Efficacy and Safety of Finalgon® Cream Multiple Doses in Acute Low Back Pain: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of Finalgon® Cream Multiple Doses in Acute Low Back Pain (NCT02300311), a randomized phase 3 study. The primary outcome is Pain Intensity Difference (PID) From Pre-dose Baseline to 8h After the First Trial Medication Application (PID8h).

2. Clinical Question

The central statistical comparison is between the groups’ reported adjusted mean pain intensity differences at 8 hours. The endpoint is defined as pain intensity at 8 hours minus pain intensity at baseline, so a negative value represents a lower pain rating at 8 hours than at baseline. The comparison asks whether that change differed between the randomized groups, not whether every participant experienced the group average change.

The record also includes outcomes at 4 hours and over the last individual treatment day, as well as patients’ assessment of efficacy. Those outcomes broaden the description of the trial’s results, but the stated primary question concerns the 8-hour measure. The registry record does not report the original sample-size justification or the plan for handling multiple outcome tests.

3. Trial Design

This was a Phase 3, randomized, double-blind, parallel-group, placebo-controlled study of Finalgon® Cream in acute low back pain. The registry lists Boehringer Ingelheim as sponsor and describes the trial as multinational. Enrollment was 138, with 69 participants listed in each group for the primary outcome. The record lists the trial as completed, with a start in 2015-01 and primary completion in 2015-05.

Participants were assigned to Finalgon® Cream containing 1.08% Nicoboxil and 0.17% Nonivamide or to matching placebo. Both group descriptions give the same regimen: a 2 cm cream line for a skin area of approximately 20 x 20 cm2, up to 3 times in a 24h period. Double masking means that the record describes the study as blinded for two parties; it does not identify those parties in the information.

The primary endpoint was pain intensity difference from pre-dose baseline to 8 hours after the first application. Pain was rated on an 11-point numerical scale from 0, no pain, to 10, worst pain possible. Ratings were scheduled at pre-dose baseline and 0.5, 1, 2, 3, 4, 6 and 8 hours after application. The primary analysis population was the full analysis set, defined as treated patients who contributed any post-treatment data for the primary efficacy endpoint.

The registry record does not report the original sample-size justification, detailed randomization procedures, the full masking procedures, or the study’s prespecified 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.

Before assignment: Multinational, multi-centre, randomised, double-blind, placebo-controlled, parallel group, 2-arm study with a treatment duration of up to 4 days

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full analysis set (FAS): All patients included in the treated set who provide any post-treatment data for the primary efficacy endpoint constituted the full analysis set.

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: Treated set (TS): All randomised patients who used at least one dose of study medication were included in the treated set.

6. Primary Endpoint

The registry lists the primary outcome as Pain Intensity Difference (PID) From Pre-dose Baseline to 8h After the First Trial Medication Application (PID8h), measured over Baseline and 8 hours after trial medication application.

The primary endpoint is Pain Intensity Difference from pre-dose baseline to 8 hours after the first trial medication application, abbreviated in the registry as PID8h. Pain intensity was assessed on an 11-point numerical rating scale, with 0 marked as “no pain” and 10 as “worst pain possible.” Ratings were scheduled at baseline and at 0.5, 1, 2, 3, 4, 6 and 8 hours after application.

The endpoint is calculated as pain intensity at 8 hours minus pain intensity at baseline. Thus, a negative pain intensity difference indicates that the recorded pain rating at 8 hours was lower than the baseline rating. The reported group means are adjusted means. The statistical focus is the difference between the groups, rather than either group’s change considered in isolation.

Using a defined rating scale and a specified assessment time gives a consistent outcome for comparing randomized groups. A continuous score retains the size of the measured change rather than reducing each participant’s experience to a binary category. The registry record does not describe the adjustment variables used to obtain the primary adjusted means, nor does it report a threshold for interpreting a change as clinically important.

7. Results Posted in the Registry

• Finalgon® Cream (Nicoboxil/ Nonivamide): mean -2.82 versus -0.98 on control; difference -1.84 (95% CI -2.44 to -1.24), standardized effect d = -1.02; z-test p = <0.001.

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.

Pain Intensity Difference (PID) From Pre-dose Baseline to 4 Hours After the First Trial Medication Application (PID4h)

• 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:
  • Finalgon® Cream (Nicoboxil/ Nonivamide): mean -2.11 versus -0.77 on control; difference -1.34 (95% CI -1.83 to -0.85), standardized effect d = -0.91; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Finalgon® Cream (Nicoboxil/ Nonivamide) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Difference of Average Pain Intensity (APID) From Pre-dose Baseline on the Last Individual Treatment Day

• 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:
  • Finalgon® Cream (Nicoboxil/ Nonivamide): mean -5.13 versus -2.17 on control; difference -2.96 (95% CI -3.72 to -2.20), standardized effect d = -1.29; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Finalgon® Cream (Nicoboxil/ Nonivamide) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The posted secondary results follow the same broad direction as the primary endpoint: the reported mean changes are more negative in the Finalgon® Cream group than in the placebo group. The registry reports a comparison for pain intensity difference at 4 hours and another for average pain intensity difference on the last individual treatment day. It also lists patient assessment of efficacy as a secondary outcome, but a result for that outcome is not reported in the registry record.

This pattern is supportive in the descriptive sense that more than one pain measure points in the same direction. The secondary outcomes differ in assessment time and definition, however, and should not be treated as interchangeable replications of the primary endpoint. The 4-hour measure is an earlier assessment after the first application, while the average pain measure is defined over the last individual treatment day.

The record reports model-based analyses for the posted secondary outcomes: a repeated-measures approach for the 4-hour endpoint and ANCOVA for the average pain endpoint. It reports p < 0.001 for each of those analyses. The registry record does not say whether these secondary tests were adjusted for testing multiple outcomes or how the listed outcomes were prioritized beyond identifying the primary endpoint.

As a general statistical concern, testing several outcomes creates more opportunities for small p-values to occur by chance if all null hypotheses are true. Unless multiplicity is controlled or the results are treated as exploratory, individual secondary p-values usually carry less confirmatory weight than the prespecified primary analysis. The consistent direction adds context, but it does not resolve that limitation or establish the importance of each secondary finding.

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

• Pain Intensity Difference (PID) From Pre-dose Baseline to 4 Hours After the First Trial Medication Application (PID4h)
• Difference of Average Pain Intensity (APID) From Pre-dose Baseline on the Last Individual Treatment Day
• Patient's Assessment of the Efficacy on the Last Individual Treatment Day

9. Statistical Interpretation

10. Statistical Methods Explained

The primary result comes from a repeated-measures analysis reported by the sponsor. The record also permits a simple recalculation from the posted group means and standard errors. These approaches answer related but not identical questions: the sponsor’s model-based comparison is the reported trial analysis, while the recalculation is an unadjusted comparison of summary statistics.

What does a repeated-measures approach do?

As a general statistical concept, repeated-measures methods analyze observations collected from the same participant at multiple times while accounting for their within-person relationship. Treating every measurement as if it came from a different person would ignore that relationship. The primary outcome includes measurements at several post-application times, and the registry identifies the analysis as a restricted maximum likelihood (REML) based repeated-measures approach. The precise model specification, covariance structure and any covariates are not reported in the registry record.

REML is a general method for estimating variance components in models that include repeated or grouped observations. The registry’s reported primary parameter is a mean difference at the final values. It gives an estimate of -1.849 points, a 95% confidence interval from -2.454 to -1.244, and p < 0.001. The description does not provide enough detail to reconstruct the fitted model from the registry record alone.

What does the simple recalculation represent?

The recalculated comparison uses the posted adjusted group means and their standard errors to obtain an unadjusted mean difference and confidence interval. It is a summary-statistic calculation, not a refit of the sponsor’s repeated-measures model. The recalculated estimate is -1.84 points, with a 95% confidence interval from -2.444 to -1.236 and p <0.001. Small differences from the reported analysis can arise because the calculation and the sponsor’s model use different statistical approaches. The registry’s discrepancy indicator is false.

As a general concept, a standard error describes the estimated uncertainty of a mean, whereas a standard deviation describes variability among individual observations. The primary arm summaries report standard errors of 0.215 and 0.221. These values should not be read as the range of participant-level pain changes.

How should the confidence interval and p-value be read?

As a general explanation, a confidence interval gives a range of effect estimates compatible with the data and the analysis procedure at the stated confidence level. It communicates precision as well as direction. A p-value measures how unusual data at least as incompatible with a specified null model would be if that model were true and the analysis assumptions held. It is not the probability that the null hypothesis is true, nor is it a measure of clinical importance. The registry reports a 95% confidence interval and p < 0.001 for the sponsor’s primary analysis.

The sign of the difference depends on the order used for subtraction. Here, the contrast is Finalgon® Cream relative to placebo. Since the endpoint is post-application pain intensity minus baseline, a negative group difference corresponds to a more negative average change in the Finalgon® Cream group. This direction describes the scale and contrast; it does not by itself make a judgment about the clinical importance of the finding.

How do the secondary methods differ?

The 4-hour pain intensity difference was analyzed using the same REML based repeated-measures approach, according to the registry. The average pain intensity difference on the last individual treatment day was analyzed using ANCOVA. As a general concept, analysis of covariance estimates a group contrast while accounting for one or more covariates. The particular covariates, model form and adjustment details for that endpoint are not reported in the registry record. The registry lists patient assessment of efficacy as a secondary outcome, but no result for that outcome is included among the posted secondary outcomes.

None of these statistical methods removes the need to consider the trial’s population, outcome definition, missing data and multiplicity. The registry record defines the primary full analysis set but does not report detailed missing-data procedures or the approach to controlling error across multiple outcomes.

11. Confidence Intervals and Precision

The sponsor’s primary estimate is a mean difference of -1.849 points, with a 95% confidence interval from -2.454 to -1.244. This interval lies entirely on the negative side of zero, indicating that the reported model estimates a more negative average PID8h in the Finalgon® Cream group than in the placebo group. The width of the interval conveys uncertainty: the analysis is compatible with a range of group differences, not only the point estimate.

As a general statistical explanation, a confidence interval is not a range expected to contain most individual participants’ outcomes. It concerns uncertainty in an estimated population contrast under the analysis procedure. It also does not establish whether every value in the interval is clinically important; the registry record does not report a threshold for clinical importance.

The simple recalculation gives -1.84 points, with a 95% confidence interval from -2.444 to -1.236. Its proximity to the sponsor’s estimate is reassuring about the broad direction and scale of the summary-statistic comparison, but the two intervals come from different approaches and should not be treated as identical analyses. The sponsor’s repeated-measures result remains the registry’s reported analysis.

The arm-level standard errors, 0.215 for placebo and 0.221 for Finalgon® Cream, describe uncertainty in the reported adjusted means. They are not confidence limits for individual observations. The registry does not report arm-level confidence intervals for these means. Precision should therefore be judged primarily from the reported between-group interval and in light of the analysis population and model details that are not fully described in the record.

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 sample-size figures are planning illustrations for a hypothetical two-group study based on fractions of the observed effect. They are participants per arm, not total event counts. The assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is the stated fraction of the observed effect. The original trial’s own design assumptions and sample-size justification are not reported in the registry record.

The 80% power column describes the number of participants per arm that the illustration estimates would be needed for an 80% chance of detecting the specified effect under those planning assumptions, if that effect and the assumptions were correct. The 90% power column describes the corresponding planning target for a 90% chance. Power is a property of a planned design under assumptions; it is not the probability that a particular result is true.

The rows compare planning for 100%, 75% and 50% of the observed effect. A smaller target effect generally requires more participants to distinguish it from no difference with the same power and significance level. The calculated figures are therefore sensitive to the assumed effect size. Because the observed effect comes from this trial, the illustration should not be mistaken for the study’s original design calculation or treated as observed power.

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 = -1.840; pooled standard deviation σ = 1.811.
2. n = 2 × (1.96 + 0.842)² × 1.811² / -1.840² = 15.2, rounded up to 16 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 <- -1.84                      # observed difference in means
sigma <- 1.81101546100523                     # 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(2300311)
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 = 16 (80% power), 21 (90% power)
 75% of observed effect: n per arm = 28 (80% power), 37 (90% power)
 50% of observed effect: n per arm = 61 (80% power), 82 (90% power)
power.t.test: 16.2 
Simulated power at n = 16 per arm: 0.788 (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’s own primary analysis used a REML based repeated-measures approach and reported a mean difference of -1.849 points, with a 95% confidence interval from -2.454 to -1.244 and p < 0.001. A simple recalculation from the posted group summaries gives -1.84 points, with a 95% confidence interval from -2.444 to -1.236 and p <0.001.

The estimates are close in direction and magnitude, but they are not identical because the recalculation is an unadjusted summary-statistic comparison rather than a reproduction of the sponsor’s repeated-measures model. The sponsor’s estimate uses the reported model analysis; the recalculation offers a transparent check based on the group summaries, not a substitute for the prespecified or fitted analysis. The registry record does not provide enough model detail to recreate the sponsor’s result independently.

The record does not flag a discrepancy. The reported and recalculated findings are consistent in indicating a negative between-group contrast for the defined endpoint, while their precision and p-values reflect their respective methods.

15. Multiplicity, Missing Data and Analysis Populations

The registry identifies one primary endpoint, PID8h, and lists secondary outcomes for pain intensity difference at 4 hours, average pain intensity difference on the last individual treatment day, and patient assessment of efficacy on the last individual treatment day. It reports results for the first two secondary outcomes, but a result for patient assessment of efficacy is not reported in the registry record.

The record does not report a multiplicity adjustment, a hierarchy for testing outcomes, or a broader prespecified statistical analysis plan. As a general statistical principle, evaluating several outcomes can increase the chance of at least one apparently strong result when no true effects exist. This is why the primary endpoint is typically given more confirmatory weight, while secondary results are interpreted in the context of how many tests were considered and whether an adjustment or testing hierarchy was used. The missing multiplicity details prevent determining from the record how the secondary p-values should be calibrated for the full set of outcomes.

The primary analysis population is defined as the full analysis set: treated patients who provided any post-treatment data for the primary efficacy endpoint. The registry lists 69 participants per group for the posted primary outcome. It does not report the number excluded from this analysis population, participant-level missingness by assessment time, or how missing outcome values were handled. It also does not report whether any imputation, sensitivity analyses or alternative analysis populations were used.

These gaps matter because the interpretation of an estimate depends partly on who contributed data and how unavailable measurements were treated. The stated full analysis set definition alone does not establish that every randomized participant contributed to the primary analysis. The registry record does not report the original sample-size justification, interim analyses, or further details of the statistical plan.

16. Safety Results

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

Other (non-serious) adverse events

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

The registry lists 69 participants at risk for serious adverse events in each group and records 0 serious adverse events in the placebo group and 0 in the Finalgon® Cream group. It also records 0 for the listed other adverse event counts in each group. These are the counts posted in the registry record for the groups and categories shown; they do not describe the severity, timing or full range of individual symptoms.

The death counts are null for both groups, so deaths are not reported in the registry record. A null entry should not be interpreted as a confirmed count of zero. The registry record also lists no serious adverse event terms. These figures are descriptive counts, not estimates of comparative safety with precise uncertainty, and a count of zero in this record does not establish that an event is impossible.

The trial’s stated objectives included investigating safety and tolerability with repeated use. The adverse-event figures alone do not provide a complete account of safety or establish how comprehensively adverse events were collected. Further safety details are not reported in the registry record.

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

The posted primary analysis estimates a negative difference between the groups in pain intensity change from baseline to 8 hours after the first application. The adjusted group means are -0.98 for placebo and -2.82 for Finalgon® Cream, and the sponsor’s reported mean difference is -1.849 points with a 95% confidence interval from -2.454 to -1.244. In the scale’s defined direction, a negative change means the 8-hour pain rating was lower than the baseline rating on average.

That statistical comparison is an average across the analysis population. It does not imply that every participant experienced the same change, nor does it describe the distribution of individual responses. The registry record does not report a threshold for clinical importance, so the numerical estimate and its precision cannot alone determine how meaningful the difference is to patients.

The randomized, double-blind, placebo-controlled design supports a between-group comparison under the study conditions, but the record does not give detailed information about the participant characteristics, allocation procedures, missing-data handling or model specification. Those limits constrain how completely the result can be assessed and to whom it applies.

The reported statistical evidence does not establish that a treatment works or does not work in a broader clinical sense. It describes the posted measurements and analysis for this trial. The secondary findings generally point in the same direction, but their interpretation is limited by unreported multiplicity procedures, and one listed secondary outcome has no result reported in the registry record. Safety counts are also limited to the posted event categories and do not amount to a complete safety assessment.

18. Why This Trial Matters Statistically

This trial illustrates why the interpretation of a clinical result depends on the endpoint’s definition and the direction of its scale. PID8h is calculated as the 8-hour pain rating minus baseline, so negative values describe a lower rating at the later assessment. Without that definition, the sign of the group difference could be easy to misread.

It also illustrates the distinction between an analysis reported by a sponsor and a simple recalculation from summary statistics. The registry’s repeated-measures analysis uses a model for the endpoint collected over time, while the recalculation compares posted group summaries. Their close estimates offer a useful check on direction and scale, but do not make the methods interchangeable. Model details remain important for reproducibility.

The confidence interval is essential context alongside the p-value. It communicates the range of group differences compatible with the analysis, while the p-value alone does not quantify effect size, clinical relevance or the probability that a hypothesis is true. The absent clinical-importance threshold makes it especially important not to equate statistical evidence with patient importance.

Finally, the record makes the limits of registry reporting visible. Multiplicity handling, missing-data procedures, original design assumptions and details of the analysis plan are not reported. These omissions do not erase the posted result, but they qualify how much can be concluded from the result alone. The trial therefore offers a clear example of reading an endpoint estimate together with its analysis method, uncertainty and reporting context.

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 registry record does not report the original sample-size justification or the assumptions used to plan the trial. Planning illustrations based on the observed effect cannot reconstruct those original decisions. The record also does not describe any interim analyses or provide a full statistical analysis plan.

Although the sponsor identifies the primary method as a REML based repeated-measures approach, the model specification, covariance structure and covariates are not reported. The adjustment variables used for the posted adjusted means are also not described. The secondary average-pain analysis is identified as ANCOVA, but its covariates and detailed model specification are not reported.

Missing-data handling is another limitation. The primary population definition requires treated participants to have some post-treatment data, but the registry does not report the number excluded, missingness at individual assessment times, or any imputation or sensitivity analyses. The listed enrollment and outcome group sizes do not resolve how incomplete data were handled.

The registry record does not report whether multiplicity was controlled across the secondary outcomes, and a result for patient assessment of efficacy is not reported. It also does not report a clinically important difference threshold, participant-level distributions, or details sufficient to assess the generalizability of the findings beyond the population described as having acute low back pain. Safety reporting is limited to the posted adverse-event counts; death counts are not reported in the registry record.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Efficacy and Safety of Finalgon® Cream Multiple Doses in Acute Low Back Pain — NCT02300311.
• Registry record last updated 2016-09-13; status last verified 2016-07.
• Results first posted 2016-09-13.
• 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

The registry describes a completed Phase 3, randomized, double-blind, parallel-group, placebo-controlled trial of Finalgon® Cream for acute low back pain. Enrollment was 138, with 69 participants listed in each group for the primary outcome. The record lists a start in 2015-01 and primary completion in 2015-05, and names Boehringer Ingelheim as sponsor.

The primary endpoint was pain intensity difference from pre-dose baseline to 8 hours after the first application, on a scale from 0 (no pain) to 10 (worst pain possible). The sponsor’s repeated-measures analysis reported a mean difference of -1.849 points, with a 95% confidence interval from -2.454 to -1.244 and p < 0.001.

The registry also reports secondary pain outcomes, lists zero serious adverse events in both groups, and does not report death counts. The record does not report detailed missing-data procedures, multiplicity handling, the original sample-size justification, or a clinically important difference threshold.