This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Tolperisone in Acute Muscle Spasm of the Back (NCT03802565), a randomized phase 2 study. The primary outcome is Mean Effect Size in Subjected-Rated Pain.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03802565 |
| Phase | Phase 2 |
| Condition | Back Pain, Acute Pain, Back Spasm Upper Back |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 415 |
| Arms in the primary outcome | 5 |
| Lead sponsor | Neurana Pharmaceuticals, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
The trial concerned male and female subjects experiencing back pain due to or associated with muscle spasm. The listed conditions include back pain, acute pain, back spasm upper back, back strain, muscle cramp, muscle spasm, and low back pain. The registry record does not report an age range or additional eligibility details in the available description.
Intervention
Participants were assigned to one of four tolperisone regimens: 50 mg, 100 mg, 150 mg, or 200 mg, each administered three times a day. The corresponding daily amounts are listed as 150 mg/day, 300 mg/day, 450 mg/day, and 600 mg/day.
Comparator
The comparator was placebo administered three times a day. The trial is described as randomized, double-blind, placebo-controlled, and parallel-group. The registry record does not describe additional comparator procedures.
Primary question
The primary question concerned mean effect size in subject-rated pain due to acute back spasm, assessed with a Numerical Rating Scale from 0, no pain, to 10, worst possible pain. The registered description specifies the rating “right now” on Day 14 and gives a Day 1 to Day 14 timeframe. Although the outcome title describes an effect between tolperisone and placebo, the posted results do not include a reported statistical contrast for each dose against placebo.
3. Trial Design
This was a phase 2, randomized, double-blind, parallel-group study comparing four tolperisone dose regimens with placebo. The registry lists the trial as completed and reports enrollment of 415. Its brief description characterizes the study as assessing efficacy and safety in male and female subjects with back pain due to or associated with muscle spasm. The registry lists the start as 2019-02-01 and primary completion as 2019-06-28.
The five listed groups are tolperisone 50 mg, 100 mg, 150 mg, and 200 mg, each taken three times a day, and placebo taken three times a day. The outcome results give group sizes of 82, 87, 83, 85, and 78, respectively. Those are the posted outcome denominators; the registry record does not explain how they relate to the enrollment figure or describe any participant flow.
Random allocation and double masking are features intended to reduce bias: randomization can help balance participant characteristics across groups, while masking can limit the influence of treatment knowledge on care or outcome assessment. These are general principles, not evidence that balance or masking was maintained in this particular trial. Details of the allocation procedure, masking procedures, adherence, and deviations from the planned regimen are not reported in the registry record.
The registry reports one outcome measure and no posted analyses. As a result, the design can be described, but the registered treatment comparisons cannot be reconstructed from the available group summaries alone. The statistical analysis plan, planned sample-size justification, and details of any interim analyses are 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.
Overall Study
| Stage | Tolperisone 50 mg | Tolperisone 100 mg | Tolperisone 150 mg | Tolperisone 200 mg | Placebo |
|---|---|---|---|---|---|
| STARTED | 82 | 87 | 83 | 85 | 78 |
| COMPLETED | 77 | 83 | 74 | 77 | 72 |
| NOT COMPLETED | 5 | 4 | 9 | 8 | 6 |
Reasons for not completing this period:
| Reason | Tolperisone 50 mg | Tolperisone 100 mg | Tolperisone 150 mg | Tolperisone 200 mg | Placebo |
|---|---|---|---|---|---|
| Adverse Event | 0 | 1 | 2 | 1 | 1 |
| Withdrawal by Subject | 2 | 2 | 2 | 0 | 1 |
| Protocol Violation | 2 | 1 | 4 | 5 | 1 |
| Lost to Follow-up | 0 | 0 | 1 | 0 | 0 |
| Subjects Related to Each Other | 1 | 0 | 0 | 2 | 1 |
| Elevated Enzymes | 0 | 0 | 0 | 0 | 2 |
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.
| Characteristic | Unit | Tolperisone 50 mg | Tolperisone 100 mg | Tolperisone 150 mg | Tolperisone 200 mg | Placebo | Total |
|---|---|---|---|---|---|---|---|
| Participants analysed | 82 | 87 | 83 | 85 | 78 | 415 | |
| Age, Customized | years | 43.5 (20 to 65) | 44.4 (19 to 65) | 44.3 (21 to 65) | 42.0 (20 to 64) | 41.6 (18 to 62) | 43.6 (18 to 65) |
| Sex: Female, Male: Female | Participants | 45 | 57 | 41 | 41 | 49 | 233 |
| Sex: Female, Male: Male | Participants | 37 | 30 | 42 | 44 | 29 | 182 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 13 | 18 | 22 | 20 | 16 | 89 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 69 | 69 | 61 | 65 | 62 | 326 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 1 | 0 | 1 | 0 | 1 | 3 |
| Race (NIH/OMB): Asian | Participants | 1 | 4 | 2 | 4 | 3 | 14 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 1 | 1 | 1 | 0 | 0 | 3 |
| Race (NIH/OMB): Black or African American | Participants | 29 | 32 | 29 | 35 | 29 | 154 |
| Race (NIH/OMB): White | Participants | 50 | 50 | 49 | 45 | 42 | 236 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 1 | 0 | 3 | 4 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 1 | 0 | 1 |
| Body Mass Index | kilogram/meter^2 | 28.23 (19.4 to 35.0) | 28.48 (20.9 to 35.0) | 28.34 (19.8 to 35.0) | 28.45 (20.0 to 35.0) | 28.53 (19.5 to 35.0) | 28.38 (19.4 to 35.0) |
6. Primary Endpoint
The registry lists the primary outcome as Mean Effect Size in Subjected-Rated Pain, measured over Day 1 to Day 14.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | score on a scale |
| Endpoint classification | Continuous Endpoint |
The primary outcome is titled “Mean Effect Size in Subjected-Rated Pain.” It concerns pain due to acute back spasm, rated by the subject using a Numerical Rating Scale. The scale is described as ranging from 0, no pain, to 10, worst possible pain. The rating is specified as pain “right now” on Day 14, with the outcome timeframe listed as Day 1 to Day 14.
A subject rating is relevant for a symptom such as pain because it records the participant’s own assessment rather than relying only on an external observer. As a general measurement principle, a numerical scale can express symptom intensity in a form that can be summarized across participants and compared between groups. A score on a subjective scale is still affected by how participants understand and use the scale, so consistent instructions and timing matter.
The registry record does not fully define how “mean effect size” was calculated, including whether the posted values are changes from baseline or another summary. It also does not provide a separate group-level baseline description. Those omissions limit what can be inferred from the negative values and prevent a clear interpretation of them as treatment-versus-placebo effects. The stated endpoint therefore identifies the symptom, scale, and assessment timing, but the posted description leaves some details of the estimand unclear.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry posts mean values of -4.2 for tolperisone 50 mg, -4.0 for 100 mg, -3.7 for 150 mg, -4.4 for 200 mg, and -3.5 for placebo. Their respective 95% confidence intervals are -9.0 to 1.0, -10.0 to 2.0, -8.0 to 1.0, -10.0 to 1.0, and -8.0 to 1.0. These are the reported group summaries; the registry does not post a treatment-versus-placebo estimate, confidence interval, or p-value for any dose.
Each reported confidence interval extends from a negative value to a positive value. In general, a confidence interval describes uncertainty around an estimate under the statistical procedure used to construct it. Here, the intervals signal that the group means are imprecisely estimated, but they should not be treated as confidence intervals for the difference between a tolperisone group and placebo. The registry labels the outcome as an effect between tolperisone and placebo, yet presents results by group and does not report the corresponding contrast estimates.
The numerical values alone do not establish whether any dose differed from placebo. A valid comparison requires an estimate of the between-group contrast and its uncertainty, or a reported test of that contrast. Comparing the locations or overlap of separate group confidence intervals is not a substitute for that analysis. The registry record reports no analyses, so there is no posted basis for identifying a statistically supported dose response or ranking the regimens by comparative effect.
The group means are close in their posted numerical range, but that observation is descriptive and does not establish equivalence. Demonstrating equivalence or ruling out a meaningful difference would require a prespecified margin and an analysis designed for that purpose; neither is reported in the registry record. The outcome description also does not fully clarify the calculation behind “mean effect size,” so the sign and clinical interpretation should be read cautiously.
In short, the posted results show group-level means and broad confidence intervals for the named endpoint. They do not supply the inferential comparison needed to answer the primary comparative question. No conclusion about whether tolperisone differs from placebo, or whether one dose differs from another, can be drawn from these summaries alone.
9. Statistical Methods Explained
Statistical methods explain how trial data are turned into estimates and how uncertainty in those estimates is assessed. The registry record gives the trial’s randomized, double-blind, parallel-group design and reports means with 95% confidence intervals for a continuous outcome. It does not report the analysis method used to obtain those estimates, a model specification, or inferential tests comparing groups.
What does a mean summarize?
As a general concept, a mean is an average of the observed values in a group. For a continuous measure such as a numerical pain rating, the mean provides a compact description of the group’s central value. It does not show how individual ratings are distributed, whether values cluster tightly or vary widely, or whether the distribution is symmetric. Those features can matter when choosing and interpreting an analysis.
The registry lists the outcome as a mean effect size and gives values for each group. It does not fully define the underlying calculation. In particular, the record does not clarify whether the values represent change from baseline, an endpoint score, or another effect summary. That missing definition matters because a negative mean has different interpretations depending on how the outcome was constructed and which direction represents improvement.
What does a confidence interval convey?
In general, a confidence interval expresses uncertainty about an estimate under the method used to calculate it. A narrower interval indicates greater precision than a wider interval, all else equal. A 95% confidence interval is not a statement that there is a 95% probability that the particular interval contains the true value. Rather, the confidence level describes the long-run performance of the procedure under its assumptions.
The intervals posted for the group means are broad and span negative and positive values. They help readers see that the group estimates are uncertain. But the intervals are attached to group-level values, not to treatment-versus-placebo contrasts. To assess the comparative question, the relevant estimate would be the difference between a tolperisone group and placebo, accompanied by its uncertainty. Those contrast results are not reported in the registry record.
Why is the contrast important?
Randomized trials are designed to compare outcomes between assigned groups. The core comparative estimate is not simply the mean in each group considered separately, but the difference or other prespecified contrast between groups. The uncertainty of that contrast depends on the uncertainty in both group estimates and on the analysis approach. A reader should therefore not infer a treatment effect by subtracting the posted means independently, particularly when the outcome calculation and analysis are not described. The registry record does not provide a recalculated comparison.
Likewise, separate confidence intervals should not be used as a shortcut for a formal comparison. Overlap or non-overlap of separate intervals does not, by itself, give the exact uncertainty or test result for a contrast. An analysis of the contrast can account directly for the structure of the trial and the chosen estimand. No such analysis is posted for this outcome.
What does the planning illustration mean?
The sample-size assumptions describe a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The illustration considers an effect to detect set as a stated fraction of the observed effect. Such calculations are prospective planning scenarios; they are not evidence of the trial’s observed power and do not replace the sponsor’s own design justification. The planned sample-size justification is not reported in the registry record. No numerical planning outputs are included in the registry record summarized for this analysis.
In general, planning calculations depend on assumptions about the target effect, variability, significance level, allocation, and analysis. If an illustration uses an effect estimated from trial results, the estimate itself is uncertain; treating it as fixed can make the resulting planning scenario appear more definite than the evidence warrants. The stated assumptions should therefore be read as hypothetical inputs, not as proof that the trial was designed to detect a particular effect. The record does not report a sample-size calculation authored by the sponsor.
Why does variability matter?
For continuous outcomes, within-group variability affects the precision of means and contrasts. Greater variability generally makes estimates less precise when other conditions are held constant. The posted results include confidence intervals, but the registry does not report standard deviations or the method used to calculate the intervals. It is therefore not possible to reproduce the uncertainty estimates from the posted summaries or assess the distributional assumptions behind them.
These methods concepts are general. For this trial, the direct statistical reading is limited to the published group means and confidence intervals, because the registry record contains no posted analyses or model details. The analysis population, treatment of missing observations, covariate adjustments, and handling of multiple comparisons are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one outcome measure and no posted analyses. It does not report whether the primary outcome was analyzed under an intention-to-treat, modified intention-to-treat, per-protocol, or other analysis population. The record also does not describe how missing pain ratings were handled, whether participants who discontinued were included, or whether any imputation or sensitivity analyses were used.
These details matter because missing outcome values can affect both the estimated group means and the uncertainty around comparisons. As a general principle, an analysis that excludes participants with missing values may target a different population or rely on assumptions about why values are missing. Imputation and sensitivity analyses also require explicit methods. No such methods are reported in the registry record, so the extent or direction of any missing-data influence cannot be assessed.
Multiplicity is the risk of increased false-positive findings when several hypotheses are tested. The trial has four tolperisone dose groups and placebo, creating the possibility of multiple dose-versus-placebo comparisons. The registry record does not report which comparisons were prespecified, whether any adjustment for multiplicity was planned, or how the primary outcome would be interpreted across doses. It also reports no p-values or pairwise estimates that would permit an assessment of the comparisons.
The planned statistical analysis, interim analyses, and analysis populations are not reported in the registry record. Without those details, the posted group summaries cannot establish how the sponsor intended to control error rates or address missing observations. The absence of these details should be treated as an evidence limitation, not as proof that a particular procedure was or was not used.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Tolperisone 50 mg | 0 | 82 | 0.0% |
| Tolperisone 100 mg | 0 | 87 | 0.0% |
| Tolperisone 150 mg | 0 | 83 | 0.0% |
| Tolperisone 200 mg | 0 | 85 | 0.0% |
| Placebo | 0 | 78 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Tolperisone 50 mg | 0 of 82 |
| Tolperisone 100 mg | 0 of 87 |
| Tolperisone 150 mg | 0 of 83 |
| Tolperisone 200 mg | 0 of 85 |
| Placebo | 0 of 78 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 2% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Tolperisone 50 mg | 7 of 82 |
| Tolperisone 100 mg | 13 of 87 |
| Tolperisone 150 mg | 12 of 83 |
| Tolperisone 200 mg | 14 of 85 |
| Placebo | 5 of 78 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Tolperisone 50 mg | Tolperisone 100 mg | Tolperisone 150 mg | Tolperisone 200 mg | Placebo |
|---|---|---|---|---|---|---|
| Headache | Nervous system disorders | 3 of 82 | 5 of 87 | 8 of 83 | 8 of 85 | 3 of 78 |
| Diarrhoea | Gastrointestinal disorders | 2 of 82 | 2 of 87 | 3 of 83 | 1 of 85 | 0 of 78 |
| Somnolence | Nervous system disorders | 0 of 82 | 3 of 87 | 0 of 83 | 1 of 85 | 2 of 78 |
| Dizziness | Nervous system disorders | 1 of 82 | 2 of 87 | 0 of 83 | 2 of 85 | 0 of 78 |
| Nausea | Gastrointestinal disorders | 1 of 82 | 1 of 87 | 1 of 83 | 2 of 85 | 0 of 78 |
The serious adverse event results list zero affected participants in each of the five groups: tolperisone 50 mg, 100 mg, 150 mg, 200 mg, and placebo. The deaths count is also zero in each group. These are the registry’s reported counts; they do not establish that serious harms are impossible or that the groups have identical safety profiles.
Zero reported serious adverse events means none were recorded in the registry results for the listed groups during the reporting period. For uncommon events, a zero count in a trial does not rule out the possibility of events in a larger population or over a different period of observation. The registry record does not provide event definitions, exposure duration for the safety analysis, or details about how events were collected and adjudicated.
The record separately lists other affected-participant counts of 7, 13, 12, 14, and 5 for the tolperisone 50 mg, 100 mg, 150 mg, 200 mg, and placebo groups, respectively. Those figures are not serious adverse event counts. The registry does not provide the terms for the most common serious events, and no serious-event terms are listed. These summaries should be read as descriptive counts, not as a definitive comparison of safety between groups.
12. What the Result Does, and Does Not, Mean
The registry record documents a randomized, double-blind, placebo-controlled study of four tolperisone dose regimens in subjects with acute back pain associated with muscle spasm. It reports group means and 95% confidence intervals for a subject-rated pain outcome, alongside serious adverse event counts. These are useful descriptive elements of the trial record, but they do not constitute a complete comparative analysis.
The posted means range from -3.5 for placebo to -4.4 for tolperisone 200 mg, with confidence intervals that extend across negative and positive values. Because the registry does not explain the precise calculation of “mean effect size” and does not post dose-versus-placebo contrasts, the numbers cannot independently establish a comparative treatment effect. They also cannot establish that the dose regimens are equivalent or that one is preferable to another.
The absence of posted analyses is important. There are no reported p-values, contrast estimates, or adjusted results for the primary question, and no secondary outcome results are listed. Therefore, the record does not show whether any observed differences between group means are compatible with chance variation under a specified statistical model. Nor does it report whether a result met a prespecified threshold for clinical importance.
The serious adverse event counts are zero in every group, and the deaths counts are zero. These observations describe the trial’s reported safety data; they do not rule out rare events or resolve safety questions beyond the trial’s recorded experience. Details about safety definitions, observation, and collection are not reported in the registry record.
The appropriate conclusion is narrow: the registry presents group-level outcome summaries and safety counts, but leaves key elements of the comparative statistical analysis unreported. The record alone does not establish whether tolperisone differs from placebo on the primary pain outcome. This is a statement about the limits of the posted evidence, not medical advice or a judgment about treatment use.
13. Why This Trial Matters Statistically
This trial is statistically notable for its dose-ranging structure. It compares four tolperisone regimens with placebo, while the primary outcome is a continuous, subject-rated pain measure. Dose-ranging designs can be used to examine whether outcome patterns vary across dose levels, but such an interpretation depends on prespecified comparisons or a clearly described dose-response analysis. Neither is reported in the registry record.
The posted group summaries illustrate why within-group estimates and between-group effects should be distinguished. The means and confidence intervals describe each group, while the primary clinical question concerns comparison with placebo. Without the contrast estimates and their uncertainty, readers cannot use the group summaries to determine whether any apparent differences support a treatment effect or a dose trend.
The record also highlights the importance of clear endpoint definitions. A mean effect size is reported for a numerical pain scale, but the calculation is not fully described. Knowing whether an estimate reflects change from baseline or an endpoint value is necessary to interpret its direction and clinical meaning. Precise outcome definitions help make results reproducible and suitable for synthesis with other evidence.
Finally, the registry reports no analyses, no secondary outcome results, and no details on missing data or multiplicity. Those omissions limit the statistical conclusions that can be drawn, even though the trial design and group summaries are available. For clinical researchers, this is a reminder that trial registration data are most informative when outcome definitions, analysis populations, comparison estimates, and uncertainty measures are reported together.
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 most important trial-specific limitation is that the registry does not post the statistical comparisons needed to answer the stated primary question. It reports a mean and 95% confidence interval for each group, but no treatment-versus-placebo estimate, p-value, or adjusted analysis. Group summaries alone cannot establish the size or precision of a comparative effect.
The endpoint is not fully defined. The record identifies a mean effect size in subject-rated pain and specifies a Numerical Rating Scale and assessment timing, but it does not clarify the exact calculation behind the mean. It also does not report baseline outcome summaries. These gaps make the direction and interpretation of the posted values less certain.
The registry record does not report standard deviations, the method used to calculate confidence intervals, the analysis population, handling of missing observations, or sensitivity analyses. It also does not describe the treatment of multiple dose comparisons. These omissions prevent independent reproduction of the analysis and make it difficult to evaluate assumptions or robustness.
Although enrollment is listed as 415, the record does not provide a participant flow account explaining the relationship between enrollment and the group denominators reported for the outcome. It does not report adherence, withdrawals, or reasons for missing outcome data. Safety results are also limited to counts, without detailed event definitions or collection procedures. These limitations concern what the registry record documents; they do not establish that the underlying trial lacked additional analyses or procedures.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Tolperisone in Acute Muscle Spasm of the Back — NCT03802565.
- Registry record last updated 2022-02-01; status last verified 2022-01.
- Results first posted 2020-11-10.
- 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.
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18. Record Summary
The registry record describes a completed phase 2, randomized, double-blind, parallel-group study of tolperisone for acute back pain associated with muscle spasm. It lists four tolperisone regimens, each administered three times a day, and a placebo group administered three times a day. Enrollment is reported as 415.
The primary outcome concerns mean effect size in subject-rated pain on a Numerical Rating Scale from 0 to 10, with a Day 14 “right now” assessment and a Day 1 to Day 14 timeframe. Group means and 95% confidence intervals are reported, but no comparative analyses are posted. The registry also reports zero serious adverse events and zero deaths in each group, along with other affected-participant counts.
Key statistical details—including the outcome calculation, analysis population, missing-data methods, and multiplicity approach—are not reported in the registry record. The available results therefore support a descriptive account of the group summaries, but not a definitive statistical conclusion about differences between tolperisone and placebo.