A Study to Compare the Bioavailability of 300 mg Trazodone Hydrochloride Extended-release Caplets and 100 mg Trazodone Hydrochloride Immediate-release Tablets (Administered Three Times Daily): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Compare the Bioavailability of 300 mg Trazodone Hydrochloride Extended-release Caplets and 100 mg Trazodone Hydrochloride Immediate-release Tablets (Administered Three Times Daily) (NCT01121900), a randomized phase 1 study. The primary outcome is Bioequivalence Based Cmax.

2. Clinical Question

3. Trial Design

This was a randomized, two-way crossover study in healthy participants, listed as Phase 1 and completed in the registry. Enrollment was 26. The study began in 2008-06, and primary completion was recorded in 2008-07. Masking was listed as none. Participants received both formulations in the crossover comparison: a single dose of the extended-release caplets and immediate-release tablets given three times daily, under fasting conditions. The registry record does not report the sequence details, washout period, or timing of each administration.

The primary pharmacokinetic analysis population comprised 23 subjects who completed the study as per protocol. The posted primary endpoint summaries also list 23.0 observations for each formulation. Because this is a crossover design, each participant’s measurements are linked across treatment conditions. That within-person structure is important when estimating a treatment contrast: paired analysis can account for how a participant’s measurements under the two conditions co-vary. The registry record does not identify the method used for the recalculated unadjusted comparison, so the posted re-calculation should not be mistaken for a reconstruction of the trial’s full crossover analysis.

The study’s objective concerned pharmacokinetic profiles rather than a clinical treatment outcome. In addition to Cmax, the registry lists outcomes for AUC(0-24), Tmax, the apparent terminal elimination rate constant, and apparent terminal half-life. The registry record does not report a protocol-level sample-size justification, the intended statistical model, or the prespecified analysis details for the primary endpoint. The displayed planning illustrations are based on observed effects and are separate from the trial’s original design assumptions.

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 Period

Reasons for not completing this period:

Washout Period of 7 Days

Reasons for not completing this period:

Second Intervention Period

Analysis population for the primary outcome, as defined in the registry: The dataset for pharmacokinetic analysis comprised the 23 subjects who completed the study as per protocol.

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 Bioequivalence Based Cmax, measured over 68 hours.

The primary endpoint is bioequivalence-based Cmax, measured in ng/mL over 68 hours. Cmax is the maximum plasma concentration observed after administration. It is used in pharmacokinetic comparisons to describe the peak concentration reached, and therefore addresses one aspect of the rate of drug absorption. It does not, by itself, describe the full concentration-time profile or total drug exposure.

The registry posts the mean and standard deviation for each formulation, using the 23 subjects who completed the study as per protocol. It also reports a mean-ratio analysis with a 90% confidence interval. Those are distinct forms of presentation: the arm-level mean summaries describe the observed concentrations, while a ratio-based analysis is intended to express the formulations’ relative values. The registry record does not state the method used for that reported mean ratio or explain how it was calculated.

For this crossover comparison, the measurements arise from the same participants under both formulations. A treatment comparison that uses the paired measurements can account for within-person association. The registry record does not provide the participant-level data or enough analysis detail to reproduce that paired analysis. Cmax is informative about peak concentration, but it is not a standalone measure of all pharmacokinetic properties or of clinical benefit.

7. Results Posted in the Registry

• Trazodone IR (Apotex Corp.): mean 2,948 versus 1,231 on control; difference 1,717 (95% CI 1,354 to 2,080), standardized effect d = 2.73; z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Area Under the Plasma Concentration vs. Time Data Pairs, for the First 24 Hours [AUC(0-24)]

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Trazodone IR (Apotex Corp.): mean 24,602 versus 18,331 on control; difference 6,271 (95% CI 3,057 to 9,485), standardized effect d = 1.13; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Trazodone IR (Apotex Corp.) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Apparent Terminal Elimination Rate Constant (λz)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Trazodone IR (Apotex Corp.): mean 0.09 versus 0.06 on control; difference 0.03 (95% CI 0.01 to 0.04), standardized effect d = 1.23; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Trazodone IR (Apotex Corp.) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Apparent Terminal Half-life (t½.z)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Trazodone IR (Apotex Corp.): mean 8.30 versus 11.80 on control; difference -3.50 (95% CI -5.32 to -1.68), standardized effect d = -1.11; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Trazodone IR (Apotex Corp.) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The posted secondary outcomes broaden the pharmacokinetic description beyond peak concentration. They cover exposure during the first 24 hours, the time to maximum concentration, and measures describing the terminal elimination phase. Across the continuous summaries, the results indicate that the two dosing regimens have differing observed pharmacokinetic profiles rather than identical values across every measure. That overall pattern is relevant context for the primary Cmax comparison, but the secondary outcomes do not replace the primary endpoint or the sponsor’s ratio-based analysis.

Secondary outcomes are useful for describing different features of a concentration-time profile. In general, peak concentration, total exposure over a time interval, time to peak, and terminal elimination measures address distinct questions. A difference in one feature does not by itself determine the pattern in another. The registry record lists four secondary outcomes, but does not report a sponsor analysis for them. Their posted mean comparisons and unadjusted p-values are therefore descriptive and exploratory unless a prespecified analysis plan establishes otherwise; that plan is not reported in the registry record.

Multiple statistical comparisons increase the chance of at least one apparently notable result arising by chance when many outcomes are tested. An unadjusted secondary p-value does not account for that multiplicity. The registry record does not report an adjustment strategy, a hierarchy for testing outcomes, or which secondary endpoints were confirmatory. Consequently, secondary findings carry less inferential weight than a clearly prespecified primary analysis, and should be read as supporting characterization of the pharmacokinetic profile rather than independent proof of a formal claim.

The study also included formation of m-chlorophenylpiperazine in its stated objective, but the posted secondary outcome list does not include a specific result for that measure. Further details about its assessment are not reported in the registry record.

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

• Area Under the Plasma Concentration vs. Time Data Pairs, for the First 24 Hours [AUC(0-24)]
• Time to Maximum Plasma Concentration (Tmax)
• Apparent Terminal Elimination Rate Constant (λz)
• Apparent Terminal Half-life (t½.z)

9. Statistical Interpretation

10. Statistical Methods Explained

Several statistical ideas help distinguish the posted descriptive values, the re-calculated contrast, and the sponsor’s reported analysis. These are general explanations; the registry record does not describe every method used in the original analysis.

What do the means and standard deviations describe?

A mean is the arithmetic average of the observed endpoint values in a group. For the primary Cmax endpoint, the registry gives a mean and standard deviation for each formulation. The standard deviation describes the spread of individual observations around the group mean. It is not the uncertainty interval for the mean, and it does not show the range of all participant values. The registry does not post the individual Cmax measurements, so the shape of the underlying distributions and the presence of unusually high or low observations cannot be assessed from the summary alone.

What does the unadjusted difference represent?

The recalculated mean difference is a comparison of the two posted means. Its units are the same as the endpoint, ng/mL. The accompanying confidence interval describes uncertainty around that estimated contrast under the assumptions used for the re-calculation. The unadjusted p-value evaluates the contrast against a zero-difference reference under those same assumptions. “Unadjusted” means that this calculation is not presented as accounting for multiple outcome comparisons or additional covariates.

These summary-based calculations are not automatically equivalent to an analysis of a randomized crossover trial. In a crossover study, a participant contributes observations under both conditions, and the two values may be correlated. A paired analysis uses that within-person relationship. Separate group means and standard deviations do not reveal the covariance between a participant’s measurements, which is needed to reconstruct the standard error of a paired contrast. The registry record does not state the exact method behind the recalculation, so its inferential results should be interpreted as unadjusted summary-based estimates rather than as a verified reproduction of the trial’s original model.

What is a confidence interval?

In general, a confidence interval gives a range of values compatible with the data and the statistical assumptions used to calculate it. Its width reflects precision: a narrower interval indicates less uncertainty on the scale of the estimate, while a wider interval indicates more. A confidence interval is not a guarantee that the true value lies inside that particular interval, and it does not convey whether a difference is clinically important. The primary re-calculated difference is reported with a 95% interval, whereas the sponsor’s mean-ratio result is reported with a 90% interval. Those confidence levels should not be treated as interchangeable.

How does a ratio differ from a difference?

A difference compares values by subtraction and retains the measurement unit. A ratio expresses one value relative to another and is unitless. For pharmacokinetic comparisons, a ratio-based presentation can be useful when the scientific question concerns relative exposure or concentration. The registry reports a mean ratio of 39.8 and its 90% interval, but does not identify the numerator and denominator, the calculation scale, or the analysis method. It is therefore inappropriate to infer those details from the reported number alone.

Why does the crossover structure matter?

Randomization helps assign treatment sequences, but the registry record does not describe the sequence allocation or the analysis of sequence and period. Crossover designs can control for stable differences between participants because each participant receives both conditions. Their analysis depends on the treatment-period structure and the within-participant measurements. The posted arm-level summaries do not contain enough information to assess those features, including whether any period effects were modeled.

Why is over-dispersion relevant in general?

General statistical models often rely on assumptions about how variable observations are. If observed variability is greater than a model expects, standard errors can be too small unless the analysis accounts for that extra variation. The registry record does not report an over-dispersion assessment for these outcomes, and there is no basis in the posted summaries to claim that over-dispersion was present. The point is methodological: uncertainty depends not only on the mean contrast but also on the variability and the model used to represent it.

What does the reported p-value not establish?

A small p-value is evidence against a specified null hypothesis under a statistical model; it is not a probability that the null is true, nor does it quantify the magnitude or importance of a result. For a bioequivalence question, the relevant inference generally depends on the estimate, its uncertainty, and prespecified acceptance criteria. The registry record does not report the criteria or explain the sponsor’s decision rule. Therefore, the unadjusted p-value attached to the recalculated difference cannot by itself answer the sponsor’s intended equivalence question.

11. Confidence Intervals and Precision

The recalculated primary mean difference is 1717.0 ng/mL, with a 95% confidence interval from 1354.0 to 2080.0. The interval is entirely above zero, consistent with the posted unadjusted test of a zero mean difference, which has p < 0.001. This interval describes precision for the recalculated absolute contrast, subject to its assumptions; it does not establish that the contrast is estimated using the original crossover analysis.

The sponsor’s reported primary result is on a different scale: a mean ratio of 39.8, with a 90% confidence interval from 34.4 to 46.0. The registry does not give the ratio’s orientation or analysis method. The endpoints of this interval therefore need to be interpreted in the context of the sponsor’s ratio definition, which is not reported in the registry record. The interval cannot be directly compared with the absolute-difference interval as though they were estimates of the same quantity.

In general, interval width conveys statistical precision, not importance. Precision depends on the amount of information, the variation in measurements, and the analysis model. The registry reports standard deviations for the primary endpoint but does not provide participant-level paired data, so the uncertainty of a fully specified crossover contrast cannot be independently assessed from the posted summary. The two intervals also use different confidence levels. Their widths should not be compared without accounting for their distinct scales, methods, and confidence levels.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The displayed planning figures are participants per arm for 80% power and participants per arm for 90% power. These are not total-event counts: the outcomes in this study are continuous pharmacokinetic measures, and the illustrations use participants per arm. They are planning illustrations rather than the actual enrollment or analysis counts.

The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set as a stated fraction of the observed effect. The planning figures therefore depend on the observed contrast and variability; they should not be read as the study’s original sample-size calculation. The original design assumptions and sample-size justification are not reported in the registry record.

In plain language, the 80% power column gives an estimated per-arm sample size for a design intended to have an 80% chance of detecting the specified effect under the planning assumptions, if that effect is real. The 90% power column uses a higher target chance of detection and generally calls for more participants. The rows illustrate planning for the full observed effect, 75% of the observed effect, and 50% of the observed effect. Smaller effects require more participants to detect under otherwise unchanged assumptions.

These figures are planning estimates, not observed power. They do not show the probability that the trial’s findings are correct or that a treatment effect exists. Because this was a crossover study, the registry’s planning illustration based on equal allocation between two arms should not be treated as a reconstruction of a crossover-specific design calculation.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 1717.000; pooled standard deviation σ = 628.047.
2. n = 2 × (1.96 + 0.842)² × 628.047² / 1717.000² = 2.1, rounded up to 3 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 <- 1717                      # observed difference in means
sigma <- 628.046534900082                     # 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(1121900)
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 (80% power), 3 (90% power)
 75% of observed effect: n per arm = 4 (80% power), 5 (90% power)
 50% of observed effect: n per arm = 9 (80% power), 12 (90% power)
power.t.test: 3.4 
Simulated power at n = 3 per arm: 0.707 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary bioequivalence-oriented analysis as a mean ratio of 39.8, with a 90% confidence interval from 34.4 to 46.0. It does not report a p-value for that analysis, identify the method, state the ratio orientation, or give the acceptance limits used to make a bioequivalence determination. Those details are needed to interpret the sponsor’s result against a formal decision rule.

The separate recalculation uses the posted arm-level means and standard deviations to estimate an unadjusted absolute mean difference of 1717.0 ng/mL, with a 95% confidence interval from 1354.0 to 2080.0 and p < 0.001. This absolute difference and the sponsor’s mean ratio are on different scales and may arise from different methods. The registry record does not provide enough information to treat them as interchangeable estimates or to reproduce the sponsor’s analysis.

There is no flagged discrepancy between the posted results and the recalculation. Even so, the sponsor’s own reported analysis is the relevant source for the trial’s intended bioequivalence question. The summary-based re-calculation is supplementary and should not replace that analysis. Since the ratio’s direction and decision limits are not reported, no conclusion about whether prespecified bioequivalence criteria were met can be drawn from the ratio alone.

15. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary pharmacokinetic endpoint and multiple secondary endpoints, but does not report how multiplicity was handled. It does not state whether secondary outcomes were tested under a prespecified hierarchy, adjusted for multiple comparisons, or treated as exploratory. The unadjusted p-values attached to recalculated outcomes should therefore not be interpreted as multiplicity-controlled evidence across the set of endpoints.

Missing-data handling is also not described in the registry record. The primary analysis population is identified as the 23 subjects who completed the study as per protocol, while enrollment was 26. The record does not explain the status or disposition of participants who were not included in that primary analysis, the reason for their non-inclusion, or whether any endpoint measurements were missing. It also does not report an imputation method or sensitivity analysis for missing observations. The difference between enrollment and the per-protocol analysis population should not be assigned a cause without those details.

The record does not report whether the analysis population was defined before unblinding, whether all randomized participants were analyzed, or whether a separate safety population was used. It does not give details of the protocol deviations considered when defining per-protocol completion. Those omissions limit assessment of how representative the analyzed participants are of all enrolled participants.

The crossover structure creates additional analysis questions. The registry record does not report the treatment sequence, period-specific data, handling of incomplete treatment sequences, or whether period and sequence effects were included in the primary model. Nor does it describe the within-person covariance used in the sponsor’s analysis. Without those details, the posted summaries cannot establish how incomplete paired observations, if any, were handled.

The original sample-size assumptions, interim analyses, and full statistical analysis plan are not reported in the registry record. Their absence means the planning illustrations based on observed effects should not be mistaken for the trial’s protocol-level design or for evidence about how analyses were selected.

16. 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 1% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists serious adverse events affecting 0 of 24 participants at risk for Trazodone Contramid® OAD and 0 of 25 participants at risk for Trazodone IR (Apotex Corp.). No serious adverse event terms are listed. These entries describe the posted counts; they do not establish that the formulations have identical safety profiles or rule out uncommon events.

Other adverse events are listed for 7 of 24 participants at risk in the extended-release group and 8 of 25 in the immediate-release group. The registry record does not provide event-level descriptions in the registry record, so the types, severity, duration, and relationship to treatment cannot be characterized. Death counts are not reported in the registry record.

The safety counts use risk denominators that differ from the 23 subjects in the primary per-protocol pharmacokinetic analysis. The registry does not explain the safety population definition or the reason for those denominators. This was a study in healthy participants focused on pharmacokinetics, and the posted counts are limited information for evaluating safety beyond the observed events recorded during the study.

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

The results describe a pharmacokinetic comparison of a single dose of extended-release trazodone and immediate-release trazodone administered three times daily under fasting conditions in healthy participants. The primary posted endpoint is maximum plasma concentration. The registry’s summaries and its reported ratio analysis give different statistical views of that comparison, and the sponsor’s mean-ratio result is the pertinent posted result for the stated bioequivalence-oriented analysis.

The reported data do not establish a clinical benefit, a treatment effect on symptoms, or a safety advantage. The study was designed around absorption and pharmacokinetic measures, not a clinical outcome. Its findings apply to the studied formulations, schedules, fasting condition, and analyzed participants; the registry record does not support extrapolation to other populations or conditions.

A difference test and an equivalence assessment are not the same. The recalculated unadjusted difference and its p-value address a zero-difference null under the calculation’s assumptions. Bioequivalence requires interpretation of a relative estimate and its confidence interval against prespecified acceptance limits. The registry record reports the mean ratio and interval but does not state those limits, the ratio orientation, or the analytical method. It is therefore not possible to infer from the posted ratio alone whether the formal bioequivalence criteria were met.

The crossover design means each participant’s measurements under both regimens are relevant to the comparison. The registry’s arm-level summaries do not disclose the paired measurements or the within-participant association needed to reproduce a paired estimate. The re-calculation should consequently be treated as a descriptive supplement, not as a substitute for the sponsor’s full analysis.

Overall, the posted results support a comparison of measured pharmacokinetic features in this study, while important details about the analysis, decision criteria, and missing data are not reported in the registry record. Those gaps constrain how far the numerical findings can be interpreted.

18. Why This Trial Matters Statistically

This trial is statistically interesting because its central question is about the shape and relative behavior of pharmacokinetic profiles, while the registry posts both absolute summaries and a ratio-based analysis. The distinction matters: an absolute difference and a relative ratio do not express the same quantity. Understanding the scale of an estimate is essential before interpreting its magnitude or comparing it with a decision threshold.

The crossover design is another important feature. Measurements from the same participant under both regimens are linked, and that pairing can improve the efficiency of a comparison when it is handled appropriately. At the same time, arm-level means and standard deviations alone do not retain the within-person association. This makes the registry’s lack of detailed analysis methods consequential: the posted summary-based recalculation cannot be assumed to reproduce the paired analysis.

The record also illustrates why statistical significance and bioequivalence are distinct ideas. The unadjusted recalculated difference has p < 0.001, but that test addresses a zero absolute difference. A formal equivalence conclusion depends on an appropriately defined relative comparison, its uncertainty, and prespecified acceptance limits. The registry reports a mean ratio and 90% confidence interval but not those limits or the method used to derive the ratio.

Finally, planning estimates based on observed effects are not the same as original design justification. They can illustrate how sample size changes when the target effect becomes smaller, but they do not document the assumptions used when the study was planned. Together, these points make the record a useful example of why endpoint definition, design structure, estimand scale, analysis population, and uncertainty all matter when reading pharmacokinetic trial results.

19. 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 leaves several trial-specific limitations in the available interpretation. Although enrollment is 26, the primary pharmacokinetic analysis includes 23 subjects who completed the study as per protocol. Reasons for the difference, participant disposition, protocol deviations, and missing measurements are not reported in the registry record. Without those details, it is not possible to assess the potential effect of exclusions on the reported summaries.

The study is identified as randomized and crossover, but the record does not describe treatment sequences, the washout period, period effects, or the statistical model. It also does not provide participant-level paired measurements or the covariance between outcomes under the two regimens. Those omissions prevent independent reconstruction of the sponsor’s crossover analysis from the posted means and standard deviations.

The sponsor’s mean ratio is reported with a 90% confidence interval, but its orientation, estimation method, and equivalence margins are not reported in the registry record. The recalculated unadjusted difference uses a different scale and should not be interpreted as a replacement for that analysis. The record also does not report the full statistical analysis plan, multiplicity handling, interim analyses, or original sample-size justification.

The study assessed pharmacokinetics in healthy participants under fasting conditions. The registry record does not provide further participant characteristics or support conclusions about other populations or conditions. Its safety entries include event counts, but event descriptions, severity, and deaths are not reported in the registry record. These limits constrain interpretation of both the pharmacokinetic and safety information.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Study to Compare the Bioavailability of 300 mg Trazodone Hydrochloride Extended-release Caplets and 100 mg Trazodone Hydrochloride Immediate-release Tablets (Administered Three Times Daily) — NCT01121900.
• Registry record last updated 2012-04-27; status last verified 2012-04.
• Results first posted 2010-08-16.
• 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.

23. Record Summary

NCT01121900 is a completed, randomized, unmasked, two-way crossover Phase 1 study sponsored by Labopharm Inc. It enrolled 26 healthy participants and compared a single dose of 300 mg trazodone hydrochloride extended-release caplets containing Contramid® with 100 mg immediate-release tablets administered three times daily under fasting conditions.

The primary endpoint was bioequivalence-based Cmax over 68 hours. The primary pharmacokinetic analysis comprised 23 subjects who completed the study as per protocol. The registry posts arm-level means and standard deviations, a summary-based unadjusted difference, and a sponsor-reported mean ratio with a 90% confidence interval. The registry record does not report the sponsor’s ratio method, orientation, or decision limits.

Secondary pharmacokinetic results address exposure, time to maximum concentration, and terminal elimination measures. The registry also posts adverse-event counts. Important details about missing data, crossover analysis methods, multiplicity, and original design assumptions are not reported in the registry record.