gaps or reconstruct the trial’s original design assumptions.

Finally, the safety figures are limited to the posted adverse-event counts. The registry does not provide detailed event descriptions or a broader account of safety follow-up in those entries. The small amount of posted safety information should not be interpreted as a comprehensive characterization of risk.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Trial to Evaluate the Effect of C21 on Endothelial Dysfunction in Subjects With Type 2 Diabetes — NCT05831644.
• Registry record last updated 2024-11-12; status last verified 2024-09.
• Results first posted 2024-11-12.
• 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.

23. Record Summary

NCT05831644 is a completed randomized, double-blind, placebo-controlled, 2-way crossover phase 1b trial sponsored by Vicore Pharma AB. It evaluated C21 in subjects with type 2 diabetes and endothelial dysfunction. The registry lists an enrollment of 11 and describes the study as single-centre.

The primary endpoint was EndoPAT-measured RHI within maximum 15 days after first Investigational Medical Product intake. The sponsor’s ANOVA reports a mean difference of -0.124, a 90% confidence interval from -0.285 to 0.037, and p = 0.193. The interval includes zero. The registry also posts an unadjusted recalculation with the same point estimate and an interval that includes zero.

The secondary outcome was change in AI score. Safety entries list zero serious adverse events and zero deaths in both treatment conditions. Details about missing data, the analysis population, multiplicity, and crossover-specific model handling are not reported in the registry record.