A Study to Assess the Safety, Tolerability and Pharmacokinetics of Multiple Doses of ASP8062 With a Single Dose of Morphine in Recreational Opioid Using Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Assess the Safety, Tolerability and Pharmacokinetics of Multiple Doses of ASP8062 With a Single Dose of Morphine in Recreational Opioid Using Participants (NCT04448561), a randomized phase 1 study. The primary outcome is Number of Participants With Adverse Events (AEs).

2. Clinical Question

3. Trial Design

This was a Phase 1 randomized, double-masked, placebo-controlled, parallel study. It was marked completed. The registry lists enrollment of 24, a start date of 2020-06-30, and primary completion on 2020-09-11. The design included four listed safety groups: ASP8062, ASP8062 in combination with morphine, placebo, and placebo in combination with morphine.

In the ASP8062 regimen, participants took an oral tablet once daily on days 1 through 10. In the combination regimen, a single oral morphine tablet was taken immediately after the day 10 ASP8062 dose. The placebo combination followed the same stated schedule, using matching placebo before the single morphine dose. These descriptions establish the timing and treatment components recorded for the groups; they do not establish that every group was compared with every other group in a formal analysis.

Randomization is intended to assign participants to treatment groups using a chance-based process, while masking is intended to limit knowledge of assignment during the trial. The registry record does not report the randomization procedure, allocation ratio, or who was masked. It identifies a parallel model but does not provide further details about the conduct of allocation.

The primary purpose was safety and tolerability assessment. Secondary outcomes covered plasma pharmacokinetics, including AUC and maximum concentration measures for ASP8062, morphine, and morphine-3β-D-glucuronide. Numeric pharmacokinetic results and detailed analysis methods are not reported in the information available for this explanation. The registry record does not report a sample-size justification or a protocol-level statistical analysis plan.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: Eligible participants were randomized to ASP8062 or placebo using 2:1 ratio according to the randomization schedule. Participants who met the inclusion criteria and met none of the exclusion criteria were enrolled. A total of 54 participants were screened, out of which 30 participants failed screening.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis population was the SAF, which consisted of all participants randomly assigned to investigational product (ASP8062 or placebo) and who took at least 1 dose of investigational product (ASP8062 or placebo).

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: Randomized: All participants who were randomized.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Adverse Events (AEs), measured over From first dose of study drug up to end of study visit (up to day 25).

The primary outcome is the number of participants with adverse events. An adverse event was defined broadly: it included an abnormality identified during a medical test when it caused clinical signs or symptoms, required active intervention, interrupted or stopped study drug, or was clinically significant. Examples of tests named in the registry include laboratory tests, vital signs, and electrocardiograms.

The stated primary-outcome timeframe runs from the first study-drug dose through the end-of-study visit, up to day 25. The registry separately defines a treatment-emergent adverse event as one that began or worsened after the first dose and up to 30 days after the last dose. These are not identical descriptions of a time window, so they should not be treated as interchangeable. The registry record does not explain how this difference was handled in the reported primary analysis.

Counting participants with events is useful in a safety study because it describes how many participants experienced an event, rather than counting repeated events as if each arose in a different person. It can summarize the occurrence of harm during a stated observation period. However, a participant count alone does not describe event severity, duration, or whether an event was considered related to treatment. The registry’s definition of serious adverse events specifies qualifying consequences such as life-threatening events or hospitalization. The posted safety figures separate serious events from other adverse events, but do not provide a single combined primary-outcome result or an inferential comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a participant count as the primary safety outcome and gives group-level counts for serious and other adverse events. It does not report the statistical test or model used for a primary comparison. The explanations below describe general principles for reading this kind of outcome; they are not claims about methods used in this trial unless explicitly stated in the registry record.

What does a participant count represent?

For a binary safety outcome, each participant is classified according to whether the outcome occurred during the defined observation period. A count of participants with an event is distinct from a count of all event episodes: one participant can experience more than one event, but a participant-level count records that person as having experienced the outcome. The registry’s primary outcome is framed as the number of participants with adverse events. Its posted safety summary separates serious events from other adverse events. The record does not clarify whether a participant could appear in both categories, so the category counts should not be combined.

Counts are most interpretable alongside the group at risk and a clear time window. The safety summary reports an at-risk count for each listed group. The primary-outcome timeframe is through the end-of-study visit, up to day 25, while the treatment-emergent definition extends to 30 days after the last dose. Because these descriptions differ, the record’s precise rule for assigning events to the primary outcome is not clear from the information available.

Why is randomization relevant?

In general, random assignment aims to make treatment groups comparable, on average, with respect to measured and unmeasured characteristics at the start of a trial. This supports a causal comparison when participants are analyzed according to an appropriate plan and follow-up is handled consistently. Randomization does not guarantee that groups will look identical, particularly in a small study. The registry labels this trial randomized, but does not report the allocation procedure or the planned primary comparison. The record therefore supports describing the design as randomized without specifying details that are not reported.

What does masking contribute?

In general, masking can reduce the influence of expectations on participant reports, clinical decisions, and outcome assessment. The registry labels the study double-masked. It does not identify which roles were masked, how masking was maintained, or whether it was assessed. A double-masked label describes the registered design, but does not on its own establish how masking operated in practice.

How should uncertainty be assessed?

In general, a confidence interval gives a range of values compatible with the data and a stated statistical procedure. Its width communicates precision: a wider interval indicates greater uncertainty about the size of an effect. For a binary outcome, an analysis might compare group risks or use another prespecified measure, but the chosen measure and its interval must be reported to interpret the result. The registry record does not report confidence intervals or an inferential comparison for the adverse-event counts. Counts alone do not show the precision of a between-group difference.

In general, a p-value addresses how compatible data are with a specified null model under the assumptions of a test. It does not measure the probability that a treatment is effective, and it does not convey the size or clinical importance of an effect. No p-value for the primary adverse-event comparison is reported in the information. It would be inappropriate to infer statistical significance from the counts or from a visual difference between them.

Why can small groups produce uncertain estimates?

In general, estimates based on limited participant counts can vary substantially from one sample to another. A count of zero serious events is still compatible with uncertainty about the underlying event risk; the observed zero is not a guarantee of zero risk. Precision depends on the amount of information and the analysis method, and is best conveyed with an appropriate interval. No interval for the serious-event counts is reported in the registry information.

What do pharmacokinetic outcomes add?

The registry lists AUC and maximum plasma concentration outcomes for ASP8062, morphine, and morphine-3β-D-glucuronide. In general, AUC summarizes drug concentration over a specified time span, while maximum concentration describes the highest measured concentration in the sampling profile. Such measures can inform pharmacokinetic comparisons, but their interpretation depends on the sampling schedule, analysis population, transformations, and comparison method. These details and numeric estimates are not reported in the information available for this explanation. No conclusion about interaction magnitude should be drawn from outcome labels alone.

How should planning estimates be read?

In general, a sample-size calculation is a planning exercise based on assumptions about the effect to detect, variability, significance level, allocation, and analysis. It is not an observed result and should not be described as observed power. The registry record gives assumptions for a planning illustration, including a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects expressed as fractions of an observed effect. Numerical planning estimates are not reported in the information. The registry also does not report its own sample-size justification, so the illustration assumptions should not be mistaken for the trial’s original design rationale.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary adverse-event outcome and a range of secondary pharmacokinetic outcomes for ASP8062, morphine, and morphine-3β-D-glucuronide. Multiple outcomes and potential group comparisons raise a general multiplicity issue: when many hypotheses are tested, the chance of at least one apparently unusual result can increase. In general, a prespecified analysis plan may identify primary comparisons or define an adjustment approach. The registry record does not report whether multiplicity was addressed, which outcomes were included in any family of tests, or whether adjustments were made. This is not evidence that no adjustment was used; the information is not reported in the registry record.

The record does not report a missing-data method for the primary outcome or the pharmacokinetic outcomes. For adverse-event counts, missing follow-up can matter if participants differ in how long they were observed or if event recording is incomplete. The stated safety population includes participants assigned to ASP8062 or placebo who took at least one dose. The record does not provide a participant flow, reasons for withdrawal, or the number with complete outcome data for each analysis. The relationship between the stated enrollment and the four listed at-risk counts is also not explained.

Analysis populations can affect interpretation because they define which participants contribute to a result. The registry explicitly describes a safety analysis population, but the information available does not specify the analysis population used for each pharmacokinetic outcome or whether the primary analysis followed another population definition. It also does not report an intention-to-treat analysis, per-protocol analysis, or sensitivity analysis. These missing details limit assessment of how exclusions, incomplete observations, and multiple outcomes may have influenced the posted results.

11. 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 0% reporting threshold.

Most frequent non-serious adverse event terms

Serious adverse events are defined in the registry by specified consequences, including death, a life-threatening event, persistent or significant disability or incapacity, substantial disruption of normal life functions, congenital anomaly or birth defect, or inpatient hospitalization or prolonged hospitalization. The safety summary reports zero serious adverse events in the ASP8062 group, zero in the ASP8062-with-morphine group, zero in the placebo group, and zero in the placebo-with-morphine group. It also reports zero deaths in each listed group.

The reported counts for other adverse events are 7 among 16 at risk with ASP8062, 11 among 15 at risk with ASP8062 and morphine, 3 among 8 at risk with placebo, and 7 among 8 at risk with placebo and morphine. These are participant counts in the registry’s categories. They are not event rates calculated here, and the categories should not be added: the record does not state whether participants could be counted in both serious and other categories.

Zero serious events is a description of what was recorded, not proof that a regimen has no serious-event risk. The record does not provide confidence intervals or a formal comparison for these figures. The number of events in a trial of this size can be insufficient to estimate uncommon risks precisely. The counts should be interpreted as safety observations during the recorded study, not as a complete account of risk outside the trial.

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

The registry describes a randomized, double-masked, placebo-controlled Phase 1 study focused on safety, tolerability, and pharmacokinetics of ASP8062, alone and with a single morphine dose. Its posted safety summary reports no serious adverse events and no deaths in any of the four listed groups. It also reports other adverse-event participant counts that vary across the groups. These registry entries describe the recorded observations; they do not by themselves establish that one regimen is safer or less safe than another.

The primary endpoint is framed as the number of participants with adverse events, but the available record does not give a single combined primary endpoint result, a formal comparison, or uncertainty estimates. The listed serious and other adverse-event categories are not enough to reconstruct a primary analysis because the registry does not say whether the categories overlap or how the primary outcome was derived from them. No comparative conclusion should be inferred from the raw counts alone.

The trial’s stated scope is also important. It studied recreational opioid-using participants and lists opioid use disorder as a condition. The registry information does not provide detailed demographic or clinical characteristics, and the findings should not be assumed to represent populations not described by the record. The follow-up window is limited to the stated study period and event definitions. It does not establish long-term safety.

The registry lists pharmacokinetic outcomes but does not report numeric estimates in the information available for this explanation. Consequently, it does not support a quantitative conclusion about how ASP8062 affected morphine exposure or how morphine affected ASP8062 exposure. The outcome names alone do not reveal the direction, size, or precision of any pharmacokinetic result.

In short, the record provides descriptive safety counts and identifies pharmacokinetic questions, but does not report enough inferential or numeric detail to establish treatment differences, equivalence, or the absence of risk. The results should be read within the limits of the recorded groups, outcome definitions, and follow-up.

13. Why This Trial Matters Statistically

This trial illustrates why the design and the analysis need to be read together. Randomization and double masking are relevant features for reducing bias in treatment comparisons, while the parallel structure and placebo regimens provide a framework for assessing the study’s safety questions. At the same time, a design label does not substitute for the actual analysis details: the registry record does not report the primary comparison, the statistical test, or uncertainty estimates for adverse-event outcomes.

The study also separates two kinds of questions. Safety outcomes count participants with adverse events, whereas pharmacokinetic outcomes describe drug exposure using measures such as AUC and maximum concentration. These outcome types require different interpretations. Safety counts describe event occurrence over a stated period; pharmacokinetic measures require concentration data, sampling details, and a defined comparison. The record lists both aims, but the available numeric results are limited to safety counts.

The four listed regimens make it especially important not to assume a single contrast. ASP8062 alone and placebo alone are listed, as are ASP8062 with morphine and placebo with morphine. A direct comparison within a pair could address a different question from comparing combination and non-combination regimens. The registry record does not identify a single primary contrast, so the counts should remain descriptive rather than being treated as a factorial or pairwise analysis.

Finally, the reported absence of serious adverse events demonstrates the distinction between observed data and certainty about risk. A zero count is an observation in the trial, not proof of zero underlying risk. Clear reporting of analysis populations, follow-up, uncertainty, and planned comparisons is essential for readers to judge how much can be learned from small safety datasets. Those details are not reported in the registry information.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record leaves several trial-specific uncertainties. It identifies the primary endpoint as the number of participants with adverse events, but the available safety results separate serious and other adverse-event counts without giving a single primary-outcome result. The record does not explain whether these categories overlap, how the primary endpoint was derived, or which comparison was intended to address the primary question.

There is a difference between the primary outcome timeframe, which runs through the end-of-study visit up to day 25, and the definition of treatment-emergent adverse events, which extends to 30 days after the last dose. The record does not explain how these time windows relate in the analysis. This limits exact interpretation of which events are represented in the primary outcome count.

The safety summary lists at-risk counts for four groups, while enrollment is recorded as 24. The registry information does not reconcile those figures or describe participant flow. It is therefore not possible to determine from these details alone how the group counts relate to the enrollment figure. The record also does not report missing-data handling, reasons for withdrawals, or the number included in each pharmacokinetic analysis.

Further limitations are the absence of reported confidence intervals, p-values, a formal adverse-event comparison, numeric pharmacokinetic estimates, and the statistical analysis plan. The record does not report the randomization procedure, allocation ratio, or the roles covered by double masking. These details matter for evaluating the precision and conduct of the analyses, but should not be inferred from the design labels. The listed planning assumptions do not supply a sample-size justification for the trial, and numerical planning estimates are not reported in the information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Assess the Safety, Tolerability and Pharmacokinetics of Multiple Doses of ASP8062 With a Single Dose of Morphine in Recreational Opioid Using Participants — NCT04448561.
• Registry record last updated 2024-11-21; status last verified 2024-10.
• Results first posted 2021-09-29.
• 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.

18. Record Summary

NCT04448561 is a completed Phase 1 randomized, double-masked, placebo-controlled, parallel study sponsored by Astellas Pharma Global Development, Inc. The registry lists enrollment of 24, a start date of 2020-06-30, and primary completion on 2020-09-11. The study assessed multiple doses of ASP8062 or placebo, alone and in combination with a single dose of morphine, in recreational opioid-using participants.

The primary outcome was the number of participants with adverse events. The posted safety counts report zero serious adverse events and zero deaths in each listed group, alongside separate counts for other adverse events. Secondary outcomes concerned plasma pharmacokinetics of ASP8062, morphine, and morphine-3β-D-glucuronide. Numeric pharmacokinetic findings, inferential comparisons for the primary outcome, confidence intervals, and the detailed statistical analysis plan are not reported in the registry information.