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 A Study to Evaluate the Efficacy and Safety of MIN-117 in Adult Patients With Major Depressive Disorder (NCT03446846), a randomized phase 2 study. The primary outcome is Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03446846 |
| Phase | Phase 2 |
| Condition | Major Depressive Disorder |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 360 |
| Arms in the primary outcome | 3 |
| Lead sponsor | Minerva Neurosciences |
| Results posted | Yes |
2. Clinical Question
Population
Adults aged 18 to 65 years with major depressive disorder were eligible for the study. The primary outcome population was the ITT population, defined in the registry as randomized patients who received at least 1 dose of study drug. The primary outcome summaries include 70 participants in the 5.0 mg arm, 76 in the 2.5 mg arm, and 149 in the placebo arm.
Intervention
Participants assigned to MIN-117 received either 5.0 mg or 2.5 mg orally each day for 6 weeks. The 5.0 mg dose consisted of two 2.5 mg capsules; the 2.5 mg dose consisted of one 2.5 mg capsule and one placebo capsule.
Comparator
The comparator was placebo, taken orally each day for 6 weeks as two placebo capsules. The study was randomized, double-blind, and parallel-group, with placebo as the reference arm for both dose comparisons.
Primary question
The primary question was whether average change in Montgomery-Asberg Depression Rating Scale (MADRS) total score at Week 6 differed between either MIN-117 dose and placebo. The registry describes change in MADRS total score as the primary outcome; the posted group means are identical across all three arms.
3. Trial Design
The registry describes a Phase 2, randomized, double-blind, parallel-group, placebo-controlled study. It is marked completed. The study began on 2018-03-30, and its primary completion date is 2019-11-21. The listed enrollment is 360. The brief summary describes a 6-week study and says approximately 324 patients were to be assigned to three arms in a 2:1:1 ratio. The distinction between the listed enrollment and the planned approximate number is not explained in the registry record.
The three arms were 5.0 mg MIN-117, 2.5 mg MIN-117, and placebo, each administered orally daily for 6 weeks. The posted primary outcome population is described as randomized patients who received at least 1 dose. The primary outcome summaries include 70 participants assigned to 5.0 mg, 76 assigned to 2.5 mg, and 149 assigned to placebo. Those outcome counts differ from the listed enrollment; reasons for the difference are not reported in the registry record.
The primary outcome was change in MADRS total score at Week 6. Secondary outcomes were change in the Hamilton Anxiety Scale (HAM-A), change in the Clinical Global Impression of Severity Scale (CGI-S), and the Clinical Global Impression of Improvement Scale (CGI-I) at Week 6. The registry identifies four outcome measures in total. It does not report a detailed statistical analysis plan, the method for handling missing outcomes, or whether any interim analyses were conducted. Those design details should not be inferred from the randomized and double-blind labels.
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 | 5.0 mg MIN-117 | 2.5 mg MIN-117 | Placebo |
|---|---|---|---|
| STARTED | 90 | 92 | 178 |
| COMPLETED | 83 | 87 | 162 |
| NOT COMPLETED | 7 | 5 | 16 |
Analysis population for the primary outcome, as defined in the registry: ITT population: all randomized patients who received at least 1 dose of study drug.
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: One patient was randomized to a particular kit # in the Electronic Data Capture system, however, the site dispensed another kit # instead in error. Consequently, the patient was randomized to placebo but received 5.0 mg MIN-117 and was, therefore, included in the (Intent-to-Treat) ITT population based on the randomized treatment to placebo and in the safety population based on the actual treatment they received (5.0 mg MIN-117).
| Characteristic | Unit | 5.0 mg MIN-117 | 2.5 mg MIN-117 | Placebo | Total |
|---|---|---|---|---|---|
| Participants analysed | 91 | 92 | 177 | 360 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 91 | 92 | 177 | 360 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 | 0 |
| Age, Continuous | years | 48 (SD 11.5) | 47 (SD 12.7) | 47 (SD 12.5) | 48 (SD 12.3) |
| Sex: Female, Male: Female | Participants | 62 | 60 | 136 | 258 |
| Sex: Female, Male: Male | Participants | 29 | 32 | 41 | 102 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 1 | 1 | 1 | 3 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 5 | 4 | 11 | 20 |
| Race (NIH/OMB): White | Participants | 85 | 87 | 165 | 337 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score, measured over Week 6.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | score on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was change in total score on the Montgomery-Asberg Depression Rating Scale (MADRS) at Week 6. The registry describes MADRS as a validated, physician-rated measure intended to assess depression severity and detect change. It contains 10 items, covering symptoms such as sadness, inner tension, sleep, appetite, concentration, interest, pessimistic thoughts, and suicidal thoughts. Each item is scored from 0 to 6, and the total score can range from 0 to 60; higher scores represent more severe symptoms.
A change score expresses the difference between a participant’s baseline assessment and a later assessment. The posted outcome is a mean change for each treatment arm, with a standard deviation describing variation among participants in that arm. The registry lists the timeframe as Week 6. The posted mean change was -12.0 in each of the three arms, with a standard deviation of 9.2 in each arm.
In general, a clinician-rated scale can provide a consistent way to quantify symptoms and track changes over time. The registry states that MADRS has high inter-rater reliability and that its ability to distinguish responders from nonresponders has been shown to be comparable to the Hamilton Rating Scale for Depression. These measurement properties explain the scale’s intended role; they do not, by themselves, establish that a treatment caused a change.
7. Results Posted in the Registry
- 5.0 mg MIN-117: mean -12.00 versus -12.00 on control; difference 0.00 (95% CI -2.61 to 2.61), standardized effect d = 0.00; z-test p = 1.000.
- 2.5 mg MIN-117: mean -12.00 versus -12.00 on control; difference 0.00 (95% CI -2.54 to 2.54), standardized effect d = 0.00; z-test p = 1.000.
Mean difference: 5.0 mg MIN-117
95% CI: -2.61 to 2.61
Recalculated from the posted summary statistics
8. Secondary Efficacy Endpoints
The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.
| Secondary outcome | Type | Effect measure | Estimate (95% CI) | Planning size, 80% power |
|---|---|---|---|---|
| Change in Hamilton Anxiety Scale (HAM-A) | Continuous Endpoint | Mean difference | -1.00 (-3.32 to 1.32) | 1,093 per arm |
| Change in Clinical Global Impression of Severity Scale (CGI-S) | Continuous Endpoint | Mean difference | 0.00 (-0.36 to 0.36) | n/a |
| Change in Clinical Global Impression of Improvement Scale (CGI-I) at Week 6 | Continuous Endpoint | Mean difference | 0.00 (-0.29 to 0.29) | n/a |
Change in Hamilton Anxiety Scale (HAM-A)
- Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
- Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
- Result:
- 5.0 mg MIN-117: mean -12.00 versus -11.00 on control; difference -1.00 (95% CI -3.32 to 1.32), standardized effect d = -0.12; z-test p = 0.398.
- 2.5 mg MIN-117: mean -11.00 versus -11.00 on control; difference 0.00 (95% CI -2.46 to 2.46), standardized effect d = 0.00; z-test p = 1.000.
- Interpretation:
- The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 5.0 mg MIN-117 and the control. The interval gives the range of effects that remain compatible with the data.
- The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 2.5 mg MIN-117 and the control. The interval gives the range of effects that remain compatible with the data.
Change in Clinical Global Impression of Severity Scale (CGI-S)
- Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
- Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
- Result:
- 5.0 mg MIN-117: mean -1.00 versus -1.00 on control; difference 0.00 (95% CI -0.36 to 0.36), standardized effect d = 0.00; z-test p = 1.000.
- 2.5 mg MIN-117: mean -1.00 versus -1.00 on control; difference 0.00 (95% CI -0.31 to 0.31), standardized effect d = 0.00; z-test p = 1.000.
- Interpretation:
- The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 5.0 mg MIN-117 and the control. The interval gives the range of effects that remain compatible with the data.
- The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 2.5 mg MIN-117 and the control. The interval gives the range of effects that remain compatible with the data.
Change in Clinical Global Impression of Improvement Scale (CGI-I) at Week 6
- Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
- Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
- Result:
- 5.0 mg MIN-117: mean 3.00 versus 3.00 on control; difference 0.00 (95% CI -0.29 to 0.29), standardized effect d = 0.00; z-test p = 1.000.
- 2.5 mg MIN-117: mean 3.00 versus 3.00 on control; difference 0.00 (95% CI -0.32 to 0.32), standardized effect d = 0.00; z-test p = 1.000.
- Interpretation:
- The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 5.0 mg MIN-117 and the control. The interval gives the range of effects that remain compatible with the data.
- The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 2.5 mg MIN-117 and the control. The interval gives the range of effects that remain compatible with the data.
The three posted secondary outcomes show a broadly similar pattern to the primary outcome: the arm-level means are close, and the recalculated mean differences against placebo are small or equal to 0.0 at the reported precision. Across the secondary summaries, no comparison has a recalculated unadjusted p-value below 0.398. This overall pattern does not suggest a clear separation between either dose and placebo in the posted averages, but it should be interpreted as a description of the registry summaries rather than a definitive set of trial conclusions.
The secondary measures address related but distinct aspects of the study outcomes. HAM-A measures anxiety symptoms, CGI-S rates severity, and CGI-I rates improvement. They are not interchangeable with MADRS, the primary measure of depression severity. Agreement in broad pattern across distinct measures can be context for reading the primary result, but it does not replace the primary comparison or independently establish a treatment effect.
The secondary comparisons are unadjusted. In general, conducting multiple statistical tests increases the chance that at least one result appears notable by chance, even when no underlying difference exists. A multiplicity adjustment or a prespecified testing sequence can address that issue, but the registry record does not report either for these outcomes. The p-values should not be treated as confirmatory evidence without knowing the analysis plan and how the outcomes were selected or prioritized.
The record lists no reported analyses for the secondary outcomes. The reported comparisons are therefore recalculated from summary statistics, and the registry does not describe model adjustments, missing-data handling, or formal inferential procedures. The secondary results can be read as supportive descriptive context, but they carry less weight than a prespecified, fully reported analysis of the primary outcome.
Secondary outcomes registered for this trial, for reference (only those above were recalculated):
- Change in Hamilton Anxiety Scale (HAM-A)
- Change in Clinical Global Impression of Severity Scale (CGI-S)
- Change in Clinical Global Impression of Improvement Scale (CGI-I) at Week 6
9. Statistical Interpretation
The posted primary results give a mean MADRS change of -12.0 for 5.0 mg MIN-117, -12.0 for 2.5 mg MIN-117, and -12.0 for placebo. Thus, the group averages are the same at the precision reported. The unadjusted recalculated mean difference is 0.0 for each MIN-117 comparison with placebo. The reported unadjusted p-value is 1.0 for each comparison.
The intervals around the recalculated mean differences extend in both directions from 0.0: -2.613 to 2.613 for 5.0 mg and -2.542 to 2.542 for 2.5 mg. They are compatible with differences favoring either arm, as well as no difference, within the ranges they describe. Their span reflects uncertainty in the estimated contrasts; it does not establish that the treatments are equivalent. The registry record does not report an equivalence or noninferiority margin.
These comparisons are simple, unadjusted recalculations from the posted summary statistics, rather than a reported sponsor analysis. No reported analyses are listed for the primary outcome. The registry record does not specify whether the sponsor used an adjusted model, how any such model was specified, or whether the posted arm summaries represent the full analysis used for the trial’s conclusions. The estimates should therefore be read as descriptive comparisons based on the posted means, standard deviations, and participant counts, not as a substitute for an unreported prespecified analysis.
The group means show that average change from baseline was the same across the three arms at the reported precision. The standard deviations indicate substantial variation among participants around those averages. A group average cannot describe every participant’s experience, and the summaries do not show the distribution of individual changes or the proportion meeting a response threshold. No responder threshold or responder analysis is reported in the registry record.
There are three arms, but the principal interpretation concerns two separate comparisons with placebo. The results do not establish a dose pattern in the posted primary means: both doses have the same mean and the same reported standard deviation as placebo. Nor do these summary statistics alone reveal whether differences in adherence, withdrawals, or missing outcome data affected the results. The registry record does not report those details or a detailed analysis plan. The defensible statistical reading is limited to the posted estimates, their uncertainty, and the absence of reported inferential analyses in the record.
10. Statistical Methods Explained
For a continuous outcome such as MADRS change, a group mean describes the average observed change among participants included in that outcome summary. The standard deviation describes how spread out individual values are around the group mean. It is not the uncertainty in the group mean itself: uncertainty in a mean depends on both the variability in observations and the number of observations. The primary outcome summaries report means and standard deviations for each arm.
What do the recalculated comparisons represent?
The posted mean differences compare each MIN-117 arm with placebo. A difference of 0.0 means the two posted arm means are equal at the reported precision. The recalculated intervals describe a range of values compatible with the estimate under the assumptions used in that calculation. In general, an interval’s width reflects both the observed variability and the amount of information available. These intervals are recalculations from arm-level summary statistics; the registry record does not identify them as the sponsor’s prespecified analysis or state the interval’s nominal coverage level.
The recalculations use the posted group means, standard deviations, and participant counts. They are unadjusted comparisons: the record does not provide adjustment for baseline values, other prognostic variables, or multiple comparisons in these calculations. The recalculated p-values are likewise unadjusted. In general, a p-value measures how incompatible the observed data are with a specified null model under its assumptions; it is not the probability that the null hypothesis is true, nor a measure of clinical importance. The registry record does not report a sponsor analysis for these outcomes, so the recalculations should not be mistaken for one.
What does the planning illustration mean?
A planning illustration uses an assumed effect and variability to estimate the number of participants per arm needed under stated design assumptions. The posted illustration is based on the observed HAM-A difference for 5.0 mg compared with placebo, with two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. It considers detecting 100%, 75%, or 50% of that observed effect. For 100% of the observed effect, the illustration gives 1,093 participants per arm for 80% power and 1,464 for 90% power. For 75%, it gives 1,944 and 2,602 participants per arm, respectively. For 50%, it gives 4,372 and 5,853 participants per arm, respectively.
These are planning illustrations, not observed power and not the trial’s original sample-size justification. Smaller assumed effects require more information to detect under otherwise similar assumptions. The values are conditional on the stated effect and method; they do not establish what effect is plausible in a future study. The registry record does not report the trial’s own sample-size justification.
Why can variability matter?
In general, greater variation among participants makes a mean difference harder to estimate precisely, while more observations can improve precision. The primary outcome standard deviation is 9.2 in every arm, and the participant counts differ across arms. Those features contribute to the widths of the recalculated intervals. A normal approximation is a method for estimating uncertainty; its suitability depends on the data and design. Participant-level data and diagnostic information are not reported in the registry record, so the recalculations cannot assess distributional assumptions, influential observations, or other model diagnostics.
In general, over-dispersion means that variability is greater than a statistical model expects. It can make standard errors too small if ignored. The primary outcome is continuous and is summarized by means and standard deviations; the registry does not report an over-dispersion assessment or a model-based correction. More broadly, the record does not describe covariate adjustment, missing-data methods, sensitivity analyses, or an interim-analysis plan. These omissions limit what can be inferred about the analyses beyond the reported summaries and recalculations.
11. Confidence Intervals and Precision
Precision concerns how narrowly an estimate is determined by the available data. The recalculated primary mean difference is 0.0 for both dose comparisons. Its interval extends from -2.613 to 2.613 for 5.0 mg MIN-117 versus placebo, and from -2.542 to 2.542 for 2.5 mg versus placebo. Both intervals include 0.0 and allow for differences in either direction. They therefore do not pinpoint the contrast to exactly zero.
The intervals are not identical in width. The outcome counts are 70 for 5.0 mg, 76 for 2.5 mg, and 149 for placebo. In general, the precision of a comparison depends on the variability and sample size in both groups. These summaries have standard deviations of 9.2 in all three arms. The larger placebo group contributes information to both comparisons, while the two MIN-117 groups have different counts. The recalculated intervals reflect those posted inputs under the calculation assumptions.
A confidence interval is generally interpreted as a range of estimates compatible with the data and a statistical procedure. The registry record does not specify the nominal coverage level for the recalculated intervals, and they are not identified as the sponsor’s reported intervals. They should not be interpreted as proof that all values inside the range are equally plausible, or that values outside it are impossible. In particular, an interval containing zero does not demonstrate equivalence. A formal equivalence conclusion requires a prespecified margin and an appropriate analysis; such a margin is not reported in the registry record.
Precision is distinct from the magnitude or importance of an effect. Here, the recalculated point estimates are 0.0 at the posted precision, while the intervals retain uncertainty about nonzero differences. The registry record does not report a threshold for a meaningful MADRS difference, so the clinical importance of particular values within those intervals cannot be determined from the record alone.
12. Multiplicity, Missing Data and Analysis Populations
The registry lists one primary outcome and three secondary outcomes. It does not report how the statistical testing across outcomes or across the two dose comparisons was controlled. In general, when several hypotheses are tested, the chance of at least one apparently unusual result can increase. Methods such as family-wise error control, a hierarchical testing sequence, or a clearly designated exploratory analysis can clarify how multiple results should be interpreted. None of these approaches is described in the registry record, so the recalculated p-values should be understood as unadjusted rather than as multiplicity-controlled evidence.
The record identifies the primary outcome population as randomized participants who received at least 1 dose of study drug. This is the registry’s stated definition; it should not be assumed to match every common use of the term intention-to-treat, which can vary in practice. The primary outcome summaries include 70 participants in the 5.0 mg group, 76 in the 2.5 mg group, and 149 in the placebo group. Reasons these outcome counts do not match the listed enrollment of 360 are not reported in the registry record.
Missing outcome data can affect estimates if participants with missing measurements differ systematically from those with observed measurements. In general, analyses may use methods such as likelihood-based models, imputation, or sensitivity analyses to examine the consequences of missingness. The registry record does not report how missing Week 6 values were handled, how many measurements were missing, or whether sensitivity analyses were conducted. It also does not report withdrawals by arm in the registry record for these results.
The registry record does not describe a detailed statistical analysis plan, covariate adjustment, interim analyses, or whether analyses were conducted according to prespecified procedures. Those omissions do not establish that such procedures were absent; they mean the record does not report them. Accordingly, the recalculated comparisons should be kept distinct from any unreported sponsor analysis, and no claims about the handling of multiplicity or missing data can be made from the registry summaries alone.
13. 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 |
|---|---|---|---|
| 5.0 mg MIN-117 | 0 | 91 | 0.0% |
| 2.5 mg MIN-117 | 1 | 92 | 1.1% |
| Placebo | 0 | 177 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| 5.0 mg MIN-117 | 0 of 91 |
| 2.5 mg MIN-117 | 0 of 92 |
| Placebo | 0 of 177 |
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 |
|---|---|
| 5.0 mg MIN-117 | 11 of 91 |
| 2.5 mg MIN-117 | 11 of 92 |
| Placebo | 13 of 177 |
Most frequent serious adverse event terms
| Event term | Organ system | 5.0 mg MIN-117 | 2.5 mg MIN-117 | Placebo |
|---|---|---|---|---|
| Feeling guilty | Psychiatric disorders | 0 of 91 | 1 of 92 | 0 of 177 |
| Major depression | Psychiatric disorders | 0 of 91 | 1 of 92 | 0 of 177 |
| Suicidal ideation | Psychiatric disorders | 0 of 91 | 1 of 92 | 0 of 177 |
Most frequent non-serious adverse event terms
| Event term | Organ system | 5.0 mg MIN-117 | 2.5 mg MIN-117 | Placebo |
|---|---|---|---|---|
| Headache | Nervous system disorders | 11 of 91 | 11 of 92 | 13 of 177 |
Serious events with the highest arm-level rate: feeling guilty (1.1%), major depression (1.1%), suicidal ideation (1.1%).
The safety summaries use groups of 91 participants for 5.0 mg MIN-117, 92 for 2.5 mg, and 177 for placebo. Serious adverse events were reported for 0 participants in the 5.0 mg arm, 1 in the 2.5 mg arm, and 0 in the placebo arm. The registry lists no deaths in any group. Other adverse events were reported for 11 participants in each MIN-117 group and 13 in the placebo group.
These are counts from the registry record, not estimates that establish whether an event was caused by study treatment. Serious events are uncommon in these summaries, and the counts are too limited to support strong comparative conclusions about safety. The registry also lists the serious-event terms Feeling guilty, Major depression, and Suicidal ideation, each at 1.1%. The record does not explain the relationship between these term percentages and the participant counts in the group summaries, so they should be read as listed rather than reconciled by assumption.
In general, adverse-event counts describe what was recorded during a study; they do not by themselves establish causality or capture every aspect of risk. The 6-week study duration and the reported counts are the available context. Broader or longer-term safety conclusions are not established by these figures.
14. What the Result Does, and Does Not, Mean
The primary summaries show the same average Week 6 MADRS change in all three arms: -12.0. The recalculated mean differences against placebo are 0.0 for both MIN-117 doses, with unadjusted p-values of 1.0. The recalculated intervals include zero and also allow for differences in either direction. This is a statement about the posted group averages and their uncertainty, not a finding that the treatments are equivalent.
The results do not show how individual participants changed. A mean can conceal a range of outcomes, and the registry record does not report responder rates or the distribution of individual changes. It also does not report a threshold for a clinically meaningful difference on MADRS. Consequently, the posted group averages cannot determine the number of participants who experienced a particular degree of change or the clinical importance of a difference within the interval.
The posted figures do not establish why the arm means are equal. They cannot determine whether the similarity reflects a true absence of a difference, limited precision, measurement variability, missing outcome data, or other factors. Information about participant-level outcomes, baseline characteristics, adherence, withdrawals, and missing-data methods is not reported in the registry record.
Nor do the summaries establish the conclusion of an unreported sponsor analysis. The recalculated comparisons use posted summary statistics and are unadjusted. They do not account for any model or analysis choices that are not described in the record. The appropriate scope is therefore narrow: the registry’s posted average changes are identical at the reported precision, and the simple recalculations do not estimate a difference between either dose and placebo. The record does not support stronger claims about equivalence, individual benefit, or the full analysis used by the sponsor.
15. Why This Trial Matters Statistically
This trial is statistically informative as an example of why an arm’s change from baseline should not be interpreted in isolation. The mean MADRS change is -12.0 in each group, including placebo. The treatment comparison is the difference between groups, not simply whether each group’s mean moved from baseline. Because the posted changes match at the reported precision, the average change alone does not indicate a separation between MIN-117 and placebo.
The study also illustrates the role of precision. A point estimate of 0.0 does not mean the underlying difference is known exactly. The recalculated intervals extend on either side of zero, leaving uncertainty about the size and direction of a possible difference. This distinction matters when describing results: the estimate, its uncertainty, and the strength of the analysis are related but not interchangeable.
Another statistical issue is the gap between registry summaries and a fully reported analysis. The registry provides arm means, standard deviations, and counts, while the recalculated contrasts are unadjusted. It does not report the sponsor’s primary outcome analysis or a detailed plan for multiplicity and missing data. Readers therefore need to distinguish descriptive summaries from confirmatory inference.
Finally, the planned allocation description, listed enrollment, and outcome counts are not the same figures. The record does not explain the differences. Recognizing such distinctions is important when assessing what population the estimates represent and how precisely they apply to the randomized participants. The example underscores that statistical interpretation depends not only on the numerical result, but also on analysis definitions and reporting detail.
16. 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 main limitation for interpreting the primary result is that the registry reports arm-level summary statistics but no sponsor analysis for the primary outcome. The recalculated comparisons are unadjusted and do not incorporate any model choices that may have been used elsewhere. The statistical analysis plan, covariate adjustment, and treatment of repeated or baseline measurements are not reported in the registry record.
The registry’s listed enrollment is 360, while the brief summary says approximately 324 patients were to be randomized, and the primary outcome summaries include 70, 76, and 149 participants across the three arms. The record does not explain these figures or identify reasons for differences in the counts. It also does not provide arm-specific withdrawal information or the number of missing Week 6 outcomes. This limits assessment of the analysis population and the possible influence of missing data.
The record does not report a MADRS threshold for clinical importance, individual response distributions, or an equivalence margin. As a result, identical posted means cannot be translated into a claim of equivalence or a description of how many participants had meaningful improvement. Nor does the record report the confidence level associated with the recalculated intervals.
For safety, the reported groups and event counts offer limited information about uncommon events, and the study’s stated treatment period was 6 weeks. The serious-event terms are listed with percentages, but their relation to the group-level counts is not explained. These trial-specific reporting gaps constrain interpretation; they do not establish that the unreported analyses or procedures were not conducted.
17. Related Tutorials
18. Related Statistical Calculators
19. Sources
- ClinicalTrials.gov: A Study to Evaluate the Efficacy and Safety of MIN-117 in Adult Patients With Major Depressive Disorder — NCT03446846.
- Registry record last updated 2020-12-17; status last verified 2020-12.
- Results first posted 2020-12-17.
- 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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20. Record Summary
The registry describes a completed Phase 2 randomized, double-blind, parallel-group, placebo-controlled study of 5.0 mg and 2.5 mg MIN-117 in adults aged 18 to 65 years with major depressive disorder. Treatment was oral and daily for 6 weeks. The primary outcome was Week 6 change in MADRS total score.
Mean change was -12.0 in each arm, with standard deviation 9.2. Recalculated unadjusted mean differences versus placebo were 0.0 for both doses. The record also lists HAM-A, CGI-S, and CGI-I as secondary outcomes. It reports no analyses for those outcomes and does not provide a detailed statistical analysis plan or missing-data methods.
Serious adverse events were reported for 0 participants in the 5.0 mg arm, 1 in the 2.5 mg arm, and 0 in placebo; no deaths were listed. The outcome summaries and safety groups have different participant counts, and the reasons are not reported in the registry record.