A Safety and Tolerability Study of Azilsartan Medoxomil in Participants With Essential Hypertension: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Safety and Tolerability Study of Azilsartan Medoxomil in Participants With Essential Hypertension (NCT00696384), a randomized phase 3 study. The primary outcome is Change From Double-blind Baseline (Week 26) in Sitting Clinic Diastolic Blood Pressure to Week 32.

2. Clinical Question

The question concerns a change in a measured blood-pressure value over the reversal phase, not a comparison of the groups’ entire treatment histories. The Week 26 measurement was the baseline for this phase. It was also the final visit of the preceding open-label phase, so the primary comparison followed an initial period in which the study groups had not been assigned to the reversal-phase treatments described in the primary outcome.

The posted primary result is a between-group contrast in change, expressed in mmHg. The estimated mean change was 0.14 in the azilsartan medoxomil group and 7.92 in the placebo group. The estimated difference, defined as azilsartan medoxomil minus placebo, was -7.78. This describes the posted measurements and their statistical contrast; it does not by itself establish how the result should be applied to an individual or to other populations.

3. Trial Design

This was a Phase 3 randomized, parallel study with an enrollment of 418 participants and a registry status of completed. The registry record identifies the overall masking as quadruple. The study title describes an 8-month study with a blinded reversal phase, while the primary outcome specifies the double-blind period from Week 26 to Week 32.

The design had distinct stages. The first was an open-label azilsartan medoxomil phase from baseline through Week 26. At Week 26, the study entered a double-blind reversal phase with an azilsartan medoxomil group and a placebo group through Week 32. The primary outcome used the Week 26 measurement as the double-blind baseline. The arm descriptions do not provide further details about the process used to assign participants to the reversal groups, and the original allocation procedures are not reported in the registry record.

The registry lists azilsartan medoxomil, azilsartan medoxomil with or without chlorthalidone and other non-angiotensin II receptor blocker antihypertensive medications, and placebo among the interventions. It does not provide full arm descriptions for those interventions. No assumptions about how background medicines were managed should be drawn from the intervention names alone.

The study was sponsored by Takeda. Its start is listed as 2007-06 and its primary completion as 2009-04. The registry record describes the purpose as evaluating long-term safety and tolerability, while the posted primary endpoint is a blood-pressure change during the blinded reversal phase. Original sample-size justification, allocation ratio, detailed masking procedures, and interim-analysis plans 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: All participants that completed the open-label phase were randomized into a double-blind reversal phase (to continue with azilsartan medoxomil or to placebo, in addition to any other antihypertensive medications received during the open-label phase).

Open Label Phase

Reasons for not completing this period:

Double Blind Phase

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full analysis set with last observation carried forward.

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 Change From Double-blind Baseline (Week 26) in Sitting Clinic Diastolic Blood Pressure to Week 32, measured over Double-blind Baseline (Week 26) and Week 32..

The primary endpoint is change in sitting clinic diastolic blood pressure from the double-blind baseline at Week 26 to Week 32, measured in mmHg. The registry defines a participant’s diastolic blood pressure as the arithmetic mean of three trough sitting diastolic blood pressure measurements. Week 26, the final visit of the open-label phase, serves as the baseline for the double-blind reversal phase.

The reported outcome is a least-squares mean, and the registry describes the analysis population as the full analysis set with last observation carried forward. The primary result compares the mean changes between the azilsartan medoxomil and placebo groups. A negative between-group difference indicates that the estimated change in the azilsartan medoxomil group was lower than the estimated change in the placebo group, given the stated subtraction order.

General statistical context: a repeated clinic measurement gives a defined outcome for comparing groups over a specified study period. Averaging multiple measurements can represent the measured value with less dependence on any one reading. The registry does not state the investigators’ specific rationale for selecting this endpoint, so the general context should not be mistaken for a reported protocol justification. The endpoint describes a change in a blood-pressure measure; it does not, on its own, summarize all safety outcomes or establish the importance of the difference to participants.

7. Results Posted in the Registry

• Azilsartan Medoxomil QD - Double Blind Reversal Phase: mean 0.14 versus 7.92 on control; difference -7.78 (95% CI -9.77 to -5.79), standardized effect d = -0.90; 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.

Change From Double-blind Baseline (Week 26) in Sitting Clinic Systolic Blood Pressure to Week 32

• 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 errors.
• Result:
  • Azilsartan Medoxomil QD - Double Blind Reversal Phase: mean 0.59 versus 12.97 on control; difference -12.38 (95% CI -15.46 to -9.30), standardized effect d = -0.93; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Azilsartan Medoxomil QD - Double Blind Reversal Phase than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry lists secondary outcomes covering blood-pressure changes during both the open-label and reversal phases, as well as adverse events. The secondary outcome with a posted numerical comparison for the reversal phase is change in sitting clinic systolic blood pressure from Week 26 to Week 32. Its ANCOVA contrast has the same direction as the primary diastolic comparison. This gives a broadly aligned statistical pattern across the two blood-pressure measures during the same phase, but the endpoints remain distinct measurements.

The registry lists additional secondary outcomes for systolic and diastolic change from the open-label baseline to Week 26 and for adverse events. Numerical results for those listed outcomes are not reported in the registry record. The absence of posted estimates means that no conclusion about their results can be drawn from the endpoint names alone.

Secondary outcomes help describe other aspects of the study, but they generally carry less weight as confirmatory evidence when several outcomes are examined. Each additional comparison creates further opportunity for a seemingly notable result to occur by chance. Statistical methods can address this issue by controlling the overall error rate or by defining a hierarchy of tests. The registry does not report whether such a multiplicity procedure was planned or used.

The secondary systolic result can be considered alongside the primary result as supportive context, not as an independent confirmation that resolves all uncertainty. It shares the same study population and reversal-phase setting, and it is subject to the limitations of the analysis and the unreported multiplicity plan. The reported endpoint-specific estimates should not be treated as a complete account of all secondary outcomes.

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

• Change From Double-blind Baseline (Week 26) in Sitting Clinic Systolic Blood Pressure to Week 32
• Change From Open Label Baseline (Week 0) in Sitting Clinic Diastolic Blood Pressure to Week 26
• Change From Open Label Baseline (Week 0) in Sitting Clinic Systolic Blood Pressure to Week 26
• Number of Participants With Adverse Events During the Open-Label Phase
• Number of Participants With Adverse Events in the Double-Blind Baseline Phase

9. Statistical Interpretation

10. Statistical Methods Explained

The registry reports an ANCOVA analysis for the primary endpoint. The posted ANCOVA result is a mean difference in final values of -7.78 mmHg, with a 95% confidence interval from -9.78 to -5.78 and p <0.001. The registry does not report the full model specification, covariates, or handling of all model assumptions. Those details should not be inferred from the method name alone.

What does the recalculation represent?

The recalculated comparison uses the posted group means and standard errors to form a simple, unadjusted contrast. It gives a mean difference of -7.78 mmHg, with a 95% confidence interval from -9.773 to -5.787 and an unadjusted p-value of <0.001. This offers a transparent comparison based on the available summary statistics, but it does not account for covariate adjustment in the way the reported ANCOVA may. The recalculation is not a substitute for the registry’s analysis.

The approximate pooled standard deviation is derived from the standard errors and group sizes, as indicated by the recalculation. It is therefore an approximation rather than a directly reported standard deviation. Standard errors describe the uncertainty of estimated group means; they are not measures of how widely individual participants’ readings vary. Confusing those quantities can make an estimate appear more or less variable than it is.

What does ANCOVA do?

General statistical explanation: analysis of covariance models an outcome while accounting for selected covariates. In a trial, that can adjust the comparison for prespecified baseline or other factors, if those factors are included in the model. The registry identifies ANCOVA but does not report which covariates were used, so it is not possible to say which adjustments contributed to this particular estimate. The reported model-based contrast and the unadjusted recalculation answer closely related but not identical statistical questions.

How should the p-value be read?

The primary p-value is reported as <0.001 for both the ANCOVA result and the unadjusted recalculation. General statistical explanation: a p-value measures how incompatible the observed data are with a specified null model, under the assumptions used for the test. It is not a measure of the probability that the result is due to chance, and it does not quantify the clinical importance of a difference. The p-value also does not replace the estimate and its confidence interval: those convey the direction, scale, and precision of the contrast.

The comparison is based on the mean of a continuous outcome. General statistical explanation: a mean summarizes a group’s central value, while a standard error describes the precision of the estimated mean. A mean difference focuses on the contrast between group averages. It does not describe the full distribution of participants’ individual changes or how many participants experienced a particular size of change.

What does the analysis population mean?

The primary endpoint is reported for the full analysis set with last observation carried forward. The registry does not define the exact membership rules for the full analysis set, so eligibility and analysis inclusion details are not reported in the registry record. Last observation carried forward uses a participant’s last recorded value when a later outcome is missing. General statistical context: this approach can preserve an analysis set, but it assumes that the last value is an adequate substitute for the missing later value. If the outcome would have changed, carrying the earlier value forward may misrepresent the later measurement. The registry does not describe other missing-data analyses or sensitivity checks.

The study was randomized and parallel, with an open-label phase followed by a double-blind reversal phase. Those design features provide context for the comparison, but they do not reveal the full statistical plan. The registry does not report whether the endpoint, model, covariates, or analysis population were prespecified in a protocol or statistical analysis plan, nor does it report interim analyses. Such details are not reported in the registry record.

General statistical explanation: over-dispersion is a concern when observed variation is greater than a model assumes, especially for outcomes such as event counts. The primary endpoint is continuous, and the listed comparison uses group means; no over-dispersion parameter is reported. The concepts and assumptions used for a continuous mean comparison should not be transferred automatically to adverse-event counts or other endpoints.

11. Confidence Intervals and Precision

The registry’s ANCOVA estimate for the primary comparison is -7.78 mmHg, with a 95% confidence interval from -9.78 to -5.78. The unadjusted recalculation gives the same point estimate, -7.78 mmHg, with a 95% confidence interval from -9.773 to -5.787. Both intervals lie on the negative side of zero, consistent with the reported p-values of <0.001. The limits differ slightly because the methods differ and the recalculation uses posted summary statistics.

General statistical explanation: a confidence interval gives a range of values compatible with the estimate and the statistical model at the stated confidence level. It conveys precision: a narrower interval indicates less statistical uncertainty about the estimated contrast than a wider interval. It is not a range containing most individual participants’ outcomes, and it does not include uncertainty about unreported design or analysis choices.

The interval’s width should be considered alongside the endpoint definition and analysis population. It concerns the group mean difference in change from Week 26 to Week 32 for the full analysis set with last observation carried forward. It does not describe changes in every participant, nor does it show whether the result would be similar in a different population or over a different period.

The secondary systolic outcome also has a posted ANCOVA estimate of -12.38 mmHg and a 95% confidence interval from -15.47 to -9.29. This estimate is another measure from the reversal phase, but its presence does not make it interchangeable with the primary diastolic endpoint. The registry does not report an adjustment strategy for interpreting multiple outcomes together, so confidence intervals for secondary outcomes should be read as endpoint-specific rather than as a complete account of uncertainty across the study.

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 express the number of participants per arm for the continuous-outcome comparison. They are not total event counts. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each illustration uses an effect to detect set at a stated fraction of the observed effect. These are planning assumptions for the illustration; the trial’s original design assumptions are not reported in the registry record.

The 80% power column gives the participants per arm that the illustration estimates would be needed for an 80% chance of detecting the specified effect under its assumptions. The 90% power column gives the corresponding number per arm for a 90% chance. Power is a design calculation for a hypothetical study under stated assumptions, not a guarantee that a study with that number will produce a statistically significant result.

The rows consider planning for the full observed effect, 75% of the observed effect, and 50% of the observed effect. The smaller the effect a future study is designed to detect, the more participants it generally needs under otherwise comparable assumptions. The displayed requirements therefore increase as the assumed effect becomes smaller. The figures are based on the effect observed in this trial, which may not be the effect chosen for a future study.

This is not observed power. It is a planning illustration, not a calculation of the probability that the completed trial detected its result. The registry does not report the original sample-size justification, so these illustrations should not be taken as evidence of how the study’s enrollment target was set.

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 = -7.780; pooled standard deviation σ = 8.657.
2. n = 2 × (1.96 + 0.842)² × 8.657² / -7.780² = 19.4, rounded up to 20 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 <- -7.78                      # observed difference in means
sigma <- 8.65668281830094                     # 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(696384)
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 = 20 (80% power), 27 (90% power)
 75% of observed effect: n per arm = 35 (80% power), 47 (90% power)
 50% of observed effect: n per arm = 78 (80% power), 105 (90% power)
power.t.test: 20.4 
Simulated power at n = 20 per arm: 0.791 (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’s reported primary analysis is an ANCOVA estimate of -7.78 mmHg, with a 95% confidence interval from -9.78 to -5.78 and p <0.001. It is the trial’s posted model-based analysis. The recalculated comparison is an unadjusted calculation from the posted group summaries, with an estimate of -7.78 mmHg, a 95% confidence interval from -9.773 to -5.787, and p <0.001.

The point estimates match at the displayed precision, while the interval limits are slightly different. That is not unexpected when a model-based analysis and an unadjusted summary-statistic calculation use different methods. The recalculation is useful as a check on the direction and approximate scale of the contrast, but it does not reproduce the ANCOVA model or its assumptions.

The registry does not provide the full ANCOVA specification, including its covariates. Interpretation of the sponsor-reported estimate should therefore remain tied to the method as described, without assuming details not in the registry record. The unadjusted result should be understood as supplementary statistical context, not as a replacement for the reported trial analysis.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary endpoint and several secondary outcomes, including additional blood-pressure measures and adverse-event outcomes. It reports a primary ANCOVA analysis and a secondary ANCOVA analysis for systolic blood-pressure change during the reversal phase. A multiplicity strategy for interpreting the multiple endpoints is not reported in the registry record. It is also not reported whether secondary tests were prespecified in a hierarchy or adjusted to control the chance of false-positive findings across outcomes.

General statistical context: when many hypotheses are tested, the chance of obtaining at least one apparently notable result can increase. Multiplicity procedures can address that concern, but they may also change how individual p-values and confidence intervals are interpreted. Since the registry does not describe a procedure, the posted secondary p-value should be read as endpoint-specific, not as evidence that the overall family of secondary results meets a particular error-rate standard.

The primary population is described as the full analysis set with last observation carried forward. The registry does not report the detailed rules for membership in that set, the number of participants with missing primary measurements, the timing or reasons for missingness, or a sensitivity analysis using another missing-data method. It therefore is not possible to assess from the registry record how missing measurements affected the estimate.

General statistical context: last observation carried forward replaces a missing later value with an earlier available value. This can be convenient, but it relies on an assumption that the earlier value reasonably represents the later outcome. If participants’ measurements would have changed after the last recorded visit, the carried-forward values may distort group averages or uncertainty. This limitation matters when interpreting an analysis that uses this approach, but the extent of any effect cannot be established from the posted information.

Interim analyses and stopping rules are not reported in the registry record. The original statistical analysis plan, full covariate specification, and trial-specific sample-size justification are also not reported. These omissions limit independent assessment of how the analysis was planned and whether all planned analyses are represented in the registry results.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hypertensive crisis (0.7%), acute coronary syndrome (0.2%), diabetic retinopathy (0.2%), eye haemorrhage (0.2%), pancreatitis (0.2%).

For the open-label phase, the registry lists 418 participants at risk and 8 participants with serious adverse events. For the azilsartan medoxomil double-blind reversal group, it lists 148 at risk and 0 with serious adverse events; for the placebo reversal group, it lists 151 at risk and 1 with a serious adverse event. The record does not report deaths for these groups.

The registry also lists 60 participants with other adverse events during the open-label phase, 5 in the azilsartan medoxomil reversal group, and 8 in the placebo reversal group. These counts describe the registry’s posted safety entries. They should not be interpreted as a complete comparison of risk without considering the different phases, group sizes, and periods represented. The registry does not provide enough detail to determine exposure time or explain the difference between the reversal-phase at-risk counts and the primary outcome analysis counts.

Serious adverse-event terms listed include hypertensive crisis at 0.7%, and acute coronary syndrome, diabetic retinopathy, eye haemorrhage, pancreatitis, and upper gastrointestinal haemorrhage, each at 0.2%. These listed terms and percentages do not provide a full account of event timing, severity, relatedness, or all safety outcomes. The registry record does not report deaths; that should not be read as proof that none occurred.

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

The primary result describes a difference in mean change in sitting clinic diastolic blood pressure between two groups during the double-blind reversal phase. The estimated contrast is -7.78 mmHg, with a reported ANCOVA 95% confidence interval from -9.78 to -5.78 and p <0.001. The direction indicates a lower estimated change in the azilsartan medoxomil group than in the placebo group, using the stated group order.

The result does not show that every participant’s blood pressure changed in the same way. Group means can conceal substantial variation among participants, and the registry does not provide individual-level distributions in the registry record. A statistically notable group contrast is also not, by itself, a judgment about clinical importance. The registry does not state a threshold for interpreting the size of the change as clinically meaningful.

The comparison is specific to participants with essential hypertension in this study, the full analysis set, the Week 26 to Week 32 period, and an endpoint analyzed with last observation carried forward. It does not estimate the effect of treatment over every stage of the study or establish what would happen with another treatment duration, another population, or a different pattern of background medication.

The record’s stated purpose includes long-term safety and tolerability, but the posted primary endpoint is a blood-pressure measure. Safety counts are descriptive and should not be treated as a complete basis for comparing risks. The registry also does not report every detail needed to assess missing data, multiplicity, or the original analysis plan. These limits do not erase the posted statistical contrast, but they define what can reasonably be concluded from it.

No treatment recommendation follows from these statistics. They describe a trial result and its uncertainty; individual decisions require clinical context that is outside the scope of the registry result.

18. Why This Trial Matters Statistically

Statistically, this study is notable for its staged structure: an open-label phase was followed by a double-blind reversal phase, and the primary comparison uses Week 26 as the baseline for that reversal. Making the phase and baseline explicit is essential to interpreting the estimate. Without that context, a reader could mistake the primary result for a comparison spanning the full study period.

The record presents both a reported ANCOVA result and a recalculated unadjusted contrast. Their point estimates match at the displayed precision, while the confidence-interval limits differ slightly. This illustrates why a model-based trial analysis and a simple summary-statistic calculation should be identified separately, even when they yield similar estimates. The recalculation provides a check on direction and scale; it does not recreate the trial’s model.

The endpoint also illustrates the distinction between a group mean contrast and individual outcomes. The comparison estimates a difference in average change, not the number of participants who changed by a particular amount. The registry’s use of a defined average of three trough measurements further emphasizes that an endpoint is shaped by its measurement definition, not just by its label.

Finally, the record illustrates how interpretation depends on information beyond a p-value. The ANCOVA specification, multiplicity procedures, detailed missing-data information, and original sample-size justification are not reported in the registry record. Their absence limits assessment of planning and robustness. The posted effect estimate and interval remain interpretable as reported, but they cannot answer every question about the study’s design or the wider evidence base.

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 primary comparison is restricted to the double-blind reversal phase from Week 26 to Week 32. The registry does not provide a primary comparison covering the full open-label and reversal period, so the result should not be generalized to the whole study duration. The initial phase was open label, while the primary analysis followed the Week 26 double-blind baseline.

The primary endpoint analysis uses the full analysis set with last observation carried forward. The registry does not provide the exact definition of the full analysis set, the number of missing measurements, reasons for missingness, or sensitivity analyses. The impact of this missing-data method cannot be assessed from the posted record alone.

The registry identifies ANCOVA but does not report the model’s covariates or other specification details. It also does not report a multiplicity plan, interim analyses, or the original sample-size justification. These gaps constrain independent evaluation of the analysis choices and the strength of conclusions across multiple outcomes.

The posted primary outcome group counts are 142 and 148, while the reversal-phase safety counts at risk are 148 and 151. The record does not explain the differences. No reconciliation should be assumed. Likewise, the registry lists intervention names that mention other antihypertensive medicines, but the arm descriptions do not clarify their use. Exposure and treatment-management details beyond the stated phase descriptions are not reported in the registry record.

Safety information is limited to the posted counts and serious-event terms. The registry does not report deaths for the groups, and does not provide enough detail in these figures to characterize duration of exposure, event relatedness, or the full clinical context of each event. The safety counts therefore need to be interpreted as registry entries, not a complete risk assessment.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Safety and Tolerability Study of Azilsartan Medoxomil in Participants With Essential Hypertension — NCT00696384.
• Registry record last updated 2012-01-04; status last verified 2011-11.
• 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

NCT00696384 is a completed Phase 3 randomized parallel study sponsored by Takeda, enrolling 418 participants with essential hypertension. The study began in 2007-06, with primary completion in 2009-04. Its design included an open-label azilsartan medoxomil phase through Week 26 and a double-blind reversal phase through Week 32.

The primary endpoint was change in sitting clinic diastolic blood pressure from Week 26 to Week 32. The registry’s ANCOVA analysis reported a mean difference of -7.78 mmHg, a 95% confidence interval from -9.78 to -5.78, and p <0.001. The registry also posts a secondary ANCOVA result for systolic blood-pressure change in the same reversal phase, with a contrast in the same direction.

The primary analysis used the full analysis set with last observation carried forward. Details of the ANCOVA specification, multiplicity plan, original sample-size justification, and interim analyses are not reported in the registry record. Safety entries list serious adverse events by phase and group, while deaths are not reported in the registry record.