Clinical Trial of Efficacy and Safety of Levopront® 30 mg/5 ml in Patients With Dry Cough: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clinical Trial of Efficacy and Safety of Levopront® 30 mg/5 ml in Patients With Dry Cough (NCT03837938), a randomized phase 3 study. The primary outcome is Number of Participants With Daytime Cough Resolution Rate by Day 8 in the PP Population.

2. Clinical Question

3. Trial Design

The registry describes a Phase 3, multicenter, randomized, open-label, parallel-group trial. Participants were assigned to Levopront® syrup or Libexin® tablets. The trial was completed, and the recorded enrollment was 184. The listed start date is 2016-11-09 and the primary completion date is 2018-03-06.

The treatment regimens were scheduled for 7 days. Levopront® was given as 10 ml (60 mg) three times daily, between meals and with intervals of at least 6 hours. Libexin® was given as 1 tablet (100 mg) three times daily. The record does not describe additional details of the randomization procedure, such as how the allocation sequence was generated or concealed.

Masking is listed as none, so this was an open-label comparison. The registry does not report whether outcome assessors were masked. The primary efficacy population was Per-Protocol: randomized participants who completed treatment with the study drug, had the primary efficacy assessment, and were considered compliant. The secondary outcomes are described for the ITT population.

The trial’s primary objective was to compare daytime cough resolution by Day 8. Secondary objectives included nighttime cough resolution, daytime and nighttime symptoms at Day 4, changes in cough severity and frequency, cough intensity, pre-bronchodilator FEV1, and adverse events. The registry record does not report the full protocol or a detailed statistical analysis plan, so other design features, including eligibility criteria and the planned handling of withdrawals, are not available.

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

Analysis population for the primary outcome, as defined in the registry: Per-Protocol population included all randomized patients completing treatment with the study drug, having primary efficacy analysis assessment done and considered to be compliant.

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: ITT population consisted of all randomized patients from both treatment groups.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Daytime Cough Resolution Rate by Day 8 in the PP Population, measured over At Visit 3, Day 8.

The primary endpoint counts participants in the Per-Protocol population who had daytime cough resolution at the Day 8 assessment, identified as Visit 3, Day 8. Daytime was defined as the period from after 08:00h up to 22:00 h. Cough was rated on a six-point scale, where 0 meant no cough during the day and 5 meant distressing cough most of the day. A score of 0 or 1 counted as resolution; scores of 2 or higher counted as cough still present. Lower scores indicate a better outcome.

A count of participants meeting a threshold is a binary outcome at the individual level: each participant is classified as having met or not met the resolution definition. The count can therefore describe how many participants reached the specified symptom state, rather than the average change in a cough score. This distinction matters because a count-based endpoint discards some information about differences among scores within the resolved and unresolved categories.

The endpoint is used to address the trial’s primary question about the proportion-like occurrence of daytime cough resolution by the specified visit. The registry states that the treatment response rates were to be reported with a non-inferiority margin of δ = 20%. However, the primary outcome comparison itself is not reported in the registry record. The endpoint definition is available, but the posted record does not establish how many participants met it in either group or how uncertain the between-group comparison was.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized parallel-group trial, with participants assigned to one of two treatment groups. Randomization is intended to make treatment groups comparable, on average, with respect to measured and unmeasured factors. It does not guarantee that groups are identical, and it does not remove the need to report how assignment was performed or how outcomes were analyzed. Those procedural details are not reported in the registry record.

What does the binary endpoint represent?

The primary outcome classifies each participant according to whether daytime cough met the specified resolution threshold by Day 8. The threshold is a score of 0 or 1; scores of 2 or higher count as cough present. A group count records the number meeting that definition. A treatment comparison would ordinarily place the group results on a common scale, such as a difference in response rates, and quantify uncertainty around the estimated contrast. The registry record does not report those efficacy counts or a comparison estimate, so no such result can be interpreted from the record.

Binary outcomes can be clinically direct because they focus on whether a defined state was reached. They also depend on the chosen threshold. Participants just on either side of a cutoff are classified differently, even if their scale scores are close. Conversely, participants with different scores can be grouped together if both fall on the same side of the cutoff. The six-point scale’s definition and the resolution rule are therefore essential to understanding what the endpoint means.

How does non-inferiority reasoning work?

In general, a non-inferiority analysis asks whether the data rule out a loss larger than a prespecified acceptable margin. The registry states a margin of δ = 20%. A formal conclusion requires a defined treatment contrast, an appropriate uncertainty interval, and a decision rule that relates that interval to the margin. The direction of the contrast and the population used for the primary analysis also need to be clear. The registry record does not report the primary comparison, confidence interval, or enough statistical-plan detail to verify the decision process. The stated margin by itself does not determine the result.

Non-inferiority assessments can be sensitive to choices about analysis populations and missing outcomes. The registered primary population is Per-Protocol, defined as randomized participants who completed treatment, had the primary efficacy assessment, and were considered compliant. The registry does not report the criteria used to determine compliance, the number included in this population, or the results from an alternative analysis population for the primary endpoint.

What can confidence intervals tell readers?

In general, a confidence interval gives a range of values compatible with the data and the statistical method, expressing the uncertainty around an estimate. It is not a guarantee that the true effect lies in the interval. For a non-inferiority question, the interval is particularly relevant because its relation to the prespecified margin informs whether the data are sufficiently precise for the intended conclusion. No primary efficacy interval is reported in the registry record, so the precision of the estimated treatment contrast cannot be assessed.

How should the safety counts be read?

The registry lists participants with serious adverse events separately from participants with other adverse events, with 92 at risk in each group. Counts describe observed events in the recorded groups; they do not, by themselves, establish a treatment-related cause or a difference in risk. A comparative interpretation would need the outcome definitions, event details, follow-up completeness, and appropriate uncertainty estimates. General statistical caution is especially important when event counts are small, because estimates can be imprecise even when no events are recorded in a category.

The registry also lists 8 outcome measures and 11 analyses. Those counts indicate that multiple outcomes or analyses were recorded, but the record does not report a multiplicity adjustment plan. In general, testing many hypotheses can increase the chance of at least one apparently unusual result if all are treated as confirmatory. Whether that concern applies, and how it was addressed, depends on the prespecified hierarchy and analysis plan, which are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures and 11 analyses, spanning cough resolution, symptom-scale changes, cough intensity, FEV1, and safety. Considering multiple outcomes creates a multiplicity question: when several hypotheses are tested, the chance of at least one result appearing statistically notable can increase. In general, a protocol may address this by identifying a primary endpoint, setting a hierarchy, or adjusting inference. The registry record does not report whether such procedures were planned or used. The primary endpoint is identified, but the detailed testing strategy is not reported in the registry record.

Missing-data handling is also not reported in the registry record. The record does not describe how participants without a Day 8 assessment were treated in the primary analysis, whether any values were imputed, or how withdrawals were handled. These details matter because a binary endpoint requires a defined status for each participant included in the analysis, and assumptions about missing outcomes can affect estimates.

The primary analysis population is Per-Protocol, with inclusion based on completing treatment, having the primary assessment, and being considered compliant. The secondary outcomes are listed for the ITT population. These populations answer related but distinct questions: a Per-Protocol analysis focuses on participants meeting the stated completion and compliance criteria, while an ITT analysis generally retains participants according to randomized assignment. The registry does not report the population counts for the primary efficacy analysis or enough detail to assess the effect of exclusions. The precise ITT definition and the handling of missing secondary outcomes are also not reported in the registry record.

Because analysis-population definitions, missing-data procedures, and multiplicity methods are unavailable, interpretation of any unreported or later-reported test results would require those details. The record’s endpoint descriptions alone do not resolve these statistical issues.

11. 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 1% reporting threshold.

Most frequent non-serious adverse event terms

For Levopront® Syrup 30 mg/5 ml, the registry lists 0 serious adverse events among 92 participants at risk, 14 participants with other adverse events among 92 at risk, and 0 deaths. For Libexin® 100 mg Tablets, it lists 0 serious adverse events among 92 participants at risk, 12 participants with other adverse events among 92 at risk, and 0 deaths.

These entries are counts of participants, not a complete account of event severity, timing, duration, recurrence, or suspected relationship to treatment. The registry’s secondary safety description refers to adverse events of various severity according to subjective complaints, but the record does not provide event-level details or a comparative statistical analysis. Zero recorded serious adverse events and zero deaths describe the posted observations; they do not establish that such events are impossible or that the treatments have identical safety profiles. The other adverse-event counts are descriptive and do not, by themselves, show whether a difference is meaningful. The registry record does not report uncertainty estimates or further information needed to assess those comparisons.

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

The record establishes that this was a randomized, open-label, parallel-group comparison of Levopront® syrup and Libexin® tablets for dry, non-productive cough associated with acute upper respiratory infection. It specifies a Day 8 primary endpoint based on whether daytime cough reached a score of 0 or 1, and identifies a Per-Protocol population for that endpoint. It also provides treatment regimens and descriptive safety counts.

The record does not report the primary efficacy comparison. It therefore does not show the Day 8 response count in either group, an estimated treatment contrast, or the uncertainty around that contrast. Although the registry names a non-inferiority margin of δ = 20%, that information alone cannot establish whether the trial met its non-inferiority objective. The data and analysis needed to assess the margin are not reported in the registry record.

The listed adverse-event counts can be described as recorded, but they do not show whether events were caused by treatment or establish a reliable difference between groups. The available record also does not support conclusions about the secondary efficacy outcomes, because their numerical results are not reported.

These limitations are about what the registry record reports, not proof that the trial did or did not produce further analyses. A treatment conclusion would require the relevant outcome estimates and the analysis details, including the handling of missing data and the basis for the non-inferiority decision. In their absence, the defensible interpretation is limited to the trial design, definitions, and posted safety counts.

13. Why This Trial Matters Statistically

This trial raises a useful statistical distinction between describing an endpoint and reporting evidence about a treatment comparison. The registry defines daytime cough resolution in operational terms: a score of 0 or 1 on a six-point scale at Day 8. That makes the outcome rule explicit, but the rule cannot answer the treatment question without the group results and an estimate of how different those results are.

The non-inferiority framework adds another important layer. A prespecified margin such as δ = 20% gives a boundary for judging an acceptable loss, but interpretation depends on the treatment contrast, its uncertainty, and the analysis population. Readers cannot infer a non-inferiority finding from the margin alone. This illustrates why statistical conclusions depend on estimates and uncertainty, not just trial labels or objectives.

The registry also identifies a Per-Protocol primary population and ITT secondary populations. These choices highlight the importance of knowing who contributed to each analysis and how missing assessments were treated. In a trial designed to assess non-inferiority, population definitions and deviations from assigned treatment can be particularly relevant to interpreting the result; the record does not provide enough detail to evaluate these issues.

Finally, the recorded safety counts illustrate the difference between observation and inference. Counts can summarize what was recorded, while comparative interpretation requires context and uncertainty. The record’s main statistical value is therefore its clear endpoint definition and description of the design, alongside a reminder that result estimates and analysis details are essential for judging a clinical comparison.

14. 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 registry record does not report the primary efficacy results, despite identifying Day 8 daytime cough resolution as the primary endpoint. It therefore does not provide group-specific response counts, an estimated treatment contrast, or an uncertainty interval. The stated non-inferiority margin cannot be evaluated without those results and the analysis rule used to compare the estimate with the margin.

The primary analysis is described as Per-Protocol, but the number of participants in that population and the criteria used to judge compliance are not reported in the registry record. The registry enrollment is 184, while the safety entries list 92 participants at risk in each group; those safety counts do not establish how many participants contributed to each efficacy analysis. The record also does not report the handling of missing Day 8 assessments or the primary outcome’s analysis population counts.

The trial was open-label, with masking listed as none. The registry record does not state whether outcome assessment was masked. This is relevant context for subjective cough ratings, though the record does not establish whether knowledge of treatment assignment affected the ratings.

Although secondary outcomes are described, their numerical efficacy results are not reported in the registry record. The multiplicity strategy, full statistical analysis plan, randomization procedures, and detailed eligibility criteria are also not reported. Safety information is limited to participant counts and does not include event-level descriptions, attribution, or comparative uncertainty. These gaps constrain interpretation of efficacy, safety, and the robustness of any non-inferiority claim.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Clinical Trial of Efficacy and Safety of Levopront® 30 mg/5 ml in Patients With Dry Cough — NCT03837938.
• Registry record last updated 2024-04-16; status last verified 2023-10.
• Results first posted 2024-04-15.
• 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.

18. Record Summary

NCT03837938 is a completed Phase 3, multicenter, randomized, open-label, parallel-group trial comparing Levopront® syrup 30 mg/5 ml with Libexin® 100 mg tablets in patients described as having dry, non-productive cough caused by acute upper respiratory infection. The registry lists enrollment of 184. The primary endpoint was the number of Per-Protocol participants with daytime cough resolution by Day 8, defined as a score of 0 or 1 on a six-point cough scale. A non-inferiority margin of δ = 20% is stated.

The primary efficacy comparison and numerical secondary efficacy results are not reported in the registry record. Safety entries list 0 serious adverse events and 0 deaths in each group, with 92 participants at risk per group; other adverse events are listed for 14 participants in the Levopront® group and 12 in the Libexin® group. These counts are descriptive and do not establish comparative effects.