Randomized, Double-blind, Placebo-Controlled, Efficacy Study of a New Formulation of Phenylephrine HCL in the Common Cold: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Randomized, Double-blind, Placebo-Controlled, Efficacy Study of a New Formulation of Phenylephrine HCL in the Common Cold (NCT03339726), a randomized phase 2 study. The primary outcome is Mean Change From Baseline in the Nasal Congestion Severity Score.

2. Clinical Question

3. Trial Design

This was a randomized, double-blind, placebo-controlled, parallel-group Phase 2 study of phenylephrine HCl for nasal congestion associated with the common cold. It enrolled 193 participants according to the registry record. The interventions were a new extended-release formulation, a marketed immediate-release formulation, and placebo. The official title identifies the formulations as extended-release 30 mg and immediate-release 12 mg. The registry record does not give fuller arm descriptions or details about the dosing schedule.

The registry record lists the study start as 2017-11-30 and primary completion as 2018-04-16. Its current status is terminated. A reason for termination is not reported in the registry record, so the status alone does not explain why the study ended or whether its planned objectives changed. The original sample-size rationale, intended enrollment by arm, and details of the recruitment plan are not reported in the registry record.

The primary analysis used the Full Analysis Set, described as randomized participants with a valid baseline nasal congestion assessment. The posted primary outcome summaries include 64 participants for placebo, 66 for PE-IR, and 63 for PE-ER. The registry record does not explain whether every randomized participant contributed to every analysis, or how participants without a valid follow-up measurement were handled.

For the primary comparisons, the sponsor reported analyses using ANOVA. Posted secondary analyses include ANOVA and ANCOVA. The statistical plan, including model specifications, covariates, handling of missing observations, and any prespecified testing hierarchy, is not reported in the registry record. The reported results therefore describe the analyses posted in the record rather than a complete reconstruction of the trial's original design or analysis plan.

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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analysis is based on the Full Analysis Set population, which included all participants who were randomized and provided a valid baseline assessment of nasal congestion severity.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Mean Change From Baseline in the Nasal Congestion Severity Score, measured over 0-12 hours.

The primary endpoint was mean change from baseline in the Nasal Congestion Severity Score, measured in units on a scale, over 0-12 hours. The score runs from 0, meaning none, to 7, meaning severe. The endpoint is an average across assessments at 2, 4, 6, 8, 10, and 12 hours, rather than a single measurement at one time point. The registry record describes the analysis as using the Full Analysis Set: randomized participants who provided a valid baseline assessment of nasal congestion severity.

A change-from-baseline measure expresses how an outcome differs from its starting assessment. Averaging repeated assessments across a stated interval can represent the pattern of measurements over that interval rather than emphasizing one particular follow-up time. That is a general description of how such endpoints can be used; the registry record does not provide a separate rationale for choosing this endpoint or averaging these assessment times.

The arm means were 1.8 for placebo, 2.03 for PE-IR, and 1.93 for PE-ER. These are reported mean changes, with standard errors of 0.156, 0.154, and 0.158, respectively. The registry record does not state in the endpoint description whether a positive change denotes improvement or worsening. Interpretation should therefore focus on the reported comparisons and their uncertainty, without assigning a clinical direction to a positive value based on an unstated coding convention.

7. Results Posted in the Registry

• PE-IR: mean 2.03 versus 1.80 on control; difference 0.23 (95% CI -0.20 to 0.66), standardized effect d = 0.18; z-test p = 0.294.
• PE-ER: mean 1.93 versus 1.80 on control; difference 0.13 (95% CI -0.31 to 0.57), standardized effect d = 0.10; z-test p = 0.558.

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.

Average Change From Baseline in the Nasal Congestion Severity Score

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • PE-IR: mean 2.39 versus 2.14 on control; difference 0.25 (95% CI -0.26 to 0.76), standardized effect d = 0.17; z-test p = 0.335.
  • PE-ER: mean 2.16 versus 2.14 on control; difference 0.02 (95% CI -0.50 to 0.54), standardized effect d = 0.01; z-test p = 0.939.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between PE-IR 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 PE-ER and the control. The interval gives the range of effects that remain compatible with the data.

Change From Baseline in the Nasal Congestion Severity Score

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • PE-IR: mean 1.24 versus 1.12 on control; difference 0.12 (95% CI -0.33 to 0.57), standardized effect d = 0.09; z-test p = 0.600.
  • PE-ER: mean 1.52 versus 1.12 on control; difference 0.40 (95% CI -0.05 to 0.85), standardized effect d = 0.31; z-test p = 0.085.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between PE-IR 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 PE-ER and the control. The interval gives the range of effects that remain compatible with the data.

Average Change From Baseline in Sinus Pressure/Tenderness Scores

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • PE-IR: mean 1.78 versus 1.67 on control; difference 0.11 (95% CI -0.32 to 0.54), standardized effect d = 0.09; z-test p = 0.612.
  • PE-ER: mean 1.74 versus 1.67 on control; difference 0.07 (95% CI -0.36 to 0.50), standardized effect d = 0.06; z-test p = 0.750.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between PE-IR 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 PE-ER and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary outcomes cover additional nasal congestion measurements and sinus pressure or tenderness scores. Across these reported comparisons, the general pattern is that the estimated differences are modest relative to their uncertainty, and the sponsor-reported confidence intervals include zero. The registry record lists 16 posted secondary outcomes, while the displayed outcome details include a subset of those measures. The secondary findings do not provide a clear contrasting pattern that overturns the primary endpoint's uncertain comparisons with placebo.

Secondary outcomes can help show whether findings are consistent across related measures or time windows. They are not interchangeable with the primary endpoint: a different measurement or timeframe answers a different question. The results should be read as supplementary evidence, especially because the primary endpoint was the designated central comparison and the record does not describe a prespecified testing hierarchy for secondary measures.

When many outcomes and comparisons are examined, the chance of obtaining apparently noteworthy results by chance can increase. A multiplicity adjustment can address this issue, but whether one was planned or applied is not reported in the registry record. The posted secondary results therefore carry less weight than a clearly prespecified primary result, particularly if individual secondary p values are considered without adjustment. They should be interpreted as exploratory unless the original protocol or statistical analysis plan establishes otherwise.

The registry record does not report a complete explanation of how all secondary endpoints relate to the study's intended clinical interpretation, nor does it provide a threshold for meaningful differences on these measures. The combined secondary pattern can add context, but it cannot by itself establish a treatment effect, equivalence, or a clinically important benefit.

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

• Average Change From Baseline in the Nasal Congestion Severity Score
• Change From Baseline in the Nasal Congestion Severity Score
• Change From Baseline in the Nasal Congestion Severity Score
• Change From Baseline in the Nasal Congestion Severity Score
• Change From Baseline in the Nasal Congestion Severity Score
• Change From Baseline in the Nasal Congestion Severity Score
• Change From Baseline in the Nasal Congestion Severity Score
• Change From Baseline in the Nasal Congestion Severity Score

9. Statistical Interpretation

10. Statistical Methods Explained

Clinical trial results typically combine an estimate of a group difference with a measure of uncertainty. For this continuous endpoint, the group summaries are means and standard errors, and the comparisons are mean differences. A mean difference describes the distance between two group averages on the outcome's scale. Here, the recalculated contrasts compare each phenylephrine arm with placebo; the sponsor also reported a direct contrast between PE-IR and PE-ER.

What does the standard error describe?

The posted arm summaries give standard errors of the mean. In general, a standard error describes the uncertainty in an estimated mean, rather than the spread of individual participant outcomes. Smaller standard errors generally correspond to more precise estimates of a group mean, all else equal. The standard errors do not show the range of individual scores, and they should not be interpreted as a description of how much participants varied from one another. The registry record does not report standard deviations for the primary arm summaries.

What does a confidence interval add?

A confidence interval gives a range of values compatible with the observed data and the statistical method used, under its assumptions. It makes the uncertainty around an estimated difference more visible than a point estimate alone. A 95% confidence interval that includes zero means the analysis does not rule out zero difference at that confidence level. It does not prove that the true difference is zero. A wide interval leaves more possible values compatible with the results; a narrow interval indicates greater precision, while still depending on the quality and assumptions of the analysis.

How should p values be read?

A p value describes how unusual the observed data, or data more extreme, would be if the null hypothesis and the model assumptions held. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of a difference. The primary sponsor-reported p values were 0.300 and 0.569 for comparisons with placebo. The direct comparison between formulations had p = 0.645. Those values should be considered alongside the estimated differences and their confidence intervals, rather than used alone to label a result positive or negative.

The recalculated p values are unadjusted, simple calculations from posted summary statistics. The sponsor's primary analyses are reported as ANOVA. ANOVA is a general method for comparing means across groups; the registry record does not report its full model specification. For the posted primary pairwise comparisons, ANOVA is the sponsor's stated method. No discrepancy flag is recorded, and the sponsor's estimates and p values are close to the simple recalculations.

What does unadjusted mean?

An unadjusted comparison is calculated without accounting for other variables or for a collection of simultaneous tests. It can be informative as a direct summary of the observed contrast, but it may differ from a model-based estimate if that model includes covariates or other design features. The registry record does not report whether the primary ANOVA included additional terms or what adjustment procedures, if any, were used for multiple comparisons. The unadjusted recalculations should therefore be treated as descriptive checks, not as a substitute for the prespecified sponsor analysis.

Why does the analysis population matter?

The primary endpoint description identifies the Full Analysis Set as randomized participants with a valid baseline assessment. A defined analysis population determines which participants' data contribute to a result. The record does not give further rules about follow-up data, withdrawals, or missing outcome measurements. In general, missing data can affect both the estimate and its precision, especially if availability of measurements is related to outcomes or group assignment. The registry record does not report the methods used to address missingness, so its potential impact cannot be assessed from the posted information.

The primary endpoint averages measurements taken at several times. In general, averaging can summarize a course of measurements across an interval, but the result depends on which assessments are included and how missing assessments are handled. The registry record specifies the assessment times and interval, but does not report a detailed computational rule for participants with incomplete repeated measurements. Nor does it report the underlying individual-level data, which would be needed to examine alternative modeling choices.

Statistical methods can describe whether a difference is estimated precisely enough to distinguish it from zero, but clinical interpretation also needs context. The registry record does not give a minimally important difference or an equivalence margin. Thus, the posted estimates can be discussed in terms of their scale and uncertainty, but they cannot independently determine whether a particular difference would be meaningful to participants.

11. Confidence Intervals and Precision

The sponsor's 95% confidence interval for PE-IR versus placebo on the primary endpoint runs from -0.205 to 0.662 around a mean difference of 0.23. For PE-ER versus placebo, the interval runs from -0.311 to 0.564 around a mean difference of 0.13. Both intervals include zero and span values on either side of it. Their width indicates that the observed comparisons leave considerable uncertainty about the size and direction of the underlying mean differences.

In general, a confidence interval describes a range of estimates compatible with the data and the method's assumptions. An interval crossing zero is not evidence that the groups are identical; rather, it means that zero difference remains among the plausible values under that analysis. The intervals also include nonzero values, so the data do not pinpoint a single effect size. The record does not report a clinical importance threshold against which to judge the full range of values.

The arm-specific standard errors were 0.156 for placebo, 0.154 for PE-IR, and 0.158 for PE-ER. These quantify uncertainty around the arm means, not participant-to-participant variability. Precision of a contrast also depends on uncertainty in both groups and on the comparison method. The sponsor's confidence intervals are the relevant reported intervals for its ANOVA comparisons.

The direct PE-IR versus PE-ER sponsor comparison also had an interval spanning zero, from -0.537 to 0.333. The interval does not establish that the formulations are equivalent; equivalence requires a prespecified margin and a corresponding analysis, neither of which is reported in the registry record. Overall, the posted primary estimates are too uncertain to support a narrow claim about the exact difference between groups.

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 participants per arm, not total events. They are illustrations based on the observed effects, not the trial's original sample-size calculation. The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. For each illustration, the effect to detect is the stated fraction of the observed effect. The registry record does not report the assumptions or calculation used for the original trial design.

The 80% power column describes the number of participants per arm estimated to give an 80% chance of detecting the specified effect if that effect were the true one and the planning assumptions held. The 90% power column uses a higher target chance of detection for that same specified effect. These are forward-looking planning calculations; they are not a measure of how much power the completed trial actually had. They are not observed power.

Each row uses a different fraction of the observed effect as the target difference. Smaller target effects require more participants to distinguish them from random variation under the same assumptions. This is why the planning counts increase when the effect to detect is reduced. The underlying observed effect is a noisy estimate from this trial, so planning directly from it can produce unstable or unusually large estimates, particularly when the estimated difference is close to zero.

The planning illustrations do not account for design features that are not included in the stated assumptions, and the record does not report whether the original trial used the same significance level, allocation, or approximation. The curves represent the general relationship between a target effect and the required participants under the specified planning setup; they do not establish that any particular sample size would be adequate for a future study without a justified target effect and a prespecified analysis plan.

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 = 0.230; pooled standard deviation σ = 1.250.
2. n = 2 × (1.96 + 0.842)² × 1.250² / 0.230² = 463.3, rounded up to 464 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 <- 0.23                      # observed difference in means
sigma <- 1.24957615314154                     # 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(3339726)
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 = 464 (80% power), 621 (90% power)
 75% of observed effect: n per arm = 824 (80% power), 1,103 (90% power)
 50% of observed effect: n per arm = 1,854 (80% power), 2,482 (90% power)
power.t.test: 464.3 
Simulated power at n = 464 per arm: 0.803 (20000 replicates)

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

14. Analyses Reported by the Sponsor

The registry record reports sponsor analyses of the primary endpoint using ANOVA. For PE-IR versus placebo, the sponsor reported a mean difference of 0.23, a 95% confidence interval from -0.205 to 0.662, and p = 0.300. For PE-ER versus placebo, it reported a mean difference of 0.13, a 95% confidence interval from -0.311 to 0.564, and p = 0.569. The reported direct comparison of PE-IR with PE-ER was -0.10, with a 95% confidence interval from -0.537 to 0.333 and p = 0.645.

The recalculated primary contrasts are simple, unadjusted calculations from the posted arm summaries. Their estimates and p values are close to the sponsor's reported analyses. For example, the recalculated unadjusted p values are 0.294 for PE-IR versus placebo and 0.558 for PE-ER versus placebo. The recalculated intervals are not a substitute for the sponsor's intervals, because the sponsor reports ANOVA and the registry record does not provide all model details.

The sponsor's own analysis is the primary reference for the trial's reported results. No discrepancy is flagged in the registry record. The close agreement in point estimates and the overall interpretation across analyses is reassuring as a consistency check, but it does not establish that every modeling assumption or analysis decision can be independently verified from the registry information.

15. Multiplicity, Missing Data and Analysis Populations

The registry record lists 17 outcome measures, 51 analyses, and 16 posted secondary outcomes. This indicates that results were recorded across multiple measures and comparisons, but the counts alone do not show which analyses were prespecified, which were exploratory, or how the testing sequence was organized. Whether the study used a family-wise error procedure, another multiplicity adjustment, or a formal hierarchy is not reported in the registry record.

Multiplicity matters because testing many hypotheses can increase the chance that at least one result appears unusual even when no underlying effect is present. In general, adjustments or prespecified hierarchies can help control how results are interpreted across a family of tests. Without the planned approach, it is not possible to determine whether posted secondary p values should be viewed as adjusted, or to reconstruct the intended interpretation of the full set of comparisons. The primary result should be distinguished from the broader collection of secondary findings.

The primary population is described as randomized participants with a valid baseline assessment. The registry record does not report the number of participants with missing follow-up outcomes, reasons for missingness, or how incomplete repeated measurements were handled. It also does not provide details about withdrawals, exclusions after randomization, or sensitivity analyses for missing data. Missing observations can affect the estimate and its uncertainty; the direction and extent of any effect cannot be inferred from the posted summaries.

Further analysis-plan details are not reported in the registry record. These include the full model specifications, covariates, assumptions used for repeated assessments, handling of protocol deviations, and whether interim analyses were planned or conducted. The trial's original sample-size justification and design assumptions are also not reported. These gaps limit independent assessment of whether the posted analyses follow the planned approach and how robust the conclusions are to alternative reasonable methods.

16. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

The registry record reports no serious adverse events in the placebo, PE-IR, or PE-ER groups. It also reports no other adverse events in those groups and no deaths. The adverse-event summaries give 64 participants at risk in the placebo group, 66 in PE-IR, and 63 in PE-ER. These figures describe the posted record; they do not establish that no adverse events of any kind occurred outside the categories represented in the summary.

Zero reported events in these groups should be read as an observation in this trial, not as proof that the interventions have no safety risks. A trial's ability to characterize uncommon events depends on the amount and duration of observation, and those details are not reported in the registry record. The record also does not provide event narratives, severity information for non-serious events, exposure duration, or a fuller account of how events were collected and classified.

The registry lists the study as terminated but does not report a reason for termination. The available adverse-event figures alone do not explain that status. These summaries are descriptive safety information from the registry record and do not support conclusions about safety in other populations or settings.

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

The posted primary results estimate mean change in nasal congestion severity over 0-12 hours for placebo and two phenylephrine formulations. The sponsor-reported comparisons with placebo have confidence intervals that include zero, and their p values do not provide evidence against a no-difference hypothesis under the reported analyses. The point estimates are relatively close, but the intervals leave uncertainty about the size and direction of the differences.

These results do not demonstrate that the groups are identical. A result that does not establish a difference is not the same as evidence of equivalence. Equivalence or noninferiority requires a prespecified margin and a suitable analysis; a margin is not reported in the registry record. Nor does the result show that a difference, if present, would or would not matter clinically, because the registry record does not report a clinically meaningful threshold for the score.

The score's scale is described from none to severe, but the endpoint record does not specify how the sign of the change was coded. Accordingly, the numerical comparisons should not be translated into a claim about improvement or worsening without that information. The trial addresses a defined population with common-cold symptoms and a particular assessment interval. Its findings do not automatically generalize to other populations, formulations, durations, or outcomes.

The registry record marks the study as terminated, without stating why. The posted data do not explain the termination or provide a full account of the original protocol and analysis plan. The appropriate interpretation is therefore limited: the available summaries do not establish a primary mean difference from placebo, and they do not settle broader questions of clinical effectiveness, equivalence, or safety.

18. Why This Trial Matters Statistically

This trial illustrates why an estimated effect, its uncertainty, and the analysis plan all matter in interpreting clinical research. The primary mean differences alone do not show how precisely the study distinguishes the groups. The sponsor's confidence intervals include zero and extend across a range of values, making it important to avoid treating a nonsignificant result as proof of no difference.

It also shows why a point estimate should not be read as a final answer. The observed effects can be used for planning illustrations, but they are themselves uncertain and may not be suitable as future-study targets without independent justification. The planning counts vary substantially depending on the effect chosen to detect. This reflects a general statistical principle: smaller effects are harder to distinguish from random variation and require more information under otherwise similar assumptions.

The registry record includes a primary endpoint, multiple secondary outcomes, and many analyses. That makes prespecification and multiplicity important to interpretation. A clearly stated testing strategy helps readers distinguish a central confirmatory question from exploratory comparisons. The record does not report such a strategy in enough detail to evaluate it.

Finally, trial status and numerical results are different kinds of information. The study is marked terminated, yet the reason is not reported. The adverse-event summary records no events in the listed categories, but that does not answer every safety question. Taken together, these features make transparent reporting of the protocol, analysis plan, missing data, and reasons for study completion essential for a full statistical assessment.

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 available record leaves important details about design and analysis unresolved. It does not report the original sample-size justification, planned enrollment by arm, or the rationale for the chosen primary endpoint and assessment interval. The stated status is terminated, but a reason for termination is not reported in the registry record. These gaps prevent a clear assessment of how the completed study compares with its original plans.

For the primary endpoint, the record provides arm means, standard errors, and sponsor-reported ANOVA comparisons, but not the complete statistical model or analysis plan. It does not report a clinically meaningful difference threshold, an equivalence margin, or a multiplicity strategy. The coding direction of a positive change is not stated in the endpoint description, which limits directional interpretation of the means.

The record does not describe the extent or handling of missing follow-up data, incomplete repeated assessments, withdrawals, or protocol deviations. It also does not provide participant characteristics in the details available for these results. Without this information, readers cannot assess how missingness, analysis-population decisions, or differences in baseline characteristics might affect estimates.

The primary analysis is described for a Full Analysis Set defined by randomization and a valid baseline assessment, but further inclusion rules are not reported. The adverse-event summary is also limited: it provides counts for serious and other adverse events and deaths, without fuller event details, observation duration, or collection procedures. These are limitations of the registry information, not proof that the trial lacked other procedures or data.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Randomized, Double-blind, Placebo-Controlled, Efficacy Study of a New Formulation of Phenylephrine HCL in the Common Cold — NCT03339726.
• Registry record last updated 2019-06-04; status last verified 2019-06.
• Results first posted 2019-06-04.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

23. Record Summary

NCT03339726 is a randomized, double-blind, placebo-controlled, parallel-group Phase 2 study of phenylephrine HCl for common-cold nasal congestion. The registry record lists an enrollment of 193 and a status of terminated; a reason for termination is not reported. The primary endpoint was mean change from baseline in the Nasal Congestion Severity Score averaged over 0-12 hours.

The sponsor-reported primary comparisons of PE-IR and PE-ER with placebo had 95% confidence intervals spanning zero. The posted results do not establish a difference from placebo for the primary endpoint. The registry record does not report the full analysis plan, multiplicity approach, original sample-size rationale, or handling of missing observations. Its adverse-event summary reports no serious adverse events, other adverse events, or deaths in the listed groups.