A Study to Evaluate Efficacy and Safety of LCI699 in Participants With Essential Hypertension: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate Efficacy and Safety of LCI699 in Participants With Essential Hypertension (NCT00758524), a randomized phase 2 study. The primary outcome is Core Period: Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 8 Last Observation Carried Forward (LOCF), as Measured by Office Blood Pressure (OBP).

2. Clinical Question

3. Trial Design

This was a phase 2, randomized, parallel-group study described in the registry as a dose-finding study of LCI699. It enrolled 628 participants and compared four LCI699 regimens with placebo and the active comparator eplerenone. The registry records quadruple masking and describes the study as double-blind in its official title.

The core treatment period lasted up to 8 weeks. Participants in the LCI699 groups received 0.25 mg once daily, 0.5 mg once daily, 1.0 mg once daily, or 0.5 mg twice daily. The active comparator group received eplerenone 50 mg twice daily. Placebo capsules matched LCI699 or eplerenone, with once-daily or twice-daily schedules described. The registry also lists a withdrawal period from Week 8 to Week 9, during which treatment or matching placebo was given for up to 1 week.

The study began on 2008-09-11, had primary completion on 2009-07-02, and is recorded as completed. Its stated purpose was to assess the blood pressure-lowering effect, safety, and tolerability of LCI699 compared with placebo and eplerenone in participants with mild-to-moderate uncomplicated essential hypertension. Further details about the randomization procedure, allocation concealment, and the specific roles covered by quadruple masking 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: A total of 628 participants were enrolled in the study. Out of 628, only 524 participants with essential hypertension were randomized to receive LCI699 or eplerenone in comparison with placebo for 8 weeks, followed by a randomized withdrawal period to either continue the treatment arm they were randomized to or to take placebo for one additional week (Week 9).

Only the first 6 of 17 groups are shown.

Core Period (Week 0 to Week 8)

Reasons for not completing this period:

Withdrawal Period (Week 8 to Week 9)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: FAS population included all randomized participants or participants that met the inclusion criteria as described in study documentation protocol excluding misrandomized participants or participants with protocol violations. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.

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.

Population: Full Analysis Set (FAS) population included all randomized participants or participants that met the inclusion criteria as described in study documentation protocol excluding misrandomized participants or participants with protocol violations.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Core Period: Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 8 Last Observation Carried Forward (LOCF), as Measured by Office Blood Pressure (OBP), measured over Baseline, Week 8.

The primary endpoint was change from baseline in mean sitting diastolic blood pressure at Week 8, using last observation carried forward. Diastolic blood pressure is the lower of the two office blood pressure readings. The endpoint is a continuous measure reported in mm Hg, with the registry listing a mean and standard error for each treatment group.

Measurements were made with an automated blood pressure device after participants had been sitting for 5 minutes. The change was calculated by comparing Week 8 readings with baseline readings. The endpoint was chosen to assess the blood pressure response during the core treatment period; the registry describes the study as a proof-of-efficacy, dose-finding study. It does not establish whether a change in this measurement leads to a change in longer-term clinical outcomes.

The registry states that the primary outcome was analyzed using an analysis of covariance model, with treatment and region as factors and baseline mean sitting diastolic blood pressure as a covariate. The primary analysis population is described as the FAS population, with misrandomized participants and participants with protocol violations excluded as described in study documentation. Further detail on the handling of missing readings beyond last observation carried forward is not reported in the registry record.

7. Results Posted in the Registry

• Core Period: LCI699 0.25 mg QD: mean -4.47 versus -3.22 on control; difference -1.25 (95% CI -3.32 to 0.82), standardized effect d = -0.19; z-test p = 0.237.
• Core Period: LCI699 0.5 mg QD: mean -5.50 versus -3.22 on control; difference -2.28 (95% CI -4.32 to -0.24), standardized effect d = -0.35; z-test p = 0.028.
• Core Period: LCI699 1.0 mg QD: mean -7.11 versus -3.22 on control; difference -3.89 (95% CI -6.32 to -1.46), standardized effect d = -0.49; z-test p = 0.002.
• Core Period: LCI699 0.5 mg BID: mean -4.25 versus -3.22 on control; difference -1.03 (95% CI -3.55 to 1.49), standardized effect d = -0.12; z-test p = 0.424.

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.

Core Period: Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 8 LOCF, as Measured by OBP

• 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:
  • Core Period: LCI699 0.25 mg QD: mean -9.00 versus -2.93 on control; difference -6.07 (95% CI -10.36 to -1.78), standardized effect d = -0.43; z-test p = 0.006.
  • Core Period: LCI699 0.5 mg QD: mean -10.69 versus -2.93 on control; difference -7.76 (95% CI -11.57 to -3.95), standardized effect d = -0.65; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Core Period: LCI699 0.25 mg QD than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Core Period: LCI699 0.5 mg QD than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Core Period: Dose Response Relationship of LCI699 as Measured by Change From Baseline in MSDBP at Week 8

• 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:
  • Core Period: LCI699 0.5 mg QD: mean -5.50 versus -4.47 on control; difference -1.03 (95% CI -2.65 to 0.59), standardized effect d = -0.19; z-test p = 0.213.
  • Core Period: LCI699 1.0 mg QD: mean -7.11 versus -4.47 on control; difference -2.64 (95% CI -4.73 to -0.55), standardized effect d = -0.38; z-test p = 0.013.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Core Period: LCI699 0.5 mg QD and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Core Period: LCI699 1.0 mg QD than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Core Period: Dose Response Relationship of LCI699 as Measured by Change From Baseline in MSSBP at Week 8

• 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:
  • Core Period: LCI699 0.5 mg QD: mean -10.69 versus -9.00 on control; difference -1.69 (95% CI -5.04 to 1.66), standardized effect d = -0.15; z-test p = 0.323.
  • Core Period: LCI699 1.0 mg QD: mean -11.93 versus -9.00 on control; difference -2.93 (95% CI -6.87 to 1.01), standardized effect d = -0.22; z-test p = 0.145.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Core Period: LCI699 0.5 mg QD 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 Core Period: LCI699 1.0 mg QD and the control. The interval gives the range of effects that remain compatible with the data.

The posted systolic blood pressure summaries show decreases from baseline across the core-period treatment groups, including placebo. Among the once-daily LCI699 groups, the reported group means become more negative across the listed dose levels, while the twice-daily LCI699 mean does not follow the same ordering. This broad pattern is directionally similar to the primary diastolic outcome, but the two measures are distinct endpoints and should not be treated as interchangeable evidence.

The registry also lists dose-response outcomes for diastolic and systolic blood pressure and ambulatory blood pressure outcomes, including 24-hour mean systolic and diastolic pressure and trough-to-hour ratios. Numerical results for all of these listed outcomes are not reported in the registry record. The reported secondary summaries therefore provide an incomplete view of the outcome set, and they cannot establish a consistent effect across office and ambulatory measurements.

Secondary results can help assess whether the primary finding fits with other measured outcomes, but they generally carry less weight when many endpoints or comparisons are considered without a reported plan for controlling multiplicity. An unadjusted result does not account for the increased chance of at least one apparently notable finding when many tests are performed. The registry does not report multiplicity-adjusted secondary analyses. In addition, the posted recalculated comparisons are not the same as formal sponsor-reported analyses, and their uncertainty should be interpreted accordingly.

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

• Core Period: Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 8 LOCF, as Measured by OBP
• Core Period: Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), and Deaths
• Core Period: Dose Response Relationship of LCI699 as Measured by Change From Baseline in MSDBP at Week 8
• Core Period: Dose Response Relationship of LCI699 as Measured by Change From Baseline in MSSBP at Week 8
• Core Period: Change From Baseline in Mean 24 Hour Ambulatory SBP at Week 8 as Measured by Ambulatory Blood Pressure Monitoring (ABPM)
• Core Period: Change From Baseline in Mean 24 Hour Ambulatory DBP at Week 8, as Measured by ABPM
• Core Period: Trough to Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory DBP at Week 8
• Core Period: Trough to Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory SBP at Week 8

9. Statistical Interpretation

10. Statistical Methods Explained

The primary measure is continuous: a blood pressure change expressed in mm Hg. For each group, the registry reports a mean change and its standard error. The mean describes the average change in the analyzed group. The standard error describes the precision of that estimated mean; it is not the range of individual participants’ changes and should not be read as a measure of how spread out all individual readings were.

Why use an analysis of covariance?

In general, analysis of covariance (ANCOVA) compares outcome values across treatment groups while accounting for a baseline measurement and other model factors. Here, the registry says that treatment and region were included as factors and baseline mean sitting diastolic blood pressure as a covariate. Accounting for baseline can help distinguish treatment-group differences from variation in starting blood pressure. The registry does not report the ANCOVA estimates, detailed model diagnostics, or additional covariates.

The primary outcome uses change from baseline and last observation carried forward (LOCF). In general, LOCF substitutes a participant’s last observed value for a later missing value when forming an analysis value. This method can make assumptions about what would have happened after the last measurement; it does not itself show how many values were missing or why. Those details, and any sensitivity analyses for missing data, are not reported in the registry record.

What do the recalculated comparisons represent?

The comparisons accompanying the arm summaries are unadjusted recalculations from posted means and standard errors. They express the difference between a treatment-group mean change and the placebo mean change. A negative difference means the treatment-group mean change was more negative than the placebo mean change. These calculations do not reproduce the described ANCOVA, which includes treatment and region factors and adjusts for baseline blood pressure. The registry does not report formal comparison analyses for these contrasts. The recalculated results are therefore useful for reading the summaries, but they should not be mistaken for sponsor-reported model results.

A confidence interval gives a range of values compatible with the estimated contrast under the method used. In general, a narrower interval indicates greater precision, while an interval spanning zero includes the possibility of no difference. The intervals accompanying these recalculated comparisons quantify uncertainty from the summary data and are not the same as intervals from the described ANCOVA. A p-value summarizes how compatible the observed data are with a null hypothesis under a statistical model. The recalculated p-values are unadjusted, and they do not account for the number of comparisons or endpoints examined.

Randomization is intended, in general, to balance participant characteristics across groups on average, while masking can reduce the influence of expectations on study conduct and assessment. The registry records randomization and quadruple masking. It does not describe the randomization sequence, concealment procedures, or which roles were masked. The parallel-group design means that participants were assigned to a treatment group for comparison over the core period, rather than crossing through multiple treatments as part of the primary comparison.

The registry defines the primary analysis population as the FAS population and gives a description that excludes misrandomized participants and participants with protocol violations. It does not provide enough detail to determine how that population relates to all randomized participants in each analysis. The group sizes listed for the primary endpoint and the safety outcomes are not identical in every treatment group, so they should be interpreted according to the specific outcome being reported rather than treated as interchangeable denominators.

The study’s stated dose-finding purpose makes the pattern across several LCI699 regimens relevant, but a pattern of group means is not by itself a formal test of a dose-response relationship. The registry lists dose-response outcomes, yet the complete statistical model and inferential results for those outcomes are not reported in the registry record. In general, formal dose-response analyses use a prespecified model or contrast and quantify uncertainty; the method used for such an analysis in this study is not reported in the registry record.

11. Confidence Intervals and Precision

The recalculated confidence intervals show how uncertain the unadjusted treatment-versus-placebo differences are. For LCI699 0.25 mg once daily, the interval extends from -3.321 to 0.821 mm Hg. For 0.5 mg once daily, it extends from -4.319 to -0.241 mm Hg, and for 1.0 mg once daily, from -6.315 to -1.465 mm Hg. The interval for 0.5 mg twice daily runs from -3.555 to 1.495 mm Hg. For eplerenone 50 mg twice daily, it runs from -6.824 to -1.716 mm Hg.

Intervals that include zero are compatible with a range of possibilities that includes no difference in mean change. Intervals that do not include zero indicate that zero is outside the interval calculated by this unadjusted method. This distinction does not account for multiplicity, and it does not convert these recalculations into the registry’s ANCOVA results.

Precision depends on both the estimated difference and the variability of the measurements, as well as the amount of information available. The group standard errors vary, and the intervals differ in width. A point estimate alone therefore does not convey how precisely the contrast has been estimated. The registry does not report confidence intervals for the described ANCOVA analysis, so the recalculated intervals should be interpreted as summary-statistic estimates rather than as the trial’s official adjusted uncertainty estimates.

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 planning values are participants per arm, not total participants or total events. They use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect used for planning is set to the stated fraction of the observed effect: 100%, 75%, or 50%. These are illustrative calculations based on the observed effect, not the original design assumptions; those original assumptions are not reported in the registry record.

The 80% power column gives the estimated participants per arm for a future two-arm study to have an 80% chance of detecting the specified effect under the stated assumptions, if the assumptions hold. The 90% power column gives the corresponding estimate for a 90% chance. For example, for the LCI699 0.5 mg once-daily comparison, planning for 100% of the observed effect gives 126 participants per arm for 80% power and 169 participants per arm for 90% power. Planning for 75% of that effect gives 224 and 300 participants per arm, respectively.

Smaller effects require more participants to detect with the same power under these assumptions. The plotted curve represents that same relationship between the effect size used for planning and the participant requirement. These values are not observed power; they are planning illustrations and do not indicate the probability that the completed trial’s result is true.

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 = -1.250; pooled standard deviation σ = 6.644.
2. n = 2 × (1.96 + 0.842)² × 6.644² / -1.250² = 443.5, rounded up to 444 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 <- -1.25                      # observed difference in means
sigma <- 6.64425197726196                     # 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(758524)
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 = 444 (80% power), 594 (90% power)
 75% of observed effect: n per arm = 789 (80% power), 1,056 (90% power)
 50% of observed effect: n per arm = 1,775 (80% power), 2,375 (90% power)
power.t.test: 444.5 
Simulated power at n = 444 per arm: 0.795 (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. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary outcome and multiple secondary outcomes, including blood pressure measures and safety outcomes. When several outcomes and treatment comparisons are examined, the chance of at least one result appearing notable by chance can increase. Statistical methods that address this issue may include a prespecified testing sequence or adjustment of significance levels, but the registry record does not report whether such methods were planned or used.

The recalculated treatment-versus-placebo p-values are unadjusted. They should not be interpreted as if they account for the multiple treatment groups or endpoints. The registry describes an ANCOVA model for the primary outcome, but does not report its comparison-specific estimates, p-values, or any multiplicity procedure. The interim-analysis plan is not reported in the registry record.

The primary endpoint uses LOCF, but the number and pattern of missing outcome measurements, reasons for missingness, and any sensitivity analyses are not reported in the registry record. In general, missing-data methods rely on assumptions about unobserved values; LOCF does not guarantee that those assumptions are appropriate.

The primary population is described as the FAS population, with misrandomized participants and participants with protocol violations excluded according to study documentation. The registry does not give further detail about exclusions or provide a full account of the analyzed population for every endpoint. The analysis population used for other outcomes is not reported in the registry record. These gaps limit assessment of whether the posted summaries reflect the intended analysis populations and how robust the findings are to missing data or alternative analysis choices.

15. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: abdominal pain (1.3%), retinal vein occlusion (1.1%).

During the core period, the registry reports one serious adverse event in the LCI699 0.25 mg once-daily group and one in the placebo group. It reports zero serious adverse events in the other core-period groups, including eplerenone. No deaths are reported in any of the listed core-period groups. These are counts from the registry record and do not establish whether an event was caused by a study treatment.

The registry lists abdominal pain at 1.3% and retinal vein occlusion at 1.1% among the serious adverse event terms. It also reports adverse event counts that are not classified as serious, with the number varying by group. Those counts should be read alongside the outcome-specific group sizes recorded for safety, not assumed to share the primary endpoint analysis population.

Safety counts are descriptive. A small number of reported serious events, or no reported deaths, does not rule out uncommon risks or establish comparative safety. The registry record does not provide the clinical details needed to assess event severity, timing, relatedness, or the basis for each attribution.

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

The primary outcome summaries describe average change in office-measured sitting diastolic blood pressure over the core treatment period. The group means were more negative in each active-treatment group than in the placebo group, but the size and precision of the unadjusted comparisons varied. These summaries describe short-term measurements; they do not demonstrate an effect on longer-term health outcomes.

The study was a phase 2 dose-finding study, and its results are best understood in that context. The once-daily LCI699 group means show a pattern of larger decreases at higher listed doses, while the twice-daily regimen does not match that pattern. The available summaries are not sufficient to treat this pattern as a definitive dose-response finding, particularly because the registry does not report complete formal dose-response analyses or adjusted comparisons.

The registry’s primary analysis description specifies ANCOVA, but the comparison estimates discussed in the recalculations come from the posted group summaries and are unadjusted. They may differ from the trial’s model-based results. The registry record does not report the sponsor’s adjusted estimates or confidence intervals, so the recalculations cannot replace them.

These findings do not establish that any treatment works or does not work. They also do not show how the treatments compare for outcomes beyond the posted measurements, or how results might differ with longer follow-up or in other populations. The safety counts are descriptive and do not establish causation or rule out uncommon events. Interpretation should account for the short core period, the range of comparisons, missing reporting on multiplicity and missing data, and the fact that some listed outcomes do not have numerical results in the registry record.

17. Why This Trial Matters Statistically

This trial is statistically informative because it compares several LCI699 dosing regimens with both placebo and an active comparator in a randomized parallel-group design. That makes it possible to examine the shape of the observed dose pattern rather than relying on a single treatment-versus-control contrast. The posted primary outcome also gives group means and standard errors, which allow readers to consider both the direction of the summaries and their precision.

At the same time, the study illustrates why a difference between group means is not a complete statistical conclusion. The registry describes an adjusted ANCOVA analysis, while the recalculated comparisons use only posted summary statistics and are unadjusted. A reader must distinguish these two forms of evidence. Confidence intervals also matter: point estimates with different precision should not be treated as equally certain.

The study highlights the difficulty of interpreting several doses and multiple endpoints without a reported multiplicity strategy. A dose-finding study can generate useful hypotheses, but a visible pattern in group means is not necessarily a confirmed dose-response relationship. The absence of reported adjusted comparisons, analysis details for some secondary outcomes, and missing-data sensitivity analyses further limits what can be inferred.

Finally, the short treatment period and blood pressure focus define the scope of the evidence. The registry provides a record of short-term measurements and safety counts, not a complete account of longer-term outcomes or rare harms. These distinctions are central to reading trial summaries responsibly.

18. Limitations

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

The primary treatment period lasted up to 8 weeks, and the registry describes a withdrawal period lasting up to 1 week. This limits the time span represented by the primary endpoint and safety summaries. The registry record does not report longer-term follow-up results.

The study focused on participants with mild-to-moderate uncomplicated essential hypertension and was described as a phase 2 proof-of-efficacy, dose-finding study. Results from this population and study purpose do not by themselves establish how findings apply to other populations or settings. The primary endpoint was an office blood pressure measure, and the listed ambulatory blood pressure outcomes do not all have numerical results reported in the registry record.

The registry gives the primary ANCOVA model description but not its treatment comparison estimates or confidence intervals. The posted recalculations are unadjusted summary-data comparisons and do not include the model’s stated adjustment for region and baseline blood pressure. Multiplicity procedures, detailed missing-data information, and sensitivity analyses are not reported in the registry record. These omissions restrict assessment of the robustness and precision of the findings.

The registry reports safety counts, but the available record does not provide enough detail to assess event timing, relatedness, or severity for each event. The group sizes also differ between the primary endpoint and safety summaries in some groups, so denominators should be interpreted outcome by outcome. The original sample-size justification and interim-analysis plan are not reported in the registry record.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: A Study to Evaluate Efficacy and Safety of LCI699 in Participants With Essential Hypertension — NCT00758524.
• Registry record last updated 2021-07-06; status last verified 2021-06.
• Results first posted 2021-07-06.
• 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.

22. Record Summary

NCT00758524 is a completed, randomized phase 2 parallel-group study of LCI699 in participants with essential hypertension. It enrolled 628 participants and compared four LCI699 regimens with placebo and eplerenone 50 mg twice daily during a core treatment period of up to 8 weeks.

The primary endpoint was change from baseline in mean sitting diastolic blood pressure at Week 8, measured by office blood pressure and analyzed using LOCF. The registry describes an ANCOVA model with treatment and region as factors and baseline blood pressure as a covariate. Posted group summaries show decreases in each core-period group, while unadjusted recalculations show varying precision across treatment-versus-placebo comparisons.

The registry also records systolic blood pressure and safety outcomes. Important details—including adjusted primary comparisons, multiplicity methods, missing-data sensitivity analyses, and results for some listed secondary outcomes—are not reported in the registry record.