Study of SPM 962 in Patients With Restless Legs Syndrome (RLS): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of SPM 962 in Patients With Restless Legs Syndrome (RLS) (NCT01084551), a randomized phase 3 study. The primary outcome is International Restless Legs Syndrome Rating Scale (IRLS) Total Score.

2. Clinical Question

The registry describes a phase 3 study of once-daily repeated dosing, with a 13-week dose-titration and maintenance period. It identifies the primary endpoint as change in IRLS total score and lists several additional measures concerning global impressions, sleep quality, individual IRLS items, and RLS symptom frequency and duration. The available primary outcome summaries show mean changes for each arm and unadjusted comparisons with placebo. They do not, by themselves, establish the full analysis plan or the basis for the trial’s original design.

3. Trial Design

This was a randomized, phase 3, multicenter, placebo-controlled, double-blind, three-arm parallel-group study sponsored by Otsuka Pharmaceutical Co., Ltd. The registry lists quadruple masking. The study began in 2010-02, reached primary completion in 2011-09, and is recorded as completed. Enrollment was 284 participants with idiopathic restless legs syndrome.

The three groups were placebo, SPM 962 4.5, and SPM 962 6.75. The 4.5 dose group started at 2.25 mg/day and titrated to 4.5 mg/day; the 6.75 dose group started at 2.25 mg/day and titrated to 6.75 mg/day. The listed treatment period was 13 weeks, and the primary endpoint timeframe runs from baseline to the end of dose-titration and dose-maintenance at week 13.

For the primary outcome, the registry reports 95 participants in the placebo group, 93 in the 4.5 group, and 94 in the 6.75 group. These are the arm counts attached to the posted outcome summaries, while the primary analysis population is described as the full analysis set with LOCF. The registry record does not report the detailed randomization procedure, allocation concealment, or the original sample-size justification. It also does not report the protocol’s planned statistical model, interim analyses, or a complete statistical analysis plan. Although the study is described as double-blind in its official title and quadruple-masked in the registry fields, the specific roles covered by the masking designation 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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full analysis set (FAS), last observation carried forward (LOCF)

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.

6. Primary Endpoint

The registry lists the primary outcome as International Restless Legs Syndrome Rating Scale (IRLS) Total Score, measured over Baseline, the end of dose-titration/dose-maintenance period (week 13).

The primary endpoint is the change in total score on the International Restless Legs Syndrome Rating Scale (IRLS) from baseline to the end of the dose-titration and dose-maintenance period at week 13. The registry describes IRLS as a ten-question measure of restless legs syndrome symptom severity. Each item is scored from 4 for the first, usually very severe, response to 0 for the last, usually none; the total is the sum of the item scores. The stated score categories are mild (1-10), moderate (11-20), severe (21-30), and very severe (31-40). A decrease in score means improvement.

Change from baseline expresses how the score differs at follow-up from each participant’s starting measurement. Comparing mean changes across randomized groups helps distinguish the average change during the study from the change observed under placebo. The endpoint is a continuous score, so its group summaries are means with standard deviations. The registry identifies the primary analysis population as the full analysis set and says missing observations were handled using last observation carried forward. Details of the precise analysis model, any adjustment for baseline values, and how other protocol decisions were incorporated are not reported in the registry record.

7. Results Posted in the Registry

• SPM 962 4.5: mean -14.30 versus -11.60 on control; difference -2.70 (95% CI -5.15 to -0.25), standardized effect d = -0.32; z-test p = 0.031.
• SPM 962 6.75: mean -14.60 versus -11.60 on control; difference -3.00 (95% CI -5.46 to -0.54), standardized effect d = -0.35; z-test p = 0.017.

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.

The Pittsburgh Sleep Quality Index (PSQI)

• 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 deviations.
• Result:
  • SPM 962 4.5: mean -3.10 versus -2.50 on control; difference -0.60 (95% CI -1.41 to 0.21), standardized effect d = -0.21; z-test p = 0.147.
  • SPM 962 6.75: mean -3.20 versus -2.50 on control; difference -0.70 (95% CI -1.54 to 0.14), standardized effect d = -0.24; z-test p = 0.101.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between SPM 962 4.5 and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between SPM 962 6.75 and the control. The interval gives the range of effects that remain compatible with the data.

Average Duration of RLS Symptoms

• 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 deviations.
• Result:
  • SPM 962 4.5: mean -3.70 versus -3.10 on control; difference -0.60 (95% CI -2.20 to 1.00), standardized effect d = -0.13; z-test p = 0.463.
  • SPM 962 6.75: mean -4.30 versus -3.10 on control; difference -1.20 (95% CI -2.80 to 0.40), standardized effect d = -0.26; z-test p = 0.141.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between SPM 962 4.5 and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between SPM 962 6.75 and the control. The interval gives the range of effects that remain compatible with the data.

Average Duration of RLS Symptoms in the Evening and Night in a Week

• 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 deviations.
• Result:
  • SPM 962 4.5: mean -1.80 versus -1.30 on control; difference -0.50 (95% CI -1.47 to 0.47), standardized effect d = -0.18; z-test p = 0.314.
  • SPM 962 6.75: mean -1.50 versus -1.30 on control; difference -0.20 (95% CI -1.17 to 0.77), standardized effect d = -0.07; z-test p = 0.686.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between SPM 962 4.5 and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between SPM 962 6.75 and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists several secondary domains: global impressions from clinicians and participants, sleep quality, individual IRLS items, symptom incidence, and duration of symptoms, including evening and night measures. It posts summaries for some continuous outcomes, including sleep quality and symptom duration, but the available record does not contain reported analyses for every listed secondary measure. The broad pattern across the posted continuous summaries is that average scores or durations decreased in all arms on the outcomes where changes are presented. The registry’s secondary outcome summaries do not show a uniform pattern of clearly separated active-dose groups across measures.

These outcomes can add context to the primary IRLS result, because they examine related aspects of perceived improvement, sleep, and symptom burden. They are not substitutes for the primary measure, and agreement across related outcomes would not independently establish a treatment effect. The primary result is the prespecified main focus described in the study objective; the secondary measures are additional questions and should be interpreted as supportive or exploratory unless the complete protocol indicates otherwise. The registry record does not report the planned status of each secondary analysis or a testing hierarchy.

Unadjusted secondary comparisons carry less inferential weight when several outcomes and dose comparisons are examined. Multiple testing raises the chance that some results may appear notable by chance, particularly when no adjustment or hierarchy is reported. Also, the posted secondary summaries have varying group counts across measures. That variation means the results may reflect different analyzed subsets, and the registry does not explain all reasons for those differing counts. Individual secondary results should therefore be read in context rather than treated as independent confirmation of the primary findings.

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

• Clinical Global Impression (CGI) Improvement
• Patient Global Impression (PGI) Improvement
• The Pittsburgh Sleep Quality Index (PSQI)
• Each Item of IRLS (10 Items)
• Incidence of RLS Symptoms
• Average Duration of RLS Symptoms
• Incidence of RLS Symptoms in the Evening and Night
• Average Duration of RLS Symptoms in the Evening and Night in a Week

9. Statistical Interpretation

10. Statistical Methods Explained

Randomization assigns participants to study groups by chance, aiming to make the groups comparable on average at the start of a trial. In this study, participants were assigned among placebo and two SPM 962 dose groups. The registry identifies the allocation as randomized, but does not report the random sequence method or allocation concealment. Masking is intended to reduce the influence of expectations on care, measurement, and reporting. The registry lists quadruple masking; the official title describes the trial as double blind. Which people were masked is not reported in the registry record.

What does a mean change represent?

The primary outcome is continuous: each participant has an IRLS total score at baseline and at week 13, and the outcome is the change between those scores. A group mean change is the average change among participants included in that arm’s summary. It does not imply that each participant changed by that amount. The standard deviation describes the spread of individual values around the group mean; it is not the uncertainty in the mean itself. The posted IRLS results use means and standard deviations and identify the analysis population as the full analysis set with last observation carried forward.

How should the group differences be read?

The mean difference compares an active-dose group’s average change with the placebo group’s average change. For the primary comparisons, the estimates are -2.7 for SPM 962 4.5 versus placebo and -3.0 for SPM 962 6.75 versus placebo. With change expressed as follow-up minus baseline, a negative difference means the active group had a more negative average change than placebo. That is a description of the posted averages and is not, by itself, a conclusion about clinical importance or causation beyond the randomized comparison.

The reported unadjusted p-values are 0.031 and 0.017 for the two primary comparisons. A p-value describes how compatible the observed comparison is with a null model of no group difference, under the assumptions of the test used. It is not the probability that the null hypothesis is true, nor does it measure the size or importance of the estimated difference. The registry does not report the sponsor’s comparative analysis method or a complete statistical plan. The p-values associated with the recalculated comparisons therefore should not be mistaken for documented sponsor-reported tests.

Why do confidence intervals matter?

A confidence interval communicates uncertainty around an estimated group difference. The primary intervals extend from -5.148 to -0.252 for the 4.5 group comparison and from -5.455 to -0.545 for the 6.75 group comparison. The interval gives a range of values compatible with the data under the method used; it is not a guarantee that the true effect lies inside that particular interval. Both intervals exclude zero, while still spanning a range of possible magnitudes. The registry does not report the method used for its own comparative interval because no sponsor-reported comparison analysis is listed.

What does variability add?

Standard deviations describe participant-to-participant variability in change. The primary outcome standard deviations are 8.2 in placebo, 8.9 in SPM 962 4.5, and 9.0 in SPM 962 6.75. When variability is large relative to a mean difference, estimates are less precise unless the study has enough participants to counterbalance that variability. A mean can therefore summarize the group while masking substantial differences in individual outcomes. General statistical interpretation should consider both the estimated difference and the spread of the observations, rather than relying on a p-value alone.

Some statistical methods also account for over-dispersion, which occurs when data vary more than a model’s assumed distribution allows. It can make standard errors too small if ignored. The primary outcome is a continuous score with standard deviations reported; the registry does not describe an over-dispersion adjustment or a model that would require one. No such adjustment should be inferred from the posted summaries.

What do LOCF and the analysis population imply?

The full analysis set is the population named for the primary endpoint, and LOCF means that the last observed value is carried forward to represent a later value when that later value is missing. This procedure can affect the estimated change because it substitutes an earlier observation for an unobserved endpoint. Its suitability depends on why data are missing and how participant outcomes evolve over time. The registry does not give the amount or pattern of missing primary outcome data, explain the missingness assumptions, or report sensitivity analyses using other approaches. Those omissions limit assessment of how robust the result is to missing-data choices.

Finally, unadjusted comparisons do not account for testing multiple doses and multiple outcomes. When many hypotheses are tested, the chance of at least one apparently notable result can increase. A prespecified testing hierarchy or other multiplicity strategy can address this concern, but the registry record does not report one. The primary endpoint has a defined role in the study objective, but the available record is insufficient to determine the complete planned inferential framework.

11. Confidence Intervals and Precision

For the primary outcome, the recalculated mean difference is -2.7 for SPM 962 4.5 compared with placebo, with a 95% confidence interval from -5.148 to -0.252. The corresponding estimate for SPM 962 6.75 is -3.0, with a 95% confidence interval from -5.455 to -0.545. In both comparisons, the interval lies on the negative side of zero, consistent with a larger mean decrease in the active group than in placebo under the stated direction of subtraction.

These intervals are informative about precision as well as direction. They extend from differences relatively close to zero to larger negative differences, so the exact magnitude is uncertain. An interval is not a range of individual participant outcomes, and it does not show how many participants improved. It represents uncertainty about the estimated group difference under the statistical method used. The registry does not report sponsor-generated comparative intervals or describe the method used to construct these intervals.

Precision is influenced by the amount of variability and the number of observations. The primary outcome standard deviations range from 8.2 to 9.0 across the three groups, while the outcome summaries include 95 placebo participants, 93 in the 4.5 group, and 94 in the 6.75 group. Even with those arm counts, the confidence intervals retain uncertainty about how large the mean differences are. The registry record does not report a clinically important threshold for the IRLS difference, so the interval cannot be classified against such a threshold from this record alone.

Confidence intervals also do not resolve the limitations of the analysis population, LOCF handling, or unreported multiplicity plan. They describe sampling uncertainty within the calculation; they do not account for every potential source of bias or uncertainty in the trial.

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 planning figures express the number of participants per arm for comparisons between two groups. They are planning illustrations calculated from the observed effect, not the trial’s original design justification. The registry does not report the trial’s original sample-size assumptions. The planning assumptions used for these illustrations are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the target effect is the stated fraction of the observed effect. These are planning calculations, not observed power.

The 80% power column gives the approximate participants per arm for a hypothetical study designed to have an 80% chance of detecting the specified effect under those assumptions, if that effect and the model assumptions were correct. The 90% power column gives the corresponding approximate number for a 90% chance. These figures concern a future planning scenario and do not change the interpretation of the participants enrolled in this completed trial.

Rows for planning at 100%, 75%, or 50% of the observed effect describe progressively smaller effects to detect. Smaller effects are harder to distinguish from random variation, so they require more participants per arm under otherwise unchanged assumptions. These figures do not incorporate an allowance for attrition, a multiplicity adjustment, or other design features unless those are explicitly included in the listed assumptions; the registry does not report such original-design details. Results for secondary outcomes have their own observed estimates and variability, so their planning illustrations should not be treated as interchangeable with those for the primary outcome.

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 = -2.700; pooled standard deviation σ = 8.553.
2. n = 2 × (1.96 + 0.842)² × 8.553² / -2.700² = 157.5, rounded up to 158 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 <- -2.7                      # observed difference in means
sigma <- 8.55339962595519                     # 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(1084551)
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 = 158 (80% power), 211 (90% power)
 75% of observed effect: n per arm = 281 (80% power), 375 (90% power)
 50% of observed effect: n per arm = 631 (80% power), 844 (90% power)
power.t.test: 158.5 
Simulated power at n = 158 per arm: 0.805 (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. Multiplicity, Missing Data and Analysis Populations

The study has two active-dose comparisons against placebo for the primary endpoint, as well as a set of secondary outcomes. Each additional comparison creates another opportunity for a result to appear statistically notable by chance. A multiplicity strategy can control the overall type I error rate, for example through a prespecified hierarchy or an adjustment across tests. The registry record does not report a multiplicity procedure, a testing hierarchy, or whether the listed p-values were adjusted. The reported comparative p-values are unadjusted, so they should not be interpreted as if an adjustment had been made.

The registry describes the primary population as the full analysis set and identifies last observation carried forward for missing values. LOCF substitutes a participant’s last available observation for a missing later value. The registry does not report how many primary endpoint values were missing, when missingness occurred, why data were missing, or whether the same approach was used for every secondary measure. It also does not report sensitivity analyses using alternative missing-data assumptions. The effect of LOCF on the results therefore cannot be assessed from this record alone.

Although outcome counts are posted by arm, the registry record does not give a participant flow accounting for enrollment, discontinuation, and analysis inclusion in sufficient detail to reconstruct all analysis populations. It does not report a per-protocol population or define other analysis sets beyond the primary full analysis set. The record also does not report interim analyses, the planned statistical model, baseline covariate adjustment, or the original sample-size justification. These gaps do not change the posted arm summaries, but they limit evaluation of whether the displayed comparisons fully reflect the intended analysis plan and how sensitive the conclusions are to analytic choices.

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 3% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: contusion (1.1%), traffic accident (1.1%), lacunar infarction (1.1%), viith nerve paralysis (1.1%).

The registry lists serious adverse events affecting 2 participants at risk in the placebo group, 0 in the SPM 962 4.5 group, and 1 in the SPM 962 6.75 group. It also lists other adverse events affecting 32, 72, and 77 participants at risk, respectively. These are separate categories in the record; the “other” counts should not be interpreted as serious events. Death counts are not reported in the registry record.

The serious-event counts are small, so they provide limited precision for comparing groups. The record lists Contusion, Traffic Accident, Lacunar Infarction, and VIIth Nerve Paralysis among the serious event terms, each at 1.1%. It does not assign those listed terms to specific arms in the posted summary. These data describe recorded events during the trial, but do not establish whether an event was caused by treatment. Differences in event counts should be interpreted cautiously, particularly without fuller information about event definitions, follow-up, and participant-level detail.

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

The posted primary outcome summaries show mean decreases in IRLS total score in the placebo and both SPM 962 dose groups through week 13. The recalculated unadjusted comparisons estimate a greater average decrease in each active-dose group than in placebo, and both 95% confidence intervals exclude zero. Those findings describe the observed group averages and the uncertainty of the unadjusted estimates; they do not indicate that every participant had a decrease or that the effect was identical for all participants.

The result does not, on its own, establish clinical importance. The registry describes the IRLS scale and its severity categories but does not report a threshold for a clinically important between-group difference. A statistically notable unadjusted comparison cannot answer that question without an appropriate clinical benchmark. The estimates also should not be read independently of the unreported multiplicity plan, missing-data details, or full statistical analysis plan.

The trial compares randomized groups over a 13-week treatment period. The record does not provide evidence about outcomes beyond that period. The secondary summaries concern related but distinct outcomes and do not replace the primary endpoint. Likewise, adverse-event counts are descriptive and do not establish causality or provide a complete account of safety.

Overall, the record supports a focused interpretation: average IRLS changes differed between each SPM 962 dose group and placebo in the recalculated unadjusted comparisons, with uncertainty represented by the confidence intervals. The record does not report enough detail to determine the impact of all prespecified analysis choices or to assess long-term outcomes. Statistical results should be kept separate from conclusions about treatment decisions; this trial summary is an account of posted data, not medical advice.

17. Why This Trial Matters Statistically

This trial is statistically useful because it has a randomized, three-arm design with a placebo comparator and a continuous primary outcome measured from baseline to week 13. The two dose groups allow separate comparisons with placebo, while the arm-specific means and standard deviations make the direction of average change and the degree of variability visible. The IRLS score also has an explicit interpretation in the registry: lower scores mean improvement.

The outcome summaries illustrate why within-group change and between-group difference are not the same question. All arms had mean decreases, but the comparative estimates concern how much the active groups’ average changes differed from placebo. The confidence intervals add information about how precisely those differences are estimated; the p-values alone do not communicate magnitude or clinical relevance.

The record also highlights important limits on registry-based interpretation. It identifies the primary analysis population and LOCF method but does not report a complete analysis plan, multiplicity strategy, interim analyses, or original sample-size justification. It lists secondary outcomes without corresponding reported analyses for every measure. These omissions demonstrate why complete methods and participant-flow reporting matter alongside numerical results. Without them, readers can describe the posted comparisons but cannot fully reconstruct the planned inferential framework.

Finally, the sample-size illustrations distinguish future planning from retrospective interpretation. They use observed effects as planning inputs and are not evidence that the completed trial had a particular probability of detecting an effect. Keeping estimation, uncertainty, and study planning separate is central to sound interpretation of clinical trial results.

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.

The registry record contains arm-level summaries but does not provide participant-level data or the sponsor’s reported comparative analyses. The mean differences, confidence intervals, and p-values discussed for the primary endpoint are unadjusted recalculations from posted summary statistics. The record does not report the statistical model, baseline adjustment, or other covariates used in the sponsor’s intended analysis, so the recalculated comparisons may not capture every planned feature.

Missing-data assessment is limited. The primary population is described as the full analysis set with LOCF, but missing counts, reasons for missingness, and sensitivity analyses are not reported. The registry also does not give a complete participant flow or explain why analyzed group counts vary across some secondary outcomes. These details matter when judging how representative the analyzed observations are of all randomized participants.

Several design and analysis details are absent, including the original sample-size justification, multiplicity handling, interim analyses, randomization implementation, and full statistical analysis plan. The record does not report a clinically important IRLS difference, so statistical separation cannot be directly translated into clinical importance using a registry-defined threshold. Secondary outcomes are only partly represented in posted analyses, and the available unadjusted results should not be treated as definitive across the full set of outcomes.

The duration of the posted primary outcome is limited to week 13. Longer-term outcomes are not reported in the registry record. Safety summaries provide event counts but do not include enough detail to establish causality or assess uncommon risks precisely. These limitations constrain what can be concluded from the posted record, even though the randomized design and arm-level outcome summaries remain informative.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Study of SPM 962 in Patients With Restless Legs Syndrome (RLS) — NCT01084551.
• Registry record last updated 2014-06-05; status last verified 2014-05.
• Results first posted 2014-06-05.
• 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

NCT01084551 is a completed phase 3 randomized, placebo-controlled, three-arm parallel-group study of SPM 962 in people with idiopathic restless legs syndrome. Enrollment was 284. Participants received placebo, SPM 962 4.5, or SPM 962 6.75 over a 13-week dose-titration and maintenance period.

The primary endpoint was change in IRLS total score from baseline to week 13; a decrease indicates improvement. Mean changes were -11.6 for placebo, -14.3 for SPM 962 4.5, and -14.6 for SPM 962 6.75. Recalculated unadjusted comparisons estimated mean differences of -2.7 and -3.0 versus placebo, with 95% confidence intervals excluding zero. The registry also lists secondary outcomes and adverse-event counts, but does not report a complete statistical analysis plan, multiplicity approach, or detailed missing-data assessment.