A Study of MK-7145 Compared to Placebo and Hydrochlorothiazide for Lowering Blood Pressure in Male Participants With Hypertension (MK-7145-009): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of MK-7145 Compared to Placebo and Hydrochlorothiazide for Lowering Blood Pressure in Male Participants With Hypertension (MK-7145-009) (NCT01370655), a randomized phase 1 study. The primary outcome is Change From Baseline in Time-weighted Average Over 24 Hours Post Dose (TWA [0-24]) in Systolic Blood Pressure (SBP).

2. Clinical Question

3. Trial Design

This was a Phase Ib, randomized, double-blind study with a crossover structure. Its official title describes four treatments delivered across two periods using an incomplete block design. In a crossover study, participants can receive different treatments in different periods; therefore, treatment comparisons may draw on observations from people who received more than one treatment. The registry does not report the randomization sequence details or the number assigned to each sequence.

The treatments were MK-7145 3 mg, MK-7145 6 mg, HCTZ 25 mg and placebo. Each treatment description specifies daily dosing for 4 weeks, with the active and placebo capsules arranged to maintain masking. The record reports an overall enrollment of 46. The treatment-specific primary-outcome denominators differ, and the analysis population is defined by treatment taken at the time of evaluation rather than by randomly assigned sequence. They should therefore be read as endpoint observations by treatment, not as a breakdown of the original randomized sequences.

Blood pressure was assessed using continuous 24-hour ambulatory monitoring on Day -1 and Day 28 of each treatment period. The primary endpoint was the change from baseline in the time-weighted average systolic blood pressure over 24 hours. The registry lists the study as completed, with a start date of 2011-06-15 and primary completion on 2011-12-19.

The stated primary hypotheses concerned superiority of MK-7145 6 mg to placebo and similarity of MK-7145 6 mg to HCTZ. The record does not report the operational definition or margin for similarity, the statistical model used to account for the crossover design, or the rationale for the planned enrollment. Those details should not be inferred from the design label alone.

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: Participants were randomly assigned to 1 of 12 treatment sequences Each 4-week treatment period was separated by a wash-out of approximately 4 weeks

Only the first 6 of 12 groups are shown.

Period 1

Reasons for not completing this period:

Period 2

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants who received at least 1 dose of study drug, complied with protocol sufficiently and had available data for endpoint. Participants are grouped by study drug taken at the time of the evaluation and not by randomly assigned sequence.

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.

Only the first 6 of 13 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Time-weighted Average Over 24 Hours Post Dose (TWA [0-24]) in Systolic Blood Pressure (SBP), measured over Baseline and Day 28.

The primary endpoint was change from baseline in time-weighted average systolic blood pressure over 24 hours after dosing, measured at Day 28. Baseline was the average systolic blood pressure during the 24-hour monitoring period on Day -1; the Day 28 value was calculated from another 24-hour monitoring period. The endpoint is expressed in mmHg, with negative changes indicating a lower recorded average at Day 28 than at baseline.

Ambulatory monitoring captures blood pressure across a full day rather than relying on a single measurement. As a general statistical rationale, repeated measurements across the day can describe the overall level during the monitoring window and reduce dependence on any one reading. A time-weighted average combines measurements over that window according to time. The registry describes the monitoring and calculation but does not report the exact weighting procedure or the underlying measurement schedule.

The endpoint is a change score, so its interpretation concerns the difference between the baseline and Day 28 measurements, not the absolute blood pressure at either time. The posted estimates are least-squares means with 90% confidence intervals. A least-squares mean is a model-based estimate; the registry does not identify the model or its adjustment terms. The endpoint description also defines an analysis population requiring treatment exposure, sufficient protocol compliance and available endpoint data, grouped by treatment taken at evaluation.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports least-squares means for the primary endpoint and differences in least-squares means for treatment comparisons. A least-squares mean is generally a model-based average adjusted for terms included in the fitted model. In contrast, a raw mean is calculated directly from observed values without model adjustment. The registry does not report which covariates, period effects, sequence effects or other terms were included, so the exact adjustment represented by these estimates is not reported in the registry record.

What does a confidence interval describe?

As a general statistical explanation, a confidence interval describes the range of estimates compatible with the data under a specified statistical procedure. Its width reflects precision: narrower intervals indicate less uncertainty under that procedure, while wider intervals indicate more. A confidence interval is not a range containing every participant’s response, and it is not the probability that the true effect lies in the particular interval. In this study, the registry reports 90% confidence intervals for the arm-level least-squares means and for most treatment contrasts, and an 80% interval for the MK-7145 6 mg versus placebo contrast.

The interval for a contrast is more directly relevant to a comparison between treatments than separate intervals around each treatment’s estimate. Overlap or non-overlap between two arm-level intervals is not a substitute for the interval calculated for the contrast itself. The posted contrast estimates and their intervals should therefore be interpreted as the registry reports them, rather than reconstructed by comparing the arm intervals visually.

How should the treatment contrasts be read?

Each reported difference in least-squares means is associated with a pair of treatments. The contrast values are negative for the comparisons as listed. Because the outcome is change from baseline, a more negative change corresponds to a greater estimated reduction from baseline. This sign interpretation depends on the listed treatment order being the subtraction order; the registry does not separately describe the sign convention. The contrasts are estimates, not a direct count of individual responses, and they do not show how consistently participants changed within each treatment.

The registry labels the 6-mg comparisons as non-inferiority or equivalence analyses, while other contrasts have other analysis classifications. Those labels do not specify the complete statistical test. In general, a non-inferiority or equivalence conclusion depends on a prespecified margin and an analysis rule that relates the confidence interval to that margin. The margin, test details and decision criteria are not reported in the registry record. Consequently, the reported contrast and interval can be described, but the label alone does not establish the intended conclusion.

Why does the crossover design matter?

As a general explanation, crossover studies compare treatments across periods, often allowing each participant to contribute observations under more than one treatment. This can help account for stable differences between participants, but the analysis must also address features such as period and treatment sequence. Carryover from an earlier treatment can also matter if its effect persists into a later period. The registry identifies a crossover design with two periods and an incomplete block, but does not report the model, washout details, period-specific results or an assessment of carryover. None of these analytical details should be assumed from the design description.

The primary endpoint population is described as participants who received at least one dose, complied sufficiently with the protocol and had data available. Participants are grouped by the treatment taken at evaluation rather than by assigned sequence. This is a treatment-received description of the analysis population. The registry does not report a separate intention-to-treat analysis or a detailed account of exclusions and missing endpoint values.

What can be said about precision and testing?

The confidence intervals quantify uncertainty in the reported estimates under the registry’s analysis, but the underlying model and standard-error calculation are not described. The registry reports no p-values for the listed primary contrasts. A p-value, when reported, summarizes how incompatible data are with a specified null hypothesis under a test procedure; it is not a measure of the size or importance of an effect. Without the p-values and test specifications, the intervals are the principal posted uncertainty measures for these comparisons.

General statistical practice also considers multiplicity when several outcomes or comparisons are examined. Testing many hypotheses can increase the chance of at least one apparently notable result if no adjustment or hierarchy is used. The registry lists 7 outcome measures and 20 analyses, but does not report whether or how multiplicity was addressed. Therefore, the confidence intervals should not be treated as multiplicity-adjusted unless the record says so; it does not.

10. Analyses Reported by the Sponsor

The registry reports sponsor analyses as differences in least-squares means, with the associated confidence intervals. For the comparison of MK-7145 6 mg with placebo, the reported difference is -7.4 mmHg with an 80% confidence interval from -10.6 to -4.1. For MK-7145 6 mg versus HCTZ 25 mg, it reports -5.4 mmHg with a 90% confidence interval from -9.2 to -1.6. The record gives no p-values for these contrasts.

No separate numerical recalculation of the treatment contrasts is stated in the registry record, so there is no recalculated estimate to compare numerically with the sponsor’s results. The arm-level least-squares means and the reported pairwise contrasts are not interchangeable: one describes an estimate for a treatment group, while the other directly represents a difference between treatments. Reconstructing a contrast from rounded arm estimates would not reproduce the sponsor’s model-based analysis and could differ because of model specification and rounding.

The reported contrast estimates should therefore be read as the sponsor’s registered analyses. The record does not provide enough information to reproduce their model, standard errors or confidence intervals independently. It also does not give the similarity margin needed to interpret the stated similarity hypothesis as a formal equivalence or non-inferiority conclusion.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcomes and analyses: 7 outcome measures and 20 analyses. It describes the primary hypotheses for systolic blood pressure and also identifies estimation of effects on natriuresis and diastolic blood pressure. A secondary outcome listed in the record is change from baseline in urine potassium at 24 hours post-dose on Day 28. The record does not explain which analyses were confirmatory, how the outcomes were ordered, or whether any multiplicity adjustment was applied.

As a general statistical point, examining several outcomes or treatment contrasts can make isolated results more likely to appear notable by chance if no prespecified control strategy is used. This does not mean that any particular estimate is false; it means that the interpretation depends partly on the planned testing structure. The registry does not report a family-wise error procedure, a hierarchical testing plan or another multiplicity strategy. The reported confidence intervals should not be assumed to account for the number of comparisons.

The primary outcome population included participants who received at least one dose, had sufficient protocol compliance and had available endpoint data. Participants were analyzed according to the study drug taken at the time of evaluation, rather than by randomized sequence. This description does not establish how missing measurements were handled or whether all randomized participants were included in every analysis. Missing-data methods, reasons for missing endpoint measurements, and sensitivity analyses are not reported in the registry record.

The record also does not report interim analyses, stopping rules or a detailed statistical analysis plan. These omissions limit the ability to assess whether outcome definitions, exclusions, contrast choices and analytical decisions were finalized before results were known. They do not demonstrate that such procedures were absent; they mean their details are not reported in the registry record.

12. 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: migraine (3.8%), asthma (3.8%), arrhythmia (3.6%).

Serious adverse events were recorded for 0 of 19 participants in the MK-7145 3 mg group, 1 of 28 in the MK-7145 6 mg group, 2 of 26 in the HCTZ 25 mg group and 0 of 19 in the placebo group. These are the treatment-specific figures reported in the safety record. They should be read as counts within the stated at-risk groups, not as estimates of comparative risk adjusted for the crossover design.

The registry lists migraine and asthma at 3.8% each and arrhythmia at 3.6% among the top serious adverse event terms. The record does not provide enough detail in these figures to determine the timing, recurrence, treatment attribution or clinical circumstances of each event. A listed event after exposure does not, by itself, establish that the study treatment caused it.

No death counts are reported in the registry record. The number of participants with other adverse events was 16 for MK-7145 3 mg, 19 for MK-7145 6 mg, 15 for HCTZ 25 mg and 9 for placebo. These counts are distinct from serious adverse event counts. Given the short treatment descriptions and the small treatment-specific groups, event counts should be interpreted descriptively; they do not establish comparative safety or exclude uncommon harms.

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

The posted results describe changes in 24-hour average systolic blood pressure from baseline to Day 28 for four treatments in a randomized, double-blind crossover study. The registry reports least-squares mean changes for each treatment and contrasts between pairs of treatments, with confidence intervals. The estimates indicate the direction and magnitude of the recorded changes in this study population; the intervals show that those estimates have uncertainty.

The 6-mg MK-7145 estimate was -10.2 mmHg, while the placebo estimate was -2.8 mmHg. Their reported contrast was -7.4 mmHg, with an 80% confidence interval from -10.6 to -4.1. The contrast with HCTZ 25 mg was -5.4 mmHg, with a 90% confidence interval from -9.2 to -1.6. The registry’s hypotheses included superiority to placebo and similarity to HCTZ, but no p-values or similarity margin are reported. The numerical contrasts should not be treated as proof that either formal hypothesis was met.

These findings do not establish what would happen in other populations, with different treatment durations or outside the study conditions. The study concerned male participants with mild-to-moderate hypertension and evaluated endpoint measurements during treatment periods. The registry does not report a basis for extending the estimates to women, other patient groups or longer-term treatment.

The record also does not provide the full statistical model, multiplicity approach, missing-data methods or sequence-level results. Those details are important for assessing the robustness of estimates from a crossover study and several reported analyses. Safety counts are descriptive and should not be interpreted as definitive comparative evidence. The results are statistical estimates from a small Phase Ib study, not medical advice and not a determination of an individual’s likely response.

14. Why This Trial Matters Statistically

This study is statistically informative because it uses a crossover design to compare several treatments while measuring blood pressure over a full 24-hour period. The design and endpoint raise questions beyond a simple comparison of two independent groups: observations may come from treatment periods within the same participant, and the analysis may need to address period and sequence effects. The registry identifies the design but does not report how those features were handled in the model.

The outcome is a change from baseline in a time-weighted average, and the registry reports both treatment-level estimates and pairwise contrasts. This distinction matters: treatment-level changes describe each group’s estimated movement from its own baseline, while contrasts quantify differences between treatments. The contrast intervals, rather than comparisons of separate arm intervals, are the direct registry-reported uncertainty measures for treatment differences.

The record also illustrates why the stated hypothesis and its statistical definition need to be considered together. Similarity requires a prespecified margin and decision rule; the term alone is not enough to determine whether the evidence met the intended criterion. Likewise, several outcomes and analyses raise questions about multiplicity, but the registry does not state whether adjustments were made.

Finally, the differing confidence levels across the posted contrasts affect how their precision should be compared. A direct comparison of interval widths is not appropriate when intervals use different confidence levels. The absence of model and analysis details limits independent reproducibility, making transparent reporting of the crossover analysis, missing-data handling and multiplicity strategy especially relevant to statistical interpretation.

15. 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 endpoint analysis population is defined by treatment exposure, sufficient protocol compliance and availability of endpoint data. The registry does not report the number excluded for each reason, missing endpoint counts by treatment period, or the method used to handle missing observations. This limits assessment of whether the analyzed observations could differ systematically from those not analyzed.

Although the official title identifies an incomplete-block crossover design, the record does not report treatment sequence counts, period-specific estimates, a washout description, or analyses of period, sequence or carryover effects. These are relevant details for understanding whether treatment comparisons adequately reflect treatment rather than design-period effects. The statistical model and its adjustment terms are not reported, so the least-squares means cannot be independently reproduced from the registry description.

The registry reports a similarity hypothesis for MK-7145 6 mg versus HCTZ but does not state a similarity or equivalence margin. Without that margin and the testing rule, the contrast estimate and confidence interval cannot determine whether a formal similarity objective was achieved. The 6-mg comparison with placebo uses an 80% confidence interval, whereas other listed comparisons use 90% intervals; the record does not explain the choice of confidence levels.

Multiplicity control, interim analyses, stopping rules and a detailed statistical analysis plan are not reported in the registry record. There is also no p-value for the listed primary contrasts. These omissions leave uncertainty about the planned hierarchy of analyses and the treatment of multiple comparisons. Safety information is reported as counts and selected event terms, without detailed timing or attribution. The overall enrollment and treatment-specific endpoint denominators describe different aspects of the study and should not be combined into a single analysis population.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of MK-7145 Compared to Placebo and Hydrochlorothiazide for Lowering Blood Pressure in Male Participants With Hypertension (MK-7145-009) — NCT01370655.
• Registry record last updated 2018-09-21; status last verified 2018-08.
• Results first posted 2017-04-04.
• 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.

19. Record Summary

NCT01370655 is a completed Phase Ib randomized, double-blind crossover study of MK-7145, HCTZ and placebo in male participants with hypertension. The registry reports enrollment of 46 and describes four treatments across two periods using an incomplete block design. Treatment descriptions specify daily dosing for 4 weeks.

The primary endpoint was change from baseline in time-weighted average systolic blood pressure over 24 hours at Day 28, measured by ambulatory monitoring. The registry reports least-squares mean changes and treatment contrasts with confidence intervals. For MK-7145 6 mg versus placebo, the reported difference was -7.4 mmHg with an 80% confidence interval from -10.6 to -4.1; for MK-7145 6 mg versus HCTZ 25 mg, it was -5.4 mmHg with a 90% confidence interval from -9.2 to -1.6.

The record does not report p-values for these comparisons, a similarity margin, the full statistical model, multiplicity handling or missing-data methods. The safety record gives treatment-specific serious adverse event counts and selected event terms; these figures are descriptive.