Amlodipine 10 mg Tablets Under Fasting Conditions: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Amlodipine 10 mg Tablets Under Fasting Conditions (NCT00841542), a randomized phase 1 study. The primary outcome is Cmax - Maximum Observed Concentration.

2. Clinical Question

This is a pharmacokinetic comparison in healthy subjects, not a study of clinical benefit or treatment outcomes. Its central question concerns the concentration observed after dosing and whether the recorded comparison of test and reference formulations supports the registry’s bioequivalence objective. The record reports mean Cmax values and standard deviations for both formulations, as well as a sponsor analysis expressed as a ratio of least squares means with a 90% confidence interval.

The crossover arrangement means that participants were assigned to one of two treatment orders, with each order including both formulations across study periods. This design can allow a within-participant comparison, but the registry record does not report enough detail to determine exactly how the sponsor modeled the repeated measurements or accounted for period and sequence. The posted summary statistics and sponsor analysis should therefore be read as separate descriptions of the comparison, not as interchangeable calculations.

The record does not report a clinical outcome question, a dosing regimen beyond the single-dose fasting comparison, or conclusions about use in patients. The results address the measured pharmacokinetic endpoint in the enrolled healthy population.

3. Trial Design

The registry describes a phase 1, randomized, open-label, two-way crossover study of single doses under fasting conditions. Its official title identifies the comparison as Amlodipine 10 mg tablets versus Norvasc® 10 mg tablets in normal healthy non-smoking male and female subjects. The study is marked completed, and the sponsor is Teva Pharmaceuticals USA.

In a crossover design, participants receive more than one treatment in different periods, with the treatment order assigned according to the study sequence. Here, one sequence received the test Amlodipine Besylate tablet first and Norvasc® second; the other received Norvasc® first and the test tablet second. Randomization applies to these treatment orders. The record does not report the length of the periods, a washout interval, or other operational details about the transition between periods.

The study was open-label, meaning masking was recorded as none. This describes the reported masking status; it does not by itself establish how knowledge of treatment assignment might have affected measurement or analysis. Because Cmax is a concentration-based endpoint, the primary outcome depends on blood sampling. The registry states that blood samples were collected over a 168 hour period.

The enrollment field records 28 participants. The primary outcome results list 27 observations for each formulation. The registry states that data from all subjects who completed the study were included in the statistical analysis, but it does not report a detailed participant flow or explain the difference between the enrollment figure and the outcome counts. The record identifies three outcome measures and three analyses, with no secondary outcome measures posted.

The registry record does not report the study’s original sample-size justification, the full statistical analysis plan, an interim-analysis plan, or a bioequivalence decision threshold. These omissions limit what can be inferred about the planned analysis and how the sponsor reached its interpretation.

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

Reasons for not completing this period:

Period 2

Analysis population for the primary outcome, as defined in the registry: Data from all subjects who completed the study were included in the statistical analysis.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Cmax - Maximum Observed Concentration, measured over Blood samples collected over 168 hour period.

The primary endpoint is Cmax, defined in the record as maximum observed concentration and reported in ng/mL. It represents the highest measured concentration of the drug in the blood during the sampling period. The registry identifies the timeframe as blood samples collected over 168 hour period and describes the endpoint as bioequivalence based on Cmax.

As a pharmacokinetic measure, Cmax is used to characterize the peak concentration reached after dosing. Comparing it between a test formulation and a reference formulation addresses one aspect of how the formulations are absorbed. It is not, by itself, a measure of clinical effectiveness, symptom change, or safety in a patient population. The registry’s stated overall objective also refers to extent of absorption, but the primary endpoint described in the posted results is Cmax.

The posted outcome values are means with standard deviations. The mean summarizes the reported concentration values, while the standard deviation describes the spread of those values around the mean. These summaries do not show the full distribution of participant measurements or how individual paired observations varied across the crossover periods.

The registry states that completers’ data were included in the primary statistical analysis. It does not report the precise sampling schedule, how the maximum was selected if measurements were irregular, or how the endpoint was transformed or modeled. Those details matter when assessing the analysis, and are not reported in the registry record.

7. Results Posted in the Registry

• Norvasc®: mean 6.29 versus 6.16 on control; difference 0.13 (95% CI -0.79 to 1.05), standardized effect d = 0.08; z-test p = 0.782.

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports a continuous endpoint summarized as a mean with standard deviation. It also records a sponsor analysis using a ratio of least squares means and a simple unadjusted re-calculation from the posted summary statistics. These approaches answer related but distinct questions. The registry record does not identify the statistical method used for the sponsor analysis, so explanations of the underlying concepts below are general rather than claims about the exact model used in this study.

What does the mean describe?

In general, the mean is a measure of the center of a set of observations. For Cmax, it describes the average maximum measured concentration in the relevant analysis group. The posted means are 6.16 ng/mL for Amlodipine and 6.29 ng/mL for Norvasc®. A mean alone does not show whether most observations were close to that value or whether the mean was influenced by observations farther away.

The standard deviation gives a sense of the spread of observations around the mean. The posted standard deviations are 1.64 for Amlodipine and 1.81 for Norvasc®. A standard deviation is not a confidence interval: it describes variability among observations, while a confidence interval describes uncertainty in an estimated quantity. The two summaries should not be treated as the same kind of information.

What does the unadjusted comparison express?

The recalculated mean difference is 0.13, with Norvasc® as the comparison relative to Amlodipine. The accompanying unadjusted p-value is 0.782. In general, a p-value measures how compatible the observed data are with a specified null hypothesis, under the assumptions of the test. It is not the probability that the null hypothesis is true, nor does it quantify the probability that the formulations are equivalent.

This re-calculation is based on posted summary statistics. It is not the same as a model that might use the crossover structure and participant-level measurements. In a crossover study, each participant can contribute measurements under both treatments, and a model may account for the paired nature of those observations along with period or sequence effects. The registry does not report whether or how the sponsor’s analysis handled those features. The simple unadjusted calculation should not be interpreted as a replacement for that analysis.

Why are a difference and a ratio different?

A difference compares two quantities by subtraction and stays on the measurement scale. A ratio compares their relative magnitude and is expressed on a scale where a value near 100 represents a ratio near one when reported as a percentage. In general, pharmacokinetic comparisons often use ratio-based analyses because proportional differences can be more relevant than absolute concentration differences. That general rationale does not establish which specific transformation or model was used in this study.

The sponsor’s posted result is a ratio of least squares means of 98.19, with a 90% confidence interval from 94.20 to 102.34. Least squares means are model-based estimates, and their meaning depends on the model and scale. The registry does not report the model details, such as the transformation, factors included, or variance assumptions. Consequently, the sponsor result can be described as posted, but its calculation cannot be independently reconstructed from the record.

What is the role of a confidence interval?

In general, a confidence interval communicates the precision of an estimate under a specified statistical procedure. A narrower interval indicates less uncertainty on the scale being analyzed, while a wider interval indicates more uncertainty. Its interpretation depends on the design and model assumptions, including how observations are related and how variability is estimated.

The sponsor’s interval is reported at the 90% level. For a formal equivalence assessment, the interval is typically evaluated against prespecified bounds; the rationale and values for any such bounds are not reported in the registry record. Without those bounds, the interval should be read as an estimate and measure of precision rather than as a standalone verdict.

Why does crossover structure matter?

In general, crossover designs can reduce variability in comparisons when participant-level responses under different treatments are correlated. An analysis that uses the paired structure can distinguish within-participant differences from variation between participants. The benefit depends on appropriate design conduct and analysis. The registry identifies randomized treatment order and two periods, but does not report the detailed model, period effects, sequence effects, or washout information. It is therefore not possible to determine from the posted record how these design features were handled statistically.

Over-dispersion is a general concern when the observed variability exceeds what a chosen model assumes. If variability is understated, uncertainty estimates can be too small; if the model is poorly matched to the data, estimates and tests may also be affected. The posted standard deviations describe spread, but the record does not report diagnostic checks or modeling assessments that would permit an evaluation of this issue.

Overall, the displayed descriptive results and sponsor ratio analysis should be kept distinct. The former support a transparent summary-statistic comparison; the latter is the registry’s report of a model-based analysis whose method details are not available in the registry record.

10. Confidence Intervals and Precision

The sponsor’s estimate is a ratio of least squares means of 98.19, with a 90% confidence interval from 94.20 to 102.34. The interval communicates uncertainty around the reported ratio under the sponsor’s analysis. Its width reflects both the estimate and the variability and information available to that analysis; it does not identify the source of uncertainty by itself.

The simple unadjusted re-calculation is on a different scale. Its estimated mean difference is 0.13, and its confidence interval includes zero. The interval bounds for that re-calculation are not repeated because the posted bounds exceed the permitted decimal precision for this explanation. The unadjusted result is not the sponsor’s ratio analysis and should not be used to infer the interval from the sponsor’s model.

Precision and statistical significance are related but not identical. A confidence interval can help assess which values remain compatible with an estimate, while a p-value summarizes evidence against a particular null hypothesis. Neither directly establishes equivalence. That requires a relevant prespecified margin and interpretation of the appropriate interval against it. The margin is not reported in the registry record.

The sponsor analysis reports a 90% interval, while the unadjusted re-calculation is a distinct comparison. The registry does not provide the model specification or enough participant-level information to evaluate how crossover pairing affects precision. Thus, the sponsor’s interval is the posted precision statement for its own analysis; the simple calculation offers a separate, unadjusted view based on aggregate summaries.

11. Planning a Similar Trial: Sample Size

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

The sample-size table gives planning illustrations as participants per arm, not total events. Its assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect being planned for is a stated fraction of the observed effect. These calculations are planning illustrations based on the observed effect, not the original trial’s design calculation; the trial’s own original design assumptions are not reported in the registry record.

For planning at 100% of the observed effect, the table gives 2,771 participants per arm for 80% power and 3,710 participants per arm for 90% power. At 75% of the observed effect, it gives 4,926 participants per arm for 80% power and 6,594 participants per arm for 90% power. At 50% of the observed effect, it gives 11,083 participants per arm for 80% power and 14,837 participants per arm for 90% power.

The 80% power column represents the planned number of participants per arm for a design with an 80% chance of detecting the assumed effect under the stated model and assumptions, if that effect is real. The 90% column describes the corresponding planning target for a 90% chance. These are not guarantees about results, and they depend on the assumptions used for the illustration. This is not observed power.

The table illustrates that smaller effects need more participants: planning for 75% or 50% of the observed effect requires larger per-arm counts than planning for the full observed effect. The sample-size curve should be read as the visual expression of this same planning relationship across effect assumptions, not as evidence about the number enrolled or a result of the trial. The study’s recorded enrollment was 28; that figure is distinct from the illustrative planning counts.

12. How the Sample Size Is Derived

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

Formula

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

Worked calculation for this trial

1. Observed difference Δ = 0.130; pooled standard deviation σ = 1.727.
2. n = 2 × (1.96 + 0.842)² × 1.727² / 0.130² = 2,770.7, rounded up to 2,771 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 <- 0.13                      # observed difference in means
sigma <- 1.72709293322624                     # 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(841542)
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 = 2,771 (80% power), 3,710 (90% power)
 75% of observed effect: n per arm = 4,926 (80% power), 6,594 (90% power)
 50% of observed effect: n per arm = 11,083 (80% power), 14,837 (90% power)
power.t.test: 2771.6 
Simulated power at n = 2,771 per arm: 0.799 (20000 replicates)

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

13. Analyses Reported by the Sponsor

The registry reports the sponsor’s own analysis as a ratio of least squares means of 98.19, with a 90% confidence interval from 94.20 to 102.34. It does not report the method used to obtain that ratio, a p-value for the sponsor analysis, or any decision bounds for interpreting it as an equivalence result.

The separate re-calculation from the posted group summaries gives an unadjusted mean difference of 0.13 and an unadjusted p-value of 0.782. This is a simple comparison on the difference scale; the sponsor’s result is on a ratio scale and is described as a least-squares-means analysis. The unadjusted calculation does not reproduce the sponsor analysis and should not be used to overrule or substitute for it.

There is no flagged discrepancy between the posted summary values and the sponsor result in the registry record. The two summaries can nevertheless differ because they use different scales and may reflect different analytic approaches. As the sponsor result is the analysis reported by the study, it is the appropriate result to cite when describing the sponsor’s own analysis. The record’s limited methodological detail prevents an independent assessment of its model or formal equivalence decision.

14. Multiplicity, Missing Data and Analysis Populations

The registry identifies three outcome measures and three analyses, while the primary endpoint discussed in the record is Cmax. No secondary outcome measures are posted. The record does not state whether all analyses were prespecified, whether any were exploratory, or how the analyses were organized in relation to a statistical hierarchy.

Multiplicity arises when several outcomes, comparisons, or analyses are considered. In general, the more statistical tests performed, the greater the chance that at least one result appears notable by chance if no adjustment or prespecified strategy is used. A statistical plan can define which analyses are confirmatory and whether adjustments are needed. The registry record does not report a multiplicity strategy, so it is not possible to determine whether or how the reported analyses were adjusted.

For missing data and analysis populations, the registry says that data from all subjects who completed the study were included in the primary statistical analysis. It does not report the number who completed the study, participant-level reasons for non-completion, or the handling of missing measurements. The outcome entries list 27 observations for Amlodipine and 27 for Norvasc®, while enrollment is recorded as 28. The record does not explain the relationship between these figures, so no participant flow should be inferred from them.

The registry does not report imputation methods, sensitivity analyses for missing data, or an intention-to-treat analysis population. It also does not report the sponsor’s detailed analysis population definition beyond the statement about completers. These omissions limit assessment of whether missingness could have affected the estimates or their precision.

More generally, in a crossover study, missing data in one period can complicate the use of paired observations. Whether this occurred and how it was handled are not reported in the registry record. The available results therefore support a description of the posted analyses, but not a full audit of multiplicity control, missing-data assumptions, or population selection.

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

The posted results describe Cmax values for Amlodipine and Norvasc® in a randomized, open-label crossover study under fasting conditions. The group means are 6.16 ng/mL and 6.29 ng/mL, respectively, with reported standard deviations of 1.64 and 1.81. The sponsor reports a ratio of least squares means of 98.19 and a 90% confidence interval from 94.20 to 102.34. These are the key statistical summaries available in the registry record.

They do not, on their own, establish a formal bioequivalence conclusion. The registry identifies bioequivalence based on Cmax as the primary endpoint, but does not report the acceptance limits or the method used for the sponsor’s analysis. Without those details, the ratio and confidence interval cannot be evaluated against the criterion that would determine a formal conclusion.

The unadjusted re-calculation gives a mean difference of 0.13 and p-value of 0.782. This indicates that the simple aggregate comparison does not show a clear difference under its null-hypothesis test. It does not prove that the formulations are identical or equivalent, and the calculation is not a substitute for an analysis that may account for the crossover design.

The findings apply to the measured pharmacokinetic endpoint in the healthy subjects described in the registry. They do not establish effects in patients, comparative clinical benefit, safety, or outcomes under conditions different from the fasting single-dose study. The record does not report clinical outcomes or a patient population.

In short, the posted means are close in magnitude and the sponsor reports a ratio with its interval, but the full statistical basis and formal decision criteria are unavailable. The results are best interpreted as a record of the measured comparison rather than a standalone determination of clinical equivalence or effectiveness.

16. Why This Trial Matters Statistically

This study offers a useful statistical example because a randomized crossover design and a formulation comparison make the analysis scale important. The posted group means and standard deviations summarize Cmax in the two treatment conditions, while the sponsor’s result is expressed as a ratio of least squares means. A difference and a ratio answer related questions but are not interchangeable, especially when the endpoint is a concentration and the design allows observations from the same participant under both formulations.

The study also illustrates why the analysis method matters. A simple calculation from group summaries gives an unadjusted difference and p-value, but cannot reconstruct any model that uses participant pairing, treatment period, or sequence. The registry reports a sponsor analysis but not its method. Readers therefore need to distinguish a transparent recalculation from the analysis used by the study sponsor.

Precision is central to bioequivalence interpretation. A ratio estimate must be considered together with its confidence interval and the decision limits specified for the analysis. The sponsor’s estimate and 90% interval are posted, but the limits and model details are not reported in the registry record. This makes it possible to describe the estimate, but not to independently verify a formal decision.

Finally, the sample-size illustrations show how planning depends on the effect assumed: smaller effects require more participants under the stated assumptions. These planning figures are not evidence of the trial’s original design rationale or of observed power. Together, the record highlights the distinction among descriptive results, model-based inference, and design planning.

17. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record does not report the statistical model used for the sponsor’s ratio analysis, including its scale, covariates, treatment of period or sequence, or variance assumptions. This limits independent reproduction and interpretation of the sponsor estimate. It also does not report the acceptance limits needed to assess a formal bioequivalence decision.

The available primary outcome summaries are means and standard deviations, not participant-level measurements. They do not reveal the distribution of Cmax values or the degree of within-participant association across the crossover periods. The simple unadjusted re-calculation consequently cannot represent all potential features of a crossover analysis.

The record lists 28 enrolled and 27 observations for each formulation but does not give a detailed flow of participants or explain these counts. It states that completers were included in the statistical analysis, but does not describe missing measurements, reasons for non-completion, imputation, or sensitivity analyses. The handling of missing data therefore cannot be evaluated.

Other design details relevant to pharmacokinetic interpretation are not reported, including the period duration, washout interval, detailed sampling schedule, and whether any assessment of period or sequence effects was performed. The record is open-label and reports no masking; it does not explain whether this had any bearing on outcome measurement or analysis.

The study concerns healthy, non-smoking male and female subjects and a single-dose fasting comparison. The record does not report evidence about patient outcomes or conditions outside that study setting. The original sample-size justification, interim analyses, and complete statistical plan are also not reported in the registry record.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Amlodipine 10 mg Tablets Under Fasting Conditions — NCT00841542.
• Registry record last updated 2024-08-20; status last verified 2024-08.
• Results first posted 2009-08-18.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

21. Record Summary

The registry record describes a completed phase 1 randomized, open-label, two-way crossover study comparing single doses of Amlodipine Besylate 10 mg tablets and Norvasc® 10 mg tablets under fasting conditions in normal healthy non-smoking male and female subjects. The primary endpoint was Cmax, measured in ng/mL from blood samples collected over 168 hour period.

Enrollment was recorded as 28. The posted outcome summaries list 27 observations for each formulation. The reported means were 6.16 for Amlodipine and 6.29 for Norvasc®, with standard deviations of 1.64 and 1.81. The sponsor’s analysis reported a ratio of least squares means of 98.19, with a 90% confidence interval from 94.20 to 102.34.

The registry does not report the sponsor’s analysis method or the decision limits needed to assess a formal bioequivalence conclusion. Its results support description of the measured Cmax comparison, with those methodological limits in view.