Cocaine and Zolmitriptan: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cocaine and Zolmitriptan (NCT05019430), a randomized early/phase 1 study. The primary outcome is Reinforcing Effects of Cocaine.

2. Clinical Question

The scientific rationale described in the registry concerns serotonin signaling and the possibility that zolmitriptan, a selective 5-HT1b agonist, could alter abuse-related effects of cocaine. The trial was designed to examine behavioral responses during controlled inpatient experimental sessions. That context matters: the question is about choices made during those sessions, not about whether participants subsequently stop using cocaine or experience a lasting change in their disorder.

The registry record does not report a formal hypothesis statement or a prespecified direction of effect for the primary endpoint. The posted outcome values can therefore be described by dose-condition entry, but the intended pairwise contrasts and their interpretation are not established by those values alone. The specific dose-to-entry mapping is also not reported in the registry record, limiting attribution of any mean to a named zolmitriptan dose or treatment combination.

3. Trial Design

This is a completed, randomized, triple-masked, crossover study classified as Early Phase 1. The registry reports enrollment of 12 participants and identifies cocaine use disorder as the condition under study. The listed interventions are cocaine, oral placebo capsule, and zolmitriptan. The inpatient design maintained participants on placebo or zolmitriptan, with acute cocaine and placebo administered during the corresponding maintenance periods.

The registry describes a placebo maintenance condition and three zolmitriptan dose conditions. The primary endpoint description covers experimental sessions over approximately four hours on each session day, generally occurring on Days 5-7, 13-15, 21-23 and 29-31 of inpatient admission. These are the time windows stated for the endpoint; further details about sequence generation, washout periods, treatment order, or the operational conduct of masking are not reported in the registry record.

Because this is a crossover study, participants could contribute outcome observations under more than one condition. The posted primary results list twelve entries titled Dose Condition 1 through Dose Condition 12, with individual sample sizes from 9 to 11. The record does not identify which specific combination of maintenance medication and acute administration corresponds to each entry. Consequently, the entries should not be assigned to named doses or interpreted as a particular ordered comparison without additional documentation.

The primary outcome population is described as subjects completing the dose condition, rather than all enrolled participants. The registry gives no further detail on how completion was defined, whether all participants completed all conditions, or how incomplete sequences were handled. The listed study dates are a start date of 2021-10-15 and a primary completion date of 2025-01-09; the overall status is completed. Recruitment details, site information, and the trial's own sample-size justification 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

Analysis population for the primary outcome, as defined in the registry: Subjects completing the dose condition

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 Reinforcing Effects of Cocaine, measured over Over approximately four hours on each experimental session day, which generally occurred on Days 5-7, 13-15, 21-23 and 29-31 of inpatient admission..

The primary endpoint is the number of times subjects chose cocaine over money, with a maximum of 5 choices. The registry reports the mean and standard deviation for each dose-condition entry. The endpoint is recorded during experimental sessions lasting approximately four hours on each session day, generally on Days 5-7, 13-15, 21-23 and 29-31 of inpatient admission.

This measure is used to characterize cocaine's reinforcing effects in a controlled behavioral task: choosing cocaine rather than an alternative represents a behavioral response under the particular session conditions. It is not a direct count of cocaine use outside the study, nor does it measure longer-term clinical outcomes. The interpretation is therefore specific to the task, the available choices, and the study setting.

Across the twelve posted entries, the reported means range from 0.6 to 4.6 choices, and the standard deviations range from 0.67 to 2.06. The individual entry values and sample sizes are important because the summary statistics describe groups of participants, not each participant's pattern of choices. The registry does not report participant-level observations, confidence intervals, or an inferential analysis for this endpoint. It also does not identify which entry corresponds to each named dose and acute treatment combination, so the endpoint values cannot be assigned to a specific treatment comparison from the labels alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is continuous in the sense that it is summarized using a mean and standard deviation, although the individual outcome is a count of choices with a maximum of 5. The registry lists twelve dose-condition means, each paired with a sample size and standard deviation. Those summaries allow readers to see the level and dispersion of observed choices within each entry, but they do not replace a treatment-effect estimate or an uncertainty interval.

What does a mean describe?

A mean is the average outcome for the participants included in a condition. Here, it represents the average number of times participants chose cocaine over money during the experimental task. A mean can be useful for describing the typical level of choices in a group, but it can conceal variation among participants. Two groups with similar means might still have different distributions of individual responses, and a mean alone does not show whether most participants made similar choices or whether responses were more mixed.

The endpoint has a task-defined upper limit of 5 choices. Because it is a bounded count, its possible values are not unrestricted in the way a measurement such as weight or elapsed time may be. General statistical methods that assume a continuous, normally distributed outcome may not fully represent the discrete and bounded nature of such data, particularly in small samples. The registry does not report the primary analysis method, so it is not possible to determine how the analysis addressed the outcome's scale.

How should the standard deviation be read?

A standard deviation describes how dispersed individual observations are around their mean. Larger values indicate more variation in the observed choices within a condition; smaller values indicate observations closer to the mean. It is not a measure of uncertainty in the mean, and it does not provide a confidence interval for a difference between treatment conditions. To estimate uncertainty for a treatment contrast in a crossover study, the relationship between repeated observations from the same participants can be important. The participant-level paired data and the method used to handle that relationship are not reported in the registry record.

Over-dispersion is a general issue that can arise when outcome variability is greater than a statistical model expects. If a model underestimates variation, its uncertainty estimates can be too small and its inferential results may be misleading. This is a general consideration for count outcomes; the registry record does not report whether over-dispersion was assessed or whether a count model was used. It is also not possible to diagnose over-dispersion from the means and standard deviations alone.

Why do crossover details matter?

In a crossover design, participants may contribute outcomes under multiple conditions. Such observations are related because measurements from the same participant can share characteristics. An analysis that accounts for this within-participant relationship can differ from an analysis treating all condition observations as independent. The registry identifies the study as crossover but does not report the model, the handling of sequence or period, or the assumptions used for the primary analysis. It is therefore not possible to infer whether the reported summaries were accompanied by an analysis that accounted for the design.

The twelve result entries are titled generically as dose conditions, and the registry does not state how each entry maps to the placebo or zolmitriptan maintenance conditions and acute administrations. That mapping is essential for interpreting a contrast as a comparison of particular treatments. The means cannot be reordered or relabeled into a dose-response sequence on the basis of the displayed titles alone.

What does an inferential result add?

An inferential analysis ordinarily estimates a contrast between conditions and describes the uncertainty around that estimate. A confidence interval gives a range of values compatible with the data under the chosen method and assumptions; a wider interval generally indicates less precision. A p-value addresses how compatible the data are with a specified null model, under the assumptions of the test. Neither measure would, by itself, establish clinical importance. No confidence intervals, p-values, or primary contrast estimates are posted for this outcome, and the registry reports zero posted analyses.

The registry also describes planning illustrations based on an observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such illustrations are not the trial's own sample-size justification and are not observed power. They are hypothetical planning calculations whose interpretation depends on the stated assumptions and effect size. The registry record does not report the original design justification or a prospective power calculation, so the planning illustrations should not be used to infer that the study had a particular probability of detecting an effect.

For this record, the most defensible statistical reading is descriptive: report the observed means, standard deviations, and condition-specific sample sizes, and recognize that the intended treatment contrasts and their uncertainty are not available in the registry record. Additional analysis detail would be needed to assess the effects of the crossover structure, missing condition data, and the bounded count outcome.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Dose Condition 1", "Dose Condition 2", "Dose Condition 3", "Dose Condition 4", "Dose Condition 5", "Dose Condition 6")
n   <- c(9, 10, 10, 10, 10, 10)
m   <- c(1.4, 4, 4.5, 0.7, 3.6, 4.5)
sp  <- c(1.96, 1.61, 1.51, 1.57, 2.06, 1.58)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Dose Condition 1  9  1.400  1.960  -0.107  2.907
CARM  Dose Condition 2  10  4.000  1.610  2.848  5.152
CARM  Dose Condition 3  10  4.500  1.510  3.420  5.580
CARM  Dose Condition 4  10  0.700  1.570  -0.423  1.823
CARM  Dose Condition 5  10  3.600  2.060  2.126  5.074
CARM  Dose Condition 6  10  4.500  1.580  3.370  5.630

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure and reports no secondary outcomes. It also reports zero posted analyses. The record does not describe a multiplicity plan, such as how inference would be handled across multiple doses, treatment contrasts, or outcome measures. Because the primary values appear across twelve dose-condition entries, any formal comparisons could involve more than one contrast, but the intended comparison set and any adjustment for multiple testing are not reported in the registry record. No claim about statistical significance or a multiplicity-adjusted result can therefore be made from these summaries.

The primary outcome population is described as subjects completing the dose condition. The registry gives a total enrollment of 12, while the condition-specific sample sizes range from 9 to 11. The posted record does not explain why counts differ among entries, whether participants missed particular sessions or conditions, or how missing outcomes were handled. It does not report an intention-to-treat analysis, a per-protocol definition, or a missing-data imputation method. The listed means should therefore be understood as based on the reported condition-specific populations, not assumed to include every enrolled participant.

In a crossover study, missingness in one condition may affect the participants available for paired comparisons. If different sets of participants contribute to different conditions, unadjusted means may not represent within-participant contrasts for a common group. The registry does not give participant-level completion patterns or paired sample sizes, so the extent of this issue cannot be assessed. The record also does not report sensitivity analyses examining assumptions about missing outcomes.

These omissions do not establish that a particular analysis or adjustment was absent from the full study; they mean the relevant details are not reported in the registry record. Interpretation should remain limited to the posted descriptive results.

12. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: blood clot (10.0%).

The registry reports adverse-event counts by zolmitriptan dose group. For serious adverse events, 1 participant among 10 in the Zolmitriptan (0 mg/Day) group was affected, corresponding to the posted 10.0% figure for blood clot. The registry reports 0 serious adverse events among 10 participants in the Zolmitriptan (2.5 mg/Day) group, 0 among 11 in the Zolmitriptan (5 mg/Day) group, and 0 among 11 in the Zolmitriptan (10 mg/Day) group. No deaths are reported in these groups.

These counts describe participants affected, not the total number of event episodes. The registry lists Blood clot as the top serious adverse-event term; it does not provide further case details or establish whether the event was attributed to a study intervention. The figures should not be interpreted as evidence of causation or as a complete assessment of safety beyond the adverse-event information posted.

For other adverse events, the registry reports 10 affected among 10 at risk in the 0 mg/Day and 2.5 mg/Day groups, and 11 affected among 11 at risk in the 5 mg/Day and 10 mg/Day groups. These broad counts do not identify the types, severity, timing, or number of events per participant. Because this was a crossover study, the group counts should be read according to the registry's dose-group reporting, not assumed to represent distinct participants across all groups.

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

The posted primary data describe how often participants chose cocaine rather than money during controlled inpatient experimental sessions. The twelve dose-condition means range from 0.6 to 4.6 choices, with standard deviations from 0.67 to 2.06 and condition-specific sample sizes from 9 to 11. These are observed summaries for participants completing each condition, not estimates of longer-term behavior or clinical outcomes.

The registry record does not identify the treatment combination represented by each generic dose-condition label. Although the study description names placebo maintenance and three zolmitriptan dose conditions, with acute cocaine and placebo administrations, the mapping to the twelve primary results is not reported. The values therefore cannot be used to claim a particular difference between placebo and a named zolmitriptan dose, or to describe a dose-response relationship.

No primary contrast estimates, confidence intervals, p-values, or posted analyses accompany the summaries. As a result, the values do not quantify the precision of a treatment comparison or show whether observed variation between entries could plausibly reflect sampling variation. The means also do not show individual response patterns. Statistical interpretation would require the relevant contrasts, analysis method, and information about the repeated observations and participants contributing to each condition.

The task captures choices during a specific experimental setting, with a maximum of 5 opportunities to choose cocaine over money. It does not directly measure community cocaine use, treatment retention, relapse, or lasting change. The study's early-phase classification and inpatient context are important boundaries on what can be inferred from the endpoint. The record gives no basis for translating these task results into a clinical recommendation.

The safety figures are similarly descriptive. They report affected-participant counts and a listed serious adverse-event term, but do not establish that an event was caused by a treatment. Taken together, the posted record offers descriptive behavioral and adverse-event information, while leaving key inferential and treatment-mapping details unavailable.

14. Why This Trial Matters Statistically

This trial illustrates why the design and the labeling of results matter as much as the numerical summaries. A crossover study can collect repeated outcomes from the same participants, making the within-participant structure relevant to analysis. Means and standard deviations for individual condition entries do not reveal how the paired observations relate, and the registry does not report the primary model or paired analysis. Readers cannot evaluate the treatment contrasts without those details.

The endpoint also illustrates the distinction between a behavioral measure and a clinical outcome. A choice between cocaine and money in a controlled task is a direct description of behavior in that setting. It may be useful for studying reinforcing effects, but it does not by itself establish whether behavior changes outside the inpatient experiment or persists over time. Keeping the measurement context explicit prevents overinterpretation.

Small condition-specific samples and variable participant counts make transparent reporting especially important. The registry reports 12 enrolled participants, with 9 to 11 contributing to each listed result. Without the reason for varying counts, the completion pattern, and the analysis population for contrasts, readers cannot determine how much the observed means reflect the same participants across conditions.

Finally, the record demonstrates the limit of descriptive summaries when treatment labels are not linked to outcome entries. The underlying study describes placebo and zolmitriptan conditions, but the twelve generic labels do not permit a clear dose-specific interpretation. Reporting the mapping, planned contrasts, uncertainty estimates, and missing-data approach would be necessary to support a fuller statistical reading. The posted data remain useful as a record of observed task outcomes, but not as a standalone estimate of a treatment effect.

15. 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 central limitation for interpreting the primary results is that the twelve dose-condition entries are not mapped to specific maintenance and acute-treatment combinations. The registry describes placebo and three zolmitriptan dose conditions, but the outcome labels alone do not identify which result belongs to which regimen. This prevents treatment-specific interpretation of the means and makes an ordered dose-response reading unsupported.

The registry reports no primary inferential analysis, contrast estimate, confidence interval, or p-value. The model and assumptions for the crossover analysis are not reported in the registry record. Consequently, uncertainty around differences cannot be evaluated, and the effects of within-participant correlation, period, or treatment sequence cannot be assessed from the posted summaries.

Condition-specific sample sizes vary from 9 to 11 despite enrollment of 12. The record does not explain this variation, describe participant completion across conditions, or state how missing outcome data were handled. The endpoint population is described as participants completing the dose condition, but the operational definition and analysis population for treatment contrasts are not reported. This limits assessment of comparability across entries.

The endpoint is a bounded count of choices with a maximum of 5, yet the registry does not report the analysis method or whether the method accounted for the outcome scale. The posted means and standard deviations cannot resolve that question. The small condition-specific counts also limit the amount of information available for detailed distributional assessment, though the precise uncertainty is not reported.

Finally, the experimental inpatient task is narrow in scope. Its outcome concerns choices during approximately four-hour sessions on specified inpatient days, not longer-term cocaine use or clinical outcomes. Safety reporting is also limited to the posted affected-participant counts and event term, without further case detail or attribution.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Cocaine and Zolmitriptan — NCT05019430.
• Registry record last updated 2025-08-05; status last verified 2025-07.
• Results first posted 2025-08-05.
• 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.

19. Record Summary

The registry record describes a completed, randomized, triple-masked crossover study of cocaine and zolmitriptan in participants with cocaine use disorder. It is classified as Early Phase 1, reports enrollment of 12 participants, and lists a start date of 2021-10-15 and primary completion date of 2025-01-09.

The primary outcome is the number of times participants chose cocaine over money, with a maximum of 5 choices, during experimental sessions. Twelve generic dose-condition entries report means, standard deviations, and condition-specific sample sizes. The means range from 0.6 to 4.6, and the sample sizes range from 9 to 11.

The registry does not map those entries to specific treatment combinations and posts no analyses, contrast estimates, confidence intervals, or p-values. It reports adverse-event counts by zolmitriptan dose group, including a serious adverse-event term of Blood clot. The available information supports descriptive interpretation of the experimental outcomes, with treatment-specific and inferential conclusions limited by unreported details.