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 Safety Extension Study of 15 and 20 mg of Vortioxetine (Lu AA21004) in Long-term Treatment of Major Depressive Disorder in Adults (NCT01323478), a na phase 3 study. The primary outcome is Number of Patients With Adverse Events (AEs).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01323478 |
| Phase | Phase 3 |
| Condition | Major Depressive Disorder |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 71 |
| Arms in the primary outcome | n/a |
| Lead sponsor | H. Lundbeck A/S |
| Results posted | Yes |
2. Clinical Question
Population
Adults with major depressive disorder who entered a long-term extension study. The registry record lists 71 participants enrolled and identifies the all-patients-treated set as the population for the primary safety outcome. Further eligibility details and the number who completed each assessment are not reported in the registry record.
Intervention
Flexible-dose vortioxetine, listed as 15 or 20 mg/day. The study was intended to evaluate safety and tolerability over 52 weeks, followed by a 4-week safety follow-up period. The registry record does not report how many participants received each dose or how dose adjustments were made.
Comparator
There was no control group. The study is recorded as single-group, with allocation listed as not applicable and masking listed as none. Results therefore describe participants in the extension study; they do not provide a randomized comparison with another treatment or with no treatment.
Primary question
The primary outcome was the number of patients with adverse events from baseline to the end of the 4-week safety follow-up period. The registry also lists changes in symptom and other assessment scores, response and remission, and suicidality as secondary outcomes. Numerical results for those secondary outcomes are not reported in the registry record.
3. Trial Design
This completed Phase 3 study was an open-label, flexible-dose, single-group extension study of vortioxetine in adults with major depressive disorder. The registry lists 71 participants enrolled. The study title and summary describe treatment with 15 or 20 mg/day over 52 weeks, with safety follow-up continuing through a 4-week period after treatment. The registry record does not state how many participants received each dose, how long individual participants remained in the study, or how many completed the planned treatment and follow-up.
There was no randomized allocation, masking, or parallel control arm. The registry lists allocation as not applicable, masking as none, and the model as single group. The design therefore supports a descriptive account of outcomes among participants in the study, rather than a direct estimate of a treatment difference against a concurrent comparison group. Open-label status also means that participants and study personnel were not masked to the treatment.
The primary outcome was the number of patients with adverse events, assessed from baseline to the end of the safety follow-up period in the all-patients-treated set. Secondary outcomes included changes in MADRS, CGI-S, and HAM-A scores; response and remission based on MADRS; SDS and ASEX scores; and suicidality assessed using C-SSRS scores. The registry lists 10 outcome measures but does not report numerical results for these secondary outcomes. Details of the protocol, dose allocation, visit schedule, and statistical analysis plan 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.
Before assignment: The study consisted of a 52-week open-label period and a 4-week Safety Follow-up Period.
Overall Study
| Stage | Vortioxetine 15 or 20 mg/Day |
|---|---|
| STARTED | 71 |
| COMPLETED | 47 |
| NOT COMPLETED | 24 |
Reasons for not completing this period:
| Reason | Vortioxetine 15 or 20 mg/Day |
|---|---|
| Adverse Event | 7 |
| Lack of Efficacy | 4 |
| Non-compliance With Study Product | 3 |
| Protocol Violation | 1 |
| Withdrawal of Consent | 1 |
| Administrative or Other Reasons | 8 |
Analysis population for the primary outcome, as defined in the registry: all-patients-treated set (APTS)
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: Age and Gender: all-patients-treated set (APTS) - all patients who took at least one dose of Vortioxetine. Study Specific Characteristics: full-analysis set (FAS) - all 71 patients in the APTS who had at least one valid post-Baseline assessment of the MADRS total score in present study, 13267B.
| Characteristic | Unit | Vortioxetine 15 or 20 mg/Day |
|---|---|---|
| Participants analysed | 71 | |
| Age, Continuous | years | 44.1 (SD 12.7) |
| Sex: Female, Male: Female | Participants | 53 |
| Sex: Female, Male: Male | Participants | 18 |
| MADRS: Baseline present study, 13267B | units on a scale | 16.2 (SD 10.0) |
| CGI-S: Baseline present study, 13267B | units on a scale | 3.0 (SD 1.3) |
| HAM-A: Baseline present study, 13267B | units on a scale | 11.9 (SD 6.6) |
| MADRS: Baseline from lead-in study 13267A (NCT01140906) | units on a scale | 31.1 (SD 3.3) |
6. Primary Endpoint
The registry lists the primary outcome as Number of Patients With Adverse Events (AEs), measured over Baseline to end of the 4-week safety follow-up period.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of patients with adverse events during the period from baseline through the end of the 4-week safety follow-up. The registry identifies the all-patients-treated set as the analysis population. An outcome based on the number of affected participants is a count: it describes how many people experienced an event, rather than how many separate event episodes occurred. The registry record does not give a fuller operational definition of an adverse event or explain how recurrent events were handled.
In general, counting participants with adverse events is a way to describe the observed safety experience during a defined period. The count is easier to interpret when its population and observation period are clear, as they are specified in the endpoint description. It does not, by itself, establish whether an event was caused by treatment. In a single-group, open-label study, the count also cannot show how the same participants’ event experience would have differed under a control condition.
The posted safety figures list 47 participants with other adverse events and 1 participant with a serious adverse event. The primary endpoint’s overall count is not separately stated in the registry record, so those categories should not be combined into a new total. Numerical results for the listed symptom, response, remission, and other secondary outcomes are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a long-term, open-label extension study with one treatment group and 71 participants enrolled. Its primary focus was safety and tolerability during treatment and the subsequent safety follow-up. The posted adverse-event figures identify 1 participant with a serious adverse event and list cholelithiasis at 1.4% among the top serious terms. The record also lists 47 participants with other adverse events. These are descriptive counts from the study, not estimates of a difference between vortioxetine and a control treatment.
The primary outcome is defined as the number of patients with adverse events, but the record does not separately state a total for that endpoint. The serious and other adverse-event figures should therefore be read as the specific categories reported, not added to create a total. The registry also does not provide a separate numerical account of deaths; that information is not reported in the registry record.
The registry lists several secondary outcomes, including changes in depression, anxiety, and global severity scores, along with response, remission, functioning, sexual-function, and suicidality measures. Their outcome titles describe what was intended to be assessed, but do not establish what the results were. Numerical estimates, uncertainty intervals, and statistical tests for these outcomes are not reported in the registry record. The presence of outcome definitions alone is not evidence of improvement or worsening.
In general, a single-group study can describe what was observed in its participants over the period assessed. It cannot isolate treatment effects from other explanations, such as the course of the condition, participant selection, changes in care, or expectations in an open-label study. Those are general interpretive limitations of this design, not findings about what occurred in this particular study.
No comparative effect estimate, confidence interval, or p-value is reported in the registry record. In general, a confidence interval communicates the precision of an estimate and the range of values compatible with the data under the analysis assumptions. Without such estimates, the precision of the posted safety counts cannot be fully characterized. The registry record also does not report the number of participants assessed at each time point, so the completeness of follow-up cannot be evaluated from the listed information.
Overall, the posted record documents a planned long-term safety assessment and reports selected adverse-event counts. It does not support a randomized comparison or a quantitative conclusion about the secondary outcomes. Any sample-size illustrations associated with this analysis are planning illustrations, not observed power and not evidence that the trial was designed around those calculations.
9. Statistical Methods Explained
What does a participant count represent?
The primary outcome is expressed as the number of participants with adverse events, rather than as a continuous score or a time-to-event estimate. The registry specifies the all-patients-treated set and the period from baseline through the end of the 4-week safety follow-up. These details define the population and observation window for interpreting the endpoint. The record does not provide an event-level definition, rules for counting repeated events, or a separate total for the primary endpoint.
In general, a participant count is a descriptive measure. It is distinct from the number of event episodes: one participant can potentially experience more than one event, while the participant count concerns whether a person experienced an event. Counts are usually read alongside the number of people observed and the completeness of follow-up. The registry lists 71 participants enrolled, but the number contributing to each outcome assessment and the handling of missing observations are not reported in the registry record.
How should uncertainty be understood?
In general, a confidence interval describes uncertainty around an estimate: it indicates a range of values compatible with the observed data under the method’s assumptions. For a count or proportion, uncertainty depends on both the observed outcome and the number of participants contributing information. The registry record does not provide a confidence interval for the adverse-event figures, nor does it report a statistical test for the primary endpoint. As a result, the precision of those figures cannot be assessed using the posted information alone.
A lack of a reported interval is not proof that an estimate is precise or imprecise. It means that the registry entry does not give the information needed to quantify that uncertainty. The reported counts should therefore be understood as descriptions of the study experience, without treating them as exact estimates of the frequency that would occur in another population or setting.
What does the single-group design permit?
The study is recorded as single group, open label, with no allocation to a comparator and no masking. In general, a single-group design can report outcomes observed during participants’ exposure and follow-up. It does not directly estimate a between-group treatment effect, because there is no concurrent control group in the record. Changes in symptom scores, even if numerical results were available, would be changes observed over time and would not by themselves separate treatment effects from other influences.
Open-label conduct means treatment knowledge was not concealed from participants and study personnel. In general, this can matter for outcomes involving participant reports or assessments, because expectations and awareness may influence reporting or measurement. The registry record does not describe additional steps used to address that possibility. No claim about the presence or size of such influence can be made from the posted details.
What can be learned from a safety count?
In general, the number of participants with serious adverse events and the number with other adverse events provide different descriptive safety information. They should not be added unless the definitions, overlap, and counting rules are clear. The registry lists 1 participant with a serious adverse event and 47 with other adverse events, but does not explain whether categories are mutually exclusive or provide a separately reported total for the primary endpoint. The serious-term listing gives cholelithiasis as 1.4%; the record does not give further detail about event timing, recurrence, or attribution.
In general, over-dispersion matters when count data vary more than a chosen statistical model expects. A model that assumes less variability than is present can produce uncertainty estimates that are too narrow. This is a general statistical consideration, not a reported feature of this trial: the registry record does not describe a count model, model checks, or a statistical analysis for the adverse-event endpoint. No conclusion about over-dispersion can be drawn for these data from the entry.
What do planning calculations mean?
The study record does not report its sample-size justification or a formal sample-size calculation. Planning illustrations based on an observed effect are hypothetical calculations for thinking about a future design; they are not the trial’s original design rationale. In general, such illustrations depend on assumptions about the target effect, significance level, allocation, and statistical method. They should not be mistaken for observed power, which is not a measure of how convincing the trial results are after data have been collected. The calculation assumptions stated for the illustrations do not establish that the trial itself used them.
The registry lists 10 outcome measures and 0 analyses. This does not establish that no analyses were performed; it describes what is recorded in the entry. Statistical methods, model specifications, adjustment choices, and analysis details for the outcomes are not reported in the registry record. Accordingly, interpretation should remain anchored to the descriptive information that is actually posted.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 10 outcome measures, including a primary safety endpoint and secondary measures covering symptom-score changes, response, remission, functioning, sexual-function scores, and suicidality. When a study assesses multiple outcomes, the chance of at least one apparently unusual statistical result can increase if many tests are performed. In general, multiplicity methods are used to address that issue, but the appropriate approach depends on the study’s aims and analysis plan. Whether any multiplicity adjustment was planned or used is not reported in the registry record.
The record lists 0 analyses, but that entry does not establish that no statistical analyses were conducted. It means that analysis details are not available in the registry entry. The statistical methods for the primary endpoint and secondary outcomes, including any prespecified testing hierarchy, are not reported in the registry record. No p-values or confidence intervals for these outcomes are posted.
The all-patients-treated set is named as the population for the primary endpoint. The registry does not describe how missing data were handled, whether participants who discontinued treatment contributed follow-up information, or how outcome-specific analysis populations were defined. The number assessed at each scheduled time and the extent of missing data are not reported in the registry record.
In general, missing observations can affect interpretation when the participants with available results differ from those without results. Without follow-up counts and a stated missing-data method, it is not possible to assess how missingness might have influenced the results. These gaps are especially relevant to outcomes described as changes from baseline or assessments at week 52, because interpreting change requires information about which participants contributed paired measurements.
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 |
|---|---|---|---|
| Vortioxetine 15 or 20 mg/Day | 1 | 71 | 1.4% |
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 |
|---|---|
| Vortioxetine 15 or 20 mg/Day | 47 of 71 |
Most frequent serious adverse event terms
| Event term | Organ system | Vortioxetine 15 or 20 mg/Day |
|---|---|---|
| Cholelithiasis | Hepatobiliary disorders | 1 of 71 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Vortioxetine 15 or 20 mg/Day |
|---|---|---|
| Nausea | Gastrointestinal disorders | 22 of 71 |
| Dizziness | Nervous system disorders | 14 of 71 |
| Headache | Nervous system disorders | 14 of 71 |
| Nasopharyngitis | Infections and infestations | 9 of 71 |
| Insomnia | Psychiatric disorders | 7 of 71 |
| Dry mouth | Gastrointestinal disorders | 5 of 71 |
| Sinusitis | Infections and infestations | 5 of 71 |
| Viral upper respiratory tract infection | Infections and infestations | 5 of 71 |
| Accidental overdose | Injury, poisoning and procedural complications | 5 of 71 |
| Abdominal pain upper | Gastrointestinal disorders | 4 of 71 |
Serious events with the highest arm-level rate: cholelithiasis (1.4%).
The registry reports that 1 participant in the Vortioxetine 15 or 20 mg/Day group had a serious adverse event, among 71 participants at risk. It lists cholelithiasis at 1.4% among the top serious terms. The record does not provide further details about the event, its timing, duration, outcome, or assessed relationship to treatment. The listing therefore supports a description of what was recorded, not a conclusion about cause.
The registry separately reports 47 participants with other adverse events among 71 at risk. It does not explain whether participants could appear in both the serious and other categories, or provide a separately stated overall count for the primary endpoint. Those figures should be kept in their reported categories rather than summed. The primary endpoint is defined over baseline through the end of the 4-week safety follow-up period.
Deaths are not reported in the registry record. The record also does not give event-level data, participant-level timing, or an account of how repeated events were handled. In general, safety counts describe events recorded in the study population and observation period; without a comparison group, they do not estimate how many events would have occurred under another condition.
12. What the Result Does, and Does Not, Mean
The registry record documents an open-label, single-group study intended to assess long-term safety and tolerability of flexible-dose vortioxetine in adults with major depressive disorder. It lists 71 participants enrolled and reports selected adverse-event counts: 1 participant with a serious adverse event and 47 with other adverse events. Cholelithiasis is listed at 1.4% among the top serious terms. These figures describe the study record and do not establish that treatment caused or prevented any event.
The design has no randomized control group, and masking is listed as none. For that reason, the posted information cannot establish a treatment difference relative to another intervention or to no treatment. A count observed in a single group also cannot distinguish treatment-related events from events that might have occurred for other reasons. This is a general limitation of the design, not a claim that any particular event had a specific cause.
The registry lists secondary outcomes on depression symptoms, anxiety, global severity, response, remission, functioning, sexual function, and suicidality. Their numerical results are not reported in the registry record. The outcome titles indicate what was assessed or planned for assessment; they do not tell readers whether scores changed, whether participants met response criteria, or how precisely any results were estimated.
The record does not separately state a total for the primary adverse-event endpoint, provide confidence intervals or p-values, or explain missing-data handling. It also does not report the number of participants contributing to every outcome assessment. Those omissions limit assessment of precision, completeness, and analysis choices.
In general, the distinction between a descriptive study result and a comparative treatment effect is important. The available information supports a cautious account of recorded safety experience in this study. It does not support a causal or comparative conclusion, nor a quantitative conclusion about the listed secondary outcomes.
13. Why This Trial Matters Statistically
Statistically, this study is an example of a long-term extension with a safety-focused primary outcome and no concurrent control group. That makes the distinction between describing observed events and estimating a comparative treatment effect especially important. The record identifies the outcome period and analysis population for the primary endpoint, which are necessary context for reading a participant count.
The registry also illustrates why endpoint definitions and numerical results are not interchangeable. Several secondary outcomes are named, including score changes and threshold-based response and remission, but their results are not reported in the registry record. Knowing what was measured does not reveal the magnitude, precision, or direction of any result. Reporting the analysis population, follow-up, and uncertainty would be needed to evaluate those outcomes more fully.
There is also a practical lesson in keeping safety categories distinct. The record reports serious and other adverse-event counts, but does not give a separate overall primary endpoint count or explain the overlap between categories. Combining reported counts without that information could misrepresent how many participants were affected.
Finally, sample-size illustrations are not the same as a trial’s design justification or observed power. The registry does not report the study’s sample-size rationale or detailed analysis plan. Recognizing those distinctions helps readers avoid treating planning assumptions or incomplete reporting as evidence about the strength of a result. The statistical value of the record is therefore chiefly descriptive: it shows the design, specified outcomes, and selected safety figures while also making clear where the available account does not quantify results.
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 main limitation specific to interpreting this study is its single-group, open-label design. Without a randomized comparator, the adverse-event counts cannot be interpreted as differences attributable to vortioxetine. Awareness of treatment may also influence participant reports or assessments in general, although the registry record does not report whether or how this was evaluated.
The study is described as using flexible doses of 15 or 20 mg/day, but the record does not state how many participants received each dose or how dose changes were managed. It is therefore not possible to interpret the posted safety figures separately by dose or determine whether exposure patterns differed among participants.
Although 71 participants were enrolled, the registry does not report the number followed through each assessment, the number completing the 52-week treatment period, or the number contributing to each secondary outcome. Missing-data methods and outcome-specific analysis populations are not reported in the registry record. This limits evaluation of follow-up completeness and the representativeness of results at later assessments.
The registry lists selected adverse-event counts but does not provide a separately stated total for the primary endpoint, event-level descriptions, or information on event timing and attribution. Numerical results for the listed secondary outcomes, along with confidence intervals, p-values, and detailed statistical methods, are also not reported. These limitations restrict both the precision of interpretation and the range of conclusions that can be drawn from the posted record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Open-label Safety Extension Study of 15 and 20 mg of Vortioxetine (Lu AA21004) in Long-term Treatment of Major Depressive Disorder in Adults — NCT01323478.
- Registry record last updated 2014-02-11; status last verified 2013-12.
- Results first posted 2014-02-11.
- 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
NCT01323478 is a completed Phase 3, open-label, single-group extension study of vortioxetine in adults with major depressive disorder. The registry lists 71 participants enrolled and describes flexible dosing at 15 or 20 mg/day over 52 weeks, with a 4-week safety follow-up period. The primary endpoint was the number of patients with adverse events in the all-patients-treated set.
The posted safety figures list 1 participant with a serious adverse event and 47 with other adverse events; cholelithiasis is listed at 1.4% among the top serious terms. The record does not separately state an overall primary endpoint count. It lists secondary symptom, response, remission, functioning, and suicidality outcomes, but their numerical results are not reported in the registry record. The single-group design provides descriptive information, not a randomized treatment comparison.