A Study to Assess the Analgesic Efficacy and Safety of ASP8062 in Subjects With Fibromyalgia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Assess the Analgesic Efficacy and Safety of ASP8062 in Subjects With Fibromyalgia (NCT03092726), a randomized phase 2 study. The primary outcome is Change From Baseline to Week 8 in Mean Daily Average Pain Score as Assessed by Numerical Rating Scale (NRS).

2. Clinical Question

3. Trial Design

This was a Phase 2a, randomized, double-blind, placebo-controlled, parallel-group study of ASP8062 in participants with fibromyalgia. The registry lists 183 enrolled participants and marks the study as completed. The recorded start date is 2017-05-08, and the primary completion date is 2018-03-06. The sponsor was Astellas Pharma Global Development, Inc.

Participants in the ASP8062 arm received 30 mg orally once daily for 8 weeks. Participants in the comparison arm received matching placebo on the same daily schedule and for the same duration. The registry record describes double masking but does not report which study roles were masked or the procedures used to maintain masking. It also does not report the randomization ratio, the method used to generate the allocation sequence, or the details of allocation concealment.

The primary outcome was change from baseline to week 8 in mean daily average pain score on the NRS. The analysis population was the full analysis set, defined in the registry as randomized participants who received at least one dose of study drug; participants with available baseline data were included. The registry reports a sponsor analysis using a mixed model for repeated measures (MMRM).

Secondary outcomes included the proportions of participants with at least 30% and at least 50% reductions in average pain score, changes in the FIQR function, symptoms and overall impact subscales, and participant improvement measured by the Patient Global Impression of Change. The registry lists 10 outcome measures and 21 analyses. The original sample-size justification and the trial’s prespecified statistical analysis plan 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.

Before assignment: Participants underwent a screening period (up to 42 days), where washout of medications and a 7-day baseline diary run-in were completed. Participants were randomized (1:1 ratio) after confirmation of eligibility (which also required a mean daily average pain score of ≥ 4 and ≤ 9 \[per Daily Average Pain Numerical Rating Scale\] to enter the study).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis population was the full analysis set (FAS), which consisted of all randomized participants who took at least 1 dose of study drug. Participants with available data at baseline were included in the analysis.

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: The analysis population was the safety analysis set (SAF), which consisted of all randomized participants who took at least 1 dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline to Week 8 in Mean Daily Average Pain Score as Assessed by Numerical Rating Scale (NRS), measured over Baseline and week 8.

The primary endpoint was change from baseline to week 8 in mean daily average pain score, measured with the Numerical Rating Scale. Participants recorded daily average pain in an electronic diary. The question asked about pain over the last 24 hours and used an 11-point scale, anchored at 0 for “no pain” and 10 for “pain as bad as you can imagine.” The registry describes the endpoint as a continuous measure and reports least-squares means with standard errors for the treatment arms.

Change scores put the week-8 measurement in relation to each participant’s baseline measurement. In the registry’s definition, a negative change indicates a reduction in pain and is considered favorable. The primary comparison is between the average changes for ASP8062 and placebo, rather than a comparison of the endpoint scores alone.

Daily recording is intended to capture participants’ reported pain over the stated recall period. The endpoint therefore represents a participant-reported measure, not an objective test of pain. The registry record does not report the minimum clinically important difference or another threshold for interpreting the size of the change. Statistical uncertainty and the comparison with placebo must be considered alongside the arm means; the endpoint alone does not establish the clinical importance of a difference.

7. Results Posted in the Registry

• ASP8062: mean -1.36 versus -1.42 on control; difference 0.06 (95% CI -0.47 to 0.59), standardized effect d = 0.03; z-test p = 0.823.

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports least-squares means for the primary endpoint and an MMRM comparison between ASP8062 and placebo. Least-squares means are model-based estimates of group means. They can account for features specified in the fitted model, but the registry record does not report the full model specification, including its covariates, covariance structure or other implementation details. The reported estimate is therefore best described as the sponsor’s MMRM result, without inferring undocumented details of how it was fitted.

What does an MMRM do?

In general, a mixed model for repeated measures analyzes measurements collected at multiple times while accounting for their relationship within a participant. This can use the pattern of available observations rather than reducing every participant to a single change value. The model’s estimates and standard errors depend on the chosen model and assumptions about the data. The registry reports MMRM for the primary comparison, but its assumptions and handling of missing measurements are not reported in the registry record. It is therefore not possible to assess from the record alone whether those assumptions were examined or whether alternative analyses were conducted.

What is the treatment difference?

The reported contrast is the ASP8062 least-squares mean minus the placebo least-squares mean. The estimate of 0.06 is on the endpoint’s scale. Since the endpoint is change from baseline and negative changes indicate reductions, the positive contrast means that the estimated change for ASP8062 was numerically less negative than the estimate for placebo. This describes the direction of the reported contrast; it does not determine whether the difference is clinically meaningful.

The recalculation uses the posted arm summaries: means of -1.42 and -1.36, standard errors of 0.19 in each arm, and the posted group sizes. It produces the same point estimate, 0.06, but a different interval and p-value from the MMRM analysis. The recalculation uses an approximate pooled standard deviation, reported as 1.819, and a standardized effect size of 0.033. These are unadjusted summary-statistic calculations, not estimates from the sponsor’s repeated-measures model. The approximate standard deviation and simplified calculation mean that they should not be treated as a substitute for the registry’s primary analysis.

How should a p-value be read?

In general, a p-value describes how unusual the observed data, or data more extreme, would be under a specified null hypothesis and statistical model. It is not the probability that the null hypothesis is true, and it does not quantify the probability that the result arose by chance in a broad, model-free sense. The sponsor-reported p-value is 0.590; the unadjusted recalculated p-value is 0.823. The different methods and assumptions account for why these values need not match. Neither value gives the size of the effect or establishes clinical importance.

Why report an interval as well?

In general, a confidence interval displays a range of effect estimates compatible with the observed data under the chosen analysis procedure. It communicates both the estimated direction and the uncertainty in the estimate. The sponsor’s 90% interval runs from -0.38 to 0.50. Because it spans zero, it is compatible with a contrast in either direction, including no difference. The registry also posts the recalculated interval from -0.467 to 0.587; that unadjusted interval is not the sponsor’s MMRM interval. The confidence level for the recalculated interval is not separately stated in the registry entries.

Why can repeated-measures methods matter?

General statistical reasoning: repeated observations from the same participant tend to be related, so treating each observation as if it came from an unrelated participant can misrepresent uncertainty. An MMRM is one way to model that within-participant structure. Its usefulness depends on appropriate specification and assumptions. The posted information identifies the method but does not give enough detail to independently evaluate the model specification, diagnostics or missing-data assumptions. No particular model limitation or violation can be inferred from the registry record.

Overall, the MMRM is the registry’s reported analysis, and the summary-statistic recalculation offers a simpler, unadjusted perspective. They answer the same broad comparison using different methods. The MMRM result should be interpreted as the sponsor-reported model-based estimate, while the recalculation should be understood as an approximate check rather than a replacement analysis.

10. Confidence Intervals and Precision

The sponsor-reported treatment difference is 0.06, with a 90% confidence interval from -0.38 to 0.50. This interval is relatively broad around the point estimate and includes zero. It is compatible with an ASP8062-minus-placebo contrast that is negative, zero or positive within the stated limits. As a result, the point estimate alone gives an incomplete picture: the interval conveys substantial uncertainty about the direction and size of the difference.

In general, a confidence interval is a range produced by a statistical procedure that, under its assumptions, would cover the target parameter at its stated confidence level over repeated applications. It is not a range containing a specified probability that the fixed treatment effect lies inside it. The 90% level applies to the sponsor-reported interval. The registry also posts an unadjusted recalculated interval from -0.467 to 0.587; it should not be confused with the sponsor’s MMRM interval, and the confidence level for that recalculated interval is not reported in the registry record.

The estimated changes in the two arms are close, but precision is not judged only by whether the point estimates look similar. The uncertainty interval and the analysis method matter. The registry does not report a clinically important difference threshold, so the bounds cannot be classified as excluding all clinically meaningful differences. It also does not report the original sample-size justification or the intended precision target. The result therefore supports a cautious reading: the estimated contrast is small, but the posted interval does not pin down its direction or practical importance.

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 events. They are planning illustrations computed from the observed effect, not the trial’s original design assumptions. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the arms, a normal approximation, and an effect to detect set at the stated fraction of the observed effect. The original design assumptions and sample-size justification are not reported in the registry record.

The 80% power column gives the planned number of participants per arm for a design with an 80% chance of detecting the chosen effect under the stated assumptions, if that effect is the true one and the model assumptions hold. The 90% power column describes the corresponding planning target for a 90% chance. These are prospective design calculations, not evidence about the probability that the completed study detected an effect or about whether a treatment effect exists.

For planning for 100% of the observed effect, the illustration gives 14,425 participants per arm for 80% power and 19,311 participants per arm for 90% power. For planning for 75% of the observed effect, it gives 25,644 participants per arm for 80% power and 34,330 participants per arm for 90% power. For planning for 50% of the observed effect, it gives 57,699 participants per arm for 80% power and 77,243 participants per arm for 90% power. Smaller effects require more participants to achieve the same planned power, all else equal.

This is not observed power. The figures depend strongly on the observed effect used as their starting point, and the observed estimate is uncertain. They should be read as illustrations under the stated assumptions, not as a recommendation or as a reconstruction of the study’s original plan.

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 = 0.060; pooled standard deviation σ = 1.819.
2. n = 2 × (1.96 + 0.842)² × 1.819² / 0.060² = 14,424.7, rounded up to 14,425 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 <- 0.0599999999999998                      # observed difference in means
sigma <- 1.81880083134146                     # 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(3092726)
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 = 14,425 (80% power), 19,311 (90% power)
 75% of observed effect: n per arm = 25,644 (80% power), 34,330 (90% power)
 50% of observed effect: n per arm = 57,699 (80% power), 77,243 (90% power)
power.t.test: 14425.6 
Simulated power at n = 14,425 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.

13. Analyses Reported by the Sponsor

The registry’s own primary analysis is the sponsor-reported MMRM result: a least-squares mean difference of 0.06, a 90% confidence interval from -0.38 to 0.50, and p = 0.590. This is the model-based analysis reported for the trial’s primary endpoint.

The unadjusted recalculation from arm summaries also gives a difference of 0.06, but its interval is -0.467 to 0.587 and its p-value is 0.823. It uses an approximate pooled standard deviation and does not reproduce the repeated-measures model. Differences between the interval and p-value are therefore expected when methods and assumptions differ. The registry does not flag a discrepancy. The recalculation is best treated as a supplementary check; it does not supersede or validate all aspects of the sponsor’s model-based analysis.

Both analyses produce an interval that includes zero, but they are not interchangeable. The sponsor-reported result is the relevant result for describing the registry’s stated analysis, while the recalculation illustrates what follows from a simpler, unadjusted use of the posted summaries. The detailed model specification and analysis plan are not reported in the registry record, limiting independent reconstruction.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists secondary outcomes covering pain reductions of at least 30% and at least 50%, FIQR function, symptoms and overall impact subscales, and participant improvement measured by PGIC. It also records 10 outcome measures and 21 analyses. Considering multiple outcomes, time points or analyses can increase the chance that at least one result appears notable even when there is no underlying effect. Statistical approaches such as prespecifying a primary comparison or adjusting for multiple tests can address some of this issue, but the appropriate approach depends on the trial’s intended claims.

The registry entries available for this analysis do not report whether the sponsor adjusted for multiplicity, which secondary analyses were confirmatory, or how the primary endpoint was prioritized among analyses. No adjustment method should be inferred. The reported primary result can be described as the sponsor’s MMRM analysis, but the record does not establish how its p-value fits into a wider testing strategy.

The registry defines the full analysis set as randomized participants who took at least one dose of study drug, with participants who had baseline data included in the primary analysis. It does not report the number of participants with endpoint data at each assessment, the amount or pattern of missingness, reasons for missing observations, or the method used to handle missing outcome data. Although an MMRM is reported, that label alone does not establish the specific missing-data assumptions or show whether those assumptions are suitable. Sensitivity analyses for missing data are not reported in the registry record.

The registry also does not report the full protocol, the complete statistical analysis plan, prespecified covariates, interim analyses, or the original sample-size justification. These absences limit assessment of whether all analyses followed the intended plan and how robust the findings are to alternative choices. They do not demonstrate that any particular analysis was omitted or that a particular bias occurred; they mean that these issues cannot be assessed from the reported details.

15. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent non-serious adverse event terms

The registry reports zero serious adverse events affecting participants in the placebo group and zero in the ASP8062 30 mg group. It also reports zero deaths in each group. These are the posted counts; they do not establish that no event of any kind occurred during the study.

For other adverse events, the registry reports 17 affected in the placebo group and 38 affected in the ASP8062 group. These are counts as recorded in the registry, not rates calculated. The registry entries do not provide event-term detail for these other adverse events, their severity, the number of events per participant, or the assessment of whether events were related to treatment. No serious adverse event terms are listed in the record.

Safety counts are descriptive and should be interpreted in light of the study’s size and duration, which was 8 weeks of assigned treatment. The registry does not report enough detail to compare event types, timing or clinical importance. The figures alone do not establish a causal relationship between treatment assignment and any adverse event.

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

The posted primary result is an estimated ASP8062-minus-placebo difference of 0.06 in change from baseline to week 8 in mean daily average pain score. The sponsor’s MMRM analysis gives a 90% confidence interval from -0.38 to 0.50 and p = 0.590. The interval crosses zero, so the data do not clearly distinguish the estimated contrast from no difference under that analysis. The arm estimates are reductions from baseline, with -1.36 for ASP8062 and -1.42 for placebo.

This result does not show that the treatments are equivalent. Equivalence requires a prespecified margin and an analysis designed to test whether the difference lies within that margin; such a margin is not reported in the registry record. Nor does a non-significant p-value prove that there is no effect. The interval leaves room for differences in either direction, and the record does not provide a threshold for deciding which differences would matter to participants.

The simple recalculation gives the same point estimate but a different interval and p-value because it is an approximate, unadjusted calculation from arm summaries rather than the sponsor’s MMRM. It should not be treated as an independent confirmation of the model’s assumptions or as a replacement for the sponsor analysis.

The study’s secondary outcomes broadened assessment to pain response thresholds, FIQR subscales and participant global impression of change. Their results are not included in the registry record for this analysis, so no conclusion about those outcomes can be drawn. The reported safety counts likewise do not describe event types or establish causation. Overall, the registry record supports a precise description of the estimated primary contrast and its uncertainty, not a medical recommendation or a claim that ASP8062 works or does not work.

17. Why This Trial Matters Statistically

This trial illustrates why a treatment comparison should be read through both its estimate and its uncertainty. The primary difference is 0.06, but the sponsor-reported 90% confidence interval ranges from -0.38 to 0.50. A point estimate by itself can appear more conclusive than the data warrant; the interval makes clear that the direction and size of the contrast remain uncertain.

It also demonstrates that the same posted arm summaries can support a simple recalculation that differs from the sponsor’s repeated-measures analysis. The recalculated difference matches the sponsor estimate, but its interval and p-value differ. Such recalculations can help readers understand the role of analytical choices, while remaining distinct from the prespecified or sponsor-reported model. The registry does not provide enough detail to reconstruct the MMRM fully.

Planning illustrations based on an observed effect also highlight how sample-size calculations depend on the target effect. The illustrations require increasingly large per-arm numbers when the target is a smaller fraction of the observed effect. That is a general design principle, not evidence that the trial was designed using these assumptions. The original design rationale is not reported in the registry record.

Finally, the registry lists multiple secondary outcomes and analyses, while reporting limited detail on multiplicity and missing-data handling. Those omissions matter because readers need to know how results were selected and how incomplete observations were addressed. Statistical interpretation therefore depends not only on a p-value, but also on design, outcome definitions, model transparency and the limits of the public record.

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 does not report the original sample-size calculation or its assumptions. The planning illustration based on the observed effect cannot reconstruct that design rationale. The randomization ratio, sequence-generation procedure and allocation-concealment details are also not reported, limiting review of those design features.

The sponsor identifies an MMRM analysis, but the available the registry entries do not specify its covariates, covariance structure, model diagnostics or missing-data assumptions. Counts of participants contributing data at each follow-up point and the pattern and reasons for missingness are not reported. The robustness of the estimate to alternative missing-data assumptions therefore cannot be assessed from these registry entries.

The registry lists multiple outcome measures and analyses but does not report a multiplicity strategy or identify which secondary analyses were confirmatory. It does not provide results for the listed secondary outcomes in the registry record used here, so those outcomes cannot be interpreted. A clinical-importance threshold for the primary pain endpoint is also not reported, making it difficult to judge the practical meaning of the confidence-interval bounds.

The study’s treatment period was 8 weeks, so the registry entries do not describe outcomes beyond that duration. The safety information available includes serious-event and death counts and counts for other adverse events, but not event terms, severity, timing or treatment relatedness for the latter. These limitations restrict interpretation; they do not establish that a particular bias, model failure or safety problem occurred.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: A Study to Assess the Analgesic Efficacy and Safety of ASP8062 in Subjects With Fibromyalgia — NCT03092726.
• Registry record last updated 2025-11-03; status last verified 2025-10.
• Results first posted 2019-03-28.
• 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 describes a completed, randomized, double-blind, parallel-group Phase 2a study of ASP8062 versus matching placebo in participants with fibromyalgia. The study enrolled 183 participants. ASP8062 was given as 30 mg orally once daily for 8 weeks; placebo was given on the same schedule.

The primary endpoint was change from baseline to week 8 in mean daily average pain score on the NRS. The sponsor-reported MMRM difference was 0.06, with a 90% confidence interval from -0.38 to 0.50 and p = 0.590. A simple unadjusted recalculation gives the same point estimate but a different interval and p-value.

The registry also lists secondary outcomes concerning pain-response thresholds, FIQR subscales and PGIC. Serious adverse event and death counts were zero in both groups; other adverse events affected 17 in the placebo group and 38 in the ASP8062 group. Important details, including the original sample-size justification, multiplicity approach and missing-data handling, are not reported in the registry record.