To Investigate the Gastrointestinal Behaviour of Two Triple Combination Products in Healthy Male Volunteers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for To Investigate the Gastrointestinal Behaviour of Two Triple Combination Products in Healthy Male Volunteers (NCT03415243), a randomized phase 1 study. The primary outcome is Mean Time to Onset of Gastric Emptying.

2. Clinical Question

3. Trial Design

This was a Phase 1, randomized, open-label, parallel-group study sponsored by GlaxoSmithKline. Its title describes a single-dose scintigraphic investigation of two triple-combination products in healthy male volunteers. The registry lists Common Cold as the condition, while the stated study population was healthy male volunteers; the primary outcome focused on gastrointestinal behavior rather than treatment of cold symptoms.

The registry reports enrollment of 28 participants, with 14 in Treatment Group A and 14 in Treatment Group B. Group A received a single sachet containing acetaminophen 650mg, dextromethorphan 20mg, and phenylephrine 10mg. Group B received two caplets containing acetaminophen 325mg, dextromethorphan 10mg, and phenylephrine 5mg. Both were single-dose administrations.

Random allocation means participants were assigned to one of the parallel groups, but the allocation method and sequence-generation details are not reported in the registry record. The study was unmasked, so participants and study personnel were not blinded according to the registry’s masking designation. The registry dates the study start to 2018-03-01 and primary completion to 2018-03-29; its status is completed.

The primary endpoint was mean time to onset of gastric emptying, assessed by scintigraphic imaging. Imaging was performed immediately after ingestion of the radiolabeled formulation, with observation described from predose until 10 hours post dose on Day 1. The primary analysis population excluded participants who vomited shortly after dosing and required sufficient data to determine gastric-emptying timing. Detailed operational procedures, including the full description of all analysis-population criteria, are not reported in the registry record.

The registry lists 29 outcome measures and one posted secondary outcome concerning participants with clinically significant changes in laboratory test values. It lists no analyses. The trial’s detailed statistical plan, including its original sample-size rationale and planned handling of the primary comparison, 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.

Before assignment: A total of 32 participants were screened, of whom 28 were randomized for treatment and 4 were screen failures.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Scintigraphy analysis population included all participants who received the radiolabeled treatments A or B and who did not vomit shortly (within 60 minutes) after study drug administration, who had sufficient data to determine time to onset and completion of gastric emptying and who had no major protocol deviations.

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 population was defined as all participants who received a radiolabeled treatment A or B irrespective of whether the participant was included in the scintigraphy analysis.

6. Primary Endpoint

The registry lists the primary outcome as Mean Time to Onset of Gastric Emptying, measured over Predose until 10 hours post dose on Day 1.

The primary endpoint was mean time to onset of gastric emptying, measured in minutes. It describes when gastric emptying began after participants ingested a study formulation. The stated assessment window ran from predose until 10 hours post dose on Day 1. The registry describes the measure as a mean and identifies standard deviation as its dispersion measure.

Scintigraphic imaging was used to follow a radiolabeled marker. The formulation was radiolabeled with not more than 108 microcurie of isotope-technetium-99m-diethylene-triamine-pentaacetate. Images were collected in a time-lapse format and corrected for radioactive decay and background radiation. Regions of interest included the stomach, proximal small intestine, distal small intestine, and colon. These procedures are intended to characterize transit through the gastrointestinal tract, with the primary endpoint focusing specifically on the onset of gastric emptying.

The primary outcome applied to participants who did not vomit within 60 minutes after study-drug administration and who had sufficient data to determine the onset and completion of gastric emptying. This restriction matters when interpreting the results: the reported endpoint concerns the eligible scintigraphy analysis population, rather than necessarily every enrolled participant. The registry’s full wording for an additional population criterion is incomplete, and its details are not reported in the registry record.

This endpoint provides a physiological timing measure. It does not directly quantify common-cold symptoms, symptom duration, or treatment benefit. The registry’s secondary outcome concerned clinically significant laboratory test changes, but no posted result for that outcome is included in the record.

7. Results Posted in the Registry

• Treatment Group B: mean 8.53 versus 1.11 on control; difference 7.43 (95% CI 3.91 to 10.95), standardized effect d = 1.56; z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous measurement: a time in minutes. The registry reports each group’s mean and standard deviation, then reports a mean difference for Group B relative to Group A. A mean summarizes the central location of observed times, while a standard deviation describes how much individual observations vary around that group’s mean. These summaries answer related but different questions: the mean difference compares group averages, and the standard deviations describe within-group dispersion.

What does the mean difference express?

The mean difference is the estimated contrast between the two group means in their original measurement units. The posted estimate is 7.427 minutes, with the comparison oriented as Treatment Group B relative to Treatment Group A. Keeping the original units makes the contrast interpretable as a difference in timing. It is not a ratio, and it does not describe the difference for every individual participant. Individual times may vary around their group mean, as the standard deviations indicate.

The registry lists a pooled standard deviation of 4.749 and a standardized effect size of 1.564. Standardizing a difference expresses it relative to a measure of variability, which can help describe the contrast on a scale that does not use minutes. It does not replace the original-unit estimate or its confidence interval. The registry record does not describe the exact formula or conventions used for the standardized effect size, so those details are not reported in the registry record.

How should the p-value be understood?

The reported p-value is unadjusted and is <0.001. In general, a p-value measures how compatible observed data are with a specified null model, assuming that model and the analysis assumptions hold. A small p-value is not the probability that the null hypothesis is true, and it does not quantify clinical importance. The registry does not name the statistical test used to obtain this p-value or provide enough detail to reconstruct the test. The test type and its assumptions are therefore not reported in the registry record.

In general, a confidence interval describes a range of values compatible with the data and the method used to construct it. Its repeated-sampling interpretation depends on the procedure’s assumptions; it is not a probability statement about a fixed parameter after the data have been observed. The posted interval for the mean difference is 3.909 to 10.95 minutes. The registry does not report the confidence-interval construction method, degrees of freedom, or whether any adjustment was used. Those methodological details are not reported in the registry record.

Why does variability matter?

Group A’s standard deviation was 1.213 minutes, compared with 6.606 minutes for Group B. In general, larger dispersion means that observations are more spread out around the group mean. It can make an estimate of a group mean or contrast less precise, depending on the sample size and analysis method. Here the reported spread differs between groups, so an analysis method’s treatment of unequal variability could matter. The registry does not state whether the primary analysis assumed equal variances or used an approach that allows unequal variances. The specific variance assumption is not reported in the registry record.

Over-dispersion is a general concern when data vary more than a chosen model expects. This endpoint is a continuous time measurement, and no over-dispersion model or diagnostic is described in the registry. It would not be appropriate to infer that such a model was needed or used. The posted standard deviations do, however, make the observed variation visible and help readers understand why an average alone does not capture the full distribution of times.

What does randomization contribute?

Randomization assigns participants to treatment groups by chance and is generally intended to reduce systematic differences between groups at baseline. This was a randomized parallel-group study, but the registry does not report the randomization sequence method, concealment procedures, or baseline characteristics for the primary analysis population. It is therefore possible to identify randomization as a design feature without assessing these implementation details. Open-label status means masking was absent, which is relevant to how study conduct and outcome assessment may be interpreted. Scintigraphic timing is an imaging-based measure, but the registry does not describe whether image analysis was blinded.

The study used radiolabel scintigraphy and describes correction for radioactive decay and background radiation. It also identifies anatomical regions of interest. These details explain how the physiological measure was obtained, but do not specify the full image-processing or statistical-analysis procedures. The registry does not report handling rules for data that could not be evaluated, the number excluded from the primary analysis, or procedures for outliers. Those details are not reported in the registry record.

What is the limit of a recalculation?

Simple unadjusted re-calculations from posted summary statistics can be useful as checks, but they may not reproduce a sponsor’s analysis if the original analysis used methods or data not represented in the summary. The posted record includes a mean difference and confidence interval, and there is no stated discrepancy between those posted results and a recalculation. The registry’s own detailed analysis methods remain unavailable, so the reported sponsor results should be distinguished from any method-based interpretation of the summary statistics.

Finally, a statistically clear contrast does not by itself establish whether the difference matters for a clinical decision. The endpoint is gastric-emptying onset in a selected analysis population, not a direct patient-centered outcome. Interpretation requires attention to the endpoint, the measurement process, the trial design, and the limits of reporting. The record does not supply enough analysis detail to evaluate every modeling choice, and no unreported method should be assumed.

10. Confidence Intervals and Precision

The posted mean difference is 7.427 minutes, and its 95% confidence interval extends from 3.909 to 10.95 minutes. The interval communicates uncertainty in the estimated contrast: values across that range are compatible with the data under the interval procedure and its assumptions. Because the registry does not state how the interval was constructed, its exact method-specific interpretation cannot be checked from the record.

The interval does not include zero. In general, zero represents no difference on a mean-difference scale, so the posted interval is consistent with a positive contrast for Group B relative to Group A. This does not mean that every participant in Group B had a later time than every participant in Group A. The group standard deviations, 1.213 minutes and 6.606 minutes, indicate variability among individual observations, and the interval pertains to the estimated group contrast rather than individual outcomes.

The interval’s width reflects both the observed variation and the amount of information available to estimate the contrast, along with the analysis method. The registry reports 14 participants in each randomized group, but the primary analysis population had additional eligibility requirements. The number included in that specific analysis is not reported in the registry record. As a result, the reported group enrollment figures should not automatically be treated as the analysis denominators.

Precision is not the same as importance. The confidence interval describes uncertainty around the statistical contrast in minutes; it does not establish whether that contrast has clinical consequences. The registry does not report a threshold for a meaningful difference in gastric-emptying onset. Nor does it report confidence intervals for the group means or for secondary outcomes. The interval should therefore be interpreted specifically as uncertainty around the posted primary mean difference, not as a complete summary of uncertainty across all outcomes.

11. 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 effect, rather than a report of the trial’s original design calculation. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning scenario uses a specified fraction of the observed effect as the effect to detect.

For planning at 100% of the observed effect, the illustration gives 7 participants per arm for 80% power and 9 participants per arm for 90% power. At 75% of the observed effect, it gives 12 participants per arm for 80% power and 16 participants per arm for 90% power. At 50% of the observed effect, it gives 26 participants per arm for 80% power and 35 participants per arm for 90% power.

In plain language, the 80% power column represents the number planned per arm under the stated assumptions for a design intended to have an 80% chance of detecting the specified effect if that effect were present. The 90% column uses the corresponding higher power target. These are design calculations, not descriptions of what happened in the completed trial. Smaller effects require more participants to detect under the same planning assumptions. This is not observed power.

The registry does not report the original sample-size justification or the assumptions used when the study was designed. The planning figures should therefore be read only as hypothetical illustrations based on the observed effect and the listed assumptions. They do not establish that the trial was planned to use those group sizes, nor do they determine whether the study was adequately designed for outcomes other than the primary comparison.

12. 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 = 7.427; pooled standard deviation σ = 4.749.
2. n = 2 × (1.96 + 0.842)² × 4.749² / 7.427² = 6.4, rounded up to 7 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 <- 7.427                      # observed difference in means
sigma <- 4.74938140393041                     # 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(3415243)
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 = 7 (80% power), 9 (90% power)
 75% of observed effect: n per arm = 12 (80% power), 16 (90% power)
 50% of observed effect: n per arm = 26 (80% power), 35 (90% power)
power.t.test: 7.5 
Simulated power at n = 7 per arm: 0.771 (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.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists 29 outcome measures, while one secondary outcome is posted: the number of participants with clinically significant change in laboratory test values. The primary outcome is mean time to onset of gastric emptying. The record lists no analyses, and no results for the listed secondary outcome are included in the available record. The full set of outcome definitions, analysis populations, and results is therefore not described in the posted information.

When a study examines multiple outcomes or makes multiple comparisons, the chance of at least one apparently unusual result can increase. In general, multiplicity procedures address this issue by controlling or otherwise accounting for repeated testing. The registry does not report whether any multiplicity adjustment was planned or applied, and the posted primary p-value is unadjusted. It is not possible to determine from the record how the primary result fits within a broader testing strategy. The multiplicity plan is not reported in the registry record.

The record identifies a scintigraphy analysis population that included participants who received a radiolabeled treatment, did not vomit within 60 minutes after administration, and had sufficient data to determine gastric-emptying onset and completion. It also refers to an additional criterion beginning with “no major pro,” but the criterion is incomplete in the registry description. Its full meaning is not reported in the registry record. The number of participants meeting the analysis criteria is also not reported in the registry record.

These criteria mean the primary endpoint applies to a defined subset rather than necessarily to everyone enrolled or assigned. The record does not give counts for exclusions, missing measurements, or vomiting within the stated period. It does not specify imputation, sensitivity analyses, or how incomplete scintigraphy data were handled. Those missing-data procedures are not reported in the registry record.

The original statistical plan, including any prespecified analysis population, covariate adjustment, interim analysis, or multiplicity strategy, is not reported in the registry record. Without that information, the posted results can be described, but the extent to which every analysis followed a prespecified plan cannot be assessed. No assumption should be made about unreported procedures or unposted outcomes.

14. 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 0% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse event figures report zero participants with a serious adverse event in Treatment Group A and zero in Treatment Group B. The record also reports zero deaths in each group. For other adverse events, one participant in Group A and two participants in Group B were recorded as affected. Each group’s adverse-event figures are reported against 14 participants at risk.

These are counts of participants affected, not counts of all event episodes. The posted figures do not describe event types for the non-serious events, their timing, severity, relationship to study treatment, or how events were collected. The registry lists no serious adverse event terms. No conclusion about comparative safety can be drawn from the zero serious-event counts alone, particularly given the study’s size and single-dose design.

The figures should be read as the registry’s reported counts for this study, not as evidence that an event cannot occur or as a prediction for other populations or settings. The detailed safety analysis and definitions are not reported in the registry record.

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

The posted result describes a difference in mean time to onset of gastric emptying after the two study formulations. The reported mean was 1.107 minutes in Group A and 8.534 minutes in Group B. The estimated mean difference for Group B relative to Group A was 7.427 minutes, with a 95% confidence interval from 3.909 to 10.95 minutes. The interval and the unadjusted p-value <0.001 describe statistical evidence and precision for this specific comparison.

The endpoint is a physiological measure obtained by scintigraphic imaging after a single dose. It is not a measure of symptom improvement, duration of a common cold, or overall health. The registry identifies healthy male volunteers as the study population, and the primary analysis required participants not to vomit within 60 minutes and to have sufficient data for the gastric-emptying assessment. The result therefore applies to that defined analysis context; the full population criteria are not completely reported.

The study was randomized, which supports a comparative design, but it was open label and involved 14 participants in each group. Randomization does not eliminate uncertainty, and the registry does not report details such as baseline characteristics for the primary analysis population or whether image assessment was blinded. The reported group standard deviations also show that participant-level times varied, particularly in Group B.

The posted numerical contrast does not, by itself, establish the clinical importance of the observed timing difference. The registry does not report a threshold for a meaningful change in this endpoint. Nor does this primary result establish effects on other outcomes, including laboratory changes or symptoms. A statistically small p-value should not be translated into a claim about treatment benefit.

The record is incomplete for evaluating the full analytic context: the detailed statistical plan, analysis denominators, handling of missing data, and multiplicity procedures are not reported in the registry record. The result is best understood as the reported comparison of gastric-emptying onset between these two formulations in the eligible scintigraphy population, with the listed uncertainty and reporting limitations.

16. Why This Trial Matters Statistically

This trial illustrates how clinical research can focus on a physiological process rather than a symptom or disease outcome. Its primary measure was the time to onset of gastric emptying after a single dose, assessed using a radiolabeled marker and scintigraphic imaging. That focus makes clear why endpoint definition matters: a result about gastrointestinal transit answers a different question from one about relief of common-cold symptoms.

The comparison also shows the value of reporting an estimate alongside uncertainty. The mean difference is expressed in minutes, and the confidence interval indicates a range of values compatible with the data under the interval method. Reporting group standard deviations adds information about variation that a mean alone cannot convey. Readers can distinguish the estimated contrast from the variability of individual observations.

At the same time, the record demonstrates limits that arise when key analysis details are absent. The primary analysis population had eligibility restrictions, but its full criteria and denominator are not reported. The registry lists multiple outcome measures, but gives no analyses and only one secondary outcome title. The statistical plan, missing-data approach, and multiplicity procedures are not reported in the registry record. These omissions constrain assessment of how the posted comparison relates to the full set of planned or conducted analyses.

Finally, sample-size illustrations based on an observed effect are not a substitute for the original design rationale. They can show how planning requirements change when the target effect changes, but they do not establish what assumptions guided this study. The trial is a useful example of reading a narrowly defined endpoint and its statistical uncertainty without extending the finding to outcomes the study did not report.

17. 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 was assessed in an analysis population with restrictions: participants had to receive a radiolabeled treatment, avoid vomiting within 60 minutes after administration, and have sufficient data to determine gastric-emptying onset and completion. The registry does not state how many participants met these criteria. Consequently, the reported group enrollment figures do not reveal the exact number contributing to the primary analysis.

The registry’s description of the population includes an additional criterion beginning with “no major pro,” but the record’s wording is incomplete. The complete criterion is not reported in the registry record. The record also does not detail missing observations, exclusions, or how incomplete imaging data were handled. These gaps limit assessment of whether the analysis population differed from the randomized groups.

The study was open label, and the registry does not state whether image readers or other outcome assessors were blinded. It describes imaging and corrections for radioactive decay and background radiation, but does not provide the full image-analysis protocol. The detailed randomization procedures, baseline characteristics for the primary analysis population, and statistical test are not reported in the registry record.

Other limitations include the absence of a reported original sample-size justification, multiplicity plan, and missing-data strategy. Although 29 outcome measures are listed, the record lists no analyses and only one secondary outcome title. Results for that secondary outcome are not included in the posted information. The study’s healthy male volunteer population and single-dose assessment also define the setting to which the primary result pertains; the record does not establish how findings extend beyond that setting.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: To Investigate the Gastrointestinal Behaviour of Two Triple Combination Products in Healthy Male Volunteers — NCT03415243.
• Registry record last updated 2019-06-24; status last verified 2019-03.
• Results first posted 2019-06-24.
• 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.

21. Record Summary

The registry describes a completed, randomized, open-label, parallel-group Phase 1 study of two triple-combination formulations in healthy male volunteers. Enrollment was 28. Treatment Group A received one sachet containing acetaminophen 650mg, dextromethorphan 20mg, and phenylephrine 10mg; Treatment Group B received two caplets containing acetaminophen 325mg, dextromethorphan 10mg, and phenylephrine 5mg.

The primary outcome was mean time to onset of gastric emptying, assessed by scintigraphic imaging from predose until 10 hours post dose on Day 1. Reported group means were 1.107 minutes for Group A and 8.534 minutes for Group B. The mean difference for Group B relative to Group A was 7.427 minutes, with a 95% confidence interval from 3.909 to 10.95 minutes and an unadjusted p-value <0.001.

The record reports zero serious adverse events and zero deaths in each group. It does not report the detailed statistical plan, primary analysis denominator, multiplicity procedures, or missing-data methods.