Phendimetrazine and Cocaine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phendimetrazine and Cocaine (NCT02233647), a non-randomized early/phase 1 study. The primary outcome is Peak Systolic Pressure.

2. Clinical Question

The clinical question is therefore about physiological responses during controlled cocaine administration under differing maintenance conditions, rather than a reported comparison of longer-term clinical outcomes. The record identifies peak systolic pressure as the primary measure and lists subjective ratings among the secondary outcomes. It does not report the effect estimate, its uncertainty, or a statistical test for the primary measure. As a result, the record supports describing the question and the planned laboratory setting, but it does not support a conclusion about the size or direction of any observed difference.

3. Trial Design

The registry describes an early phase 1, non-randomized, triple-masked crossover study. It lists 11 participants and a completed status. The study start is recorded as 2014-09 and primary completion as 2015-12. These dates describe the registry record; they do not provide detail about participant follow-up or analysis timing.

The treatment descriptions cover placebo maintenance and three phendimetrazine maintenance levels: low, intermediate, and high. Under each maintenance condition, the descriptions include acute cocaine administration and acute placebo administration. This arrangement allows the research question to concern responses during acute challenges in the context of different maintenance conditions. However, the registry record does not explain the sequence in which participants experienced these conditions, whether condition order was balanced, or how long participants remained in each condition.

A crossover design means that participants may contribute observations under more than one condition, so comparisons can involve within-participant information. This can reduce the influence of stable differences between participants when the design and analysis appropriately account for the repeated observations. The registry’s crossover label alone does not establish how observations were paired or modeled. The record does not report the analysis population, period effects, carryover assessment, or the details of any washout procedure.

Although masking is described as triple, the masked roles and the procedures used to maintain masking are not reported in the registry record. Allocation is explicitly non-randomized. The named arms and condition descriptions should therefore not be interpreted as evidence of randomized, parallel-group assignment. In particular, the record cautions that the arms are not a like-for-like control comparison. Detailed eligibility criteria, actual dose amounts, participant flow, and reasons for any exclusions are also not reported.

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: Eleven subjects were enrolled (i.e., signed consent), but only 10 subjects completed. Due to the within-subject nature of this study (i.e., missing data from the 11th subject cannot be analyzed with repeated-measures ANOVA), only data from the 10 subjects who completed the protocol were analyzed and reported.

Overall Study

Reasons for not completing this period:

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: These are data for completing subjects only. Eleven subjects were enrolled (i.e., signed consent), but only data from completing subjects were included here and in the outcomes listed throughout this report.

6. Primary Endpoint

The registry lists the primary outcome as Peak Systolic Pressure, measured over This measure was completed at 15 minute intervals after sampling each cocaine dose under both phendimetrazine and placebo maintenance conditions..

The primary endpoint is peak systolic pressure, measured in mm Hg. Systolic pressure is the pressure in the arteries during the heart’s contraction. The registry says it was measured using an automated monitor and that higher values represent greater systolic pressure.

For each cocaine dose, peak scores were calculated from multiple assessments made after sampling. Measurements were taken at 15 minute intervals under both phendimetrazine and placebo maintenance conditions. Using a peak captures the highest recorded systolic pressure across the specified assessments rather than describing the whole time course. This may be useful when the question concerns the largest observed physiological response during a challenge. It also means that a peak does not, by itself, describe how long a response lasted or how values changed between assessments.

The endpoint is reported as a mean with standard error as its dispersion measure. In general, a mean describes the central value of a group of observations, while a standard error describes the precision of the estimated mean. Neither is available as a numerical result in the registry record. The registry record also does not state how peaks were handled when assessments were missing, how repeated observations were incorporated into comparisons, or whether the primary endpoint was analyzed using an adjusted model.

The primary measure is physiological, not a direct measure of subjective experience or a longer-term clinical outcome. The record lists subjective ratings as secondary outcomes, including ratings of stimulant and sedative effects and several visual analog scale ratings. No numerical results for the primary endpoint or those secondary outcomes are reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as continuous and reports it as a mean with standard error. These summaries answer different questions. A mean gives a central summary of observed values. A standard error describes how precisely the mean is estimated from the observations contributing to it; it is not the spread of individual participants’ measurements. In general, a confidence interval combines an estimate with its uncertainty to show a range of values compatible with the data under the method used. No confidence interval or numerical estimate for this outcome is reported in the registry record.

What does a peak measure?

The peak systolic pressure is derived from repeated pressure assessments after sampling each cocaine dose. The registry states that these assessments occurred at 15 minute intervals and that peak scores were calculated for each dose under the maintenance conditions. A peak summarizes the highest recorded value across those assessments. It is distinct from an average over the assessment period and does not describe the pattern of values over time. Two conditions could have similar peaks while differing in their time course, or different peaks while having overlapping values at other assessments. The registry record does not provide the repeated measurements or the numerical peak summaries needed to explore those patterns.

Why does the crossover label matter?

In general, a crossover design collects information from participants under more than one condition. Comparisons may then use within-participant contrasts, which can account for stable characteristics shared across the participant’s observations. The record identifies this study as crossover, but it does not state the order of conditions, whether order was randomized, how periods were defined, or whether a washout was used. Allocation is listed as non-randomized. These omissions matter because time trends, order effects, or effects that persist from an earlier condition can complicate interpretation. The statistical model and any assessment of such effects are not reported in the registry record.

Repeated measurements from the same participant are generally correlated rather than independent. A suitable analysis needs to reflect that structure when estimating uncertainty. Treating every measurement as independent can make uncertainty appear smaller than it is, while ignoring the paired nature of observations can discard useful information. These are general statistical considerations, not claims about the analysis used in this study. The registry lists 0 analyses, so the model, variance assumptions, handling of repeated measures, and adjustment strategy are not reported.

What does the standard error tell readers?

As a general concept, the standard error concerns uncertainty in an estimated mean, whereas a standard deviation describes variability among observations. It does not indicate the range of individual responses, and it does not by itself establish whether a difference is clinically important or statistically distinguishable from no difference. For a comparison, readers would need the estimate and its uncertainty, together with a clear account of the method used. Neither the primary estimate nor its uncertainty is reported in the registry record.

How should sample-size illustrations be understood?

In general, a sample-size calculation asks how many participants might be needed under specified assumptions about an effect, variability, allocation, and a significance threshold. It is a planning exercise, not a result from enrolled participants and not a measure of observed power. The registry’s accompanying planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. The record also distinguishes participant counts per arm from total event counts for time-to-event calculations. These assumptions do not establish that the trial itself was designed using that calculation. The trial’s own sample-size justification is not reported in the registry record. No numerical planning illustration should be interpreted as the number actually analyzed or as proof that the study could detect a particular effect.

What can be inferred from the analysis record?

The registry lists 26 outcome measures and 0 analyses. That is a reporting-status description, not evidence that no analyses were conducted outside the registry. It does mean that the registry record does not provide inferential results to evaluate. In general, a complete interpretation would use the endpoint estimates, uncertainty intervals, methods, analysis populations, and handling of missing observations. Those elements are not reported in the registry record. Any recalculation from summary statistics would require posted numerical summaries; none are available for the primary endpoint in this record.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies peak systolic pressure as the primary outcome and lists 26 outcome measures, including secondary subjective ratings. When a study considers multiple outcomes or comparisons, the chance of finding an apparently notable result by chance can increase. General approaches include prespecifying a primary comparison, adjusting inference across a family of tests, or treating additional analyses as exploratory. The registry record does not report a multiplicity plan, a hierarchy among the secondary outcomes, or results for the listed measures.

The record lists 0 analyses. It therefore does not provide a statistical analysis plan, model specifications, test results, confidence intervals, or an account of how repeated observations were handled. Whether the sponsor conducted analyses not entered in the registry is not reported in the registry record. The posted record alone cannot establish whether multiplicity was addressed in any analysis.

Missing data are also not described. The registry record does not report how many participants completed each condition, whether measurements were missing, why any data might be missing, or what methods were used to handle missing observations. In a crossover study, incomplete condition data can affect which within-participant comparisons are available. The registry does not specify an analysis population such as all enrolled participants, participants who completed all conditions, or participants with outcome measurements meeting a defined rule. No such population definition should be inferred from enrollment alone.

These gaps limit assessment of how the reported enrollment relates to each outcome and whether the analysis matched the design. They also prevent evaluation of selective outcome reporting or the influence of missing observations. The registry record does not provide enough information to resolve these questions.

11. Safety Results

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

Other (non-serious) adverse events

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

Most frequent non-serious adverse event terms

The safety summary lists a group titled Phendimetrazine Dose Escalation. It records 11 participants at risk for serious adverse events and 0 participants affected by a serious adverse event. For other adverse events, it records 11 participants at risk and 1 participant affected. These are counts for the group in the registry summary; they do not identify the event term, timing, severity beyond the serious-versus-other classification, or relationship to treatment.

The death count is not reported in the registry record. A missing death count should not be read as a reported count of zero. Likewise, the absence of serious-event terms in the summary does not supply detail about how events were collected or classified. The summary is limited to the listed group and does not describe event counts separately for each maintenance condition or acute challenge.

Adverse-event counts are not estimates of the primary systolic-pressure outcome, and they do not provide a comparative safety analysis. Because the study is labeled non-randomized and crossover, the registry record’s cautions about arm comparability remain relevant. The summary supports only a narrow description of the recorded counts and denominators; it does not establish causation or characterize all possible risks.

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

The registry record documents an early phase 1 laboratory study of phendimetrazine maintenance conditions during acute cocaine and placebo administration. It identifies peak systolic pressure as the primary endpoint and lists subjective ratings as secondary outcomes. It also records a non-randomized, triple-masked crossover design, enrollment of 11, and completed status. These details describe the study’s setting and stated question.

The record does not report the primary endpoint values or a comparison estimate. It therefore does not show whether peak systolic pressure differed across maintenance conditions, how large any difference was, or how precisely it was estimated. The absence of numerical results is not evidence of no difference. Nor does the stated study aim establish a finding about safety, tolerability, or subjective effects.

The laboratory design is focused on responses to controlled acute challenges. Its primary physiological measure does not, by itself, address longer-term outcomes. The registry record does not report longer-term follow-up, clinical outcomes, or evidence about use of phendimetrazine outside the described study conditions. The actual dose amounts and detailed administration schedule are also not reported.

The record’s limited adverse-event summary lists 0 serious adverse events and 1 other adverse event among 11 participants at risk in the named group, with the death count not reported. These counts should not be generalized beyond the summary or treated as a full assessment of comparative safety. The lack of analysis details further limits interpretation of the crossover observations.

Accordingly, the record can be used to understand what the investigators set out to examine and how the study was classified. It cannot, on its own, support a conclusion about the magnitude, precision, or clinical meaning of the primary comparison. It also cannot establish whether the observed data were analyzed with methods that address repeated measurements, missingness, and multiple outcomes.

13. Why This Trial Matters Statistically

This study illustrates why a registry description and a statistical result answer different questions. The record identifies the research question, the crossover structure, the primary physiological measure, and the broad treatment conditions. Those features help readers understand what a comparison would need to represent. But without estimates and uncertainty, the result itself cannot be evaluated.

The crossover designation is statistically important because observations from the same participant can be related. A within-participant comparison may control for stable differences between people, but it requires appropriate handling of repeated observations and condition order. The registry labels allocation as non-randomized and warns that the arms are not a like-for-like control comparison. The order, period structure, and analysis method are not reported, so the design label cannot substitute for a detailed assessment of the comparison.

The primary measure is a peak derived from assessments made at 15 minute intervals after sampling each cocaine dose. Choosing a peak focuses attention on the highest recorded value, while leaving the time pattern outside that summary. This distinction matters when interpreting what an endpoint represents. The registry’s use of a mean and standard error also highlights the difference between describing a central value and describing its precision.

The record lists 26 outcome measures but 0 analyses. This makes transparent the difference between registering outcomes and reporting findings. It also raises ordinary questions about multiplicity, missing data, analysis populations, and selective reporting that cannot be resolved from the posted record. The trial is therefore useful statistically as an example of how design and outcome labels can be informative while still leaving essential inferential details unavailable.

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.

Several limitations are specific to the information recorded for this study. The registry lists enrollment of 11, but does not report participant flow, the number contributing data to each outcome, or reasons for any missing measurements or exclusions. It is therefore not possible to connect enrollment to endpoint-specific analysis counts.

The study is labeled crossover and non-randomized, but the condition sequence, period structure, washout details, and handling of potential order or carryover effects are not reported. Masking is labeled triple, while the roles masked and procedures used to maintain masking are not described. The actual low, intermediate, and high phendimetrazine dose amounts are also not reported.

The primary endpoint is defined as peak systolic pressure from repeated assessments, but the record does not provide the values, estimates, uncertainty intervals, or inferential results. The statistical model and method for accounting for repeated observations are not reported. The registry lists 26 outcomes and 0 analyses, and does not describe a multiplicity strategy or outcome hierarchy beyond identifying the primary measure.

The adverse-event summary is limited to one named group and gives counts for serious and other events. It does not report event terms or timing, and the death count is not reported. The record does not provide enough detail for a complete comparative safety interpretation.

Finally, the registry does not report a sample-size justification for the trial, detailed eligibility criteria, or a statistical analysis plan. These omissions restrict assessment of the intended precision, generalizability, and analysis decisions. They should be treated as limits of the registry record rather than evidence that the information does not exist elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Phendimetrazine and Cocaine — NCT02233647.
• Registry record last updated 2017-09-27; status last verified 2017-09.
• Results first posted 2016-09-15.
• 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

The registry identifies an early phase 1, completed, non-randomized, triple-masked crossover study with enrollment of 11 participants and the condition of cocaine use disorder. It describes placebo and three phendimetrazine maintenance levels, with acute cocaine and placebo administrations under the maintenance conditions. The stated purpose concerns safety, tolerability, and subjective and physiological responses.

The primary endpoint is peak systolic pressure in mm Hg, summarized as a mean with standard error. Measurements were taken at 15 minute intervals after sampling each cocaine dose. The registry lists 26 outcome measures and 0 analyses. Numerical primary and secondary results, analysis methods, missing-data procedures, and analysis populations are not reported in the registry record. The adverse-event summary lists 0 serious and 1 other adverse event among 11 participants at risk in the named group; the death count is not reported.