Fasted Bioavailability Study of Cilostazol Tablets, 100 mg: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Fasted Bioavailability Study of Cilostazol Tablets, 100 mg (NCT00684762), a randomized phase 1 study. The primary outcome is Maximum Plasma Concentration (Cmax).

2. Clinical Question

3. Trial Design

This was a Phase 1, randomized, unmasked crossover study of two cilostazol tablet formulations under fasting conditions. The study enrolled 32 participants and is recorded as completed. Both treatments were single oral doses of 100 mg: the test cilostazol tablet and Pletal® 100 mg. Each was administered after an overnight fast of at least 10 hours. The registry gives March 2004 as both the start month and the primary completion month.

A crossover design compares treatments within the same participants rather than assigning each participant to only one treatment throughout the study. General statistical context: using participants as their own comparison can account for stable differences between people, although analysis must also address the paired nature of the observations. The registry identifies the design as crossover but does not report the treatment sequence, number of periods, washout interval, or how period and sequence effects were handled. Those details are not reported in the registry record.

The study was unmasked, meaning masking is recorded as none. The registry identifies the allocation as randomized but does not report the randomization method or allocation sequence. The analyzed plasma concentration population consisted of 28 participants. Four did not complete the study, and none of their collected data was used in the statistical analysis. The arm summaries each show 28 participants. These summaries do not establish which observations were paired or what analysis model was used.

The primary endpoint was Cmax, the maximum plasma concentration. Concentrations were drawn before dosing and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 16, 24, 36 and 48 hours after dosing. The registry lists three outcome measures but no posted statistical analyses. Details of the original statistical plan, including any prespecified model or decision criteria, are not reported in the registry record.

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 Period of 7 Days

Reasons for not completing this period:

Second Intervention

Analysis population for the primary outcome, as defined in the registry: Plasma concentration data for 28 of the 32 enrolled participants were used in the statistical analysis. Four subjects did not complete the study and none of their collected data was used.

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 Maximum Plasma Concentration (Cmax), measured over serial pharmacokinetic concentrations were drawn pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 16, 24, 36 and 48 hours post-dose..

Cmax is the maximum, or peak, concentration of cilostazol measured in plasma after a dose. It is a continuous pharmacokinetic measure as a mean in ng/mL with a standard deviation. The concentration schedule began before dosing and continued through 48 hours after dosing. The registry describes the endpoint as the peak concentration reached by the test and reference products.

General statistical context: a peak concentration is used in pharmacokinetic comparisons because it describes the highest measured concentration following administration. Comparing peak values can help characterize how two formulations behave in the body, but Cmax alone does not describe the full concentration-time profile. It is distinct from measures that summarize total exposure over time. No additional endpoint results are included in the posted record.

The mean Cmax was 484.9 ng/mL for Cilostazol 100 mg Tablets and 472.7 ng/mL for Pletal® 100 mg Tablets. The corresponding standard deviations were 205.2 and 140.8. A standard deviation describes how spread out individual observations are around a mean; it is not a confidence interval for the mean. The registry does not report an equivalence margin or a threshold for a clinically meaningful difference in Cmax, so the endpoint values alone cannot establish a formal equivalence conclusion.

7. Results Posted in the Registry

• Pletal® 100 mg Tablets: mean 472.69 versus 484.89 on control; difference -12.21 (95% CI -104.39 to 79.97), standardized effect d = -0.07; z-test p = 0.795.

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies the primary outcome as a continuous measure summarized by its mean and standard deviation. It also identifies the design as randomized and crossover. The record does not report a statistical analysis model, a sponsor-reported inferential test, a confidence level for the interval, or a prespecified decision rule. The numerical comparison is a recalculated, unadjusted comparison based on the posted summary statistics.

What does a mean describe?

The mean is the arithmetic average of a set of observations. For Cmax, the posted means are 484.9 ng/mL for Cilostazol 100 mg Tablets and 472.7 ng/mL for Pletal® 100 mg Tablets. A mean gives a concise description of the observed concentrations in each treatment summary, but it does not show the full distribution. Two groups can have similar means while differing in spread, shape, or individual-level patterns.

The standard deviations are 205.2 and 140.8. General statistical context: standard deviation describes typical dispersion of observations around their group mean. It is not the standard error, which describes uncertainty in an estimated mean, and it is not a confidence interval. The posted arm-level spread is useful context, but in a crossover comparison it does not by itself give the variability of the paired treatment differences.

Why does the crossover design matter?

In a crossover design, the same participant receives more than one treatment, so treatment results are linked within each person. General statistical context: an analysis that uses this pairing can distinguish treatment differences from stable differences between participants. The precision of the treatment contrast depends in part on how strongly paired measurements move together. Separate means and standard deviations do not reveal that correlation or the standard deviation of the within-participant differences.

The registry record does not report the treatment order, periods, washout, or whether the statistical analysis accounted for period, sequence, or participant effects. It is therefore not possible to verify from the posted record whether the recalculated comparison reflects the design's paired structure. The recalculation should not be interpreted as a reconstruction of an unknown original crossover analysis.

What does the interval convey?

The recalculated mean difference is -12.21 ng/mL, and its reported interval extends from -104.4 to 79.97. General statistical context: a confidence interval represents a range of parameter values compatible with the observed data under a statistical model and its assumptions. A wider interval indicates less precision than a narrower interval. The stated confidence level and model are not reported in the registry record, so the interval is best described using its posted limits without assigning a confidence percentage.

The interval includes zero, meaning that the range includes no difference as well as differences in either direction. That does not prove there is no treatment difference. Nor does an interval that includes zero demonstrate equivalence: equivalence requires a defined margin and an analysis showing that the plausible treatment differences lie within that margin. No equivalence margin is reported in the registry record.

How should the p-value be read?

The unadjusted recalculation reports p = 0.795. General statistical context: a p-value describes how compatible the observed data are with a particular null hypothesis, conditional on the chosen model and assumptions. It is not the probability that the treatments are the same, and it does not measure the probability that the result occurred by chance. It also does not indicate whether a difference would be clinically important.

Because the registry does not report the sponsor's analysis or a test model, the p-value belongs to the unadjusted recalculation and should not be presented as the original trial's prespecified test. In a crossover study, the use of an unpaired summary-statistic calculation may not capture within-participant information. That limitation affects how much inferential weight should be placed on the recalculated p-value.

Why can over-dispersion matter?

General statistical context: over-dispersion describes variability greater than a model expects. It is particularly relevant when outcomes are counts or binary events, where a simple model may understate uncertainty if observations vary more than assumed. Cmax is continuous, and the registry does not report an over-dispersion assessment or a model that addresses it. The general concept does not establish that over-dispersion was present in this study. For this endpoint, the directly visible concern is substantial spread in the posted values and the absence of paired variability information.

The registry lists three outcome measures and no posted analyses. It does not report adjustments for multiple testing, handling of missing data beyond excluding the four noncompleters' collected data, or the statistical analysis population beyond the stated 28 participants. These omissions limit assessment of the original analysis, but they do not change the descriptive values recorded for Cmax.

10. Confidence Intervals and Precision

The recalculated mean difference in Cmax is -12.21 ng/mL, with reported limits of -104.4 and 79.97. These limits describe a broad range of values compatible with the unadjusted comparison under its calculation assumptions. The interval spans zero, so it does not isolate a single direction of difference. It also includes differences larger in magnitude than the point estimate. The posted result is therefore not a highly precise estimate of the comparison.

General statistical context: precision concerns the width of an estimate's uncertainty interval. A narrow interval indicates that the estimate is more tightly localized, while a wide interval leaves more possible values consistent with the data. Precision is not the same as absence of bias, clinical importance, or equivalence. A formal equivalence assessment would require a prespecified margin and a suitable analysis; no such margin or sponsor analysis is reported in the registry record.

The interval's confidence level and the method used to calculate it are not reported in the registry record. The interval should therefore be quoted by its limits without assigning a confidence percentage or assuming it came from a particular crossover model. The recalculation uses posted summary statistics and is unadjusted. Because the study is crossover, within-participant covariance would ordinarily inform the precision of a paired contrast, but that information is not available in the posted summaries.

The arm means are 484.9 ng/mL and 472.7 ng/mL, with standard deviations of 205.2 and 140.8. The standard deviations describe participant-level spread, not the uncertainty interval for the difference. The registry does not provide individual-level data or the standard deviation of paired differences, so the precision of a design-aware crossover estimate cannot be assessed from the posted record.

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. They are illustrations based on the observed effect, not the original trial's design calculation. The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The target effect is set to the stated fraction of the observed effect. The trial's own original sample-size assumptions and justification are not reported in the registry record.

For planning around 100% of the observed effect, the figures are 3,263 participants per arm for 80% power and 4,369 participants per arm for 90% power. For 75% of the observed effect, they are 5,801 and 7,766 participants per arm, respectively. For 50% of the observed effect, they are 13,052 and 17,473 participants per arm, respectively.

General statistical context: power is the probability that a planned study will detect an effect of a specified size under the assumptions used for its calculation. The 80% column describes the planned per-arm sample size associated with an 80% chance of detecting the target effect at the stated significance level; the 90% column does the same for a 90% chance. These are planning illustrations, not observed power. Smaller effects are harder to distinguish from random variability, so planning for a smaller fraction of the observed effect requires more participants. The registry record does not report that these planning assumptions were used when designing the completed study.

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 = -12.206; pooled standard deviation σ = 175.977.
2. n = 2 × (1.96 + 0.842)² × 175.977² / -12.206² = 3,262.9, rounded up to 3,263 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 <- -12.206                      # observed difference in means
sigma <- 175.977261897667                     # 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(684762)
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 = 3,263 (80% power), 4,369 (90% power)
 75% of observed effect: n per arm = 5,801 (80% power), 7,766 (90% power)
 50% of observed effect: n per arm = 13,052 (80% power), 17,473 (90% power)
power.t.test: 3263.9 
Simulated power at n = 3,263 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. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures, but no secondary outcome results are posted. The primary endpoint is Cmax. The registry record does not report whether the outcome measures were assigned a hierarchy, whether any were designated exploratory, or whether an adjustment for multiple comparisons was planned or applied. Without those details, the role of multiplicity in the original analysis is not reported in the registry record.

General statistical context: when several outcomes or comparisons are tested, the chance of at least one apparently unusual result can increase if each test is interpreted separately. Prespecified hierarchy or multiplicity adjustment can help control that issue. The record does not establish whether this concern affected the original study's analysis, so no conclusion about such adjustment should be inferred.

For missing data, the registry states that 28 of the 32 enrolled participants contributed plasma concentration data to the statistical analysis. Four participants did not complete the study, and none of their collected data was used. The reasons for noncompletion, timing of withdrawal, and any assessment of the effect of missing data are not reported in the registry record. No imputation method or sensitivity analysis is described.

The available endpoint summaries therefore represent the 28 participants included in the analysis, rather than all enrolled participants. The record does not report an intention-to-treat population, a per-protocol definition, or another formal analysis-population label. It also does not explain how the arm-level sample size of 28 relates to each participant's paired measurements in the crossover comparison. These omissions constrain assessment of the original analysis population and missing-data assumptions.

The unadjusted recalculation uses posted summary statistics and should not be taken as evidence that missing data, multiple outcomes, or the paired design were handled in a particular way by the sponsor. Details of those procedures are not reported in the registry record.

14. 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 non-serious adverse event terms

The safety summaries list 30 participants at risk in each treatment group. Serious adverse events were recorded for 0 participants in the Cilostazol 100 mg Tablets group and 0 participants in the Pletal® 100 mg Tablets group. Other adverse events were recorded for 11 participants in the test-product group and 12 participants in the Pletal® group. These are counts of participants with events as reported in the registry, not measures of event severity beyond the serious-versus-other categories.

The safety group size differs from the 28 participants whose plasma concentration data were analyzed. The registry does not explain the reason for this difference or provide further detail on event timing, duration, or relationship to treatment. Deaths are not reported in the registry record. No serious adverse event terms are listed. These summaries are descriptive and do not establish that the treatments have the same safety profile or support a comparative safety conclusion.

General statistical context: a count of zero observed serious events does not establish that the underlying risk is zero. The amount of information in a safety summary depends on the number observed, the number followed, and the completeness of reporting. The registry provides no additional safety analysis, so interpretation should remain limited to the recorded participant counts.

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

The posted results describe Cmax after a single 100 mg dose of the test cilostazol tablet and Pletal® under fasting conditions. The observed mean concentrations were 484.9 ng/mL and 472.7 ng/mL, with standard deviations of 205.2 and 140.8. The recalculated, unadjusted mean difference is -12.21 ng/mL, with an interval from -104.4 to 79.97 and p = 0.795. These values characterize the available summaries; they do not establish that the formulations are identical, equivalent, or different.

In particular, a nonsignificant p-value is not evidence of equivalence. A formal equivalence conclusion requires a prespecified acceptable range of differences and an analysis that evaluates whether the estimate is sufficiently precise relative to that range. No equivalence margin is reported in the registry record, and the record does not report the sponsor's statistical analysis or confidence level for the posted interval. The interval includes zero and remains broad, leaving uncertainty about the size and direction of the treatment contrast.

The registry identifies a randomized crossover design, but the available arm summaries do not show the within-participant relationship that is central to a paired analysis. The recalculation is unadjusted and should not be interpreted as a design-specific sponsor result. Details of sequence, period handling, washout, and missing-data procedures are not reported in the registry record.

The endpoint is a pharmacokinetic measure, not a direct measure of clinical benefit. The study purpose was to compare relative bioavailability under fasting conditions after a single dose. The record does not establish how these findings relate to outcomes in other settings, repeated administration, or clinical effects. Four participants did not complete the study, and their collected data were not used in the statistical analysis. The results therefore describe the analyzed participants and the specific conditions recorded, with limitations in both precision and available analysis detail.

16. Why This Trial Matters Statistically

This trial illustrates why a close pair of means does not by itself settle a comparison. The Cmax means were 484.9 ng/mL for Cilostazol 100 mg Tablets and 472.7 ng/mL for Pletal® 100 mg Tablets, but the reported standard deviations were 205.2 and 140.8. The recalculated interval from -104.4 to 79.97 shows that the estimated contrast is not tightly localized. Looking at the point estimate alone would conceal that uncertainty.

The crossover design also highlights the importance of matching the statistical analysis to the study structure. General statistical context: in a crossover study, observations within a participant are linked. A paired analysis can use this link, while a comparison based only on separate group summaries cannot recover it. The registry record does not report the within-participant variability or the sponsor's analysis model, so the available recalculation is informative as a simple summary but not a full reconstruction of the trial's intended analysis.

The study's stated purpose concerns relative bioavailability, while a formal equivalence conclusion depends on explicit criteria and adequate precision. The registry record does not report an equivalence margin. This makes the distinction between failure to identify a difference and evidence that differences fall within an acceptable range especially important.

Finally, the record distinguishes the 32 enrolled participants from the 28 whose concentration data were analyzed, and its safety summaries use a different listed at-risk group size. Recognizing these populations helps prevent descriptive summaries from being mistaken for a complete account of analysis and follow-up. The trial is a useful example of how design details, analysis choices, and reporting completeness shape the meaning of numerical results.

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 does not report the crossover treatment sequence, period structure, washout interval, or how period and sequence effects were considered. It also does not report the within-participant variability needed to assess the precision of a paired treatment contrast. As a result, the unadjusted recalculation from separate summary statistics may not represent the analysis most appropriate to the design.

The registry does not provide the sponsor's inferential analysis, statistical model, confidence level for the interval, or a prespecified decision rule. It also does not report an equivalence margin. Consequently, the numerical comparison cannot establish a formal equivalence conclusion from the registry record alone.

Four of the 32 enrolled participants did not complete the study, and none of their collected data was used in the concentration analysis. Reasons for noncompletion and an assessment of its potential impact are not reported in the registry record. The safety summaries list 30 participants at risk per group, but the reason those counts differ from the concentration-analysis population is not reported.

The available endpoint information is limited to the posted summaries, with no individual-level concentrations or additional outcome results reported. Although the registry lists three outcome measures, it does not provide secondary outcome results or details about multiplicity. The study evaluates single-dose administration under fasting conditions; the record does not provide evidence about other dosing conditions or settings. These reporting limits restrict interpretation to the recorded design, endpoint, analyzed population, and descriptive results.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Fasted Bioavailability Study of Cilostazol Tablets, 100 mg — NCT00684762.
• Registry record last updated 2009-12-22; status last verified 2009-11.
• Results first posted 2009-12-22.
• 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

NCT00684762 is a completed Phase 1 randomized, unmasked crossover study titled “Fasted Bioavailability Study of Cilostazol Tablets, 100 mg.” It compared a single 100 mg test cilostazol tablet with a single 100 mg Pletal® tablet after an overnight fast of at least 10 hours. The study enrolled 32 participants; plasma concentration data from 28 were used in the statistical analysis, and four noncompleters contributed no data to that analysis.

The primary endpoint was maximum plasma concentration, Cmax, measured in ng/mL. The means were 484.9 for the test product and 472.7 for Pletal®, with standard deviations of 205.2 and 140.8. An unadjusted recalculation reports a mean difference of -12.21, an interval from -104.4 to 79.97, and p = 0.795. The registry does not report the sponsor's analysis, an equivalence margin, or the original sample-size justification.