Effects of Nasulin Versus Placebo on Blood Glucose Control in Patient Volunteers With Type 2 Diabetes Mellitus: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effects of Nasulin Versus Placebo on Blood Glucose Control in Patient Volunteers With Type 2 Diabetes Mellitus (NCT00850096), a randomized phase 2 study. The primary outcome is Continuous Glucose Monitoring (CGM).

2. Clinical Question

3. Trial Design

This was a randomized, parallel-group, placebo-controlled Phase 2 study. The official title describes it as Phase 2A, double-blind, and multicenter; the registry classifies masking as triple. The people or roles included in that masking classification are not reported in the registry record. The study status is completed.

The registry reports 94 participants randomized, with 47 assigned to each group. The posted primary outcome includes 44 participants in the placebo group and 45 in the Nasulin group who completed the study. These outcome counts are smaller than the randomized counts; reasons for non-completion and how missing outcome data were handled are not reported in the registry record.

The Nasulin intervention is described as an intranasal insulin spray at 1%, and the comparator as a placebo spray. The study population was described as receiving basal insulin and oral antidiabetic medicines, excluding secretagogues. Although the study purpose refers to assessing Nasulin at 50 IU and 100 IU, how participants were assigned to doses, and whether dose-specific comparisons were planned, are not reported in the registry record.

The registry gives a start date of 2009-01 and a primary completion date of 2010-03. The stated primary outcome timeframe is baseline and weeks 5-6. The randomization method, allocation concealment procedures, detailed visit schedule, and protocol deviations are not reported in the registry record. The registry lists one secondary outcome, Overall Glycemic Control, and does not post a separate analysis record for that outcome.

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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: 47 patients were randomized to the placebo/oral antidiabetic arm while 47 others were randomized to the Nasulin/oral antidiabetic arm of the study. Forty-four patients in the placebo + oral antidiabetic arm and 45 patients in the Nasulin + oral antidiabetic arm completed the study.

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 Continuous Glucose Monitoring (CGM), measured over Baseline and 5-6 weeks.

The primary outcome is Continuous Glucose Monitoring (CGM), expressed as the mean percentage of a 24h day spent in euglycemia. Euglycemia was defined as blood glucose from 70 to 180 mg/dl. The endpoint is a change score: the mean percentage of time in that range at weeks 5-6 minus the baseline mean. A positive change indicates more time in the specified range relative to baseline; a negative change indicates less time in that range relative to baseline.

Continuous monitoring captures glucose readings across the day rather than relying only on a measurement taken at a single moment. As a general statistical point, this type of outcome can describe the distribution of glucose exposure over the monitoring period and can reflect both time inside and outside the stated range. It is not the same measure as a single average glucose value, and it does not by itself describe every aspect of glycemic control.

The registry states that CGM data were collected at baseline and during the last two weeks of the study, and that changes from baseline to weeks 5-6 were assessed. It identifies the measure as a mean with standard error as the dispersion statistic. Specific CGM collection rules, handling of incomplete monitoring records, and the statistical model used for the sponsor's primary analysis are not reported in the registry record.

7. Results Posted in the Registry

• Nasulin: mean -0.72 versus -6.23 on control; difference 5.51 (95% CI -3.72 to 14.74), standardized effect d = 0.25; z-test p = 0.242.

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.

Overall Glycemic Control

• 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:
  • Nasulin: mean 163.34 versus 174.64 on control; difference -11.30 (95% CI -22.52 to -0.08), standardized effect d = -0.42; z-test p = 0.048.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Nasulin than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry lists one secondary outcome, Overall Glycemic Control, measured in mg/dl at weeks 5-6. The posted mean is 174.6 in the placebo group and 163.3 in the Nasulin group. The unadjusted recalculated mean difference is -11.3 mg/dl, with a 95% confidence interval from -22.52 to -0.077 and a p-value of 0.048.

This secondary outcome is a different measure from the primary CGM change score. It is an overall glycemic measure at follow-up, whereas the primary endpoint describes change from baseline in the percentage of time within the defined euglycemic range. The two outcomes can complement one another by describing different aspects of glucose control, but one does not directly validate the other. In particular, the secondary result does not resolve the uncertainty in the primary comparison.

The registry lists no reported analysis records for the secondary outcome. The numerical comparison is an unadjusted recalculation from posted summary statistics. The record does not report whether this outcome was prespecified in a detailed statistical analysis plan, how it was analyzed, or whether any adjustment was made for examining multiple outcomes. Thus, the result should be interpreted with caution and should not be treated as confirmatory evidence independent of the primary outcome.

As a general statistical principle, testing several outcomes increases the chance that at least one result will appear noteworthy by chance, even when none reflects a genuine effect. The more outcomes or analyses considered, the more important it is to know which were planned and whether an adjustment or testing hierarchy was used. Those details are not reported in the registry record. The secondary finding is therefore best viewed as a potential signal that needs interpretation in the context of the study's overall evidence, rather than as a definitive stand-alone conclusion.

The registry includes only one posted secondary outcome, so a broader pattern across multiple secondary measures cannot be assessed from the posted results. The overall interpretation remains anchored to the primary CGM outcome and its imprecision, while recognizing that the secondary measure points in a different direction on its own scale.

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

• Overall Glycemic Control

9. Statistical Interpretation

10. Statistical Methods Explained

The primary measure is continuous: it is a mean percentage of the day spent in a specified glucose range. The registry identifies the reported group values as means and the dispersion as standard errors. A standard error describes the uncertainty in an estimated mean, rather than the spread of individual participant values. As a general statistical distinction, a standard deviation describes participant-to-participant variability, while a standard error reflects how precisely a sample mean is estimated.

What does the change score represent?

For each group, the reported primary outcome is the mean change from baseline to weeks 5-6. The change is defined as the later mean percentage of time in euglycemia minus the baseline value. The group means are -6.23 for placebo and -0.72 for Nasulin. These are changes in the endpoint, not the groups' absolute percentages of time in range at follow-up. Baseline and final absolute means are not reported in the registry record.

Comparing change scores accounts for each participant's baseline value in the outcome being analyzed. The posted registry description does not specify whether the sponsor instead used a model that adjusted for baseline, repeated measurements, or other covariates. Such methods can produce estimates that differ from a simple comparison of group changes. The sponsor's analysis model is not reported in the registry record.

How should the mean difference be read?

The posted unadjusted recalculation compares Nasulin with placebo by subtracting the placebo group mean change from the Nasulin group mean change. The resulting mean difference is 5.51 percentage points. A positive value means the mean change was higher in the Nasulin group than in the placebo group. It is a difference between group averages; it does not mean that every participant experienced a change of that size, or even a change in the same direction.

The recalculated comparison uses the posted summary statistics and is unadjusted. It is not identified in the registry as a sponsor-reported analysis. The registry lists no posted analysis records for the primary outcome. A recalculation from summary statistics can provide a transparent numerical comparison, but cannot reproduce features of an unavailable individual-level or prespecified analysis.

What does the confidence interval add?

A confidence interval describes uncertainty around an estimate under the assumptions of the statistical method. For the primary mean difference, the interval runs from -3.715 to 14.74. Because it includes zero, the posted estimate does not clearly distinguish a positive difference from no difference or a negative difference at the conventional two-sided 0.05 significance level. The interval is also useful for seeing the range of effects compatible with the data and method; it should not be read as a list of equally likely values.

The p-value of 0.242 is another summary of compatibility between the observed data and a null model of no group difference, under the recalculation's assumptions. It is not a measure of the clinical importance of the estimate, and it does not quantify the probability that an effect exists. The registry record does not report the sponsor's primary p-value or an adjusted analysis.

Why can over-dispersion matter?

As a general statistical concept, over-dispersion occurs when variability in the data is greater than a model assumes. If a model understates variability, its standard errors may be too small and its confidence intervals too narrow; if variability is modeled appropriately, inference is better calibrated. Continuous glucose data can have complex within-person and between-person variation, so the choice of analytic model and assumptions can matter. The registry does not report a model assessment or an over-dispersion analysis, and no claim about over-dispersion in this trial can be made from the posted summary statistics alone.

The posted standard errors for the two primary group means are 3.295 and 3.361. The recalculated confidence interval and p-value are based on the summary-statistic comparison; they do not reveal whether the sponsor used a different model or incorporated the repeated nature of CGM observations. The registry record does not report details of how observations within a participant were summarized or modeled.

What does randomization contribute?

Random assignment is intended to make treatment groups comparable on average at the start of a trial, including with respect to factors that were not measured. The registry identifies the study as randomized, but does not report the randomization sequence method or allocation concealment procedures. Randomization alone does not resolve concerns about missing outcomes, adherence, outcome measurement, or analysis choices. The posted group counts and summary statistics should therefore be read alongside the limited information about those procedures.

The analysis population is also not clearly specified. Although 47 participants were randomized to each group, the primary outcome summaries include 44 placebo participants and 45 Nasulin participants. Whether these represent an intention-to-treat population, a per-protocol set, or another analysis population is not reported in the registry record. The statistical methods and population definitions are therefore not fully recoverable from the registry results.

11. Confidence Intervals and Precision

The primary mean difference is 5.51 percentage points, with a 95% confidence interval from -3.715 to 14.74. The interval is wide enough to include a difference in either direction, as well as zero. This means the point estimate alone gives an incomplete picture: uncertainty around it is substantial, and the posted data do not precisely determine the direction or size of the group difference.

As a general explanation, a confidence interval is a range produced by a statistical procedure that, under its assumptions, reflects uncertainty in an estimate. It is not a guarantee that the true value lies in the particular interval, nor does it assign a probability to each value within the interval. In this comparison, the inclusion of zero corresponds to the lack of a clear difference at the conventional two-sided 0.05 level under the recalculated method.

The standard errors for the group means are 3.295 for placebo and 3.361 for Nasulin. These quantify uncertainty in each estimated mean, not variation among individual participants. Individual-level standard deviations for the primary outcome are not posted as the dispersion statistic, and the registry does not report participant-level distributions or the number of usable CGM records per person.

The confidence interval comes from an unadjusted recalculation from posted summary statistics. The registry record does not report a sponsor confidence interval or enough information to assess whether the sponsor used a different model. The interval also reflects only statistical uncertainty under the calculation's assumptions; it does not account for possible bias from missing outcomes, protocol deviations, or selective reporting.

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 events. They are illustrations based on the observed effect, not the trial's original design assumptions. The stated 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 the stated fraction of the observed effect. The trial's own original sample-size assumptions are not reported in the registry record.

For the primary outcome, planning for 100% of the observed effect corresponds to 256 participants per arm for 80% power and 342 participants per arm for 90% power. Planning for 75% of the observed effect corresponds to 454 participants per arm for 80% power and 607 participants per arm for 90% power. Planning for 50% of the observed effect corresponds to 1,021 participants per arm for 80% power and 1,366 participants per arm for 90% power.

In plain language, a design with 80% power has an 80% chance of detecting an effect of the specified size under the planning assumptions, if that effect is truly present. The 90% power column describes a higher chance of detecting that specified effect, which requires more participants per arm under these assumptions. Smaller effects are harder to distinguish from random variation, so planning for a smaller fraction of the observed effect requires more participants.

These are planning illustrations, not observed power. They do not indicate the probability that the trial's result is correct, and they do not replace a sample-size justification based on a clinically chosen target effect, outcome variability, and analysis plan.

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 = 5.510; pooled standard deviation σ = 22.208.
2. n = 2 × (1.96 + 0.842)² × 22.208² / 5.510² = 255.0, rounded up to 256 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 <- 5.51                      # observed difference in means
sigma <- 22.2080566513571                     # 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(850096)
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 = 256 (80% power), 342 (90% power)
 75% of observed effect: n per arm = 454 (80% power), 607 (90% power)
 50% of observed effect: n per arm = 1,021 (80% power), 1,366 (90% power)
power.t.test: 256 
Simulated power at n = 256 per arm: 0.804 (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. Multiplicity, Missing Data and Analysis Populations

The registry lists one secondary outcome and no reported analysis records for that outcome. It does not report a statistical analysis plan, an outcome hierarchy, a multiplicity adjustment, or whether interim analyses were conducted. These features are not reported in the registry record, so it is not possible to determine whether the posted secondary analysis was designated as confirmatory or exploratory before results were known.

Multiplicity refers to the problem of interpreting several statistical tests or outcome measures together. As a general concept, when many comparisons are made, the chance of at least one apparently unusual result can increase. Methods such as adjustment procedures or a prespecified testing hierarchy can address this issue, but the registry does not report whether any such approach was used. The secondary p-value of 0.048 should therefore not be interpreted as though it were necessarily the result of a single, isolated, prespecified test.

For the primary outcome, the registry gives a recalculated unadjusted comparison but no posted sponsor analysis record. The statistical analysis plan, adjustment for baseline or other covariates, handling of repeated measurements, and any planned sensitivity analyses are not reported in the registry record. It is consequently unclear whether the recalculation matches the sponsor's planned primary analysis.

Missing-data handling is also not reported. The primary outcome summaries include 44 participants in the placebo group and 45 in the Nasulin group, while 47 participants in each group were randomized. Reasons for missing primary outcomes, whether all randomized participants were included in any other analysis, and the assumptions used for missing values are not reported in the registry record. No conclusion about the impact of missing data can be made from the available summaries.

The analysis populations are not defined. The registry does not state whether the posted results represent an intention-to-treat population, a per-protocol population, or another set of participants. In general, different population definitions can answer different questions, and excluding randomized participants can affect comparability if exclusions relate to outcomes or treatment. Without those details, the posted results should be interpreted as summaries of the participants included in the registry outcome record, rather than as a fully documented account of the trial's planned analysis.

15. 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: abscess intra abdominal (2.1%), abdominal wall seroma (2.1%), nasal irritation (2.1%), elevated blood cell count (2.1%), arthralgia (2.1%).

The registry reports serious adverse events among 3 of 47 participants in the placebo group and 2 of 47 participants in the Nasulin group. Other adverse events are reported for 35 of 47 placebo participants and 28 of 47 Nasulin participants. These are descriptive counts and do not, by themselves, establish a difference between groups or explain the nature, timing, severity, or relatedness of every event.

The registry lists serious adverse event terms including Abscess intra abdominal, Abdominal wall seroma, Nasal irritation, Elevated blood cell count, Arthralgia, and Abdominal distension, each reported as 2.1%. The term listing does not provide enough detail to determine how the listed terms were distributed by group, whether any participant had more than one event, or whether investigators judged an event to be related to treatment.

Deaths are not reported in the registry record. The record also does not report the full adverse-event listing, exposure-adjusted event rates, severity grades, or treatment discontinuations due to adverse events. The safety counts should therefore be read as a limited summary of reported events during the study, not as a complete comparative safety analysis.

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

The primary result is an imprecise estimate of the difference between groups in change in time spent in the euglycemic range. The point estimate is 5.51 percentage points for Nasulin minus placebo, but the confidence interval includes zero and extends from -3.715 to 14.74. The unadjusted p-value is 0.242. These results do not provide clear statistical evidence of a difference in the primary outcome under the recalculated comparison, while also leaving a broad range of possible effects compatible with the data.

Not finding a clear difference is not the same as proving that the groups are equivalent. An equivalence or non-inferiority conclusion would require a prespecified margin and an analysis designed for that question; such details are not reported in the registry record. Conversely, the positive point estimate does not establish that Nasulin improves the outcome. It is one estimate from a small completed trial with incomplete information about the analysis and missing observations.

The secondary Overall Glycemic Control comparison is statistically borderline by its unadjusted p-value, but it is a separate measure and does not settle the primary result. The registry does not report multiplicity procedures or a prespecified hierarchy for outcomes. The secondary finding should therefore be treated as less definitive than a result from a clearly documented confirmatory analysis.

The trial studied patient volunteers with Type 2 diabetes in the context of basal insulin and oral antidiabetic medicines excluding secretagogues. Generalization beyond that context is not established by these results. The follow-up period for the primary outcome is weeks 5-6, so the registry outcome does not describe longer-term effects.

These findings are statistical summaries, not individualized clinical guidance. They do not establish the overall balance of benefits and harms, and they do not answer questions about outcomes that were not posted. The record's limited reporting of analysis methods, missing-data handling, safety details, and dose-specific results constrains what can be concluded.

17. Why This Trial Matters Statistically

This trial illustrates why the point estimate, uncertainty interval, and analysis context need to be considered together. The primary mean difference is positive, but its confidence interval spans both negative and positive values and includes zero. The unadjusted p-value alone would obscure how much uncertainty remains about the direction and size of the difference.

It also shows the distinction between a change in a continuous outcome and a comparison of group averages. The primary endpoint is a change from baseline in time spent within a defined glucose range. It is not an absolute follow-up value, and it does not describe every participant's individual trajectory. Understanding the outcome definition is essential before interpreting the estimated difference.

The secondary result offers a further statistical lesson. It has an unadjusted p-value of 0.048, while the primary comparison is not statistically clear by its unadjusted recalculation. Without a reported analysis plan, multiplicity handling, or hierarchy of outcomes, a secondary result should not be elevated into a decisive conclusion. The relevant question is not only whether a p-value crosses a threshold, but also whether the outcome and analysis were planned and how many opportunities there were to find a noteworthy result.

Finally, posted summary data allow transparent recalculation, but they do not reconstruct every feature of an original trial analysis. The registry's absence of details about the model, missing observations, analysis populations, and dose-specific comparisons limits independent evaluation. This makes careful separation of observed summaries, recalculated comparisons, and unreported methods especially important.

18. 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 sponsor's primary analysis, its statistical model, or a detailed statistical analysis plan. The primary group comparison discussed in the posted results is an unadjusted recalculation from summary statistics. It may not reproduce a planned analysis that incorporates baseline values, repeated measurements, or other covariates.

The outcome summaries use 44 placebo participants and 45 Nasulin participants, although 47 participants were randomized to each group. Reasons for the difference between randomized and analyzed counts, missing-data methods, and the analysis population definition are not reported in the registry record. This limits assessment of possible attrition bias.

The primary endpoint relies on continuous glucose monitoring. The registry does not report the amount of usable monitoring data per participant, criteria for acceptable recordings, or how incomplete monitoring was handled. The posted standard errors provide information about precision of the group means, but not the full distribution of participant-level changes.

The study purpose refers to Nasulin doses of 50 IU and 100 IU, but dose assignment and dose-specific outcome results are not reported in the registry record. The available group summaries therefore do not allow a dose-response assessment. The registry also does not report detailed adherence, concomitant treatment changes, or protocol deviations.

The outcome timeframe is weeks 5-6, and longer-term results are not reported in the registry record. Safety reporting is limited to counts and a list of serious adverse event terms; deaths, event relatedness, severity, and full event-level details are not reported. These reporting gaps restrict the breadth of conclusions that can be drawn from the trial.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Effects of Nasulin Versus Placebo on Blood Glucose Control in Patient Volunteers With Type 2 Diabetes Mellitus — NCT00850096.
• Registry record last updated 2013-12-13; status last verified 2013-11.
• Results first posted 2012-05-15.
• 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.

22. Record Summary

NCT00850096 is a completed randomized, parallel, placebo-controlled Phase 2 study of Nasulin versus placebo in patient volunteers with Type 2 diabetes receiving basal insulin and oral antidiabetic medicines excluding secretagogues. The registry reports 94 randomized participants, with 47 assigned to each group.

The primary outcome was change from baseline to weeks 5-6 in mean percentage of the day spent in euglycemia, defined as 70 to 180 mg/dl, based on continuous glucose monitoring. The unadjusted recalculated mean difference was 5.51 percentage points, with a 95% confidence interval from -3.715 to 14.74 and p = 0.242. One secondary outcome, Overall Glycemic Control, is posted.

The registry does not report the sponsor's analysis plan, missing-data methods, or analysis-population definitions. The posted results should be interpreted with those limitations in mind.