Dose Ranging Study Of Bococizumab (PF-04950615; RN316) In Hypercholesterolemic Japanese Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dose Ranging Study Of Bococizumab (PF-04950615; RN316) In Hypercholesterolemic Japanese Subjects (NCT02055976), a randomized phase 2 study. The primary outcome is Percent Change From Baseline in Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Day 85.

2. Clinical Question

The central question is about a laboratory outcome over the treatment period, not a clinical event or long-term health outcome. The study enrolled participants in two distinct treatment settings: people already receiving a stable dose of atorvastatin and people who were treatment naïve. In the first population, bococizumab was considered alongside continued atorvastatin; in the second, bococizumab was studied without background lipid-lowering treatment. The trial also included placebo in both settings and an ezetimibe group among participants taking atorvastatin.

The registered primary endpoint is the percent change in fasting LDL-C from baseline to Day 85. The sponsor-reported analyses compare the bococizumab groups with the corresponding placebo groups. This is a dose-ranging Phase 2 study, so its results describe the measured lipid response over the specified period and the uncertainty around those estimates. They do not by themselves establish the effect on clinical outcomes, durability beyond the observed period, or how results would apply outside the enrolled Japanese population.

3. Trial Design

This completed Phase 2 study was randomized, triple masked, parallel group and placebo controlled. It enrolled 218 participants with hypercholesterolemia. The registry gives a study start of 2014-03 and primary completion of 2015-01. The official title describes subcutaneous bococizumab doses given twice monthly, and the brief summary specifies administration every two weeks.

Participants belonged to one of two populations. Population A comprised participants whose LDL-C was not controlled on a stable dose of atorvastatin. They were randomized among five groups: three bococizumab dose groups, atorvastatin with placebo, and atorvastatin with ezetimibe 10 mg. Population B comprised treatment-naïve participants whose fasting LDL-C was not controlled. They were randomized among four groups: three bococizumab dose groups and placebo. The registry describes nine groups across the two populations.

The primary analysis population, called the full analysis set in the registry, included randomized participants who received at least one dose of study treatment. The primary endpoint was assessed at Day 85, with baseline defined using the last two available measurements before the first dose when both fell within the specified window; if only one measurement was available in that window, it served as baseline.

The registry record does not report the original sample-size justification, the trial's planned statistical significance level, or the details of any interim analyses. Although the posted sample-size illustrations state their own assumptions, those are not the study's original design assumptions. The full statistical plan, including all model terms and procedures for controlling multiplicity, is 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.

Only the first 6 of 9 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full analysis set (FAS) included all the participants who were randomized and administered at least 1 dose of study treatment.

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: Safety analysis set included all randomized and non-randomized participants who were administered at least 1 dose of study treatment.

Only the first 6 of 10 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Percent Change From Baseline in Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Day 85, measured over Baseline, Day 85.

The primary endpoint is percent change from baseline in fasting low density lipoprotein cholesterol (LDL-C) at Day 85. LDL-C is cholesterol carried in the bloodstream by low density lipoprotein. Fasting was required for at least 10 hours before blood collection. Baseline was defined as the mean of the last two non-missing measurements obtained before the first study dose, provided both were within 10 days before that dose. If only one measurement was available in that period, that measurement was used as baseline.

Percent change expresses the Day 85 measurement relative to the participant's baseline measurement. This makes the outcome a measure of change rather than simply the LDL-C value at the end of follow-up. The endpoint is continuous, so results are reported as group means and standard deviations, and comparisons can be expressed as differences in mean percent change. Negative values indicate a decrease from baseline under the endpoint's definition.

LDL-C is used as a biochemical measure directly related to the study's stated objective of assessing LDL-C lowering. The endpoint does not measure cardiovascular events, symptoms, quality of life, or mortality. Nor does the Day 85 assessment establish whether any observed changes persisted after that time. Interpretation should therefore remain tied to this laboratory endpoint, the enrolled population, and the period assessed. The registry record does not report a clinically meaningful threshold for interpreting the size of a percent change.

7. Results Posted in the Registry

• Atorvastatin + PF-04950615 50 mg: mean -55.65 versus -5.91 on control; difference -49.74 (95% CI -58.01 to -41.47), standardized effect d = -3.31; z-test p = <0.001.
• Atorvastatin + PF-04950615 100 mg: mean -68.25 versus -5.91 on control; difference -62.34 (95% CI -71.65 to -53.03), standardized effect d = -3.75; z-test p = <0.001.
• Atorvastatin + PF-04950615 150 mg: mean -74.00 versus -5.91 on control; difference -68.09 (95% CI -75.99 to -60.19), standardized effect d = -4.83; z-test p = <0.001.
• Atorvastatin + Ezetimibe 10 mg: mean -18.56 versus -5.91 on control; difference -12.65 (95% CI -21.30 to -4.00), standardized effect d = -0.84; z-test p = 0.004.

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.

Terminal Elimination Half-Life (t1/2) of PF-04950615

• 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:
  • PF-04950615 100 mg: mean 9.57 versus 7.72 on control; difference 1.85 (95% CI 0.14 to 3.57), standardized effect d = 0.92; z-test p = 0.034.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for PF-04950615 100 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry lists secondary outcomes covering LDL-C, total cholesterol and apolipoprotein B, including changes from baseline and percent changes at Day 85 and Day 113. These outcomes provide related biochemical measures and later assessments that can add context to the primary LDL-C result. The registry also includes a pharmacokinetic outcome, terminal elimination half-life of PF-04950615.

The secondary results should not be treated as a single uniform body of evidence. The posted results span many outcome measures and analyses, but the detailed values summarized for the secondary endpoint data include a comparison of terminal elimination half-life, rather than a complete set of estimates for every listed lipid outcome. In that comparison, the mean was 9.57 days in the PF-04950615 100 mg group and 7.716 days in the atorvastatin-plus-PF-04950615 50 mg group; the unadjusted mean difference was 1.854 days, with a 95% interval of 0.142 to 3.566 and p=0.034. The registry does not report sponsor analyses for that secondary comparison.

The primary endpoint is the Day 85 percent change in fasting LDL-C. Related lipid outcomes can help describe whether the primary finding is accompanied by changes in other measured markers or at another assessment time, but they do not replace the primary comparison. The available details are insufficient to claim a consistent pattern across every secondary endpoint or to assess all such relationships comprehensively.

Many secondary tests create more opportunities for apparently notable results to occur by chance. Unless an adjustment or hierarchy is specified, individual secondary p-values are commonly considered exploratory and carry less evidential weight than the prespecified primary result. The registry record does not report the complete multiplicity strategy or enough detail to determine which secondary analyses were confirmatory. Secondary results should therefore be interpreted cautiously and in the context of the number of outcomes and analyses.

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

• Low Density Lipoprotein-Cholesterol (LDL-C)
• Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) at Day 85 and Day 113
• Total Cholesterol (TC)
• Change From Baseline in Total Cholesterol (TC) at Day 85 and Day 113
• Percent Change From Baseline in Total Cholesterol (TC) at Day 85 and Day 113
• Apolipoprotein B (ApoB)
• Change From Baseline in Apolipoprotein B (ApoB) at Day 85 and Day 113
• Percent Change From Baseline in Apolipoprotein B (ApoB) at Day 85 and Day 113

9. Statistical Interpretation

10. Statistical Methods Explained

What does a mean difference describe?

The primary outcome is continuous, and the registry reports a mean for each treatment group. A mean summarizes the group's average percent change from baseline. The sponsor's adjusted mean difference compares the estimated mean in a bococizumab group with the estimated mean in its placebo comparator, accounting for the sponsor's model. A negative difference indicates a lower mean percent change in the bococizumab group. This is a group-level comparison; it does not imply that every participant had the same response.

The simple recalculations use posted group means and standard deviations to form unadjusted comparisons. They are not the sponsor's model-based estimates. Adjustment can change an estimate because a model may account for design features or covariates; the registry record does not report enough model detail to specify which factors were included. When the two approaches differ, the sponsor's own analysis takes precedence for interpreting the trial's reported results.

How should a p-value be read?

A p-value describes how incompatible the observed data are with a specified null hypothesis, under the assumptions of the analysis. For the sponsor-reported primary comparisons, the posted values are <0.001. This does not give the probability that the null hypothesis is true, nor is it a measure of the size or clinical importance of an effect. It also does not quantify the probability that an individual participant will experience a particular result.

The recalculated comparisons include unadjusted p-values. Such values assess each contrast on its own and do not account for the possibility of multiple comparisons unless an adjustment is specifically applied. Whether or how the sponsor adjusted for multiplicity is not reported in the registry record. Thus, the primary sponsor-reported estimates and their stated uncertainty should be distinguished from exploratory recalculated comparisons.

What does a confidence interval add?

A confidence interval combines an estimate with its uncertainty. A narrower interval indicates greater precision for the estimated group difference, while a wider interval indicates less precision. For the sponsor's primary results, the registry reports 95% confidence intervals. Under the statistical model and its assumptions, the interval gives a range of effect estimates compatible with the observed data. It is not a guarantee that the true effect lies within the particular interval, and it does not describe the range of individual participant outcomes.

Because each sponsor-reported primary interval lies below zero, the estimates are consistent with a negative group difference at the stated confidence level. The limits also convey that the point estimate is not exact: plausible values span a range. The interval does not resolve limitations such as possible bias, missing data, model misspecification, or questions about generalizability.

Why distinguish adjusted and unadjusted results?

An adjusted model can estimate group differences while accounting for features specified in the analysis plan. The sponsor reports mixed models analyses and adjusted mean differences for the primary contrasts. The registry record does not report the model specification, the covariance structure, the handling of missing observations, or all assumptions. It is therefore not possible to reproduce the sponsor's estimates from the posted summary statistics alone.

In contrast, the recalculations use each group's reported mean, standard deviation and sample size. They provide an unadjusted comparison based on summary data, not participant-level data. In this record, the recalculation control for several contrasts is the atorvastatin-plus-placebo group, whereas sponsor analyses use the matching placebo for treatment-naïve participants. The discrepancy matters: comparisons should be interpreted against the appropriate comparator, and the sponsor's own analysis takes precedence.

What can the dose groups show?

Dose-ranging studies include multiple doses to describe how measured outcomes vary across dose groups. The posted mean changes are more negative at higher doses within each population, though that descriptive ordering alone is not a formal test of a dose-response relationship. The registry reports pairwise sponsor analyses against placebo, not a reported test of trend across doses. The record does not report a prespecified dose-response model or a formal test comparing the bococizumab doses with one another.

The sample-size illustrations use observed effects to show how planning requirements might change under specified assumptions. They are not estimates of the trial's original design calculations and are not observed power. Planning based on a large observed effect can produce small illustrative participant counts; these should not be read as evidence that the trial was designed with those counts or that the reported result is certain. A smaller effect requires more participants to detect under otherwise similar planning assumptions.

More generally, statistical interpretation depends on the population analyzed, outcome definition, model, missing-data handling, multiplicity approach and design. Some of these details are available in the registry, such as the full analysis set definition and the sponsor's use of mixed models. Other details, including the full statistical analysis plan and original sample-size justification, are not reported in the registry record. Accordingly, the numerical results support a bounded description of the posted primary outcome, not a complete audit of the analysis.

11. Confidence Intervals and Precision

The sponsor-reported primary contrasts include 95% confidence intervals, which show the uncertainty around each adjusted mean difference. For the atorvastatin population, the intervals are -57.335 to -42.340 for 50 mg, -74.523 to -58.986 for 100 mg, and -79.284 to -63.784 for 150 mg. For the treatment-naïve population, they are -55.511 to -39.551 for 50 mg, -70.557 to -54.691 for 100 mg, and -72.128 to -56.409 for 150 mg. Each interval lies below zero, consistent with the negative adjusted differences reported by the sponsor.

The width of an interval reflects precision: a narrower interval indicates a more precisely estimated group difference, while a wider interval leaves greater uncertainty about its size. These intervals are ranges for the adjusted mean contrasts under the sponsor's model, not ranges containing most individual participant responses. The group standard deviations describe variation among participant outcomes and answer a different question.

Precision should not be confused with validity or clinical relevance. A confidence interval does not account for unreported aspects of the model, possible bias, multiplicity, or the limits of applying results to other populations. The registry record does not report a threshold that would define a clinically important difference in this endpoint. The intervals therefore help assess statistical uncertainty in the Day 85 group comparisons, but cannot by themselves determine the practical importance or longer-term implications of the 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 illustrations express required sample sizes as participants per arm for 80% power and participants per arm for 90% power. They are not total event counts: this is a continuous-outcome analysis, and the illustrations concern participants in each of two equally allocated arms. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect set to the stated fraction of the observed effect.

The 80% power column represents the planned chance of detecting the selected effect under those assumptions if that effect is present. The 90% power column uses a higher target chance of detection. These are planning concepts, not probabilities that the trial's conclusion is correct. For each contrast, the illustrations show results for planning for 100%, 75% or 50% of the observed effect. Planning for a smaller effect requires more participants, all else being equal.

These figures are illustrative calculations from observed group summaries, not the trial's original design calculations. The original sample-size justification and its assumptions are not reported in the registry record. The displayed figures are not observed power and should not be read as a post-trial measure of how capable the completed trial was. In particular, estimates based on observed effects can be unstable, and the apparent sample requirement depends on the selected effect size and the stated statistical assumptions. The illustrations are most useful for showing how planning changes when the target effect is made smaller, not for determining what the trial's original enrollment target should have been.

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 = -49.740; pooled standard deviation σ = 15.038.
2. n = 2 × (1.96 + 0.842)² × 15.038² / -49.740² = 1.4, rounded up to 2 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 <- -49.74                      # observed difference in means
sigma <- 15.0378409225608                     # 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(2055976)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 2 (80% power), 2 (90% power)
 75% of observed effect: n per arm = 3 (80% power), 4 (90% power)
 50% of observed effect: n per arm = 6 (80% power), 8 (90% power)
power.t.test: 2.8 
Simulated power at n = 2 per arm: 0.441 (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 sponsor reports mixed models analyses for the primary dose-versus-placebo comparisons. In the atorvastatin population, the adjusted mean differences were -49.838, -66.754 and -71.534 for 50 mg, 100 mg and 150 mg, respectively, with each p-value <0.001. In the treatment-naïve population, the adjusted mean differences were -47.531, -62.624 and -64.268 for the same respective doses, also with each p-value <0.001. The registry reports a 95% confidence interval for each estimate.

Simple recalculations from posted summary statistics are unadjusted. More importantly, the recalculation uses the atorvastatin-plus-placebo arm as the control for all contrasts, including the treatment-naïve groups. The sponsor's analyses instead compare treatment-naïve doses with the treatment-naïve placebo group. Because the comparator differs and the sponsor reports adjusted model estimates, the two sets of results do not represent identical analyses. The discrepancy is flagged in the record; the sponsor's own analysis takes precedence.

The posted detail does not give enough information to reconstruct the mixed model, including all terms and missing-data procedures. The recalculation can be a useful independent check of the broad pattern in group summaries, but it is not a replacement for the sponsor's analysis. The sponsor's reported estimates should anchor interpretation of the primary comparisons.

15. Multiplicity, Missing Data and Analysis Populations

The study includes a primary endpoint, numerous secondary outcome measures, multiple dose groups and two participant populations. This creates multiple statistical comparisons. When many hypotheses are tested, the chance of finding at least one apparently notable result by chance can increase. Procedures such as a prespecified testing hierarchy or multiplicity adjustment can address that concern, but the registry record does not report the sponsor's complete approach to multiplicity. The reported primary p-values should therefore be read as the sponsor presents them, without assuming an unreported adjustment or claiming that all possible comparisons were controlled.

The record reports a full analysis set defined as randomized participants who received at least one dose of treatment. It does not provide the participant-level data or enough detail to evaluate all exclusions, missing measurements, imputation decisions, or sensitivity analyses. The baseline rule for the primary endpoint is described, but the method used to handle missing Day 85 outcomes is not reported in the registry record. This limits independent assessment of whether missingness could affect the estimates.

The sponsor states that mixed models were used for the primary comparisons and reports adjusted mean differences and 95% confidence intervals. The precise model specification, assumptions, covariates, and missing-data mechanism are not reported in the registry record. The original sample-size rationale, planned significance level and details of interim analyses are also not reported. The planning illustrations have explicit assumptions, but those are retrospective illustrations and do not fill the gap in the original design information.

These omissions do not invalidate the posted results, but they narrow what can be independently verified. The primary estimates can be described as reported, while questions about multiplicity control, robustness to missing data and exact model construction remain unresolved from the registry information alone.

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: cellulitis (4.0%), spinal compression fracture (4.0%), angina pectoris (3.8%).

The safety figures report the number of participants at risk and the number with at least one serious adverse event or other adverse event in each group. Serious adverse events were reported for 1 of 25 participants in the atorvastatin plus bococizumab 50 mg group, 1 of 26 in the atorvastatin plus placebo group, and 1 of 25 in the bococizumab 100 mg group without atorvastatin. The other listed groups had zero serious adverse events. Death counts are not reported in the registry record.

Other adverse events were reported in every group. The counts ranged from 2 of 22 in the atorvastatin plus ezetimibe group to 12 of 24 in the atorvastatin plus bococizumab 100 mg group and 12 of 24 in the atorvastatin plus bococizumab 150 mg group. These are counts of participants, not counts of distinct event episodes, and the figures alone do not establish causation or comparative safety.

The listed serious adverse event terms include cellulitis and spinal compression fracture, each reported as 4.0%, and angina pectoris, reported as 3.8%. The registry record does not provide enough context in these summary figures to attribute these events to a specific treatment or to assess comparative risk. Rare event counts from groups of this size are especially limited as a basis for broad safety conclusions.

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

The primary results indicate that, at Day 85, the sponsor's adjusted mean percent change in fasting LDL-C was lower in each bococizumab dose group than in its matching placebo group, in both the atorvastatin and treatment-naïve populations. All six sponsor-reported primary comparisons have negative adjusted mean differences, 95% confidence intervals below zero, and p-values <0.001. These are findings about the measured laboratory outcome in the participants analyzed.

The result does not establish that every participant's LDL-C changed in the same way. Group averages can conceal individual variation, and the reported confidence intervals describe uncertainty in group differences rather than the distribution of individual responses. The registry record also does not state a threshold for clinical importance, so statistical evidence for a nonzero contrast should not be equated with a judgment about how important that contrast is in practice.

The study assessed a short-term endpoint at Day 85. It does not establish whether the measured changes persisted beyond the reported assessment, whether they translate into differences in cardiovascular events, or how the findings apply to populations unlike the enrolled Japanese participants. The registry's secondary outcomes include later and related biochemical measures, but the posted summaries do not provide a complete basis for conclusions across all secondary outcomes.

Safety counts also require restrained interpretation. Serious adverse events were uncommon in the reported groups, but the sample sizes and event counts do not allow a broad comparative safety conclusion. The record's null death entries mean deaths are not reported in the registry record, rather than demonstrating that no deaths occurred. Overall, the trial informs the measured Day 85 LDL-C outcome and associated uncertainty; it does not resolve questions outside that scope.

18. Why This Trial Matters Statistically

This study is statistically informative because it separates two treatment contexts rather than treating all participants as though they had the same background therapy. Participants taking stable atorvastatin were analyzed within a population that included an atorvastatin-plus-placebo comparator, while treatment-naïve participants had a separate placebo group. That distinction matters when interpreting a treatment contrast: the appropriate comparator depends on the population and its treatment setting.

The dose-ranging structure also makes it possible to describe the primary outcome across several bococizumab doses in each population. The posted means show a progressively more negative pattern across the three dose levels within both settings, while sponsor-reported comparisons provide adjusted estimates against placebo. This pattern is descriptive; the registry does not report a formal test of dose trend or a direct statistical comparison between doses.

The record illustrates why statistical outputs need context. Sponsor-adjusted contrasts and unadjusted recalculations are not interchangeable, particularly when they use different comparator groups. The discrepancy reinforces the importance of checking the analysis population and control group before interpreting a numerical difference. The sponsor's reported analysis is the appropriate anchor for the primary comparison.

Finally, the study makes clear that statistical evidence for a short-term biochemical difference is distinct from evidence about clinical outcomes or long-term effects. Confidence intervals help communicate the precision of the reported contrasts, while missing details about multiplicity, missing-data handling and original design assumptions define limits on independent assessment. These features make the trial useful for understanding its specific endpoint and analytic context without supporting conclusions beyond what was measured.

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 endpoint is a laboratory measure at Day 85. The registry record does not report clinical outcome measures that would establish whether the observed group differences correspond to changes in cardiovascular events, symptoms, or other patient-centered outcomes. It also does not establish persistence of the measured changes beyond the reported follow-up.

Although the trial enrolled 218 participants, individual groups were relatively small, and serious adverse event counts were sparse. Those data limit the ability to compare uncommon safety outcomes reliably. Death counts are not reported in the registry record. The listed adverse-event summaries also do not, on their own, establish that an event was caused by a particular treatment.

The study population was Japanese and met specific conditions concerning LDL-C control and background treatment. Results may not transfer directly to other populations or treatment settings. The registry record does not report enough information to assess representativeness beyond those enrollment criteria.

The sponsor reports adjusted mixed models analyses, but the exact model specification and missing-data procedures are not reported in the registry record. Multiplicity procedures, the original sample-size justification, planned significance level and details of interim analyses are also not reported. The discrepancy with the simple recalculations adds a further reason to rely on the sponsor's primary analyses rather than the unadjusted contrasts. Finally, although multiple secondary outcomes are listed, the detailed secondary results available for interpretation do not establish a comprehensive pattern across all measures or times.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Dose Ranging Study Of Bococizumab (PF-04950615; RN316) In Hypercholesterolemic Japanese Subjects — NCT02055976.
• Registry record last updated 2019-02-08; status last verified 2018-09.
• Results first posted 2019-02-08.
• 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

NCT02055976 is a completed randomized, triple-masked, parallel-group, placebo-controlled Phase 2 dose-ranging study of bococizumab in 218 Japanese participants with hypercholesterolemia. It included participants taking stable atorvastatin and treatment-naïve participants, with separate placebo comparators and an ezetimibe group in the atorvastatin population.

The primary endpoint was percent change from baseline in fasting LDL-C at Day 85. Sponsor-reported adjusted mean differences favored lower mean percent change for each bococizumab dose versus the matching placebo group, with all reported p-values <0.001 and 95% confidence intervals below zero. Because the simple recalculations differ in adjustment and comparator use, the sponsor's own analysis takes precedence.

The results describe a short-term laboratory endpoint. The registry record does not report the original sample-size justification, complete multiplicity approach, full model specification or missing-data procedures. Safety summaries include few serious adverse events, and deaths are not reported in the registry record.