This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Bioequivalence Between Two Tablet Formulations Of Doxycycline Carragenate (NCT00939562), a randomized phase 4 study. The primary outcome is Maximum Plasma Concentration (Cmax) of Doxycycline.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00939562 |
| Phase | Phase 4 |
| Condition | Bacterial Infection |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | None (open label) |
| Enrollment | 24 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Pfizer |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled normal healthy male subjects. The registry describes the pharmacokinetic concentration population as all subjects who were randomized and treated and had at least one concentration measurement in at least one treatment period. The recorded enrollment was 24. The registry does not report further participant characteristics or eligibility details.
Intervention
The intervention was a doxycycline carragenate tablet. The registry identifies this as a drug intervention and lists the primary outcome as maximum plasma concentration of doxycycline. The record does not provide further formulation details or dosing instructions.
Comparator
The comparator was a doxycycline monohydrate tablet. The registry identifies it as a drug intervention. In the posted outcome results, the mean maximum plasma concentration was 2.526 ug/mL for monohydrate and 2.442 ug/mL for carragenate.
Primary question
The primary question was whether the two tablet formulations have comparable pharmacokinetic exposure as assessed by maximum plasma concentration. The registry’s own analysis reports a ratio of 102.95 with a 90% confidence interval from 94.74 to 111.86. The record does not report the decision rule or equivalence limits used to interpret that interval, so the result alone does not establish whether a prespecified bioequivalence criterion was met.
This was a formulation comparison, not a comparison against no treatment or placebo. The clinical context recorded in the registry is bacterial infection, but the participants were described as healthy male subjects. The study therefore addresses a pharmacokinetic question in the recorded study population. It does not directly report clinical outcomes among people being treated for bacterial infection.
3. Trial Design
The registry describes an open-label, randomized, two-treatment, two-period crossover study. The two treatments were doxycycline monohydrate tablets and doxycycline carragenate tablets. In a crossover design, participants receive more than one treatment in separate periods, allowing a comparison within participants as well as between treatment sequences. That is a general description of the design; the registry record does not report the sequence details or the interval between periods.
Allocation was randomized, while masking was listed as none. Thus, the record identifies randomization but does not describe blinding of participants or study personnel. The official title specifies normal healthy male subjects. The study was classified as phase 4, and the registry lists Pfizer as sponsor. Its status is completed. The recorded start was 2008-11 and primary completion was 2008-12.
Enrollment was 24. The outcome summaries list 24 for each treatment group, and the pharmacokinetic population definition includes randomized and treated subjects with at least one concentration in at least one period. Because this is a crossover study, the treatment-group summaries should not be read as evidence that separate groups of participants received only one formulation. Each participant’s treatment sequence and the handling of incomplete periods are not reported in the registry record.
The primary outcome was maximum plasma concentration of doxycycline, reported as a mean with standard deviation and measured in ug/mL. Concentrations were scheduled at predose and at postdose times through 72 hours. The registry records one primary outcome and two outcome measures overall, but it does not report further endpoint definitions, protocol details, or the original design assumptions for sample size.
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.
Period 1
| Stage | Doxycycline Monohydrate, Then Doxycycline Carragenate | Doxycycline Carragenate, Then Doxycycline Monohydrate |
|---|---|---|
| STARTED | 12 | 12 |
| COMPLETED | 12 | 12 |
| NOT COMPLETED | 0 | 0 |
Period 2
| Stage | Doxycycline Monohydrate, Then Doxycycline Carragenate | Doxycycline Carragenate, Then Doxycycline Monohydrate |
|---|---|---|
| STARTED | 12 | 12 |
| COMPLETED | 12 | 12 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: The pharmacokinetic (PK) concentration population was defined as all subjects randomized and treated who had at least 1 concentration in at least 1 treatment period.
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.
| Characteristic | Unit | Entire Study Population |
|---|---|---|
| Participants analysed | 24 | |
| Age, Customized: < 18 years | participants | 0 |
| Age, Customized: 18 to 44 years | participants | 24 |
| Age, Customized: 45 to 64 years | participants | 0 |
| Age, Customized: > = 65 years | participants | 0 |
| Sex: Female, Male: Female | Participants | 0 |
| Sex: Female, Male: Male | Participants | 24 |
| Race/Ethnicity, Customized: Asian | participants | 24 |
6. Primary Endpoint
The registry lists the primary outcome as Maximum Plasma Concentration (Cmax) of Doxycycline, measured over 0 (predose), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 60, and 72 hours postdose..
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | ug/mL |
| Endpoint classification | Continuous Endpoint |
Maximum plasma concentration, commonly abbreviated Cmax, describes the highest measured concentration of a substance in plasma over a specified observation period. It is a pharmacokinetic measure: it characterizes drug concentration over time rather than a clinical outcome such as symptom improvement or infection resolution. The unit recorded for this endpoint is ug/mL.
The registry lists measurements at predose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 60, and 72 hours postdose. These scheduled measurements provide the basis for describing the peak concentration observed during the sampling period. The registry does not state precisely how the maximum was derived if a scheduled measurement was missing, nor does it report details about concentration assay procedures.
Cmax is used in pharmacokinetic comparisons because a formulation can affect the magnitude of the peak concentration as well as the timing and overall pattern of concentrations. Comparing Cmax between formulations therefore addresses one aspect of drug exposure. It does not, by itself, describe all aspects of exposure, and it does not establish a clinical effect. The record reports no secondary posted outcome measures, so interpretation should remain focused on the stated primary concentration endpoint and the registry’s reported comparison.
7. Results Posted in the Registry
- Doxycycline Carragenate: mean 2.44 versus 2.53 on control; difference -0.08 (95% CI -0.36 to 0.19), standardized effect d = -0.17; z-test p = 0.548.
Mean difference: Doxycycline Carragenate
95% CI: -0.36 to 0.19
Recalculated from the posted summary statistics
8. Statistical Interpretation
The posted group means for maximum plasma concentration were 2.526 ug/mL for doxycycline monohydrate and 2.442 ug/mL for doxycycline carragenate. The reported standard deviations were 0.509 and 0.459, respectively. These summaries describe the observed concentration values in the registry’s treatment groups. They do not alone show the uncertainty in the treatment comparison or establish a bioequivalence conclusion.
The unadjusted recalculation expresses the comparison as a mean difference, with carragenate compared with monohydrate. The estimated difference is -0.084 ug/mL, and the unadjusted p-value is 0.548. The recalculated confidence interval extends to values on both sides of no mean difference. This is a simple summary-statistics re-calculation, not the sponsor’s reported ratio-based analysis. A difference scale and a ratio scale express the comparison differently, so their estimates should not be treated as interchangeable.
The registry’s own analysis reports a ratio of 102.95 and a 90% confidence interval from 94.74 to 111.86. The analysis method and a p-value for this reported result are not reported in the registry record. The ratio-based result is the relevant posted analysis for the registry’s bioequivalence question, but the record does not state the acceptance limits or decision rule needed to judge it against a formal bioequivalence criterion. A confidence interval’s location alone cannot supply a missing criterion.
The unadjusted p-value answers a different question from an equivalence assessment. In a conventional difference test, a p-value describes how compatible the observed data are with a null hypothesis of no difference, under the assumptions of that test. A large p-value does not demonstrate that two formulations are equivalent. Evidence of equivalence requires an appropriate analysis and prespecified bounds defining how large a difference can be while remaining acceptable. Those bounds are not reported in the registry record.
These results are also specific to the recorded endpoint and study population. The trial assessed maximum plasma concentration in healthy male subjects, not clinical outcomes in people with bacterial infection. The record does not provide results for symptom response, infection resolution, or other patient outcomes. Its concentration findings therefore answer a pharmacokinetic comparison question only, and the reported precision and analysis details limit how far the result can be interpreted.
9. Statistical Methods Explained
The primary endpoint is continuous: maximum plasma concentration is measured on a numeric scale in ug/mL. The registry reports a mean and standard deviation for each treatment. A mean describes the central value of the observed measurements, while a standard deviation describes their spread around that mean. The standard deviation is not the same as the uncertainty in the mean or in the treatment comparison.
What does the mean difference describe?
The recalculated comparison is a mean difference, with carragenate minus monohydrate. Its estimate is -0.084 ug/mL. A negative value indicates that the carragenate group mean is lower on this subtraction scale. The recalculation is unadjusted and based on the posted summary statistics; it is not a model-based reconstruction of the crossover analysis. The registry does not report enough detail to reproduce the sponsor’s method.
A difference is measured in the same units as the endpoint. It is useful for expressing the absolute separation between group means. The interpretation of a difference depends on the scientific question and any decision thresholds set before the study. The registry does not report a clinically meaningful difference threshold for Cmax.
Why is a ratio also reported?
The registry’s analysis reports a ratio of 102.95, with a 90% confidence interval from 94.74 to 111.86. A ratio expresses one treatment’s result relative to the other rather than as an absolute change in ug/mL. Ratio-based comparisons are commonly used for formulation comparisons because they describe relative exposure. The registry does not identify the precise calculation method, so the reported estimate should be read as the registry’s own result rather than as a ratio reconstructed from the group means.
Difference and ratio analyses answer related but distinct questions. A difference focuses on absolute separation; a ratio focuses on relative separation. The numerical values lie on different scales and should not be compared by simply subtracting one from the other. The record does not report the model, transformations, sequence terms, period terms, or other details behind the sponsor’s ratio analysis.
What does the p-value say?
The unadjusted recalculation reports p = 0.548. In general, a p-value summarizes how unusual data at least as incompatible with a specified null hypothesis would be if that null hypothesis and the analysis assumptions were correct. It does not give the probability that the null hypothesis is true, and it does not measure the probability that the result occurred by chance in a broad everyday sense.
The recalculated p-value concerns a no-difference contrast, not a formal equivalence conclusion. Failure to find evidence against no difference is not the same as evidence that the difference is acceptably small. Equivalence is ordinarily assessed against prespecified bounds using a suitable confidence interval or testing procedure. The registry record does not report those bounds or the sponsor’s method, so the p-value from the unadjusted re-calculation cannot substitute for the registry’s ratio-based analysis.
Why does the crossover design matter?
General statistical explanation: a crossover design can compare treatments within the same participants, which may reduce the influence of stable differences between people. But the analysis must account for the paired structure and may need to consider treatment sequence and period effects. The registry identifies a randomized, two-treatment, two-period crossover design, but it does not report the analysis method or the handling of period, sequence, or carryover effects. The simple re-calculation from group summaries does not account for the within-participant correlation, so its uncertainty should not be treated as a substitute for a crossover-specific analysis.
In general, missing observations in a crossover study can matter differently from missing observations in a parallel-group study: a participant may contribute information for one treatment period but not the other. The registry defines the pharmacokinetic concentration population as randomized and treated subjects with at least one concentration in at least one treatment period. It does not report how many subjects contributed paired observations, whether any periods were incomplete, or how missing concentration measurements were handled.
Why can variability affect precision?
General statistical explanation: when individual measurements vary more widely, the estimated treatment contrast is often less precise unless the study has enough information to offset that variability. In a crossover trial, the within-participant variability and correlation between period measurements can be especially relevant. The posted standard deviations describe group-level spread, but they do not give the within-participant covariance needed to assess the precision of a paired treatment contrast. That information and the sponsor’s model are not reported in the registry record.
The statistical methods available for interpretation are therefore limited. The posted means and standard deviations support a descriptive comparison, and the unadjusted recalculation gives a simple difference-scale estimate. The registry also reports a ratio and confidence interval from its own analysis, but does not report the method used to obtain them. No further analysis details, multiplicity strategy, or missing-data procedures are reported.
10. Confidence Intervals and Precision
Precision concerns how narrowly the data estimate a treatment contrast. A confidence interval gives a range of values compatible with the data and the analysis assumptions at its stated confidence level. It is not a guarantee that the true value lies within the interval, and it does not by itself determine whether a result is important or meets a decision criterion.
The registry’s ratio analysis reports a 90% confidence interval from 94.74 to 111.86 around the ratio estimate of 102.95. This interval communicates uncertainty on the ratio scale. Whether its width is sufficiently narrow for a bioequivalence conclusion depends on acceptance limits and a decision rule, neither of which is reported in the registry record. Without those limits, the interval should be described as an estimate with uncertainty rather than classified as passing or failing a formal criterion.
The unadjusted mean-difference recalculation also has a confidence interval, which spans values on both sides of zero. That interval belongs to a simple unadjusted comparison based on posted summary statistics. The crossover design’s paired structure is not incorporated in that re-calculation, and the registry does not report the sponsor’s analysis method for comparison. It is therefore important not to treat the recalculated interval as the sponsor’s uncertainty estimate.
Precision is distinct from statistical significance and from equivalence. A narrow interval can still be centered at a value that does not meet a specified criterion; a broad interval can leave substantial uncertainty even when a point estimate appears close to a reference value. The registry’s reported ratio interval is the relevant posted precision statement for its own analysis, while missing criteria and methods constrain further interpretation.
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.
| Effect to detect | Participants per arm, 80% power | Participants per arm, 90% power |
|---|---|---|
| 100% of the observed effect | 523 | 699 |
| 75% of the observed effect | 929 | 1,243 |
| 50% of the observed effect | 2,089 | 2,796 |
The planning values are participants per arm, not total events. They are illustrations based on the observed effect, not the trial’s original design assumptions. The calculations assume a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. Each row uses a stated fraction of the observed effect as the effect to detect: 100% of the observed effect, 75% of the observed effect, or 50% of the observed effect.
The 80% power column gives the number of participants per arm in the planning calculation for an 80% chance of detecting the specified effect under those assumptions. The 90% power column gives the number of participants per arm for a 90% chance under the same assumptions. These are design illustrations; they do not describe what happened in the completed study. This is not observed power.
For 100% of the observed effect, the illustration gives 523 participants per arm for 80% power and 699 for 90% power. For 75% of the observed effect, it gives 929 participants per arm for 80% power and 1,243 for 90% power. For 50% of the observed effect, it gives 2,089 participants per arm for 80% power and 2,796 for 90% power.
The pattern reflects a general feature of power calculations: smaller effects are harder to detect and require more participants, all else equal. These illustrations use the observed effect as their starting point and do not establish a preferred target effect. The trial’s own original sample-size justification and design assumptions are not reported in the registry record. The posted calculation assumptions should not be confused with the assumptions used when the study was planned.
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 z1−α/2 = 1.960) and the desired power (z1−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
- Observed difference Δ = -0.084; pooled standard deviation σ = 0.484.
- n = 2 × (1.96 + 0.842)2 × 0.4842 / -0.0842 = 522.0, rounded up to 523 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 <- -0.0839999999999996 # observed difference in means
sigma <- 0.484408531097461 # 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(939562)
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 = 523 (80% power), 699 (90% power)
75% of observed effect: n per arm = 929 (80% power), 1,243 (90% power)
50% of observed effect: n per arm = 2,089 (80% power), 2,796 (90% power)
power.t.test: 523
Simulated power at n = 523 per arm: 0.800 (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
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| not stated | Ratio 102.95 | 94.74 to 111.86 | not reported |
The registry’s own analysis is ratio-based: it reports a ratio of 102.95 and a 90% confidence interval from 94.74 to 111.86. The analysis method and p-value are not reported in the registry record. The mean-difference estimate of -0.084 ug/mL and p-value of 0.548 are an unadjusted re-calculation from posted summary statistics, not the sponsor’s reported result.
The two results use different scales and different analysis detail. The re-calculation uses treatment-group summaries and does not account for the crossover pairing. It should therefore be used as a supplementary descriptive check, not as a replacement for the registry’s own analysis. No discrepancy is flagged between the posted information and the re-calculation in the registry record.
The ratio and its confidence interval are the most direct posted evidence for the registry’s formulation-comparison question. However, the record does not state the equivalence margins, decision rule, or method behind the sponsor’s estimate. The ratio result can be described accurately, but a formal conclusion about whether the trial met its bioequivalence criterion cannot be made from the registry record alone.
14. Multiplicity, Missing Data and Analysis Populations
The registry lists two outcome measures overall and one primary outcome: maximum plasma concentration of doxycycline. It reports no secondary posted outcome measures. The analysis count is listed as two, but the record does not explain whether those analyses address distinct endpoints, populations, or statistical approaches. The two analyses should not be assumed to represent independent confirmatory tests.
Multiplicity arises when several hypotheses or outcomes are tested. In general, testing more hypotheses can increase the chance of at least one apparently notable finding if no adjustment or prespecified hierarchy is used. A statistical plan may address this through an adjustment, a hierarchy, or another approach. The registry record does not report a multiplicity strategy, so it is not possible to determine whether any adjustment was planned or applied.
The concentration population is defined as all randomized and treated subjects with at least one concentration in at least one treatment period. This definition clarifies who was eligible to contribute to the pharmacokinetic concentration analysis, but it does not give the number who met that definition or the number with usable measurements in both periods. The record also does not report a separate intention-to-treat population, a per-protocol population, exclusions from analysis, or reasons for missing observations.
Missingness may affect a crossover comparison because complete information for both treatment periods can be important for a within-participant contrast. General statistical explanation: conclusions can depend on whether missing measurements are unrelated to the unobserved values or connected to participant characteristics, treatment, or measured outcomes. The registry does not report the amount, pattern, or treatment of missing concentration data, so the effect of missingness on the posted estimates cannot be assessed.
The sponsor’s analysis method, model specification, handling of period or sequence effects, and treatment of incomplete crossover data are not reported in the registry record. The original statistical plan, interim-analysis plan, and sample-size justification are also not reported. These absences limit assessment of prespecification and reproducibility; they do not establish that such procedures were absent from the study.
15. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Doxycycline Monohydrate | 0 | 24 | 0.0% |
| Doxycycline Carragenate | 0 | 24 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Doxycycline Monohydrate | 1 of 24 |
| Doxycycline Carragenate | 2 of 24 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Doxycycline Monohydrate | Doxycycline Carragenate |
|---|---|---|---|
| Leukopenia | Blood and lymphatic system disorders | 0 of 24 | 1 of 24 |
| Excoriation | Injury, poisoning and procedural complications | 0 of 24 | 1 of 24 |
| Urticaria | Skin and subcutaneous tissue disorders | 1 of 24 | 0 of 24 |
The posted serious adverse event figures are zero for doxycycline monohydrate and zero for doxycycline carragenate. The registry lists 24 at risk for each treatment. No serious adverse event terms are listed. These counts describe the registry’s posted serious-event record; they do not establish that no other safety events occurred or characterize events beyond the reported categories.
The registry also lists other adverse events affecting 1 participant in the monohydrate group and 2 participants in the carragenate group. The record does not provide the event terms or further detail in the information, so the types, timing, severity, and relationship to treatment cannot be assessed from these counts alone. Death counts are not reported in the registry record.
These figures are descriptive safety summaries from a study in healthy male subjects. They are not a comparative safety analysis, and the record does not report a statistical comparison of adverse events. Event counts should be interpreted in light of the recorded population, observation period, and available reporting detail; those details are not sufficient to characterize broader safety.
16. What the Result Does, and Does Not, Mean
The results show that the two formulations had similar reported group means for maximum plasma concentration in the posted summaries: 2.526 ug/mL for doxycycline monohydrate and 2.442 ug/mL for doxycycline carragenate. The registry’s own analysis reports a ratio of 102.95 with a 90% confidence interval from 94.74 to 111.86. These are pharmacokinetic findings, not clinical outcome results.
The record’s purpose is to assess bioequivalence, but it does not report the equivalence limits or decision rule. Therefore, the ratio and interval can be reported without declaring that a formal bioequivalence criterion was met. The unadjusted difference and its p-value do not resolve this missing criterion: a test of no difference is not equivalent to a test that the difference lies within acceptable bounds.
The study does not report whether the formulations differ in infection outcomes, symptoms, or other measures of benefit. It enrolled normal healthy male subjects, and the primary endpoint was a plasma concentration measure. The findings should not be extended to clinical effectiveness or to populations not described in the record.
The reported estimates also have analysis limitations. The method behind the sponsor’s ratio analysis is not reported, and the unadjusted mean-difference re-calculation does not account for the paired structure of a crossover design. The record does not provide the information needed to assess missing measurements, period effects, sequence effects, or the precision of a crossover-specific model. These limitations do not erase the posted estimates, but they narrow the claims those estimates support.
In short, the registry records a ratio-based pharmacokinetic comparison and descriptive treatment summaries. It does not report enough information to independently verify a formal bioequivalence decision, and it does not provide evidence about clinical outcomes. The scope of interpretation is the concentration endpoint in the study population and the analysis information recorded.
17. Why This Trial Matters Statistically
This study illustrates why the statistical scale must match the research question. An absolute mean difference describes separation in ug/mL, while a ratio describes relative exposure. For a formulation comparison, the registry reports a ratio-based result. The separate unadjusted difference calculation is useful as a descriptive summary, but it is not a substitute for the registry’s own analysis or for a prespecified equivalence assessment.
It also demonstrates why a non-significant difference test cannot establish equivalence. The recalculated p-value is 0.548, but that value addresses a no-difference null hypothesis. Equivalence requires defined bounds for acceptable differences and an analysis that evaluates those bounds. Since the record does not report the limits or decision rule, a reader cannot infer a formal equivalence conclusion solely from the point estimate or p-value.
The crossover design raises an important analysis issue. Comparisons within participants can use information about each person’s responses to both treatments, but statistical precision depends on the within-participant relationship. Group means and standard deviations do not reveal that relationship. The simple recalculation from treatment summaries therefore cannot reproduce the crossover-specific analysis.
Finally, the study separates pharmacokinetic evidence from clinical evidence. Maximum plasma concentration characterizes one aspect of drug exposure. It does not directly show how participants with bacterial infection respond. The registry’s endpoint, analysis details, and population together define a narrow question; clear interpretation depends on keeping those limits in view.
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.
Several trial-specific details needed to evaluate the result are not reported in the registry record. The sponsor’s statistical method, model specification, equivalence limits, and decision rule are not available. Without the criterion, the reported ratio and confidence interval cannot be classified as meeting or not meeting a formal bioequivalence standard.
The study is identified as a randomized crossover trial, but the record does not describe treatment sequences, the interval between periods, or the handling of possible period or sequence effects. The unadjusted mean-difference recalculation uses posted group summaries and does not account for paired measurements. It should not be read as a replacement analysis for the crossover design.
The concentration population definition requires at least one measurement in at least one treatment period, but the record does not state how many participants contributed measurements in both periods or how incomplete data were handled. It does not describe missing-data patterns, assay procedures, protocol deviations, or exclusions from the analysis population. These omissions restrict assessment of the robustness and reproducibility of the result.
The registry records healthy male subjects and a pharmacokinetic endpoint. It does not provide results for clinical outcomes or additional participant groups. The safety record reports limited event counts without event terms or detailed context. These features mean the results should be interpreted within the population, endpoint, and reporting detail recorded rather than generalized to questions the study did not report answering.
19. Related Tutorials
20. Related Statistical Calculators
21. Sources
- ClinicalTrials.gov: Bioequivalence Between Two Tablet Formulations Of Doxycycline Carragenate — NCT00939562.
- Registry record last updated 2009-12-23; status last verified 2009-11.
- Results first posted 2009-12-23.
- 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.
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22. Record Summary
NCT00939562 is a completed phase 4, randomized, open-label, two-treatment, two-period crossover study sponsored by Pfizer. It compared doxycycline monohydrate and doxycycline carragenate tablets in normal healthy male subjects. Enrollment was 24; the recorded start was 2008-11 and primary completion was 2008-12.
The primary outcome was maximum plasma concentration of doxycycline, measured in ug/mL. The registry reports treatment means and standard deviations, a ratio-based analysis with a 90% confidence interval, and adverse-event counts. A separate unadjusted re-calculation estimates a mean difference of -0.084 ug/mL with p = 0.548. The registry does not report the sponsor’s analysis method or the equivalence limits and decision rule needed to interpret the ratio against a formal bioequivalence criterion.
The record supports a description of the posted pharmacokinetic comparison, but not conclusions about clinical outcomes or an independently verified formal equivalence decision.