Memantine-enhanced Buprenorphine Treatment for Opioid-dependent Young Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Memantine-enhanced Buprenorphine Treatment for Opioid-dependent Young Adults (NCT01052662), a randomized phase 2, phase 3 study. The primary outcome is Change of Opioid Use From Week 1 to 13.

2. Clinical Question

The study was designed to examine opioid-abusing behavior, early relapse, and tolerability when memantine is combined with buprenorphine. Its stated aim also includes evaluating whether the combination might offer shorter-term treatment for opioid dependence. Those aims describe the study’s motivation, not conclusions established by the posted outcome statistics.

The central statistical comparison in the posted arm results is between memantine 30mg/day plus buprenorphine and each of the other two groups. The registry reports mean differences of 0.27 for the 15mg/day group and 0.39 for the 0mg/day group, relative to the 30mg/day group. Because the outcome is a proportion of opioid use, these values describe differences on the outcome scale; they are not percentages or relative effects.

The clinical question should be read alongside the outcome definition and analysis details. The primary outcome description combines reported days of use and positive urine results into a weekly measure. The registry does not report enough information to establish how missing weekly measurements were handled, how the endpoint was represented in the reported model, or how the planned analyses treated multiple comparisons.

3. Trial Design

This was a randomized, quadruple-masked, parallel-group study listed in phases 2 and 3. The registry reports enrollment of 87, a start date of 2009-10, primary completion in 2013-06, and a completed status. The sponsor was University of Massachusetts, Worcester.

The three listed groups received memantine 30mg/day plus buprenorphine, memantine 15mg/day plus buprenorphine, or memantine 0mg/day plus buprenorphine. The 0mg/day group is the placebo condition. Posted outcome group sizes are 27, 24, and 29, respectively. The registry describes the primary analysis population as 80 subjects intent-to-treat; it does not explain the relationship between that analysis population and the enrollment or the group sizes in the posted outcome results.

For all groups, the arm descriptions say participants were inducted onto buprenorphine/naloxone sublingual tablets during the first week. The dose was titrated from 8mg to 16mg over three days and remained at 16mg until the last day of week 8. Each description then mentions a 7-day discontinuation of buprenorphine-naloxone, but the text ends after the word “week”; the timing and any further protocol details are not reported in the registry record.

The primary outcome was assessed weekly from week 1 to 13. The registry also lists treatment retention as a secondary outcome. It reports three outcome measures and three analyses, but does not report a full protocol or a complete analysis plan. Original sample-size assumptions, the reason for the selected enrollment, and whether any interim analyses were planned are not reported in the registry record.

Randomization, masking, and the parallel-group structure describe the intended comparison framework. The record does not give further details about the randomization procedure or the people covered by quadruple masking. Such details should not be inferred from the design labels alone.

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: 229 individuals of the 354 persons who were interested in the study were assessed not eligible to participate. Of the 125 subjects that were screen over one week, only 87 subjects meet criteria for study participation. Reason for exclusion included: declined (N=22), psychiatric (N=6), other SUD (N=6), abnormal labs (N=3) and medical reason (N=1)

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 80 subjects intent-to-treat.

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: Intent-to-treat sample

6. Primary Endpoint

The registry lists the primary outcome as Change of Opioid Use From Week 1 to 13, measured over Weekly from week 1 to 13.

The primary outcome is titled “Change of Opioid Use From Week 1 to 13.” Its unit is the mean proportion of opioid use in week 13, and the registry describes the outcome as a change from baseline in the mean proportion of weekly opioid use. Weekly use was assessed using the time-line follow-back method, based on self-reported days of use and/or a positive urine drug screen during the previous week.

The registry description says each positive urine result counted as 1, as did each self-reported day of use. Each participant’s total was divided by 8, and the group mean was calculated by averaging participant proportions. Thus the endpoint expresses opioid use as a continuous proportion-based measure rather than as a simple yes-or-no event. The registry does not explain in the posted description why the divisor was 8.

Repeated weekly measurement can characterize the pattern of use over time and provides a basis for assessing changes across the study period. The outcome description covers weekly measurements from week 1 to 13. The arm results, however, give a mean proportion for week 13, while the sponsor’s reported analysis is a mixed models analysis of slope. These are related descriptions of the study’s repeated outcome, but the registry does not report enough detail to reconstruct the precise model or the contrast that generated the slope.

A continuous outcome can retain differences in degree of reported use that would be lost if observations were reduced to categories. Its interpretation depends on the scoring rules, measurement completeness, and handling of repeated observations. Further detail on those aspects is not reported in the registry record.

7. Results Posted in the Registry

• Memantine 15mg/Day + Buprenorphine: mean 0.27 versus 0.00 on control; difference 0.27 (95% CI 0.07 to 0.47), standardized effect d = 0.80; z-test p = 0.007.
• Memantine 0mg/Day + Buprenorphine: mean 0.39 versus 0.00 on control; difference 0.39 (95% CI 0.12 to 0.66), standardized effect d = 0.72; z-test p = 0.005.

8. Statistical Interpretation

9. Statistical Methods Explained

The registry contains a sponsor-reported longitudinal analysis and posted group summaries that allow simple unadjusted comparisons. These answer related but distinct statistical questions. Keeping them separate helps prevent the week 13 summaries from being mistaken for the sponsor’s model result.

What does a mean summarize?

The endpoint is continuous: it is a mean proportion of opioid use. A group mean combines the participant-level proportions into one average. It can describe the overall level in a group, but it does not show how values are distributed among participants. The same mean could arise from a relatively similar set of individual values or from more varied values. The registry reports standard errors for the arm means, but does not report the individual-level distribution in the outcome summary.

The proportion is constructed from self-reported days and urine drug screen results, with the registry stating that a positive urine and each self-reported day each counted as 1. A participant’s total was divided by 8. This definition is essential to interpretation: the result is a score based on those components, not a direct count of all days in the study period. The registry does not explain the divisor or describe how overlapping self-report and urine results were handled.

What does the standard error describe?

A standard error describes the precision of an estimated mean under a statistical model; it is not the spread of individual participant observations. Smaller standard errors generally indicate a more precisely estimated mean, while larger standard errors indicate more uncertainty in the estimate. The posted standard error for the 30mg/day group is 0.0. That value is reported as posted and should not be read as proof that every participant had the same outcome or that the mean is known without uncertainty. The registry does not explain why that standard error is zero.

The posted results give no arm-level confidence intervals around the means. The recalculated comparisons include confidence intervals for differences, which describe uncertainty around those particular unadjusted contrasts. Neither kind of interval resolves uncertainties about measurement, missing observations, or the analysis plan.

How do the unadjusted comparisons work?

A mean difference is the difference between two group means on the endpoint’s scale. The recalculated comparisons use the 30mg/day group as the reference and compare it separately with the 15mg/day and 0mg/day groups. They are unadjusted comparisons based on the posted summary statistics. They do not incorporate covariates or the full pattern of weekly observations through a repeated-measures model.

For the 15mg/day comparison, the posted means are 0.0 and 0.27, and the recalculated difference is 0.27. Its confidence interval ranges from 0.074 to 0.466. For the 0mg/day comparison, the posted means are 0.0 and 0.39, and the recalculated difference is 0.39. The p-values for these comparisons are unadjusted. They should not be treated as though they were adjusted for all outcomes, group contrasts, or model choices.

A confidence interval gives a range of values reasonably compatible with the data and the calculation’s assumptions. A narrower interval indicates greater precision than a wider interval, but precision is not the same as freedom from bias. The intervals pertain to the simple recalculated mean differences, not to the sponsor’s mixed-model slope.

Why use a mixed model for repeated measurements?

Repeated weekly measurements from the same participant are usually correlated: a participant’s measurements over time are not independent observations. A mixed model can represent this repeated structure and estimate a pattern such as change over time while accounting for within-participant dependence. The registry identifies the sponsor’s method as “Mixed Models Analysis” and the parameter as “Slope.” It reports a slope of -0.009 and a p-value of 0.009.

Those labels alone do not specify the model. The registry record does not report the precise fixed effects, random effects, covariance structure, coding of time or group, adjustment variables, or handling of missing weekly measurements. It also does not report a confidence interval for the slope. The slope’s sign and p-value should therefore be described as reported, without assuming a more detailed model interpretation than the record supports.

Why can over-dispersion matter?

In general, over-dispersion means that observed variability is greater than a statistical model expects. When that occurs, standard errors from a model that assumes less variability can be too small, making uncertainty look narrower than it is. This is a general statistical consideration, not a finding about this study. The registry does not report a diagnostic for over-dispersion or identify a model for which it was assessed, so no conclusion about over-dispersion in this trial is warranted.

What does a p-value add?

In general, a p-value measures how surprising data at least as incompatible with a specified null model would be if that model and its assumptions were true. It is not the probability that the null hypothesis is true, the probability that a finding is due to chance, or a measure of clinical importance. The recalculated p-values address individual unadjusted mean comparisons. The sponsor-reported p-value accompanies a different, longitudinal slope analysis. Because the registry does not report the full analysis plan or multiplicity approach, neither type of p-value alone gives a complete account of evidential strength.

Finally, statistical methods rely on assumptions about data collection and analysis. The posted description does not establish how missing outcome data were treated or whether all randomized participants were included in each analysis. Those details matter when interpreting both estimates and their uncertainty.

10. Confidence Intervals and Precision

The recalculated difference for memantine 15mg/day plus buprenorphine versus memantine 30mg/day plus buprenorphine is 0.27, with a confidence interval from 0.074 to 0.466. The interval lies above zero, so the posted summary statistics are compatible with a positive difference on the stated scale under the assumptions of this unadjusted calculation. It also indicates that the estimated difference is not known with exact precision. The interval is for the difference between group means, not for either group mean separately.

For the comparison of memantine 0mg/day plus buprenorphine with the 30mg/day group, the recalculated difference is 0.39. Its reported confidence interval has a lower and upper endpoint, and the lower endpoint is above zero; the exact lower endpoint is not repeated because the registry reports more than three decimal places. This interval also concerns the unadjusted difference in week 13 means, not the sponsor’s slope estimate.

Confidence intervals describe uncertainty in an estimate under the assumptions used to calculate them. They do not account automatically for missing observations, selection effects, measurement error, or choices among multiple outcomes and comparisons. The registry does not report a confidence interval for the sponsor-reported slope, and it does not give confidence intervals for the individual arm means.

Precision should also be considered in relation to the posted standard errors: 0.0 for the 30mg/day group, 0.1 for the 15mg/day group, and 0.14 for the 0mg/day group. In particular, a standard error reported as 0.0 does not mean uncertainty is absent. The registry does not explain how that value arose or provide additional details that would resolve the issue.

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 event counts. The calculation is an illustration based on the observed effect, not the trial’s original design assumptions. It uses a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. For the displayed scenarios, the effect to detect is set to the stated fraction of the observed effect. The original trial’s own sample-size assumptions are not reported in the registry record.

The 80% power column describes the number of participants per arm that the planning calculation estimates would be needed to have an 80% chance of detecting the specified effect under the calculation’s assumptions. The 90% power column uses a higher target chance of detection, so it gives a larger planning count for the same effect scenario. These are planning illustrations and are not observed power.

The rows describe planning for the full observed effect, 75% of the observed effect, and 50% of the observed effect. For the comparison of 15mg/day with 30mg/day, the 80% planning figures are 25, 44, and 98 participants per arm across those scenarios; the corresponding 90% figures are 33, 58, and 130. For the comparison of 0mg/day with 30mg/day, the 80% figures are 31, 55, and 122 participants per arm, and the 90% figures are 41, 73, and 163.

The pattern illustrates a general planning principle: smaller effects are harder to distinguish from random variation and therefore need more participants for a given power target. These counts depend on the assumed effect and calculation method. They do not show the power achieved by the completed trial, and they should not be treated as a replacement for the trial’s original design rationale, which is not reported in the registry record.

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 = 0.270; pooled standard deviation σ = 0.336.
2. n = 2 × (1.96 + 0.842)² × 0.336² / 0.270² = 24.3, rounded up to 25 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 0.27                      # observed difference in means
sigma <- 0.335638289270592                     # 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(1052662)
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 = 25 (80% power), 33 (90% power)
 75% of observed effect: n per arm = 44 (80% power), 58 (90% power)
 50% of observed effect: n per arm = 98 (80% power), 130 (90% power)
power.t.test: 25.3 
Simulated power at n = 25 per arm: 0.794 (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. Analyses Reported by the Sponsor

The sponsor’s reported result is a mixed models analysis of slope across the three groups. The registry reports a slope of -0.009 and a p-value of 0.009, without a confidence interval or a detailed model specification. This is the sponsor’s own analysis of the repeated outcome and should be distinguished from the recalculated comparisons of the week 13 group means.

The recalculated comparisons are simple, unadjusted differences based on the posted arm summaries. They compare each of the 15mg/day and 0mg/day groups with the 30mg/day group at week 13. They do not reproduce the sponsor’s longitudinal model, which uses repeated weekly measurements and reports a slope parameter. The two analyses therefore need not have the same estimate or answer precisely the same question.

The registry does not report a discrepancy between the sponsor analysis and the recalculated summaries. Even so, the recalculation is supplementary and does not replace the sponsor’s analysis. Details needed to reproduce the mixed model—including its specification, missing-data handling, and exact contrast—are not reported in the registry record. The sponsor’s result should be presented as reported, while the recalculated differences should be understood as descriptive, unadjusted comparisons of the posted summaries.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures and three analyses. It identifies change in opioid use as the primary outcome and treatment retention as a secondary outcome, but the titles or definitions of all posted measures and analyses are not available in the record. A prespecified hierarchy of outcomes, an adjustment for multiple testing, or a strategy for choosing among comparisons is not reported in the registry record.

Multiplicity matters when researchers examine several outcomes, time points, groups, or model contrasts. In general, the more statistical tests considered, the greater the chance that at least one result may appear notable by chance alone if each is interpreted without accounting for the testing strategy. This is a general statistical issue, not proof that the reported findings are false. The unadjusted p-values for the two recalculated mean comparisons should be read as individual comparisons rather than as multiplicity-adjusted evidence.

The sponsor’s mixed-model p-value concerns the reported slope analysis. The registry does not say whether that was the sole primary inferential test, how it related to the stated week 13 endpoint, or whether any other analyses were designated in advance. Interim analyses and stopping rules are not reported in the registry record.

The primary outcome description refers to an intent-to-treat population of 80 subjects. However, the registry does not explain how the intent-to-treat population was defined, whether all randomized participants were included, or how participants without a week 13 measurement were handled. It does not describe imputation, likelihood-based handling of incomplete repeated measurements, sensitivity analyses, or reasons for missingness. These details are important because missing outcomes can affect both the estimated group means and the validity of model-based inferences.

The posted group sizes for the outcome results are 27, 24, and 29. The record does not explain how those group-specific figures relate to the stated intent-to-treat population or whether the same analysis population was used for all comparisons. Attrition, protocol deviations, adherence, and the handling of participants who discontinued treatment are not sufficiently described in the registry record. These reporting gaps limit assessment of whether the analyses preserved the benefits of randomization and how robust the results are to incomplete data.

15. 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.

Most frequent non-serious adverse event terms

The registry’s serious adverse event summary reports zero affected participants in each of the three groups: memantine 30mg/day plus buprenorphine, memantine 15mg/day plus buprenorphine, and memantine 0mg/day plus buprenorphine. The reported numbers at risk for this summary are 27, 24, and 29, respectively. No serious adverse event terms are listed.

Other adverse events are reported separately. The record lists 18 affected participants in the 30mg/day group, 15 in the 15mg/day group, and 23 in the 0mg/day group. These figures are not serious adverse events and should not be conflated with the serious-event counts. The registry does not provide the event terms in the registry record for these results.

Zero serious adverse events reported in a group does not establish that no serious event occurred outside the reporting framework or that a treatment is free of risk. It is a registry count within the posted safety summary. The record does not report deaths, so death counts cannot be interpreted from these results. Further detail on event definitions, timing, severity, relatedness, or statistical comparison is not reported in the registry record.

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

The results describe week 13 opioid-use means that are lower in the 30mg/day memantine group than in the 15mg/day and 0mg/day groups. The recalculated differences quantify those contrasts on the mean-proportion scale. The sponsor also reports a longitudinal mixed-model slope, but the model details and confidence interval are not reported. These findings are summaries of the posted data and analyses; they do not by themselves establish that one treatment caused a change in opioid use.

The trial’s stated aims included examining opioid use, early relapse, tolerability, and the possibility of shorter-term treatment. The posted information does not provide enough detail to draw firm conclusions about all of these aims. Treatment retention is listed as a secondary outcome, but detailed retention results are not included in the registry record for the posted results. The record also does not provide enough information to assess early relapse separately.

The statistical results do not establish clinical importance. The registry does not report a threshold for a clinically meaningful difference, and the outcome scale’s construction includes both self-reported use and urine results. Interpretation depends on the measurement process, the unexplained divisor in the scoring description, and how incomplete observations were handled.

The arm comparisons are unadjusted recalculations from summary statistics, whereas the sponsor’s analysis uses a mixed model and reports a slope. Neither should be confused with the other. The sponsor’s analysis is the appropriate description of the sponsor-reported longitudinal result; the recalculations provide a separate view of the posted week 13 means.

The sample-size illustrations are prospective planning examples based on observed effects, not evidence about how well the completed trial was powered. The record does not report the original sample-size rationale. Safety figures are likewise limited to the posted adverse-event counts and do not establish absence of risk. Overall, the registry supports a description of the reported outcomes and their statistical uncertainty, but leaves important questions about analysis details, missing data, multiplicity, and clinical interpretation unresolved.

17. Why This Trial Matters Statistically

This trial is statistically instructive because it presents the same general outcome in more than one way: group means at week 13 and a sponsor-reported slope from a mixed models analysis. Those summaries are not interchangeable. A single-week comparison describes group levels at that time point, while a longitudinal slope represents a pattern across repeated measurements, subject to the model’s specification.

The outcome itself combines self-reported days of use with urine drug screen results. A continuous proportion can preserve gradations in the measured outcome, but its meaning depends on the scoring rules and how the data are collected. The registry provides some scoring details, including the division by 8, but does not explain that choice or describe how overlapping reports and test results were handled.

The record also illustrates why estimates, uncertainty, and analysis context belong together. The recalculated comparisons have unadjusted p-values and confidence intervals, while the sponsor’s model result has no reported interval in the registry. The record lists multiple outcomes and analyses but no multiplicity plan. The standard error of 0.0 for one arm mean is another reminder that a displayed summary needs context before it can be interpreted as exact or error-free.

Finally, incomplete reporting about the intent-to-treat population and missing weekly outcomes makes it difficult to assess the full analysis. These gaps do not erase the posted results, but they limit what can be concluded from them. The case demonstrates the value of distinguishing a sponsor’s planned or reported inferential analysis from simple recalculations, and of treating planning figures as illustrations rather than evidence about the completed study.

18. 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.

Several limitations are specific to the reporting available for this trial. The arm descriptions are incomplete: each ends after mentioning a 7-day discontinuation of buprenorphine-naloxone on a week that is not specified. The registry therefore does not report the full treatment schedule or the continuation of the protocol descriptions.

The primary outcome description refers to change from baseline, but the posted arm summaries are labeled as mean proportions in week 13. The sponsor analysis is reported as a slope across the groups. The registry does not explain the relationship among these presentations in enough detail to reproduce the primary analysis or determine the precise contrast represented by the slope.

The posted standard error for the 30mg/day group is 0.0. The registry does not explain whether this reflects rounding, an analytic feature, or another issue. Individual participant distributions and arm-level confidence intervals for the means are not reported. The recalculated differences are based on summary statistics and cannot address these reporting uncertainties.

The registry describes an intent-to-treat population of 80 subjects, but does not explain its definition or how it relates to the group sizes reported with the outcome. Missing-data methods, the extent and reasons for missing weekly measurements, adherence, and sensitivity analyses are not reported in the registry record. The original sample-size assumptions, multiplicity plan, detailed model specification, and interim-analysis plan are also not reported.

Finally, the registry’s safety information gives counts of affected participants but does not provide event terms for the other adverse events in the information. Death counts are not reported. These limits mean the posted results should be interpreted as a partial statistical account rather than a complete description of the trial’s conduct, analysis, and safety findings.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Memantine-enhanced Buprenorphine Treatment for Opioid-dependent Young Adults — NCT01052662.
• Registry record last updated 2015-04-01; status last verified 2015-03.
• Results first posted 2015-03-06.
• 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.

22. Record Summary

The registry record describes a completed randomized, quadruple-masked, parallel-group study sponsored by University of Massachusetts, Worcester, with enrollment of 87 and phases 2 and 3 listed. It compared memantine 30mg/day and 15mg/day, each alongside buprenorphine, with memantine 0mg/day plus buprenorphine.

The primary outcome was change in opioid use measured through weekly self-report and urine drug screen information, with an endpoint summary for week 13. Posted means were 0.0, 0.27, and 0.39 across the 30mg/day, 15mg/day, and 0mg/day groups. The sponsor reported a mixed models slope analysis. Unadjusted recalculations compare the week 13 means, but do not replace the sponsor’s analysis.

The record also lists treatment retention as a secondary outcome and reports serious adverse event counts of zero in each group. Important details—including the full analysis plan, missing-data handling, and the original sample-size rationale—are not reported in the registry record.