Study of Safety and Efficacy Of Ertugliflozin (PF-04971729, MK-8835) In Participants With Type 2 Diabetes And Hypertension (MK-8835-042): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Safety and Efficacy Of Ertugliflozin (PF-04971729, MK-8835) In Participants With Type 2 Diabetes And Hypertension (MK-8835-042) (NCT01096667), a randomized phase 2 study. The primary outcome is Baseline 24-hour Average Systolic Blood Pressure (SBP).

2. Clinical Question

3. Trial Design

This was a Phase 2, randomized, double-blind, placebo-controlled, dose-ranging, parallel-group study. The registry lists 194 participants enrolled and describes five treatment groups: placebo, ertugliflozin 1 mg, ertugliflozin 5 mg, ertugliflozin 25 mg, and HCTZ 12.5 mg. Treatment was once daily for 28 days. Placebo treatments resembling the study drugs were used so that treatment assignments could remain masked. The study status is completed.

The stated purpose was to assess safety, tolerability, and efficacy in people with type 2 diabetes and hypertension. The registry describes inadequate glycemic and blood pressure control as part of the study population context. Randomization supports comparisons between assigned groups, while double masking is intended to reduce the influence of treatment knowledge on participants and study conduct. These design features do not by themselves establish what analysis was performed or whether the posted results answer the stated hypothesis.

The summary identifies change from baseline in average 24-hour systolic blood pressure on Day 28 as the primary hypothesis. In contrast, the posted primary outcome is titled baseline 24-hour average systolic blood pressure and reports baseline group means and standard deviations. This distinction is central when interpreting the statistics: baseline differences describe starting measurements, not changes during treatment. The original protocol’s analysis plan, allocation details beyond randomization, and original sample-size justification are not reported in the registry record.

The registry reports 26 outcome measures and 60 analyses overall. The posted results include 24 secondary outcomes, although the record excerpted for statistical comparison includes only baseline seated systolic pressure, baseline seated diastolic pressure, and baseline heart rate. These are baseline descriptions rather than reported treatment-period changes. Results for the other outcomes are not reported in the registry record summarized for these statistics.

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: Prior to randomization, 194 participants received placebo for at least 3 weeks (completed the run-in period). Treated participants included all randomized participants who received at least one dose of study drug.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All randomized participants who received at least one dose of study drug and had a baseline measurement for average 24-hour SBP.

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: Baseline analysis population includes participants who received at least 1 dose of blinded treatment regimen.

6. Primary Endpoint

The registry lists the primary outcome as Baseline 24-hour Average Systolic Blood Pressure (SBP), measured over 24 hours.

The listed primary outcome is baseline average systolic blood pressure over 24 hours, measured in mmHg. The registry says this measurement used 24-hour ambulatory blood pressure monitoring (ABPM). ABPM collects measurements across a full day and night rather than relying on a single clinic reading, so it characterizes blood pressure over the stated monitoring period. The outcome is reported as a mean with standard deviation.

The registry’s primary hypothesis concerns a different quantity: change from baseline in average 24-hour systolic blood pressure on Day 28. Change measures how an outcome differs after treatment relative to the starting measurement. Comparing that change between treatment groups is relevant to the stated question of whether systolic pressure shifted differently during the study. Baseline values instead describe the groups before treatment-period change is assessed.

The posted primary outcome population is described as randomized participants who received at least one dose of study drug and had a baseline measurement for average 24-hour systolic blood pressure. The record gives baseline means for placebo and each active-treatment group, along with group sizes and standard deviations. It does not report a Day 28 change estimate, its confidence interval, or the analysis for the stated primary hypothesis in the material summarized by these statistics. Therefore, the displayed baseline results should not be treated as a direct estimate of treatment effect on the stated primary question.

7. Results Posted in the Registry

• Ertugliflozin 1 mg: mean 133.13 versus 136.11 on control; difference -2.98 (95% CI -8.97 to 3.01), standardized effect d = -0.23; z-test p = 0.330.
• Ertugliflozin 5 mg: mean 135.08 versus 136.11 on control; difference -1.03 (95% CI -7.28 to 5.22), standardized effect d = -0.07; z-test p = 0.747.
• Ertugliflozin 25 mg: mean 135.59 versus 136.11 on control; difference -0.52 (95% CI -6.71 to 5.67), standardized effect d = -0.04; z-test p = 0.869.
• HCTZ 12.5mg: mean 139.55 versus 136.11 on control; difference 3.44 (95% CI -2.78 to 9.66), standardized effect d = 0.25; z-test p = 0.279.

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.

Baseline Seated, Triplicate Trough SBP

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Ertugliflozin 1 mg: mean 134.23 versus 135.17 on control; difference -0.94 (95% CI -7.16 to 5.28), standardized effect d = -0.07; z-test p = 0.767.
  • Ertugliflozin 5 mg: mean 137.31 versus 135.17 on control; difference 2.14 (95% CI -4.39 to 8.67), standardized effect d = 0.15; z-test p = 0.520.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Ertugliflozin 1 mg 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 Ertugliflozin 5 mg and the control. The interval gives the range of effects that remain compatible with the data.

Baseline Seated, Triplicate Trough DBP

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Ertugliflozin 1 mg: mean 83.08 versus 84.89 on control; difference -1.81 (95% CI -5.64 to 2.02), standardized effect d = -0.21; z-test p = 0.354.
  • Ertugliflozin 5 mg: mean 83.79 versus 84.89 on control; difference -1.10 (95% CI -5.02 to 2.82), standardized effect d = -0.13; z-test p = 0.582.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Ertugliflozin 1 mg 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 Ertugliflozin 5 mg and the control. The interval gives the range of effects that remain compatible with the data.

Baseline Seated, Triplicate Trough Heart Rate

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Ertugliflozin 1 mg: mean 78.73 versus 77.07 on control; difference 1.66 (95% CI -2.41 to 5.73), standardized effect d = 0.18; z-test p = 0.424.
  • Ertugliflozin 5 mg: mean 77.30 versus 77.07 on control; difference 0.23 (95% CI -4.62 to 5.08), standardized effect d = 0.02; z-test p = 0.926.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Ertugliflozin 1 mg 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 Ertugliflozin 5 mg and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcome descriptions include baseline and Week 4 blood pressure measures, including daytime and nighttime systolic pressure, seated trough systolic and diastolic pressure, and 24-hour and daytime diastolic pressure. However, the posted secondary comparisons included in these statistics are for baseline seated, triplicate trough systolic pressure, baseline seated, triplicate trough diastolic pressure, and baseline heart rate. These are starting measurements rather than treatment-period changes.

The available secondary comparisons do not show one consistent pattern that can be used to answer the primary question. Their estimates and confidence intervals are baseline contrasts, and the listed intervals include zero. They provide descriptive context about the groups’ starting measurements but do not establish what happened after treatment began. The other posted secondary outcomes are not represented by detailed comparison estimates in the record summarized by these statistics; their results are not reported in the registry record.

Secondary outcomes can help characterize a study, but they do not replace the prespecified primary endpoint. A result on a secondary measure may differ from the primary result because it measures a different aspect of blood pressure, uses a different measurement period, or has different precision. Here, the central limitation is that the posted secondary comparisons are baseline values, while the stated primary question concerns change at Day 28.

Unadjusted secondary results generally carry less inferential weight when many outcomes and comparisons are considered. In general, examining multiple results can increase the chance of apparently unusual findings arising by chance. A prespecified multiplicity strategy can help control that risk, but the strategy is not reported in the registry record. Accordingly, the secondary statistics should be regarded as descriptive rather than as independent confirmation of the primary hypothesis.

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

• Baseline Average Daytime and Nighttime SBP
• Change From Baseline on Daytime Average SBP at Week 4
• Change From Baseline on Nighttime Average SBP at Week 4
• Baseline Seated, Triplicate Trough SBP
• Change From Baseline in Seated, Triplicate Trough SBP at Week 4
• Baseline 24-hour, Daytime and Nightime Average Diastolic Blood Pressure (DBP)
• Change From Baseline on 24-hour Average DBP at Week 4
• Change From Baseline on Daytime Average DBP at Week 4

9. Statistical Interpretation

10. Statistical Methods Explained

These results involve continuous measurements, including blood pressure in mmHg and heart rate in beats per minute. A mean is the arithmetic average within a group. A standard deviation describes how spread out individual measurements are around that group average; it is not the uncertainty in the mean itself. The primary outcome summaries list both group sizes and standard deviations, allowing the observed baseline averages to be described alongside the within-group variation.

What does a mean difference represent?

A mean difference compares the average in one group with the average in another. In the posted primary comparisons, placebo is the reference group, and each active-treatment group is compared with it. A negative estimate means the active group’s baseline average was lower than placebo’s; a positive estimate means it was higher. This direction describes the baseline values only. It does not indicate whether pressure fell or rose during treatment.

The mean differences and confidence intervals in these comparisons are simple unadjusted re-calculations from the posted group summaries. They are not a substitute for the trial’s own prespecified analysis. The record does not report an adjusted model for the primary hypothesis concerning change on Day 28. The discrepancy flag is false, so there is no noted conflict between the posted summary and the re-calculation that would require giving a sponsor analysis precedence.

How should a confidence interval be understood?

A confidence interval expresses uncertainty about an estimate. In general, a wider interval indicates less precision, while a narrower interval indicates greater precision. For the baseline mean differences, the intervals include zero and also extend to values on either side of zero. Thus, the data do not pin down a single direction for the baseline contrast. A confidence interval is not a guarantee that the true value lies within its endpoints, and it does not by itself establish whether a result is important in practice.

What do the p-values convey?

The listed p-values are unadjusted comparisons. In general, a p-value describes how compatible the observed data are with a specified null hypothesis under the assumptions of the statistical test. It does not give the probability that the null hypothesis is true, and it does not measure the size or practical importance of a difference. Because these comparisons concern baseline values and are unadjusted, they should not be read as formal tests of the treatment-period primary hypothesis.

Why does variation matter?

Group averages are interpreted in relation to variation and sample size. Greater variability makes it harder to estimate a group mean precisely when the number of observations is limited. The posted standard deviations describe participant-level spread; the confidence intervals convey uncertainty in the between-group estimates. General statistical reasoning distinguishes these two quantities because they answer different questions.

Over-dispersion is a general concern when data vary more than a statistical model assumes. If a model understates variability, its standard errors can be too small and its intervals too narrow. The record does not report that over-dispersion occurred or identify the model used for the original primary analysis, so this is a general consideration rather than a finding about this study.

Why does the endpoint definition matter?

A baseline measurement and a change-from-baseline outcome are not interchangeable. Baseline describes the starting level; change uses both starting and follow-up measurements. The registry’s stated primary hypothesis concerns change by Day 28, while the posted primary outcome summaries concern baseline averages. Without the follow-up or change estimates, the posted baseline contrasts cannot answer whether the treatment groups changed differently.

The registry describes the primary population as randomized participants who received at least one dose and had a baseline measurement. The exact analysis set used for the stated primary hypothesis, the handling of missing follow-up measurements, and any covariate adjustment are not reported in the registry record. Those details can affect how treatment estimates are constructed and how uncertainty is quantified.

Several different outcomes and analyses are listed in the record. When many outcomes or comparisons are examined, the chance of obtaining an apparently notable result by chance can increase. Adjusting for multiple comparisons is one general way to address that issue, but the multiplicity strategy for this trial is not reported in the registry record. As a result, unadjusted comparisons should be treated as exploratory descriptions rather than as a complete account of confirmatory inference.

11. Confidence Intervals and Precision

The primary baseline comparisons are estimated with substantial uncertainty. The 95% confidence interval for ertugliflozin 1 mg versus placebo extends from -8.974 to 3.014 mmHg. For ertugliflozin 5 mg, the interval is -7.278 to 5.218 mmHg; for 25 mg, it is -6.71 to 5.67 mmHg; and for HCTZ 12.5 mg, it is -2.782 to 9.662 mmHg. Every interval includes zero, so the posted baseline data do not distinguish a baseline difference from no difference with high precision.

The interval endpoints also show that the estimates do not rule out differences in either direction. This is a statement about the range of values compatible with the data and method, not proof that all such values are equally likely or clinically consequential. The registry does not report a threshold for a clinically important difference, so the clinical importance of any value within these ranges cannot be determined from the posted record.

Precision is related to the size of the groups and the variation in measurements. The primary baseline comparison groups contain 37 to 39 participants, while their standard deviations range from 10.87 to 15.3 mmHg. With individual measurements varying within groups, estimates based on these group sizes can remain uncertain. This statistical explanation is general; it does not infer the original design rationale.

Most importantly, these intervals are for differences in baseline averages. They do not quantify precision for change from baseline on Day 28. A confidence interval for that primary hypothesis is not reported in the registry record. The baseline intervals therefore should not be used to make claims about the precision of treatment effects.

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 figures are illustrations of how many participants per arm might be needed for a future two-group comparison under the stated assumptions. They are based on the observed effect in each listed comparison and show plans for detecting 100%, 75%, or 50% of that observed effect. The assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The figures are participants per arm, not total participants or total events.

The 80% power column describes a planning target in which the assumed design would have an 80% chance of detecting the specified effect under the model and assumptions. The 90% power column uses a higher target chance of detection and therefore generally requires more participants per arm. These are planning quantities, not a report of the trial’s achieved statistical performance. The figures are not observed power.

Smaller effects require more participants to distinguish them from random variation under otherwise comparable assumptions. That is why planning for 75% or 50% of an observed effect generally yields larger group sizes than planning for the full observed effect. When an observed effect is close to zero, planning figures can become very large because detecting a small contrast reliably requires substantial information.

These calculations use the baseline comparisons, whereas the registry’s stated primary hypothesis concerns change on Day 28. They are therefore not evidence that the original study was designed around these sample sizes, nor do they reconstruct the trial’s original planning. The original design assumptions and sample-size justification are not reported in the registry record.

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 = -2.980; pooled standard deviation σ = 13.210.
2. n = 2 × (1.96 + 0.842)² × 13.210² / -2.980² = 308.5, rounded up to 309 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 <- -2.98000000000002                      # observed difference in means
sigma <- 13.2100223295022                     # 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(1096667)
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 = 309 (80% power), 413 (90% power)
 75% of observed effect: n per arm = 549 (80% power), 735 (90% power)
 50% of observed effect: n per arm = 1,234 (80% power), 1,652 (90% power)
power.t.test: 309.4 
Simulated power at n = 309 per arm: 0.799 (20000 replicates)

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

14. Multiplicity, Missing Data and Analysis Populations

The registry lists 26 outcome measures and 60 analyses, and the posted results include 24 secondary outcomes. Considering many outcomes and comparisons raises a general multiplicity issue: even if each test is interpreted at its own nominal threshold, the chance of at least one apparently notable result can increase across the collection of tests. Statistical plans may address this through a hierarchy, adjustment, or by identifying some results as exploratory. The multiplicity approach for this trial is not reported in the registry record.

The listed pairwise comparisons are unadjusted. Their p-values should therefore not be interpreted as though they necessarily control the overall error rate across all outcomes, doses, and comparisons. The registry record does not describe a testing hierarchy, adjustment method, or confirmatory status for the secondary analyses. This absence does not show that no plan existed; it means the plan is not reported in the registry record.

Missing-data handling is also not reported for the primary change-from-baseline question. The primary outcome population is described as randomized participants who received at least one dose and had a baseline measurement. The record excerpted for these statistics does not state how missing Day 28 measurements were handled, whether participants with incomplete follow-up were included in the primary analysis, or what assumptions were made about missingness.

The exact analysis population for the stated primary hypothesis, any covariate adjustment, interim analyses, and the original statistical analysis plan are not reported in the registry record. The reported baseline group summaries remain interpretable as baseline descriptions, but they do not resolve these questions about the intended primary analysis. These missing details limit assessment of how the original statistical evidence was constructed and how robust it may be to analytic choices.

15. 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: extradural haematoma (2.6%), skull fracture (2.6%), hematuria (0.5%).

The registry reports serious adverse events affecting 1 participant in the placebo group and 0 participants in each of the three ertugliflozin groups and the HCTZ group. The listed serious-event risk groups contain 38 participants for placebo, 39 for ertugliflozin 1 mg, 38 for ertugliflozin 5 mg, 39 for ertugliflozin 25 mg, and 39 for HCTZ 12.5 mg. These counts are descriptive and do not establish that treatment caused or prevented an event.

The record also includes a pre-randomization group, with 1 serious adverse event among 194 participants at risk. That group is separate from the randomized treatment-arm comparisons and should not be combined with an assigned treatment group. The registry lists serious-event terms including extradural haematoma and skull fracture at 2.6% each, and hematuria at 0.5%. Death counts are not reported in the registry record.

Serious adverse events are not the same as all other adverse events. The posted figures list other adverse events affecting 3 participants on placebo, 4 on ertugliflozin 1 mg, 8 on ertugliflozin 5 mg, 6 on ertugliflozin 25 mg, and 6 on HCTZ 12.5 mg. Interpretation should account for the short 28-day treatment period and the small group sizes; these counts alone do not provide a complete comparative safety assessment.

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

The registry describes a randomized, double-blind study designed to evaluate ertugliflozin in participants with type 2 diabetes and hypertension. Its stated primary hypothesis concerns whether ertugliflozin was superior to placebo for change from baseline in average 24-hour systolic blood pressure on Day 28. That is the question the planned endpoint would need to address.

The posted primary results instead report baseline 24-hour average systolic blood pressure. Their unadjusted comparisons show baseline group differences with confidence intervals that include zero. These results describe how the groups’ starting averages compare; they do not show the change during treatment or estimate a treatment effect on the primary hypothesis. A baseline difference, whether positive or negative, is not itself evidence of a treatment response.

Consequently, the posted statistics cannot establish from the registry record whether the primary hypothesis was met, how large any Day 28 effect was, or how precisely that effect was estimated. The treatment-period primary analysis and its confidence interval are not reported in the registry record. The study’s design and stated aim should not be mistaken for a reported finding.

The short treatment period, the number of participants in each arm, and the broad uncertainty around the baseline comparisons are relevant context. They do not prove that the trial could or could not detect a clinically important treatment effect, because the original design assumptions and the primary change analysis are not reported. The planning illustrations based on observed baseline differences are not a substitute for the trial’s original sample-size justification.

Safety counts are also descriptive. They identify reported serious and other adverse events by group, but small counts and a limited treatment period do not establish causal relationships or fully characterize risks. Overall, the record supports a careful account of design, baseline measurement summaries, and posted adverse-event counts. It does not, in the statistics, provide the Day 28 change result needed to answer the stated efficacy question.

17. Why This Trial Matters Statistically

This study illustrates why an endpoint’s label and timing matter as much as the numerical comparison. The registry describes a primary hypothesis about change from baseline on Day 28, but the posted primary outcome statistics are baseline averages. Those data are useful for describing starting values, yet they do not answer whether groups changed differently during treatment. Matching the reported statistic to the stated scientific question is essential before interpreting an estimate as an effect.

It also demonstrates the distinction between a randomized design and a complete report of a randomized comparison. Randomization and masking are important design features, but the reader still needs the outcome definition, analysis population, follow-up result, and uncertainty estimate for the primary comparison. When these are not reported in the registry record, conclusions should be bounded by the available information rather than inferred from the trial’s stated purpose.

The posted confidence intervals reinforce the importance of precision. They include zero and span values on both sides, so the baseline contrasts are not estimated tightly enough to settle their direction. This is not a finding about treatment efficacy; it is a description of uncertainty in the baseline comparisons. In general, statistical significance, effect size, precision, and clinical importance are different concepts and should not be collapsed into one judgment.

Finally, the study lists numerous outcomes and analyses, while the multiplicity strategy is not reported. This is a reminder that isolated unadjusted findings among many comparisons require cautious interpretation. Clear reporting of the primary endpoint analysis, multiplicity approach, missing-data handling, and design assumptions helps readers distinguish confirmatory conclusions from descriptive or exploratory information.

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.

A central limitation is the mismatch between the stated primary hypothesis and the posted primary outcome statistics. The hypothesis concerns change from baseline in average 24-hour systolic blood pressure on Day 28, whereas the reported primary outcome is baseline average systolic pressure. The posted comparisons therefore do not provide the treatment-period estimate needed to evaluate the stated question.

The registry record summarized for these statistics does not report the primary change estimate, its confidence interval, or the statistical analysis used for that endpoint. It also does not report the original sample-size justification, design assumptions, or a full statistical analysis plan. As a result, the planning illustrations should not be treated as a reconstruction of the study’s intended power or design.

Details about missing follow-up data, the primary analysis population beyond the population description, covariate adjustment, interim analyses, and multiplicity control are not reported in the registry record. These omissions limit assessment of analytic choices and the strength of inferential claims. They do not establish that those procedures were absent from the study.

The secondary comparisons included in these statistics are baseline measurements, while several registry outcomes are described at Week 4. Detailed results for the other secondary measures are not reported in the registry record summarized by these statistics. Safety counts come from relatively small treatment groups and a 28-day treatment period, so they offer only a limited description of adverse events. The record’s death counts are not reported.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Study of Safety and Efficacy Of Ertugliflozin (PF-04971729, MK-8835) In Participants With Type 2 Diabetes And Hypertension (MK-8835-042) — NCT01096667.
• Registry record last updated 2018-09-13; status last verified 2018-08.
• Results first posted 2017-12-13.
• 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

NCT01096667 is a completed Phase 2, randomized, double-blind, parallel-group study of ertugliflozin in participants with type 2 diabetes and hypertension. It enrolled 194 participants and compared placebo, ertugliflozin 1 mg, 5 mg, and 25 mg, and HCTZ 12.5 mg over 28 days.

The stated primary hypothesis concerned change from baseline in 24-hour average systolic blood pressure on Day 28. The posted primary outcome statistics describe baseline 24-hour average systolic pressure, with unadjusted comparisons against placebo and confidence intervals that include zero. They do not report the stated primary change result. The registry also lists baseline secondary measurements and adverse-event counts. Original design assumptions, multiplicity handling, missing-data methods, and the primary change analysis are not reported in the registry record.