Desmopressin Acetate 0.2 mg Tablets, Fasting: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Desmopressin Acetate 0.2 mg Tablets, Fasting (NCT00835211), a randomized phase 1 study. The primary outcome is Cmax - Maximum Observed Concentration.

2. Clinical Question

The clinical question is one of relative bioavailability, not a comparison of clinical outcomes. The endpoint concerns the maximum concentration observed in blood during sampling over a 12 hour period. The registry record does not report a patient-centered or therapeutic outcome, and the study population is identified as healthy rather than as people being treated for a condition.

The study was designed around a single-dose comparison under fasting conditions. The record identifies the two formulations and dose but does not report the dosing sequence, period schedule, or washout interval. Those details should not be inferred from the description of a two-way crossover.

3. Trial Design

This was a Phase 1, randomized, single-dose, two-way crossover study of desmopressin acetate tablets and DDAVP® tablets in healthy adult subjects. The study title describes a 0.8 mg dose under fasting conditions. Enrollment was 48, and the registry lists the study as completed. Its recorded start was 2003-07 and its primary completion was 2003-08.

In a crossover design, each participant generally receives more than one study condition in a sequence, so comparisons can be made within participants. That is a general feature of crossover studies; the registry record identifies this study as a crossover but does not report its sequence assignment, period structure, washout interval, or details of how period and sequence effects were handled. Randomization is recorded, while masking is recorded as none.

The primary outcome was Cmax, the maximum observed concentration, measured in pg/mL. Blood samples were collected over a 12 hour period. The primary analysis population is described as data from all subjects who completed the study. The registry’s endpoint summaries list 43 observations for each formulation. The record does not explain how those endpoint counts relate to the total enrollment, so reasons for any difference are not reported in the registry record.

The interventions are named Desmopressin Acetate 0.2 mg Tablets and DDAVP® 0.2 mg Tablets. The arm descriptions themselves contain no further details. The record does not report the original sample-size justification, planned number of participants to complete the study, or the design assumptions used when the trial was planned. These unknowns are distinct from the later planning illustration based on the observed effect.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

First Intervention

Reasons for not completing this period:

Washout: 7 Days

Reasons for not completing this period:

Second Intervention

Analysis population for the primary outcome, as defined in the registry: Data from all subjects who completed the study were included in the statistical analysis.

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 Cmax - Maximum Observed Concentration, measured over Blood samples collected over 12 hour period.

Cmax is the maximum observed concentration of a substance in the blood during the defined sampling period. In this study, it was measured in pg/mL from blood samples collected over 12 hour period. The endpoint therefore captures the highest observed concentration after the single dose rather than the full concentration-time profile or the total exposure across time.

In general, maximum concentration is used in pharmacokinetic comparisons because it describes one aspect of the concentration profile and can help compare how two formulations behave after administration. The registry explicitly identifies bioequivalence based on Cmax. That description explains the endpoint’s role in the study, but it does not by itself state a decision rule or establish a conclusion.

The posted summary reports the mean and standard deviation for each formulation. For Desmopressin Acetate, the mean Cmax was 78.1 pg/mL and the standard deviation was 52.54. For DDAVP®, the mean was 82.89 pg/mL and the standard deviation was 64.22. These group summaries describe the observed endpoint values; they do not show each participant’s paired results or the distribution of individual within-person differences.

The registry record does not report additional detail about sampling times, assay methods, handling of values below a measurement limit, or whether any Cmax observations were missing. Those details can affect how an endpoint is measured or analyzed, but they cannot be assumed from the endpoint name alone.

7. Results Posted in the Registry

• DDAVP®: mean 82.89 versus 78.10 on control; difference 4.79 (95% CI -20.02 to 29.59), standardized effect d = 0.08; z-test p = 0.705.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is continuous: Cmax is recorded numerically in pg/mL. For a continuous measure, a mean describes the arithmetic average of observed values, while a standard deviation describes how dispersed individual observations are around that average. In general, a larger standard deviation indicates more spread in the observed values, but it does not reveal the shape of the distribution or the pattern of paired differences. The registry reports means and standard deviations for both formulations.

What does the crossover design mean statistically?

In general, a crossover design compares treatments within the same participants, which can account for stable differences between people when the analysis uses paired information appropriately. The registry identifies randomization and a two-way crossover, but it does not report the sequence allocation, period structure, washout details, or statistical model. The listed endpoint counts are 43 for each formulation. The record does not provide individual paired observations or the within-participant correlation, so those features cannot be reconstructed from the group summaries.

The registry’s primary population statement says that data from all subjects who completed the study were included in the statistical analysis. That description identifies a completer-based analysis population. It does not explain the status of participants who did not complete, the reasons for noncompletion, or how missing values were handled. It also does not say whether any additional analysis populations were used.

What is the recalculated mean difference?

The posted recalculation is an unadjusted mean difference for DDAVP® relative to Desmopressin Acetate. It reports an estimate of 4.786 pg/mL, a 95% confidence interval from -20.02 to 29.59, and an unadjusted p-value of 0.705. The recalculation uses the posted summary statistics rather than a reported crossover model. It does not incorporate any unreported within-participant covariance or adjustment for period or sequence. Its role is to provide a simple comparison from the summaries, not to reproduce the sponsor’s analysis.

In general, an unadjusted comparison does not control for other factors through a model. In a crossover study, a model may account for the paired nature of the data or other design features. Whether and how those features were handled by the sponsor is not reported in the registry record. No particular analysis model should be attributed to the sponsor because the method field for the reported analysis is not specified.

What is the sponsor’s ratio analysis?

The registry reports a test/reference ratio of least-squares means multiplied by 100, with an estimate of 97.5 and a 90% confidence interval from 87.8 to 108.3. In general, least-squares means are model-based estimates, and a ratio expresses one estimated mean relative to another. The registry’s description identifies the form of the reported quantity but does not identify the fitted model, transformations, covariates, or exact definition of test and reference. Those details are not reported in the registry record.

The registry classifies the analysis as noninferiority or equivalence. Such analyses generally rely on prespecified comparison limits and an interval or test-based decision rule. The record does not provide the limits or decision rule. Therefore, the ratio and confidence interval can be reported as the sponsor analysis, but the available record does not support reconstructing its full inferential procedure or independently applying its intended criterion.

How should confidence intervals and p-values be read?

In general, a confidence interval gives a range of values compatible with the observed data and the assumptions of the method. Its width reflects precision: narrower intervals indicate less uncertainty about the estimated quantity, while wider intervals indicate more. A confidence interval is not a guarantee that the true value lies within the particular interval, and it does not show the range of individual participant outcomes.

A p-value is calculated relative to a null hypothesis and a statistical model. It is not the probability that the null hypothesis is true, nor is it a measure of clinical importance. The reported unadjusted p-value pertains to the recalculated mean-difference comparison; the sponsor’s ratio analysis has no p-value reported. The record does not state a multiplicity adjustment for either result.

What is not established by the record?

The registry lists three outcome measures and three analyses, but only the primary endpoint information and one reported analysis are detailed in the record used for this account. No secondary outcome results are posted. The statistical plan, handling of multiple comparisons, missing-data approach, and original sample-size justification are not reported in the registry record. Absence of these details is not evidence that a particular procedure was or was not used; it means the procedure cannot be described from this record.

10. Confidence Intervals and Precision

The unadjusted recalculated mean difference is 4.786 pg/mL, with a 95% confidence interval from -20.02 to 29.59. This interval describes uncertainty around the difference estimated from the posted group summaries. Its range includes values on both sides of zero, so the estimate does not pin down the direction of the unadjusted difference with high precision. The unadjusted p-value is 0.705, which is consistent with the interval’s broad uncertainty under the recalculation’s assumptions.

The sponsor’s own analysis reports a test/reference ratio of least-squares means multiplied by 100 of 97.5, with a 90% confidence interval from 87.8 to 108.3. This interval describes precision on a relative scale. It is distinct from the 95% interval for the unadjusted difference: the estimands, scales, and confidence levels differ. The registry does not report the acceptance limits for its noninferiority or equivalence analysis, so the interval cannot be evaluated against a decision boundary from the record alone.

In general, interval width depends on the amount of information in the data, variability, study design, and analysis method. The endpoint standard deviations are 52.54 for Desmopressin Acetate and 64.22 for DDAVP®, while the reported endpoint sample size is 43 for each. Those summaries do not reveal the within-participant correlation that can matter in a crossover comparison. The registry does not provide enough detail to determine how that feature contributed to the sponsor’s interval.

Precision is not the same as importance. An estimate can be numerically close to a reference value yet remain uncertain, and a confidence interval does not describe effects in populations or conditions that were not studied. These intervals concern Cmax in the recorded study setting.

11. 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. The illustration assumes a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It uses an effect to detect equal to the stated fraction of the observed effect. The original trial’s own design assumptions and sample-size justification are not reported in the registry record.

The 80% power column gives the illustrated number of participants per arm for a design with an 80% chance of detecting the specified effect under those planning assumptions, if that effect and model assumptions were correct. The 90% power column gives the corresponding number per arm for a 90% chance. These are planning quantities, not probabilities that the completed study reached a result, and they are not estimates of the trial’s observed power.

The rows describe planning for 100%, 75%, and 50% of the observed effect. For 100% of the observed effect, the illustration gives 2,360 participants per arm for 80% power and 3,159 for 90% power. For 75% of the observed effect, it gives 4,195 per arm for 80% power and 5,616 for 90% power. For 50% of the observed effect, it gives 9,438 per arm for 80% power and 12,635 for 90% power. Smaller effects need more participants to detect under the same assumptions, which is why the illustrated counts increase as the effect fraction decreases.

The illustration is based on the observed effect from an unadjusted comparison and is not the study’s original design calculation. The record does not report the original planned sample size assumptions, and these planning values should not be read as observed enrollment targets or as evidence about the trial’s success.

12. 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 = 4.786; pooled standard deviation σ = 58.675.
2. n = 2 × (1.96 + 0.842)² × 58.675² / 4.786² = 2,359.4, rounded up to 2,360 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 <- 4.786                      # observed difference in means
sigma <- 58.6751092718625                     # 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(835211)
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 = 2,360 (80% power), 3,159 (90% power)
 75% of observed effect: n per arm = 4,195 (80% power), 5,616 (90% power)
 50% of observed effect: n per arm = 9,438 (80% power), 12,635 (90% power)
power.t.test: 2360.4 
Simulated power at n = 2,360 per arm: 0.803 (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.

13. Analyses Reported by the Sponsor

The sponsor’s reported result is a test/reference ratio of least-squares means multiplied by 100: 97.5, with a 90% confidence interval from 87.8 to 108.3. The registry classifies it as a noninferiority or equivalence analysis and describes the primary endpoint as bioequivalence based on Cmax. The method field is not specified, and the record does not provide the acceptance limits, model details, or p-value. Those omissions prevent a full reconstruction of the sponsor’s inferential analysis from the registry record.

The recalculated result is a simple unadjusted mean difference, DDAVP® minus Desmopressin Acetate, of 4.786 pg/mL, with a 95% confidence interval from -20.02 to 29.59 and an unadjusted p-value of 0.705. This calculation uses the posted summary statistics. It is not the same estimand or scale as the sponsor’s ratio of least-squares means, and it does not reproduce any unreported model adjustments.

The two results should therefore be read as related but distinct summaries. The sponsor’s analysis is the registry’s own reported analysis for its ratio-based comparison. The recalculation offers a supplementary, unadjusted view of the posted means. No discrepancy is flagged in the registry record, but the recalculation should not be substituted for the sponsor’s analysis or used to infer an unreported equivalence margin.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures and three analyses, but it posts no secondary outcome results in the record. The available endpoint information concerns Cmax. The record does not report whether the outcomes were tested as a family, whether a hierarchy or gatekeeping procedure was used, or whether any multiplicity adjustment was applied. It is therefore not possible to characterize the overall false-positive error control across outcomes or analyses.

The primary analysis population is described as data from all subjects who completed the study. This is a completer-based description. The registry does not report reasons for noncompletion, a participant flow account, a missing-data method, or sensitivity analyses. Although the reported endpoint sample size is 43 for each formulation and enrollment was 48, the record does not explain the relationship between those figures. No reason for the difference should be inferred.

The trial is identified as randomized and crossover, but sequence details and the analysis model are not reported. The record does not explain whether period, sequence, or participant effects were included, or how any carryover concerns were considered. These details matter to interpreting an analysis from a crossover design, but their absence from the registry record does not establish that they were ignored in the underlying study.

The sponsor analysis is classified as noninferiority or equivalence, yet its method and acceptance limits are not reported. The registry also does not report the original sample-size justification, interim analyses, or the full statistical plan. Accordingly, the posted results support description of the reported estimates, but they do not permit a complete audit of prespecification, multiplicity, missing-data handling, or model selection.

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

The registry reports a single-dose comparison of two desmopressin tablet formulations in healthy adults under fasting conditions, with Cmax as the primary endpoint. The observed means were 78.1 pg/mL for Desmopressin Acetate and 82.89 pg/mL for DDAVP®. The sponsor’s ratio estimate was 97.5, with a 90% confidence interval from 87.8 to 108.3. These are the reported pharmacokinetic summaries for the stated study setting.

The unadjusted recalculation gives a mean difference of 4.786 pg/mL and a 95% confidence interval from -20.02 to 29.59, with an unadjusted p-value of 0.705. The interval conveys uncertainty in the difference estimated from group summaries. It does not demonstrate that the formulations are identical, and the p-value is not the probability that there is no difference.

The registry characterizes the sponsor analysis as noninferiority or equivalence and states that bioequivalence is based on Cmax. However, the decision limits and method are not reported in the registry record. The estimate and interval can be described, but the available record does not supply the criteria needed to independently determine whether a particular bioequivalence standard was satisfied.

These results do not answer questions about clinical benefit, safety, repeated dosing, or outcomes in people with a medical condition. The study population is recorded as healthy, and the comparison is a single-dose assessment under fasting conditions. Generalizing beyond those conditions would require evidence not reported in this record. The findings should be understood as a comparison of the stated endpoint in the stated study population and setting, rather than as a treatment recommendation or a conclusion about clinical effectiveness.

16. Why This Trial Matters Statistically

This study illustrates how a statistical question depends on the chosen scale and analysis. The sponsor reports a ratio of least-squares means, while the supplementary recalculation reports an unadjusted mean difference. Each expresses a comparison differently: ratios are relative, whereas differences retain the endpoint’s measurement unit. Their confidence intervals also use different confidence levels, so the two results are not interchangeable.

The crossover design is another important statistical feature. In general, crossover comparisons can use within-participant information, which may affect precision. But the registry record does not report the paired data, correlation, sequence, period structure, or sponsor model. The group means and standard deviations alone cannot show how the crossover structure influenced the reported estimate.

The record also distinguishes the analysis population from total enrollment. It reports 48 enrolled and endpoint summaries with 43 observations for each formulation, while describing the primary analysis as including subjects who completed the study. Without a participant flow account or missing-data details, the relationship between those counts remains unclear. This is a reminder that sample size should be interpreted alongside the analysis population and reporting details.

Finally, a bioequivalence label does not replace the underlying statistical criteria. The sponsor’s ratio and interval are reported, but acceptance limits and method details are absent. A reader can identify the estimate and its uncertainty without assuming an unreported threshold or conclusion. That separation between observed results and decision rules is central to careful interpretation.

17. 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 is limited in its description of the crossover design. Although it identifies a randomized two-way crossover study, it does not report treatment sequences, periods, washout interval, or how the analysis accounted for crossover features. The sponsor analysis method is also unspecified. These omissions restrict independent review of the model and of the role of within-participant information.

The endpoint summaries include 43 observations for each formulation, while enrollment is 48 and the primary population is described as subjects who completed the study. The record does not explain the count difference, describe participant disposition, or report the reasons for noncompletion. Missing-data handling and sensitivity analyses are not reported in the registry record.

The sponsor’s ratio estimate and 90% confidence interval are posted, but the acceptance limits and decision rule are not. The record therefore does not allow the reader to verify the sponsor’s equivalence or noninferiority interpretation against stated margins. The analysis method and p-value are also not reported.

The record lists three outcome measures and three analyses but provides no secondary outcome results. It does not report multiplicity handling, interim analyses, or the original sample-size justification. The planning illustration based on the observed effect is not a substitute for the original design rationale.

Finally, the study concerns a single dose in healthy adult subjects under fasting conditions. Its endpoint is Cmax, not a clinical outcome. The registry record does not establish how results extend to other populations, dosing schedules, or conditions.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Desmopressin Acetate 0.2 mg Tablets, Fasting — NCT00835211.
• Registry record last updated 2009-09-11; status last verified 2009-09.
• Results first posted 2009-08-04.
• 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.

21. Record Summary

NCT00835211 is a completed Phase 1 randomized, unmasked, two-way crossover study sponsored by Teva Pharmaceuticals USA. It compared Desmopressin Acetate 0.2 mg Tablets with DDAVP® 0.2 mg Tablets after a single 0.8 mg dose under fasting conditions in healthy adult subjects. Enrollment was 48; the recorded start was 2003-07 and primary completion was 2003-08.

The primary endpoint was Cmax in pg/mL, based on blood samples collected over 12 hour period. The reported means were 78.1 for Desmopressin Acetate and 82.89 for DDAVP®, with standard deviations of 52.54 and 64.22. The sponsor reported a test/reference ratio of least-squares means multiplied by 100 of 97.5, with a 90% confidence interval from 87.8 to 108.3. An unadjusted recalculation reported a mean difference of 4.786 pg/mL, with a 95% confidence interval from -20.02 to 29.59 and p = 0.705.

The registry record does not report the sponsor’s method, equivalence limits, original sample-size justification, missing-data procedures, or multiplicity handling.