This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Open Label Multi-Site Study of Safety and Effects of MDMA-assisted Therapy for Treatment of PTSD (NCT03282123), a na phase 2 study. The primary outcome is Change From Baseline to Visit 19 in CAPS-5 Total Severity Scores.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03282123 |
| Phase | Phase 2 |
| Condition | PTSD |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 38 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Resilient Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned people diagnosed with at least severe PTSD. The primary outcome population is identified as the Safety Set. The registry record lists enrollment of 38, but does not explain how that enrollment relates to the Safety Set.
Intervention
Participants received manualized MDMA-assisted therapy. The regimen described three therapy sessions with flexible midomafetamine HCl dosing from 80 to 120 mg and an optional supplemental dose equal to half the initial dose, taken 1.5 to 2 hours later. The broader schedule included non-drug preparatory and integrative therapy sessions.
Comparator
There was no separate comparator group. The registry lists allocation as NA, masking as none, and the model as single group. Consequently, the record does not describe a randomized, blinded comparison with another treatment or with no treatment.
Primary question
The stated primary question was whether three open-label sessions of MDMA-assisted therapy reduce PTSD symptoms. The primary measure was change from baseline to Visit 19 in CAPS-5 total severity score, over the timeframe from baseline to 18 weeks post-enrollment. The registry record does not report the estimated change, its confidence interval, or an analysis result that answers the question.
3. Trial Design
This was a completed Phase 2, open-label, multi-site study with a single-group design. The registry lists enrollment of 38 and identifies PTSD as the condition. The study start date is 2017-11-16, and primary completion is recorded as 2019-08-10. These dates describe the registry record; they do not establish how long any individual participant was followed.
Participants were to receive three non-drug preparatory sessions, followed by three sessions of MDMA-assisted therapy. Each MDMA-assisted therapy session was followed by three non-drug integrative therapy sessions. The intervention record names midomafetamine and manualized therapy. The arm description specifies flexible midomafetamine HCl dosing from 80 to 120 mg, with an optional supplemental dose half the initial dose 1.5 to 2 hours later.
There was no separate control arm: allocation is listed as NA and the model as single group. Masking is listed as none. The resulting design can describe the observed course of symptoms and adverse events among participants in the study, but does not provide a like-for-like control comparison. Without such a comparison, changes over time cannot be separated from other influences such as expectations, concurrent care, or the natural course of symptoms.
The primary endpoint was assessed from baseline to Visit 19, with a stated timeframe of baseline to 18 weeks post-enrollment. The primary outcome population is identified as the Safety Set. The registry record does not report details of site-level procedures, eligibility criteria beyond the brief description, or the rationale for the enrollment target.
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
| Stage | MDMA-assisted Psychotherapy |
|---|---|
| STARTED | 38 |
| COMPLETED | 33 |
| NOT COMPLETED | 5 |
Reasons for not completing this period:
| Reason | MDMA-assisted Psychotherapy |
|---|---|
| Withdrawal by Subject | 5 |
Analysis population for the primary outcome, as defined in the registry: Safety Set
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: Safety Set
| Characteristic | Unit | MDMA-assisted Psychotherapy |
|---|---|---|
| Participants analysed | 33 | |
| Age, Continuous | years | 36.42 (SD 11.09) |
| Sex: Female, Male: Female | Participants | 20 |
| Sex: Female, Male: Male | Participants | 13 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 32 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 1 |
| Race (NIH/OMB): Asian | Participants | 5 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 |
| Race (NIH/OMB): White | Participants | 24 |
| Race (NIH/OMB): More than one race | Participants | 2 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Baseline CAPS-5 Total Severity Score | score on a scale | 45.4 (SD 6.70) |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline to Visit 19 in CAPS-5 Total Severity Scores, measured over Baseline to 18 weeks post-enrollment.
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | score on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was change from baseline to Visit 19 in CAPS-5 total severity score. CAPS-5 is a clinician-administered and scored structured interview assessing PTSD symptoms according to DSM-5. Its total severity score sums symptom frequency and intensity scores for the re-experiencing, avoidance, and hypervigilance subscales. The scale ranges from 0 to 136, with higher scores indicating greater PTSD symptom severity.
A change measure is intended to describe how the recorded symptom score differs between the baseline assessment and a later assessment. In this study, the later assessment is identified as Visit 19, within the timeframe from baseline to 18 weeks post-enrollment. A clinician-administered structured measure offers a consistent way to assess symptoms using defined questions and scoring rather than relying only on an informal impression.
The registry identifies the primary summary as a least-squares mean and its dispersion as a 95% confidence interval. The least-squares mean is a model-based estimate; its interpretation depends on the analysis model, which is not described in the registry record. Neither the estimated change nor its confidence interval is reported, and the record does not state the coding convention used for the change score. Therefore, the size and precision of the primary outcome cannot be assessed from the reported record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a symptom endpoint and a study schedule, but it does not report the primary outcome estimate. In particular, the least-squares mean change in CAPS-5 total severity score and its 95% confidence interval are not reported in the registry record. Without those values, the magnitude and precision of the observed change cannot be evaluated. The record also lists 0 analyses, so it does not contain a reported analysis result to interpret.
The design limits what can be concluded even if a before-and-after change estimate were available. This was an open-label, single-group study without a separate comparator. Any observed change over time would describe participants’ scores during the treatment schedule, but would not by itself establish that the intervention caused the change. A control group can help distinguish an intervention-associated difference from changes that could also occur through expectations, concurrent care, natural symptom fluctuation, or other influences. Those explanations are general considerations, not findings about this study.
The listed endpoint is clinically oriented: CAPS-5 total severity scores reflect symptom frequency and intensity across specified symptom domains, with higher scores indicating greater severity. A reported estimate would need to be read alongside its confidence interval. In general, a confidence interval expresses the statistical uncertainty around an estimate under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval, but neither width nor location can be assessed because the interval itself is absent.
The record describes a Safety Set for the primary outcome population, while separately listing overall enrollment and safety-event risk counts. It does not explain the population definitions or the relationship among those counts. This prevents a reader from determining from the record alone how complete endpoint follow-up was or which participants contributed to each analysis.
The serious adverse event information is descriptive and should be read separately from the symptom endpoint. The record lists 1 participant with a serious adverse event and 0 deaths in the safety group, and identifies suicide attempt as a top serious term at 3.0%. These entries do not provide a comparative estimate of risk. The posted record therefore supports description of the recorded study design and event counts, but does not supply enough outcome information for a statistical assessment of the primary symptom question.
9. Statistical Methods Explained
The registry identifies the primary outcome summary as a least-squares mean with a 95% confidence interval. These terms describe how a result is intended to be summarized, but they do not reveal the numerical result. The least-squares mean is generally a model-based mean estimate, potentially adjusted for variables included in the model. Which model, covariates, or repeated-measure structure was used is not reported in the registry record, so the precise adjustment and assumptions cannot be reconstructed.
What does a confidence interval convey?
In general, a confidence interval conveys uncertainty around an estimated quantity under the analysis assumptions. It is not a range containing every participant’s score, and it does not describe the spread of individual responses. A confidence interval can help readers judge how precisely a mean change has been estimated. For this endpoint, the registry names a 95% confidence interval, but does not report its bounds. The interval’s width, direction, and compatibility with different possible changes therefore cannot be evaluated.
What does the single-group design imply?
The model is listed as single group, allocation as NA, and masking as none. There is no randomized treatment contrast in the registry record. A within-group change can be estimated by comparing participants’ scores at different times, but such a change does not establish what would have happened to comparable participants without the intervention. This is a general limitation of uncontrolled before-and-after evidence, not a claim that any particular alternative explanation occurred in this study.
Open-label treatment also means that participants and clinicians were not masked to the intervention, as reflected by the masking entry. Expectations and knowledge of treatment can influence experience, reporting, clinical interaction, and assessment. CAPS-5 is described as clinician-administered and scored, which gives the endpoint a structured assessment format, but the registry does not report masking of assessors or procedures for limiting assessment bias.
How should the sample-size assumptions be read?
The record describes a planning illustration based on the observed effect, rather than the trial’s own design. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. The record says that time-to-event planning uses total events, while other planning results are participants per arm. These are general planning conventions and do not constitute evidence that this study used those assumptions to choose its enrollment target. No numerical planning results or sample-size justification are reported in the registry record.
Planning calculations are not observed power. In general, a planning illustration asks what sample size would correspond to an assumed effect and analysis framework. It does not show the probability that the completed study detected a true effect, and it cannot substitute for a reported estimate and uncertainty interval. The assumptions also refer to two arms, whereas this trial is listed as single group; they should not be mistaken for a randomized comparison in this study.
Why does over-dispersion matter in general?
For outcome types where a statistical model assumes a particular level of variability, over-dispersion means that the observed variability exceeds what the model assumes. If it is ignored, standard errors can be too small and confidence intervals too narrow. This is a general statistical consideration. The primary endpoint in this record is continuous, and no model details or diagnostics are reported that would establish whether over-dispersion was relevant to its analysis.
What can be inferred from the reported method labels?
The endpoint summary and confidence level describe a planned or named reporting approach, not a complete statistical analysis plan. The record does not report the model formula, handling of repeated measurements, assumptions checks, estimation procedure, or sensitivity analyses. It also contains no reported primary estimate or analysis result. Accordingly, statistical explanations can clarify what the labels generally mean, but cannot fill in the absent analysis details or determine whether the assumptions were met.
10. Multiplicity, Missing Data and Analysis Populations
The record lists 2 outcome measures and names change from baseline to Visit 19 in Adapted SDS Total Score as a secondary outcome. It does not report how multiple outcomes were handled statistically, whether any adjustment for multiple testing was planned, or which outcomes were treated as confirmatory. Multiplicity matters in general because evaluating several outcomes can increase the chance of at least one apparently unusual result. No multiplicity-adjusted or unadjusted outcome results are reported in the registry record, so the issue cannot be assessed from results.
Missing-data procedures are not reported in the registry record. There is no description of how missing baseline or follow-up scores were handled, whether the analysis used all available measurements, or whether imputation or sensitivity analyses were performed. The record also does not report outcome completion counts or reasons for missing assessments. Those omissions matter because an analysis of available measurements can be affected if missingness is related to symptoms, treatment experience, or other factors.
The primary outcome population is identified as the Safety Set, but its definition is not reported. The record lists enrollment of 38 and safety-event risk counts of 33; it does not explain the relationship between these populations or the inclusion rules for the endpoint analysis. No primary outcome analyses are listed. The record therefore does not establish which participants contributed to the primary estimate, how incomplete observations were treated, or whether the reported population matches the planned analysis population.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| MDMA-assisted Psychotherapy | 1 | 33 | 3.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| MDMA-assisted Psychotherapy | 0 of 33 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| MDMA-assisted Psychotherapy | 33 of 33 |
Most frequent serious adverse event terms
| Event term | Organ system | MDMA-assisted Psychotherapy |
|---|---|---|
| Suicide attempt | Psychiatric disorders | 1 of 33 |
Most frequent non-serious adverse event terms
| Event term | Organ system | MDMA-assisted Psychotherapy |
|---|---|---|
| Headache | Nervous system disorders | 22 of 33 |
| Muscle Tightness | Musculoskeletal and connective tissue disorders | 18 of 33 |
| Nausea | Gastrointestinal disorders | 11 of 33 |
| Insomnia | Psychiatric disorders | 11 of 33 |
| Anxiety | Psychiatric disorders | 9 of 33 |
| Suicidal Ideation | Psychiatric disorders | 9 of 33 |
| Fatigue | General disorders | 8 of 33 |
| Nystagmus | Nervous system disorders | 8 of 33 |
| Dizziness | Nervous system disorders | 5 of 33 |
| Abdominal Discomfort | Gastrointestinal disorders | 4 of 33 |
Serious events with the highest arm-level rate: suicide attempt (3.0%).
The safety record lists a group titled MDMA-assisted Psychotherapy. For this group, 33 participants are listed as at risk for serious adverse events, and 1 as affected. For other adverse events, 33 are listed as at risk and 33 as affected. The record lists 0 deaths. Suicide attempt is identified among the top serious terms at 3.0%.
These entries are counts from the registry record, not comparative risk estimates. The study has no separate control group, so the counts do not show how event occurrence compares with another treatment or with no treatment. The record does not provide event timing, duration, severity beyond the serious classification, relatedness assessments, or participant-level detail. It also does not define whether participants could contribute to more than one event category. The serious-term percentage is reported as 3.0%; its derivation and denominator are not explained in the record.
Seriousness is a regulatory classification and is not the same as symptom intensity or severity. The absence of listed deaths does not mean that no serious adverse events occurred: the record lists 1 participant affected by a serious event. These safety data should be interpreted as descriptive reporting for the named group, with the limitations of the available definitions and follow-up information.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a completed, open-label, single-group Phase 2 study examined MDMA-assisted therapy for people described as having at least severe PTSD. It identifies a primary symptom endpoint, CAPS-5 total severity score change from baseline to Visit 19, and describes the treatment schedule. It also reports selected serious adverse event counts. These details characterize the study and the outcomes it set out to assess.
The record does not report the primary outcome estimate or its 95% confidence interval. It therefore does not show the size or precision of the measured symptom change. The absence of a reported estimate should not be interpreted as evidence of no change, nor as evidence of a particular direction or magnitude. It means that the primary numerical result is not reported in the registry record.
Even a reported change in this single-group study would not, on its own, establish that the intervention caused that change. There is no separate comparator group and no masking. Changes observed during the study could reflect the intervention, but could also be influenced by other factors. This is a general limitation of the design rather than a conclusion about what happened to participants.
The safety entries document the reported counts for the study group, including 1 participant affected by a serious adverse event and 0 deaths. They do not quantify a comparative risk or answer how those events relate to treatment. The registry record does not provide enough context to make a broader assessment of safety, just as it does not provide enough outcome information to evaluate the primary symptom question.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of the difference between a study question and a reported result. The registry defines a primary endpoint and identifies a least-squares mean with a 95% confidence interval as the intended summary. Yet the primary estimate and interval are not reported in the registry record, and the record lists 0 analyses. Without an estimate and its uncertainty, the central quantitative outcome cannot be evaluated.
The design also matters for interpretation. An open-label, single-group study can describe changes during a treatment program, but does not isolate an intervention effect from time-related or other influences. That distinction is important when reading any within-group change: statistical precision around a change estimate would not by itself address the absence of a control comparison.
The endpoint is a structured clinician-administered measure with a defined score range and symptom domains. Such definition supports consistent measurement, while the lack of a reported result, model specification, missing-data method, and analysis population details limits reproducibility and interpretation. The registry’s safety counts are also useful descriptive information, but without a comparator and additional event detail they cannot establish relative risk.
Overall, this record highlights why statistical interpretation depends on more than an endpoint name or study status. The design, analysis details, population definitions, outcome estimate, uncertainty, and safety context all contribute to what can be concluded. Several of those elements are not reported in the registry record.
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 primary limitation is that the registry record does not report the primary CAPS-5 change estimate or its 95% confidence interval. It also lists 0 analyses. As a result, the magnitude, precision, and statistical uncertainty of the primary outcome cannot be assessed from the record.
The study is open-label and single group, with no separate comparator. This prevents a direct treatment contrast and limits causal interpretation of any before-and-after change. The registry does not report whether outcome assessors were masked, despite describing CAPS-5 as a clinician-administered and scored measure.
Important analysis details are not reported, including the statistical model, missing-data handling, outcome completion, and sensitivity analyses. Although the primary outcome population is named as the Safety Set, its definition and its relationship to the listed enrollment and safety-event populations are not explained. The record names a secondary outcome but does not report results or describe multiplicity procedures.
Safety reporting is limited to selected counts and a top serious term. The record does not provide event timing, duration, relatedness, or a detailed accounting of event-level information. The reason that safety-event risk counts are smaller than the listed enrollment is not reported in the registry record; no explanation for that difference can be inferred from these entries alone.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Open Label Multi-Site Study of Safety and Effects of MDMA-assisted Therapy for Treatment of PTSD — NCT03282123.
- Registry record last updated 2025-06-05; status last verified 2025-05.
- Results first posted 2021-07-29.
- 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.
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18. Record Summary
NCT03282123 is a completed, open-label, multi-site Phase 2 study of MDMA-assisted therapy for PTSD. The registry describes a single-group design, with enrollment of 38, no masking, and no separate comparator. The treatment schedule combined non-drug preparatory and integrative therapy sessions with three MDMA-assisted therapy sessions.
The primary outcome was change from baseline to Visit 19 in CAPS-5 total severity score, with a stated timeframe of baseline to 18 weeks post-enrollment. The outcome was to be summarized as a least-squares mean with a 95% confidence interval. The registry record does not report that estimate, its interval, or an analysis result.
The safety record lists 1 participant affected by a serious adverse event, 0 deaths, and suicide attempt at 3.0% among the top serious terms. Missing-data procedures, detailed analysis methods, and the relationship between the enrollment and Safety Set populations are not reported in the registry record.