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 Pharmacokinetics and Tolerability of Vortioxetine (Lu AA21004) in Child and Adolescent Patients With Depressive or Anxiety Disorder (NCT01491035), a non-randomized phase 2 study. The primary outcome is Cmax of Vortioxetine.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01491035 |
| Phase | Phase 2 |
| Condition | Depressive Disorder, Anxiety Disorder |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 48 |
| Arms in the primary outcome | n/a |
| Lead sponsor | H. Lundbeck A/S |
| Results posted | Yes |
2. Clinical Question
The study asked how vortioxetine and its metabolites behave in the body during repeated oral dosing in child and adolescent patients diagnosed with a depressive or anxiety disorder. Its primary endpoint was Cmax, the maximum plasma concentration of vortioxetine. This is a pharmacokinetic question: it concerns drug concentration over time, rather than whether symptoms improve compared with a control treatment.
Population
Children and adolescents with a DSM-IV-TR diagnosis of depressive or anxiety disorder. The planned enrollment was 48 participants, arranged in child and adolescent cohorts.
Intervention
Multiple oral dosing of vortioxetine at assigned dose levels. The safety groups identify 5 mg, 10 mg, 15 mg, and 20 mg dose levels for both age groups.
Comparator
There was no randomized control group. The registry describes a non-randomized, single-group, open-label study; dose-level cohorts are not a like-for-like randomized comparison.
Primary question
What maximum plasma concentration of vortioxetine was observed after dosing, using scheduled pharmacokinetic samples? The numerical Cmax results are not reported in the registry record.
The study record lists eight cohorts: four cohorts of children and four of adolescents, with 6 participants in each. The record identifies the primary endpoint’s sampling schedule and the pharmacokinetic analysis population, but does not provide the endpoint estimates. It therefore establishes the type of question examined, but not the concentration findings needed to characterize the observed pharmacokinetics.
3. Trial Design
This completed phase 2 study was open-label, non-randomized, and described as a single-group study. Its title identifies an evaluation of pharmacokinetics and tolerability during multiple oral dosing of vortioxetine in child and adolescent patients with a DSM-IV diagnosis of depressive or anxiety disorder. The brief summary specifies DSM-IV-TR. Enrollment was 48.
The registry lists eight cohorts, each with 6 participants: four child cohorts and four adolescent cohorts. The safety groups identify four dose levels in each age group: 5 mg, 10 mg, 15 mg, and 20 mg. Because allocation was non-randomized and there was no control arm, these groups should not be read as randomized comparisons. Differences among their posted outcomes, if available, would not by themselves establish that dose caused a difference.
The study began in 2012-04, had primary completion in 2014-12, and is marked completed. The registry lists vortioxetine as the intervention. It does not report a detailed dosing schedule, treatment duration, eligibility criteria beyond the stated diagnoses and age categories, or the method used to assign participants to cohorts. Those details are not reported in the registry record.
The record identifies seven outcome measures and a primary Cmax endpoint, but provides no numerical pharmacokinetic estimates in the information available for this analysis. It also lists zero analyses. The registry record does not report a randomized treatment comparison or a statistical analysis plan. These features matter when interpreting the study: its stated purpose is pharmacokinetic and tolerability evaluation, and its design does not support a controlled estimate of comparative treatment effect.
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.
Only the first 6 of 8 groups are shown.
Overall Study
| Stage | Adolescents, 5 mg | Adolescents, 10 mg | Adolescents, 15 mg | Adolescents, 20 mg | Children, 5 mg | Children, 10 mg |
|---|---|---|---|---|---|---|
| STARTED | 6 | 6 | 6 | 6 | 6 | 6 |
| COMPLETED | 6 | 6 | 6 | 6 | 5 | 6 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 1 | 0 |
Reasons for not completing this period:
| Reason | Adolescents, 5 mg | Adolescents, 10 mg | Adolescents, 15 mg | Adolescents, 20 mg | Children, 5 mg | Children, 10 mg |
|---|---|---|---|---|---|---|
| Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: Pharmacokinetic analysis set = all patients who took at least one dose of IMP and who contributed with both Day 1 pre-dose pharmacokinetic sampling data and sufficient post-dose sampling data for estimation of the pharmacokinetic parameters.
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.
Only the first 6 of 9 groups are shown.
| Characteristic | Unit | Adolescents, 5 mg | Adolescents, 10 mg | Adolescents, 15 mg | Adolescents, 20 mg | Children, 5 mg | Children, 10 mg |
|---|---|---|---|---|---|---|---|
| Participants analysed | 6 | 6 | 6 | 6 | 6 | 6 | |
| Age, Continuous | years | 15.7 (SD 1.9) | 15.3 (SD 1.9) | 15.2 (SD 1.2) | 14.8 (SD 1.9) | 10.3 (SD 1.2) | 9.7 (SD 1.2) |
| Sex: Female, Male: Female | Participants | 3 | 3 | 5 | 4 | 3 | 3 |
| Sex: Female, Male: Male | Participants | 3 | 3 | 1 | 2 | 3 | 3 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 2 | 1 | 2 | 1 | 4 |
| Race (NIH/OMB): White | Participants | 4 | 4 | 4 | 4 | 4 | 2 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 1 | 0 | 1 | 0 | 1 | 0 |
| Region of Enrollment: United States | participants | 6 | 6 | 6 | 3 | 4 | 6 |
| Region of Enrollment: Germany | participants | 0 | 0 | 0 | 3 | 2 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Cmax of Vortioxetine, measured over Pre-dose and 1, 3, 5, 8, 12 and 24 hours post-dose on Day 14, 16, 18, or 20, depending on assigned dose level.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Standard Deviation |
| Unit | ng/mL |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is Cmax of vortioxetine, defined in the registry as the maximum plasma concentration. It is measured in ng/mL. Concentration is assessed using samples collected pre-dose and at 1, 3, 5, 8, 12, and 24 hours post-dose on Day 14, 16, 18, or 20, depending on assigned dose level.
In general, Cmax describes the highest measured or estimated concentration over a specified sampling period. Pharmacokinetic researchers use it to characterize exposure after dosing and to compare concentration profiles across groups or dosing conditions. It is not a measure of symptom change or clinical benefit. The endpoint’s interpretation depends on the timing and adequacy of samples and on the rules used to estimate the peak concentration; those estimation details are not reported in the registry record.
The registry labels the parameter as a median and the dispersion as standard deviation. It does not provide a numerical Cmax estimate, a standard deviation, or a confidence interval. The registry record therefore identifies what was intended to be measured and when, but does not report the result needed to describe the observed concentration level or its variability.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry establishes that this was a pharmacokinetic study of repeated oral vortioxetine dosing in children and adolescents, with Cmax as the primary endpoint. It does not report numerical Cmax values. Consequently, the posted record does not allow the magnitude, spread, or precision of the primary pharmacokinetic result to be assessed. No numerical comparison of age groups or dose levels can be made from the available record.
The endpoint is defined with a sampling schedule spanning pre-dose through 24 hours post-dose, on a study day that depended on assigned dose level. That schedule identifies the intended observation window, but does not show what concentrations were measured at each time or how the peak was estimated. The record also does not provide a confidence interval. In general, a confidence interval expresses uncertainty around an estimate; without an estimate and interval, the precision of Cmax cannot be judged.
The study’s design is important to interpretation. It was open-label and non-randomized, with no control group. The cohorts are described by age and dose, but they are not randomized comparison arms. Even if numerical outcomes were available for each group, differences could reflect factors other than dose or age. A controlled causal comparison is not described.
The safety figures report zero participants with serious adverse events in each listed group, with 6 participants at risk in each group. They also report other adverse events affecting 4 or 5 participants in each group, depending on the group. These are group-level counts, not a description of event type, timing, severity, or relation to treatment. The registry does not list serious adverse event terms. Death counts are null, so they should not be interpreted as confirmed zero deaths.
The record lists seven outcome measures but the available information does not include numerical results for those outcomes. It lists zero analyses, and does not report inferential estimates, p-values, confidence intervals, or a statistical analysis plan. The conclusions that can be drawn are therefore limited to the study purpose, design, endpoint definition, and posted safety counts. The missing numerical pharmacokinetic results prevent assessment of the actual concentration findings or their uncertainty.
9. Statistical Methods Explained
The registry identifies a primary pharmacokinetic endpoint, Cmax, and labels its parameter as a median with standard deviation as the dispersion measure. It does not provide an analysis description, numerical endpoint estimate, or the underlying concentration data. The statistical methods used to produce the endpoint are therefore not reported in the registry record. The explanations below describe general statistical concepts, not methods confirmed to have been used in this study.
What does Cmax measure?
In general, a pharmacokinetic profile describes how a drug concentration changes over time after dosing. Cmax is the maximum concentration identified during the specified observation window. A sampling schedule helps locate the peak, but discrete samples may not capture the exact time of the true maximum. The registry specifies pre-dose and post-dose sampling times, but does not say whether Cmax was taken directly from observed samples or estimated using a model. It also does not report how samples outside the planned schedule, if any, were handled.
The registry gives the unit ng/mL and defines the endpoint as maximum plasma concentration. A concentration estimate describes exposure in plasma; it is not itself a clinical outcome such as symptom improvement. Interpreting an age- or dose-group concentration pattern would ordinarily require the numerical estimates, information on variability, and a clear account of the analysis population and estimation procedure. The record does not supply those results.
How should median and standard deviation be understood?
In general, the median is the middle value after observations are ordered. It is often used to describe a typical value when a distribution is skewed or contains extreme observations. The standard deviation describes spread around a mean and is most straightforward to interpret alongside a mean. The registry labels the primary parameter as median and its dispersion as standard deviation, but does not explain this pairing or report either value. The distribution of Cmax in the study cannot therefore be assessed from the record.
A confidence interval, in general, gives a range of values compatible with an estimate under a specified statistical procedure. Its width conveys information about precision. A narrow interval indicates greater precision than a wide interval, all else equal. No confidence interval is reported for Cmax. The record also does not report a standard error or a model-based estimate, so precision cannot be reconstructed from the posted information.
What does non-randomized allocation imply?
In general, random allocation helps balance measured and unmeasured participant characteristics across treatment groups, on average. This study is identified as non-randomized and single-group, with no masking. The dose-level cohorts should therefore not be treated as randomized arms or as a controlled comparison. The registry does not report how dose levels were assigned or whether other factors influenced assignment. Without that information and without a control group, observed differences across cohorts would not isolate a dose effect.
Even a descriptive comparison across age groups would need cautious interpretation. The child and adolescent cohorts may differ in characteristics besides age, and the record does not provide baseline characteristics or adjusted estimates. A statistical adjustment cannot be assumed: the registry lists zero analyses and does not describe a model or covariate set.
Why can over-dispersion matter?
In general, over-dispersion occurs when observed variability is greater than a model assumes. If a model underestimates variability, standard errors can be too small and intervals can be too narrow. This concept can matter for outcomes whose values vary substantially across participants. The record does not report a distributional model, an over-dispersion assessment, or a method for handling skewed concentration data. It is not possible to say whether over-dispersion was assessed or relevant to the analysis performed.
Pharmacokinetic data are often analyzed with methods that account for repeated measurements and concentration profiles, but no particular model or approach is reported. It would be inappropriate to attribute a population pharmacokinetic model, a noncompartmental method, or any other technique to this study based only on the endpoint definition.
What can be inferred from the analysis record?
The registry lists seven outcome measures and zero analyses. That does not establish that no analyses were conducted; it means analysis results and methods are not reported in the registry record. There are no posted test statistics, p-values, confidence intervals, model specifications, or estimates in the available record. Accordingly, inferential claims about dose, age, or the precision of concentrations cannot be evaluated.
The described pharmacokinetic analysis population includes patients who took at least one dose of IMP and contributed both Day 1 pre-dose pharmacokinetic sampling data and sufficient post-dose sampling data to estimate pharmacokinetic parameters. This definition indicates that inclusion depended on dosing and availability of certain samples. The number included in that analysis population, the number excluded, and the handling of incomplete sampling are not reported. In general, analysis-population definitions affect which participants contribute to an estimate; without counts and missing-data methods, the possibility of selection related to data availability cannot be assessed.
Overall, the registry gives a useful endpoint definition and sampling schedule, but not the statistical details or results needed to evaluate the numerical pharmacokinetic findings. General statistical principles can explain what those details would mean, but cannot substitute for the study’s unreported estimates and methods.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists seven outcome measures and identifies Cmax of vortioxetine as the primary endpoint. It lists zero analyses. A statistical analysis plan, the full hierarchy of outcome testing, and any adjustment for multiple comparisons are not reported in the registry record. It is therefore not possible to determine whether multiple outcome measures were tested inferentially, whether some were descriptive only, or how multiplicity was handled.
In general, multiplicity arises when many hypotheses or outcomes are examined. Repeated testing can increase the chance of finding an apparently notable result by chance, so an analysis plan may specify how outcomes and tests are prioritized or adjusted. That general concern should not be confused with evidence that this study did or did not use a particular procedure.
The stated pharmacokinetic analysis population includes patients who took at least one dose of IMP and contributed Day 1 pre-dose sampling data and sufficient post-dose data for estimation. The number of participants in that population is not reported. Nor are the number of participants with incomplete samples, reasons for missing data, exclusions, or any imputation or sensitivity-analysis methods. In general, missing pharmacokinetic samples can affect whether a concentration profile or endpoint can be estimated; the extent and direction of any effect cannot be assessed without those details.
The registry does not report how participants were handled if they discontinued dosing, missed a sample, or had data judged insufficient. It also does not report whether analyses used all available observations or required complete profiles. These are unresolved reporting gaps, not evidence that data were missing or that a particular method was used.
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 |
|---|---|---|---|
| Adolescents, 5 mg | 0 | 6 | 0.0% |
| Adolescents, 10 mg | 0 | 6 | 0.0% |
| Adolescents, 15 mg | 0 | 6 | 0.0% |
| Adolescents, 20 mg | 0 | 6 | 0.0% |
| Children, 5 mg | 0 | 6 | 0.0% |
| Children, 10 mg | 0 | 6 | 0.0% |
| Children, 15 mg | 0 | 6 | 0.0% |
| Children, 20 mg | 0 | 6 | 0.0% |
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 |
|---|---|
| Adolescents, 5 mg | 4 of 6 |
| Adolescents, 10 mg | 4 of 6 |
| Adolescents, 15 mg | 5 of 6 |
| Adolescents, 20 mg | 5 of 6 |
| Children, 5 mg | 5 of 6 |
| Children, 10 mg | 5 of 6 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Adolescents, 5 mg | Adolescents, 10 mg | Adolescents, 15 mg | Adolescents, 20 mg | Children, 5 mg | Children, 10 mg |
|---|---|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | 2 of 6 | 1 of 6 | 3 of 6 | 2 of 6 | 2 of 6 | 0 of 6 |
| Sedation | Nervous system disorders | 1 of 6 | 1 of 6 | 3 of 6 | 2 of 6 | 3 of 6 | 0 of 6 |
| Headache | Nervous system disorders | 3 of 6 | 1 of 6 | 2 of 6 | 1 of 6 | 2 of 6 | 0 of 6 |
| Abdominal pain upper | Gastrointestinal disorders | 0 of 6 | 0 of 6 | 1 of 6 | 0 of 6 | 3 of 6 | 1 of 6 |
| Fatigue | General disorders | 2 of 6 | 2 of 6 | 0 of 6 | 1 of 6 | 0 of 6 | 0 of 6 |
| Vomiting | Gastrointestinal disorders | 0 of 6 | 1 of 6 | 1 of 6 | 0 of 6 | 1 of 6 | 0 of 6 |
| Abdominal pain | Gastrointestinal disorders | 0 of 6 | 0 of 6 | 0 of 6 | 0 of 6 | 2 of 6 | 0 of 6 |
| Irritability | General disorders | 2 of 6 | 0 of 6 | 0 of 6 | 0 of 6 | 0 of 6 | 0 of 6 |
| Decreased appetite | Metabolism and nutrition disorders | 0 of 6 | 2 of 6 | 0 of 6 | 0 of 6 | 0 of 6 | 0 of 6 |
| Akathisia | Nervous system disorders | 0 of 6 | 2 of 6 | 0 of 6 | 0 of 6 | 0 of 6 | 0 of 6 |
The registry reports serious adverse events by age and dose group. Each group lists 6 participants at risk and 0 participants affected by serious adverse events. No serious adverse event terms are listed. The record therefore reports no affected participants in these groups, but does not provide event-level details or further context for interpreting the observation.
Other adverse events are reported separately. The counts of participants affected are 4 or 5 in each group, with 6 participants at risk in each group. These figures describe the number of participants affected, not the total number of events. The registry does not give the event terms, severity, timing, duration, or whether investigators considered events related to treatment. The counts should not be treated as a comparison of risk across dose levels, because the study was non-randomized and had no control group.
Death counts are null in the record. A null value is not the same as a reported count of zero; deaths are not reported in the registry record. The safety figures describe what was posted, not a complete characterization of tolerability.
12. What the Result Does, and Does Not, Mean
This record documents a completed, open-label, phase 2 study designed to evaluate pharmacokinetics and tolerability of multiple oral dosing of vortioxetine in child and adolescent patients with depressive or anxiety disorders. It identifies Cmax as the primary endpoint, gives the sampling schedule, defines a pharmacokinetic analysis population, and reports adverse-event counts by age and dose group.
It does not report numerical Cmax results, estimates of variability, confidence intervals, or statistical analyses. The actual concentration findings therefore cannot be described or judged for precision. The record also does not provide numerical results for the other listed outcomes. Its information is insufficient to establish what concentration patterns were observed across dose levels or age groups.
The design does not include a randomized comparator. As a result, the listed cohorts do not provide a controlled estimate of the difference between vortioxetine and another treatment or no treatment. Non-randomized group comparisons could be influenced by differences among participants or by assignment factors that are not described. The registry record does not report adjusted comparisons that might address measured differences.
The safety data show zero participants with serious adverse events in each listed group and report other adverse events in 4 or 5 participants per group. These counts do not establish comparative safety, and the record does not provide the event descriptions needed to characterize them. Null death entries should not be read as confirmed zero deaths.
In general, a study’s purpose and design define the questions its data can address. This study was intended to evaluate pharmacokinetics and tolerability, not to provide a randomized test of clinical benefit. The registry supports a description of the intended endpoint, population, and posted safety counts, but not a conclusion about symptom outcomes, comparative effects, or the numerical pharmacokinetic profile.
13. Why This Trial Matters Statistically
This study is statistically notable for the distinction between a pharmacokinetic endpoint and a clinical efficacy endpoint. Cmax is a concentration measure, with a defined sampling schedule, rather than a measure of change in depressive or anxiety symptoms. Readers need to match their interpretation to the endpoint actually identified in the record.
The study also illustrates why design labels matter. A non-randomized, single-group study without masking is not equivalent to a randomized controlled comparison. Cohorts categorized by age and dose can describe the groups enrolled, but cannot automatically support causal claims about differences between dose levels. Assignment details and baseline characteristics are not reported, and there is no control group.
Another statistical issue is the separation between endpoint definition and endpoint results. The registry is specific about Cmax’s unit, parameter label, dispersion label, and sample timing, but does not report numerical estimates. Those design details are useful for understanding what was intended to be measured; they cannot show the observed concentration level or its precision without results.
The record further demonstrates why analysis-population definitions and missing-data reporting matter. The pharmacokinetic population requires dosing and sufficient pre-dose and post-dose sampling. The number meeting that definition and the handling of incomplete data are not reported. In general, these details help readers understand who contributed to an estimate and how sample availability may affect interpretation.
Finally, the adverse-event counts are descriptive and group-specific. The record reports serious-event counts and other adverse-event counts, but not event terms or comparative analyses. These limitations make careful separation of posted observations from broader claims especially important.
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 numerical primary endpoint results are not reported in the registry record. Cmax values, variability estimates, confidence intervals, and numerical results for the other outcome measures are unavailable in the record. This prevents assessment of the observed pharmacokinetic profile and its precision.
The registry identifies the primary parameter as a median and its dispersion as standard deviation but does not provide estimates or explain the pairing. It does not report the method used to estimate Cmax from the scheduled samples, any pharmacokinetic model, or rules for handling samples that were absent or outside the planned schedule.
The study was open-label, non-randomized, and single-group, with no control group. The registry does not explain how participants were assigned to dose-level cohorts or report baseline characteristics that would help assess differences among them. The cohorts are not a randomized basis for dose comparisons.
The number in the pharmacokinetic analysis population, participant exclusions, missing-sample counts, and missing-data methods are not reported. The record lists seven outcome measures and zero analyses, but does not include an analysis plan, inferential estimates, or multiplicity procedures. It is therefore not possible to assess how outcomes were analyzed or prioritized.
Safety reporting is also limited: serious adverse event terms are absent, other adverse event terms and event-level details are not reported, and death entries are null. Treatment duration, detailed eligibility criteria, and dosing schedule are not reported in the registry record. These gaps constrain interpretation of both pharmacokinetic and tolerability findings.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Pharmacokinetics and Tolerability of Vortioxetine (Lu AA21004) in Child and Adolescent Patients With Depressive or Anxiety Disorder — NCT01491035.
- Registry record last updated 2017-03-16; status last verified 2017-02.
- Results first posted 2016-01-15.
- 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.
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18. Record Summary
NCT01491035 is a completed phase 2, open-label, non-randomized, single-group study of multiple oral vortioxetine dosing in children and adolescents with depressive or anxiety disorders. Enrollment was 48. The registry lists four child cohorts and four adolescent cohorts, each with 6 participants, across dose groups identified as 5 mg, 10 mg, 15 mg, and 20 mg.
The primary endpoint is Cmax of vortioxetine in ng/mL, with scheduled sampling pre-dose and at 1, 3, 5, 8, 12, and 24 hours post-dose on Day 14, 16, 18, or 20, depending on assigned dose level. Numerical endpoint results and statistical analyses are not reported in the registry record. Safety figures report zero participants with serious adverse events in each group and 4 or 5 participants with other adverse events in each group; death counts are null.