Bioequivalence Study For 5 Mg Amlodipine Orally-Disintegrating Tablet: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Bioequivalence Study For 5 Mg Amlodipine Orally-Disintegrating Tablet (NCT01004614), a randomized phase 1 study. The primary outcome is Area Under the Concentration-Time Curve From Zero Time Until the Last Sampling Time (AUCt).

2. Clinical Question

The comparison concerns pharmacokinetic exposure after a single dose, rather than a clinical outcome or a treatment effect on illness. AUCt represents exposure accumulated from dosing through the last sampling time. The study measured concentrations before dosing and at scheduled post-dose times through 144 hours. The study description frames the question around whether the new formulation and the commercial formulation are bioequivalent; that is a specific statistical question about whether exposure estimates satisfy prespecified bounds, not simply whether their averages look close.

The two cohorts also differed in whether the tablets were taken with water. This means the formulation comparisons should be understood within their respective administration conditions. The posted results include sponsor-reported adjusted geometric mean ratios, alongside arm means and unadjusted recalculations. The registry record does not report a complete mapping of the sponsor estimates to each cohort or the margins used to interpret them.

3. Trial Design

The registry identifies this as a randomized, open-label, phase 1 study with a crossover model. Its official title describes a two-period, single-dose crossover study. The two formulations were assigned as test and reference treatments, with separate cohorts for administration with water and without water. The arm descriptions specify 24 planned subjects in each cohort, with 12 per sequence. The posted primary endpoint results contain 23 observations in each with-water arm and 24 in each without-water arm.

In a crossover study, participants receive more than one treatment at different periods, allowing within-person comparisons when the data are analyzed accordingly. The registry record does not report the washout interval, randomization sequence details beyond the arm descriptions, or the statistical model used for the sponsor's analysis. It also does not explain the relationship between the official title's crossover description and the separate cohort structure in further detail.

Masking is listed as none, so the study was open-label. The endpoint is an objective pharmacokinetic measure, but the registry does not report whether laboratory personnel or analysts were masked. The trial is marked completed. The recorded start was 2009-11 and primary completion was 2009-12. Those dates describe the registry entry and should not be taken as a substitute for information about participant follow-up or the timing of each treatment period.

The primary analysis population is described as the pharmacokinetic parameter analysis set: all randomized and treated subjects who completed the study. The registry does not report the number excluded from that set or a separate intention-to-treat analysis. The study's original sample-size justification and design assumptions 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.

Before assignment: This study consisted of 2 cohorts (I and II). The design of each cohort was an open-label, randomized, 2-periods, crossover, single-dose study in healthy adult male subjects. A washout period of at least 14 days was taken between each administration in Periods 1 and 2.

First Intervention

Washout

Reasons for not completing this period:

Second Intervention

Analysis population for the primary outcome, as defined in the registry: The PK parameter analysis set was defined as all subjects randomized and treated who completed the study.

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 Area Under the Concentration-Time Curve From Zero Time Until the Last Sampling Time (AUCt), measured over prior to dosing, 2, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 120 and 144 hours post dose.

The primary endpoint is AUCt, the area under the plasma concentration-time curve from zero time until the last sampling time. It summarizes drug exposure over the observed portion of the concentration-time profile: concentration measurements are integrated across time, rather than relying on one measurement at a single time point. The registry reports the unit as ng*h/mL and the endpoint as a mean with standard deviation.

Sampling was scheduled before dosing and at 2, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 120 and 144 hours after dosing. AUCt is relevant to a bioequivalence question because overall exposure is a key pharmacokinetic feature used to compare formulations. In general, bioequivalence assessments often use ratios of exposure measures and judge them against prespecified acceptance bounds. Those bounds and the complete sponsor analysis specification are not reported in the registry record, so the arm means alone cannot establish that a formal bioequivalence criterion was met.

The endpoint is not a direct measure of symptom change, clinical benefit, or long-term safety. It characterizes plasma exposure after a single dose in the studied population. Its interpretation therefore depends on the pharmacokinetic analysis and the study's prespecified comparison criteria, not merely on whether the group averages appear similar.

7. Results Posted in the Registry

• Cohort I: 3rd OD Tablet (Test) With Water: mean 126.36 versus 129.48 on control; difference -3.12 (95% CI -24.33 to 18.09), standardized effect d = -0.09; z-test p = 0.773.
• Cohort II: 3rd OD Tablet (Test) Without Water: mean 122.33 versus 129.48 on control; difference -7.15 (95% CI -28.04 to 13.74), standardized effect d = -0.20; z-test p = 0.502.
• Cohort II: 2nd OD Tablet (Reference) Without Water: mean 119.75 versus 129.48 on control; difference -9.73 (95% CI -29.58 to 10.12), standardized effect d = -0.28; z-test p = 0.337.

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.

Apparent Terminal Elimination Phase Rate Constant (Kel)

• 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:
  • Cohort I: 3rd OD Tablet (Test) With Water: mean 0.02 versus 0.02 on control; difference -0.00 (95% CI -0.00 to 0.00), standardized effect d = -0.15; z-test p = 0.608.
  • Cohort II: 3rd OD Tablet (Test) Without Water: mean 0.02 versus 0.02 on control; difference -0.00 (95% CI -0.00 to 0.00), standardized effect d = -0.45; z-test p = 0.126.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Cohort I: 3rd OD Tablet (Test) With Water and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Cohort II: 3rd OD Tablet (Test) Without Water and the control. The interval gives the range of effects that remain compatible with the data.

Apparent Terminal Elimination Half-Life (T-half)

• 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:
  • Cohort I: 3rd OD Tablet (Test) With Water: mean 41.45 versus 40.27 on control; difference 1.18 (95% CI -4.10 to 6.46), standardized effect d = 0.13; z-test p = 0.662.
  • Cohort II: 3rd OD Tablet (Test) Without Water: mean 45.04 versus 40.27 on control; difference 4.77 (95% CI -0.57 to 10.11), standardized effect d = 0.51; z-test p = 0.080.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Cohort I: 3rd OD Tablet (Test) With Water and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Cohort II: 3rd OD Tablet (Test) Without Water and the control. The interval gives the range of effects that remain compatible with the data.

Mean Residence Time (MRT)

• 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:
  • Cohort I: 3rd OD Tablet (Test) With Water: mean 61.29 versus 59.77 on control; difference 1.52 (95% CI -5.87 to 8.91), standardized effect d = 0.12; z-test p = 0.687.
  • Cohort II: 3rd OD Tablet (Test) Without Water: mean 66.18 versus 59.77 on control; difference 6.41 (95% CI -1.06 to 13.88), standardized effect d = 0.49; z-test p = 0.093.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Cohort I: 3rd OD Tablet (Test) With Water and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Cohort II: 3rd OD Tablet (Test) Without Water and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary pharmacokinetic outcomes cover additional features of the concentration-time profile, including AUClast and AUCinf, elimination rate and half-life, residence time, and time to maximum observed concentration. The reported outcome list includes these measures, but the available numeric secondary summaries and recalculated contrasts cover only some endpoints. For the outcomes without posted numerical results in the record, findings are not reported in the registry record.

Across the secondary summaries with recalculated contrasts, estimates are not uniformly in one direction across outcomes and conditions. The confidence intervals are generally broad relative to their estimates, and the displayed unadjusted comparisons do not provide a consistent pattern that can substitute for the primary AUCt assessment. They can provide context about other pharmacokinetic characteristics, but each measure represents a distinct feature of exposure and disposition.

These secondary comparisons carry less weight for the primary bioequivalence question. Multiple outcomes and contrasts create more opportunities for apparently notable results to arise by chance when each is examined without adjustment. The registry record does not report a multiplicity strategy for secondary endpoints or a prespecified hierarchy for interpreting them. Thus the recalculated secondary p-values should be treated as exploratory descriptions, not as confirmatory evidence. The primary endpoint and the sponsor's formal analysis remain central to the stated study question; secondary results neither replace that analysis nor establish equivalence on their own.

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

• Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast), Area Under the Plasma Concentration-Time Curve to Infinity (AUCinf)
• Apparent Terminal Elimination Phase Rate Constant (Kel)
• Apparent Terminal Elimination Half-Life (T-half)
• Mean Residence Time (MRT)
• Time to Reach Maximum Observed Plasma Concentration (Tmax)

9. Statistical Interpretation

10. Statistical Methods Explained

The endpoint is continuous: each participant has a numerical AUCt value, expressed in ng*h/mL. The posted arm summaries report means and standard deviations. A mean describes the central level of the observed values, while a standard deviation describes their spread around that mean. These summaries are useful for describing each arm, but they do not by themselves account for the crossover structure or establish the sponsor's adjusted treatment comparison.

What does the recalculated mean difference represent?

The displayed recalculation subtracts the reference arm mean from the test arm mean for the indicated comparison. A negative estimate means the test-arm mean is lower in that contrast; a positive estimate means it is higher. For the primary endpoint, the with-water contrast is -3.12 and the without-water contrast is -7.15. These are unadjusted between-arm calculations based on posted summary statistics. They do not represent a model-based within-participant treatment effect, and they do not include adjustment for period, sequence, or other factors unless those adjustments are already reflected in the posted summaries. The registry record does not report that they are.

How should a confidence interval be read?

A confidence interval expresses the uncertainty around an estimate under the assumptions of the analysis. A wider interval indicates less precision, while a narrower interval indicates greater precision. For a difference, an interval that spans zero is compatible with data ranging from a lower test mean to a higher test mean under the recalculation. It does not prove that the treatments are the same. For equivalence, the relevant question is whether an appropriate interval for the prespecified estimand lies entirely within prespecified equivalence bounds. The bounds are not reported in the registry record.

Why distinguish the unadjusted calculation from the sponsor result?

The sponsor results are described as ratios of adjusted geometric means and include 90% confidence intervals. A geometric mean is commonly used for pharmacokinetic measures that are analyzed on a logarithmic scale and then expressed as a ratio. Adjustment can account for features of the design or analysis model. The registry record does not specify the sponsor's exact model, the adjustment terms, or the mapping of each ratio to a cohort. The recalculated mean differences use arithmetic means and are not interchangeable with adjusted geometric mean ratios. They answer different statistical questions and should not be treated as a reproduction of the sponsor analysis.

What does a p-value say?

The recalculated unadjusted p-values are 0.773 for the with-water comparison and 0.502 for the without-water comparison. A p-value summarizes how unusual the observed result, or a more extreme result, would be under a specified null hypothesis and model. It does not give the probability that the null hypothesis is true, measure the size of an effect, or show that two formulations are equivalent. It also does not account for multiple outcomes or comparisons unless the analysis explicitly incorporates such adjustment. These p-values are not reported sponsor analyses.

Why can over-dispersion matter?

In general, over-dispersion means that observed variability is greater than a statistical model assumes. If a model understates variability, standard errors can be too small and confidence intervals too narrow, making apparent precision misleading. This concept is relevant when the outcome distribution or the design does not fit the simple assumptions behind a calculation. AUCt is continuous, so the count-data problem often called over-dispersion is not directly the issue for these arm summaries. More generally, however, the recalculation assumes a simple comparison and does not model within-person correlation in the crossover. The registry record does not provide diagnostics or enough model detail to assess those assumptions for the sponsor analysis.

The reported primary population consists of randomized and treated participants who completed the study. A completed-study analysis population may differ from the full randomized population if participants do not complete, but the registry record does not report exclusions or missing endpoint values. Without those details, it is not possible to assess the impact of missing data or to compare results across analysis populations.

11. Confidence Intervals and Precision

The recalculated 95% confidence interval for the with-water AUCt mean difference runs from -24.33 to 18.09, around an estimate of -3.12. For the without-water comparison, it runs from -28.04 to 13.74, around an estimate of -7.15. Both intervals span zero and include differences in either direction. Their width indicates that these unadjusted calculations do not pin down a precise mean difference.

These intervals describe uncertainty under the simple recalculation, not the sponsor's adjusted geometric mean ratio analysis. They should not be compared directly with the sponsor's 90% intervals as if the estimates shared the same scale and model. The sponsor reports 98.61 with a 90% confidence interval from 93.09 to 104.46, and 101.29 with a 90% confidence interval from 97.28 to 105.45. The registry record does not report the acceptance bounds needed to determine whether either interval meets a formal bioequivalence criterion.

Confidence intervals are not guarantees that the true value lies within the displayed limits. Rather, they communicate the range of values compatible with the estimate under the method's assumptions. Precision depends on factors including variability, sample size, study design, and analysis. Although crossover designs can use within-participant information, the unadjusted recalculations do not account for that pairing. Consequently, their precision may not reflect the sponsor's design-based analysis. Neither a confidence interval spanning zero nor a point estimate near zero, by itself, establishes equivalence.

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 sample-size illustrations are expressed as participants per arm, not total events. They are planning calculations based on the observed effect and use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. The trial's original design assumptions and sample-size justification are not reported in the registry record.

The 80% power column gives the modeled number of participants per arm for an 80% chance of detecting the specified effect under those assumptions, if that effect and model are appropriate. The 90% power column gives the corresponding planning number for a 90% chance. These are not guarantees: actual power depends on the true effect, variability, analysis, and design. In the primary endpoint illustrations, planning for 75% of the observed effect requires more participants per arm than planning for the full observed effect, and planning for 50% requires more still. Smaller effects are harder to distinguish from random variation, so they require larger samples to achieve the same target power.

The calculations use an unadjusted two-arm planning framework. They do not reconstruct the crossover design or the sponsor's adjusted analysis, and the registry does not report that they were used to design this study. These figures are planning illustrations, not observed power. Observed study outcomes cannot be used to turn a nonsignificant result into evidence that the study had inadequate or adequate power; the effect estimates and their uncertainty are more informative for interpreting the results.

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 = -3.120; pooled standard deviation σ = 36.701.
2. n = 2 × (1.96 + 0.842)² × 36.701² / -3.120² = 2,172.2, rounded up to 2,173 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 <- -3.11999999999999                      # observed difference in means
sigma <- 36.701433895694                     # 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(1004614)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 2,173 (80% power), 2,908 (90% power)
 75% of observed effect: n per arm = 3,862 (80% power), 5,170 (90% power)
 50% of observed effect: n per arm = 8,689 (80% power), 11,632 (90% power)
power.t.test: 2173.1 
Simulated power at n = 2,173 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.

14. Analyses Reported by the Sponsor

The registry reports two sponsor analyses of ratios of adjusted geometric means: 98.61 with a 90% confidence interval from 93.09 to 104.46, and 101.29 with a 90% confidence interval from 97.28 to 105.45. The analyses are labeled as legacy non-inferiority or equivalence results. The registry record does not report the analysis method, the equivalence margins, or an unambiguous mapping of each reported ratio to a specific water condition.

The recalculated comparisons instead use posted arithmetic means to estimate unadjusted mean differences. They do not reproduce the sponsor's adjusted analysis, and the estimates are on different scales. In a crossover study, a sponsor model can use paired participant information and other design features that cannot be recovered from arm means and standard deviations alone. The registry record does not provide enough detail to reconstruct that model.

The discrepancy flag is false, so the record does not identify a conflict between the posted sponsor results and the recalculations. This does not make the calculations interchangeable. For the study's formal bioequivalence question, the sponsor's own analysis takes precedence. The registry record does not include sufficient information about margins or decision rules to independently determine whether the reported intervals satisfy the trial's formal criteria.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple pharmacokinetic outcomes and reports more than one comparison. When several hypotheses are tested, the chance of at least one apparently unusual result can rise if each is assessed separately at the same significance threshold. A multiplicity plan can address this through methods such as adjusted thresholds or a prespecified testing sequence. The registry record does not report whether such a plan was used for the sponsor analyses or for secondary outcomes.

The posted recalculated p-values are unadjusted. They should therefore be interpreted as individual descriptive comparisons rather than as results protected against multiplicity. The record does not identify a complete hierarchy of primary and secondary hypotheses beyond naming AUCt as the primary endpoint and listing secondary pharmacokinetic measures.

The primary pharmacokinetic analysis population is described as all randomized and treated participants who completed the study. The record does not report how many participants were excluded, whether any endpoint values were missing, how missing values were handled, or whether sensitivity analyses were conducted. It also does not report a separate analysis using all randomized participants or a comparison of results across analysis populations. These omissions limit assessment of possible bias from incomplete observations or exclusions.

The crossover structure makes details of the analysis population and missingness particularly important: a missing period or treatment measurement can affect whether a participant contributes a paired comparison. The registry record does not describe how incomplete crossover data were handled. It also does not report the sponsor's model specification, period or sequence effects, or other sensitivity checks. These details should not be inferred from the posted arm summaries.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The adverse-event results report zero participants with serious adverse events in each listed group. The at-risk counts are 23 for the with-water test group, 24 for the with-water reference group, and 24 in each without-water group. These are group-specific figures for the reported safety categories; they should not be combined into a distinct-participant total because participants received treatments across periods in a crossover design.

Other adverse events affected 7 participants in the with-water test group, 6 in the with-water reference group, 2 in the without-water test group, and 3 in the without-water reference group. These counts do not indicate severity or causality beyond the categories stated in the registry record. The death counts are not reported in the registry record.

These figures describe events recorded during this study; they do not establish comparative safety beyond the study's size, duration, population, and reporting. The study involved healthy male subjects and single-dose treatment periods. The record does not provide event terms for the reported other adverse events or additional detail about follow-up and attribution.

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

The results describe a single-dose pharmacokinetic comparison of two amlodipine orally-disintegrating tablet formulations in healthy male subjects, with separate administration conditions for taking the tablet with or without water. The posted primary summaries show similar-looking group means, while the unadjusted recalculated confidence intervals remain broad and include differences in either direction. The sponsor also reports adjusted geometric mean ratios with 90% confidence intervals.

Those findings do not, on their own, establish whether the formal bioequivalence criterion was met. Bioequivalence is assessed against specified bounds using a defined estimand and analysis. The registry record does not report the bounds, full model, or a clear mapping of the sponsor's two estimates to water conditions. The unadjusted recalculation is not a substitute for that analysis.

The findings also do not establish that one formulation is clinically better or worse, or that the formulations have identical effects in all settings. AUCt is a pharmacokinetic measure, not a clinical outcome. The study does not address repeated use, populations other than the healthy male subjects described, or outcomes beyond the registered measurements. The posted safety counts likewise describe the recorded study period and are not a comprehensive comparison of longer-term risk.

The appropriate statistical reading is therefore bounded: the record contains arm-level pharmacokinetic summaries, sponsor-reported adjusted ratios, unadjusted recalculations, and adverse-event counts. The precision and interpretation of those results depend on analysis details and criteria that are not reported in the registry record.

18. Why This Trial Matters Statistically

This trial illustrates why a close pair of sample means is not enough to answer a bioequivalence question. The inferential target is not simply whether a difference test fails to detect a separation. It is whether an appropriate estimate, with its uncertainty, satisfies prespecified limits. Without the margins and analysis details, arm-level summaries cannot complete that assessment.

It also illustrates the importance of matching a calculation to the design. A crossover can provide within-person comparisons, while the unadjusted recalculations use arm summaries and do not account for pairing. The sponsor's adjusted geometric mean ratios and the recalculated arithmetic mean differences are different estimands on different scales. Keeping those analyses distinct prevents a descriptive recalculation from being mistaken for the trial's formal analysis.

Finally, the trial's conditions and population define the reach of its evidence. The with-water and without-water cohorts are not interchangeable, and the study concerns healthy male subjects after single-dose administration. Secondary outcomes broaden the pharmacokinetic description but raise multiplicity considerations. Together, these features make the registry record a useful example of how design, analysis, precision, and reporting completeness shape statistical interpretation.

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 important details of the formal analysis unspecified. It does not report equivalence margins, the sponsor's statistical model, the mapping of the two adjusted geometric mean ratios to the two water conditions, or a full description of model adjustments. As a result, the sponsor's formal decision cannot be independently checked from the registry information alone.

The recalculated comparisons are unadjusted contrasts of posted arm means. They do not account for the pairing inherent in a crossover design and should not be interpreted as a reconstruction of the sponsor analysis. The posted record also does not explain the relationship between the two-cohort structure and the crossover periods in further detail.

The analysis population is limited to randomized and treated participants who completed the study. Exclusions, missing measurements, and handling of incomplete data are not reported in the registry record. The registry also does not report the original sample-size rationale or a multiplicity plan for the several pharmacokinetic outcomes and comparisons.

The study's scope is narrow: it involved healthy male subjects and single-dose administration. The record does not support extending these findings to other populations, repeated dosing, or clinical outcomes. Safety information is limited to the reported group counts; event terms, death counts, and further follow-up details are not reported in the registry record.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Bioequivalence Study For 5 Mg Amlodipine Orally-Disintegrating Tablet — NCT01004614.
• Registry record last updated 2021-01-28; status last verified 2021-01.
• Results first posted 2012-01-04.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

23. Record Summary

NCT01004614 is a completed, randomized, open-label, phase 1 crossover study of 5 mg amlodipine orally-disintegrating tablets in healthy male subjects. It compared a 3rd tablet formulation with a 2nd, commercial formulation, with separate cohorts taking the tablets with water or without water. The primary endpoint was AUCt, measured through the last scheduled sampling time.

The registry reports arm-level means and standard deviations, two sponsor-reported adjusted geometric mean ratios with 90% confidence intervals, and recalculated unadjusted comparisons. The sponsor's formal analysis takes precedence over the recalculations, but the equivalence margins and full analysis details are not reported in the registry record. The posted adverse-event results list zero serious adverse events in each group.