Zaleplon 10mg Capsules Under Fasting Conditions: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Zaleplon 10mg Capsules Under Fasting Conditions (NCT00829998), a randomized phase 1 study. The primary outcome is Cmax - Maximum Observed Concentration.

2. Clinical Question

3. Trial Design

This was a randomized, open-label, phase 1 crossover study. The registry lists enrollment of 40 and a completed status. It records a start and primary completion in 2004-02. Randomization assigned participants to a treatment sequence: either Zaleplon 10 mg Capsule in the first period followed by Sonata® 10 mg Capsule in the second period, or Sonata® first followed by Zaleplon second. Thus, the comparison involved both products within the crossover design, rather than separate parallel groups receiving only one product.

The study objective concerned relative bioavailability under fasting conditions in healthy, non-smoking adults. The registry identifies Teva Pharmaceuticals USA as sponsor. Masking is listed as none, so the record describes the study as unmasked. It does not report additional details about how randomization was generated, whether any washout interval separated periods, or the timing and conduct of dosing beyond the sequence descriptions.

The primary outcome was Cmax, defined in the registry as maximum observed concentration, with blood samples collected over a 10 hour period. The posted primary analysis population comprises subjects who completed the study. The outcome summaries list 40 observations for Zaleplon and 40 for Sonata®. Those treatment-specific counts describe the posted endpoint summaries; the registry record does not provide a further account of participant flow or explain whether any enrolled participant did not complete the study.

Three outcome measures and three analyses are listed, but the record identifies only the primary Cmax result in the registry record for this comparison. No secondary outcomes are posted. The registry record does not report the original design assumptions, a sample-size justification, detailed period or sequence modeling, or other protocol-level analysis details. The design supports a within-participant product comparison, but the posted arithmetic re-calculation does not itself reproduce a crossover model.

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

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 10 hour period.

Cmax is the maximum observed concentration of a drug in blood during the specified sampling period. Here it is expressed in ng/mL, and the registry states that blood samples were collected over a 10 hour period. The endpoint is a continuous measure: each participant’s concentration profile yields a maximum value, and the analysis compares those values between the capsule products.

For a relative-bioavailability comparison, Cmax describes the peak concentration observed after administration. It is one way to characterize how much drug reaches the bloodstream at the highest measured point in the sampling window. It does not by itself describe the entire concentration-time profile, the time at which the peak occurs, or total exposure. Those would require other measurements, and the registry record does not identify them as the primary endpoint.

The registry describes the primary endpoint as “Cmax - Maximum Observed Concentration” and gives bioequivalence based on Cmax as its description. The sponsor’s posted analysis reports a ratio of geometric means, while the treatment-level summaries report arithmetic means and standard deviations. Those are distinct summaries of continuous data, so their estimates answer the comparison on different scales. The arithmetic summaries can describe the observed group-level values, but they do not substitute for the sponsor’s geometric-mean analysis or provide all details of the crossover analysis.

Interpretation depends on the sampling window, the endpoint definition, and the analysis scale. The posted result concerns peak concentration over the stated collection period; it is not a direct summary of every aspect of drug exposure.

7. Results Posted in the Registry

• Sonata®: mean 27.49 versus 27.08 on control; difference 0.41 (95% CI -5.10 to 5.91), standardized effect d = 0.03; z-test p = 0.885.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is continuous, so it can be summarized using a mean and a measure of spread. The posted arithmetic summaries use means and standard deviations. A mean describes the average observed Cmax within a treatment summary; a standard deviation describes how dispersed individual observations are around that average. The registry lists values of 27.08 and 27.49 ng/mL for the treatment means, and standard deviations of 12.37 and 12.76. The treatment summaries each list 40 observations.

The recalculated comparison is an unadjusted difference between the arithmetic means. Its reported estimate is 0.407 ng/mL, with a 95% confidence interval from -5.101 to 5.915, and an unadjusted p-value of 0.885. “Unadjusted” means that this summary comparison is not presented as accounting for additional design features or covariates. In particular, it should not be mistaken for a fitted crossover model simply because the trial itself used a crossover design. A participant’s values under the two treatments may be related, and an analysis that uses that relationship can differ from a comparison based only on treatment-level summaries. The information needed to reproduce such a model is not reported in the registry record.

A confidence interval describes a range of values reasonably compatible with the data under the statistical method used. It conveys uncertainty around the estimate, rather than giving a guarantee that the true value lies within the particular interval. For the unadjusted arithmetic difference, the reported interval extends from -5.101 to 5.915 ng/mL. Because the interval covers differences below and above no difference, the posted summary does not narrowly pin down the direction or size of the arithmetic-scale difference. The p-value of 0.885 is also from the unadjusted recalculation. It does not establish equivalence, and it should not be read as the probability that the treatments are the same.

The effect-size estimate d is 0.032. This is a standardized description of the estimated difference relative to a pooled measure of spread; it expresses the comparison on a scale that is not in ng/mL. It provides context for the planning illustration, but it is not a clinical threshold and does not determine whether the products meet an equivalence criterion. A small standardized estimate can coexist with uncertainty, especially when the estimate is based on a limited set of observations and the data are variable.

The sponsor’s reported analysis uses a ratio of geometric means rather than the arithmetic mean difference. The registry reports a value of 97.4 and a 90% confidence interval from 89.4 to 106. A geometric mean is based on a multiplicative scale and is often used when an analysis is framed in terms of ratios. Its ratio answers a different statistical question from an arithmetic difference. The two results should therefore be kept distinct rather than converted into one another using assumptions not reported in the record. The registry does not state the sponsor model, its covariates, its handling of period and sequence, or an equivalence margin.

Over-dispersion is a general statistical concern when observed variation is greater than a model’s assumptions would allow. In that situation, model-based standard errors and confidence intervals can be too narrow if the extra variation is ignored. This is general context, not a reported finding about this study: the registry record does not identify an over-dispersion assessment or indicate that it was relevant to the sponsor analysis. Similarly, it does not report distributional checks or the method used to derive the sponsor’s geometric-mean interval.

The trial’s crossover structure permits a general distinction between within-participant and between-participant information. In a within-participant analysis, each participant’s response under one treatment is considered in relation to that same participant’s response under the other treatment. Shared participant characteristics can then be accounted for in the comparison. A simple difference between treatment-level means does not retain the participant-by-participant pairing. The posted recalculation is labeled unadjusted and is based on the posted summary statistics; its numbers should not be represented as a paired estimate.

Randomization concerns the assignment of treatment sequence, while masking concerns whether treatment assignment is concealed from participants or study personnel. The registry lists randomized allocation and no masking. These design labels do not, by themselves, explain the exact randomization procedure or how expectations were addressed. Those details are not reported in the registry record.

Statistical significance and equivalence are different objectives. A conventional test of a difference asks whether the data are inconsistent with a no-difference value under a specified model. An equivalence analysis instead evaluates whether the uncertainty is sufficiently contained within prespecified acceptable bounds. The sponsor result is classified in a legacy noninferiority-or-equivalence category, but the bounds and detailed decision criteria are not reported. A non-significant unadjusted p-value cannot take the place of those criteria.

The registry’s sample-size illustration uses the observed effect as its starting point and scales the effect to detect to stated fractions of that observed effect. It assumes a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. These are planning assumptions for the illustration, not reported original design assumptions for the trial. The registry record does not report the trial’s own sample-size justification, original target effect, or planned power. The illustration is not observed power; it describes hypothetical planning quantities under its stated assumptions, not the probability that the completed study detected an effect.

Finally, the endpoint population is described as subjects who completed the study. That is the available analysis-population description. The registry does not provide a fuller account of exclusions, missing endpoint observations, or analysis-set definitions. Without those details, it is not possible to assess how the analysis population was formed beyond the stated completion criterion.

10. Confidence Intervals and Precision

The unadjusted arithmetic mean difference is reported as 0.407 ng/mL, with a 95% confidence interval from -5.101 to 5.915. The estimate is close to no difference on the arithmetic scale, but the interval is much broader than the point estimate and includes values on either side of no difference. The data therefore do not determine the direction of the underlying arithmetic difference with precision. The reported p-value of 0.885 is consistent with substantial uncertainty under this unadjusted comparison; it is not evidence that the products are equivalent.

The sponsor’s ratio of geometric means is 97.4, with a 90% confidence interval from 89.4 to 106. This interval represents uncertainty on the ratio scale and should be interpreted separately from the 95% interval for the arithmetic mean difference. The two intervals differ in both the quantity being estimated and the reported confidence level. The registry does not report an equivalence margin, so the interval cannot be assessed against a stated acceptance range from the available record.

Precision depends on the estimate, variability, sample information, and analysis method. The arithmetic standard deviations are 12.37 for Zaleplon and 12.76 for Sonata®, while each treatment summary lists 40 observations. In a crossover study, within-participant association can also affect the precision of a paired comparison. The registry does not report the covariance or enough model details to quantify that contribution from the sponsor analysis.

Confidence intervals are not guarantees about the true effect, and their width does not by itself decide whether a result is important. Here, the posted intervals allow a range of plausible values rather than a sharply determined result. The sponsor’s geometric-mean analysis is the relevant posted result for its stated bioequivalence framing, while the arithmetic recalculation is an unadjusted descriptive comparison. Neither should be overstated beyond its scale, method, and reported precision.

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 estimates are participants per arm, not total events. They use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is set in turn to 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. These are planning illustrations computed from the observed effect, not the trial’s original design assumptions; the original sample-size justification is not reported in the registry record.

The 80% power column gives the estimated number of participants per arm for a hypothetical design intended to have an 80% chance of detecting the specified effect, under those assumptions. The 90% power column gives the corresponding planning estimate for a 90% chance. These are design calculations, not results measured in the completed trial. They do not indicate the probability that the actual study found a true effect, and they are not observed power.

The estimates increase as the effect to detect becomes smaller. That is the general planning relationship: if a study aims to distinguish a more subtle difference from random variation, it usually requires more information, often through more participants. The illustration applies that principle to fractions of the observed effect and the assumptions stated above. It does not establish that the observed effect is the right target for a future study, nor does it provide a justification for the original enrollment.

These calculations are based on a simplified two-arm planning framework. The actual trial was a randomized crossover study, and the registry does not report whether or how the original design calculations accounted for its crossover structure. The planning estimates should therefore be read as illustrations under the stated assumptions, not as a reconstruction of the study’s protocol or a recommendation for a future design.

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 = 0.407; pooled standard deviation σ = 12.568.
2. n = 2 × (1.96 + 0.842)² × 12.568² / 0.407² = 14,967.5, rounded up to 14,968 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 <- 0.407                      # observed difference in means
sigma <- 12.5675441117189                     # 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(829998)
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 = 14,968 (80% power), 20,038 (90% power)
 75% of observed effect: n per arm = 26,609 (80% power), 35,622 (90% power)
 50% of observed effect: n per arm = 59,871 (80% power), 80,150 (90% power)
power.t.test: 14968.5 
Simulated power at n = 14,968 per arm: 0.799 (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 registry reports the sponsor’s own analysis as a ratio of geometric means of 97.4, with a 90% confidence interval from 89.4 to 106. It labels this analysis under a legacy noninferiority-or-equivalence category. No p-value is reported for this analysis. The registry does not give the model details, equivalence margin, or decision rule associated with it.

The arithmetic re-calculation is a separate, unadjusted comparison based on the posted treatment means and standard deviations. It estimates a mean difference of 0.407 ng/mL, with a 95% confidence interval from -5.101 to 5.915 and an unadjusted p-value of 0.885. The calculation is not a substitute for the sponsor’s analysis: the sponsor’s result is a geometric-mean ratio, whereas the recalculation is an arithmetic difference. The different scales and confidence levels mean the results should not be treated as if they were duplicate estimates of the same quantity.

The registry indicates no discrepancy between the posted analysis and the recalculation. Where a recalculation differs from a sponsor analysis, the sponsor’s own analysis takes precedence for describing the trial’s reported analysis. In this case, both results can be reported with their distinct estimands and limitations. The record does not permit an independent assessment of the sponsor’s model or its equivalence decision criteria.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures and three analyses, but the available primary result concerns Cmax. It lists no secondary outcomes as posted. The record does not describe a multiplicity adjustment, a hierarchy of outcomes, or a prespecified strategy for controlling the chance of false-positive findings across multiple analyses. It would therefore be inappropriate to claim that the reported p-value was adjusted for multiple testing, or to infer that no adjustment was planned.

The endpoint population is described as data from all subjects who completed the study. The treatment summaries list 40 observations for each product. The registry record does not provide a participant flow account, the number of participants who may have withdrawn, reasons for any noncompletion, or details about missing samples or missing endpoint values. It also does not explain how incomplete concentration profiles were handled when determining Cmax.

The record does not report whether the analysis used an intention-to-treat, per-protocol, or other named analysis set. The description based on study completers is the only stated population detail for the primary analysis. It does not specify the handling of protocol deviations or whether all randomized participants were included in any analysis.

For a crossover trial, the analysis can depend on the treatment sequence, period, and the relation between measurements from the same participant. The registry record does not report whether these features were included in the sponsor’s model, nor does it describe tests or assumptions concerning carryover. The unadjusted recalculation is not a substitute for that missing model description.

These omissions limit how completely the statistical analysis can be audited from the registry record. They do not show that a particular method was or was not used; the relevant information is not reported in the registry record.

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

The results describe Cmax after Zaleplon 10 mg Capsules and Sonata® 10 mg Capsules under fasting conditions in the study population of healthy, non-smoking adults. The posted arithmetic means are 27.08 ng/mL for Zaleplon and 27.49 ng/mL for Sonata®, and the sponsor reports a geometric-mean ratio of 97.4 with a 90% confidence interval from 89.4 to 106. The unadjusted arithmetic recalculation estimates a mean difference of 0.407 ng/mL, with a 95% confidence interval from -5.101 to 5.915.

These numbers do not by themselves establish that the products are equivalent. A conclusion of equivalence depends on prespecified criteria and an appropriate analysis. Although the registry classifies the sponsor result in a legacy noninferiority-or-equivalence category, it does not report the equivalence limits or decision rule. The arithmetic re-calculation is not an equivalence test, and its unadjusted p-value of 0.885 does not establish equivalence either.

The endpoint is a peak concentration measure over a 10 hour sampling period. It does not summarize the full concentration-time profile or establish conclusions about other pharmacokinetic measures. Nor does this registry record provide a basis for conclusions about clinical outcomes, adverse effects, or use outside the studied conditions. The registry entries describe a phase 1 crossover comparison in healthy adults, not a clinical effectiveness assessment in patients.

The posted estimates also have uncertainty. The unadjusted confidence interval includes values in both directions around no difference, and the sponsor interval has its own uncertainty on the geometric-mean ratio scale. Interpretation should preserve the distinction between these estimands and avoid treating a lack of a statistically significant arithmetic difference as proof of sameness.

In short, the registry reports close treatment-level arithmetic averages and a sponsor geometric-mean ratio with an interval, but the available record does not provide enough detail to make an independent equivalence determination. The result is specific to Cmax, the stated products and fasting conditions, and the analysis information recorded for this study.

16. Why This Trial Matters Statistically

This trial illustrates why the analysis scale matters. Arithmetic mean differences and geometric-mean ratios describe continuous outcomes in different ways. Their estimates and confidence intervals cannot be compared as though they were the same quantity. The registry’s posting of both treatment-level arithmetic summaries and a sponsor geometric-mean ratio makes that distinction important to a careful reading.

The crossover design also highlights the difference between a trial’s structure and a simple recalculation from group summaries. Participants were assigned to sequences that exposed them to both products, making within-participant information potentially relevant. The unadjusted re-calculation uses the posted treatment summaries rather than a reported paired model. Without the sponsor’s model details, a reader cannot verify how the crossover structure contributed to the reported uncertainty.

Equivalence questions require more than a non-significant difference test. An equivalence interpretation relies on specified acceptable bounds and an analysis that evaluates those bounds. The registry categorizes the sponsor’s analysis as noninferiority-or-equivalence-related, yet does not report the bounds or the decision rule. This makes the distinction between a reported ratio estimate and a formal equivalence conclusion especially important.

The planning illustration provides another useful statistical lesson: estimates of required sample size depend on the effect a study aims to detect and on assumptions about the design and analysis. Smaller target effects require more participants under the stated planning framework. Those calculations are illustrative and do not reveal why the original trial enrolled 40 participants, since its original design assumptions are not reported.

Overall, the study is a compact example of how design, estimand, uncertainty, and analysis-population details shape interpretation. The numerical result is only one part of the statistical account; the missing protocol and modeling details define the limits of what can be concluded from the registry record.

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 record contains limited methodological detail for evaluating the primary analysis. It does not report the sponsor’s model, how the randomized sequence and study period were handled, or whether the within-participant structure was incorporated. The unadjusted recalculation cannot answer those questions, because it is derived from posted treatment-level summaries rather than a reported paired analysis.

The sponsor’s result is reported as a ratio of geometric means with a 90% confidence interval, but its equivalence margin and decision rule are not reported in the registry record. Without those criteria, the ratio and interval cannot be used to independently determine whether a formal equivalence standard was met. The registry also does not report the method used to calculate that interval.

The primary analysis population is described as subjects who completed the study. The record does not include detailed participant flow, reasons for noncompletion, missing sample information, or the method used to handle incomplete concentration profiles. This limits assessment of potential effects of exclusions or missing data.

The endpoint is Cmax over a 10 hour sampling period. The registry record does not provide further information about the sampling schedule or other pharmacokinetic outcomes in the registry record for this comparison. Therefore, interpretation should remain focused on the stated endpoint and conditions, rather than extending to other measures of exposure.

The study concerns healthy, non-smoking adults under fasting conditions. The registry record does not establish how results would generalize to other populations or conditions. Finally, the original sample-size assumptions and justification are not reported. The planning illustration is based on the observed effect under stated assumptions and cannot be used to reconstruct the original design rationale.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Zaleplon 10mg Capsules Under Fasting Conditions — NCT00829998.
• Registry record last updated 2024-08-21; status last verified 2024-08.
• Results first posted 2009-08-18.
• 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

NCT00829998 is a completed, randomized, unmasked phase 1 crossover study sponsored by Teva Pharmaceuticals USA. The registry lists enrollment of 40 and a start and primary completion in 2004-02. The objective was to compare the relative bioavailability of Teva Zaleplon 10 mg Capsules with Sonata® 10 mg Capsules under fasting conditions in healthy, non-smoking adults.

The primary outcome was Cmax, maximum observed concentration in ng/mL, based on blood samples collected over a 10 hour period. The sponsor’s posted analysis reports a geometric-mean ratio of 97.4 with a 90% confidence interval from 89.4 to 106. An unadjusted recalculation from the posted arithmetic summaries reports a mean difference of 0.407 ng/mL, with a 95% confidence interval from -5.101 to 5.915 and an unadjusted p-value of 0.885.

The registry record does not report the sponsor’s detailed model, equivalence criteria, original sample-size assumptions, or fuller missing-data and analysis-population details. Those omissions limit independent interpretation of the formal bioequivalence question.