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 Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Fixed Dose Study Evaluating the Efficacy and Safety of Orvepitant in Subjects With Major Depressive Disorder (NCT00880399), a randomized phase 2 study. The primary outcome is Change From Baseline in the 17-item Hamilton Depression Rating Scale (HAM-D) Total Score.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00880399 |
| Phase | Phase 2 |
| Condition | Depressive Disorder, Major |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 328 |
| Arms in the primary outcome | n/a |
| Lead sponsor | GlaxoSmithKline |
| Results posted | Yes |
2. Clinical Question
Population
Participants had a diagnosis of major depressive disorder, with symptoms considered moderate or severe. The registry describes an Intent-to-Treat population comprising randomized participants who received at least one dose of double-blind medication and had at least one post-randomization assessment. Only participants available at each specified time point were analyzed.
Intervention
Orvepitant was studied at fixed daily doses of 30 mg and 60 mg. Participants were assigned to one of the study groups for a six-week treatment phase.
Comparator
The comparator was placebo, described as inactive and matched in appearance to the two orvepitant dosage forms. The study description states that participants had an equal chance of assignment to any of the three groups, a 1:1:1 ratio.
Primary question
The primary endpoint was change from baseline to Week 6 in the 17-item Hamilton Depression Rating Scale (HAM-D) total score. The registry record does not report the group estimates or a comparison of either orvepitant dose with placebo, so it does not establish the size or precision of any treatment contrast.
3. Trial Design
This was a randomized, parallel-group, placebo-controlled phase 2 study sponsored by GlaxoSmithKline. The registry record lists enrollment of 328 and a study start date of 2009-03-01, with primary completion on 2010-06-01. Its status is recorded as terminated. The reason for termination is not reported in the registry record.
The brief description calls the study double-blind and states that treatment continued for six weeks. The design metadata lists quadruple masking, while the study description uses the term double-blind; the registry record does not explain how those descriptions relate to one another. It describes screening before randomization, including a screening phase of at least 7 days and no longer than 21 days. Eligible participants were assigned to orvepitant 30 mg/day, orvepitant 60 mg/day, or placebo, with equal chance of assignment to each group.
The primary measure was the HAM-D total score, assessed from baseline on Day 1 to Week 6. Other efficacy measures listed in the record include the Quick Inventory of Depressive Symptomatology, Clinical Global Impression measures, and further symptom and functioning scales. The record lists 17 outcome measures and 122 analyses, but does not give a complete account of the analysis plan or explain how those analyses were organized. Specific allocation concealment procedures, details of the randomization sequence, and the rationale for the planned enrollment 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: A total of 787 participants were screened for study eligibility, of which 331 participants were randomized. Out of 331 participants, 3 did not receive the study medication. All subjects population included all participants who had received at least one dose of the study medication and comprised of 328 participants.
Overall Study
| Stage | Placebo | Orvepitant 30 mg | Orvepitant 60 mg |
|---|---|---|---|
| STARTED | 108 | 113 | 107 |
| COMPLETED | 77 | 84 | 81 |
| NOT COMPLETED | 31 | 29 | 26 |
Reasons for not completing this period:
| Reason | Placebo | Orvepitant 30 mg | Orvepitant 60 mg |
|---|---|---|---|
| Adverse Event | 4 | 6 | 5 |
| Lack of Efficacy | 1 | 4 | 2 |
| Protocol Violation | 4 | 4 | 6 |
| Study closed/terminated | 3 | 7 | 4 |
| Lost to Follow-up | 8 | 5 | 3 |
| Physician Decision | 5 | 0 | 3 |
| Withdrawal by Subject | 6 | 3 | 3 |
Analysis population for the primary outcome, as defined in the registry: The Intent-to-Treat (ITT) population comprised of all participants who were randomized and received at least one dose of double blind medication and for whom at least one post-randomization assessment was available. Only those participants available at the specified time points were analyzed.
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.
| Characteristic | Unit | Placebo | Orvepitant 30 mg | Orvepitant 60 mg | Total |
|---|---|---|---|---|---|
| Participants analysed | 108 | 113 | 107 | 328 | |
| Age, Continuous | Years | 39.7 (SD 11.67) | 41.0 (SD 11.45) | 38.2 (SD 11.15) | 39.7 (SD 11.45) |
| Sex: Female, Male: Female | Participants | 76 | 68 | 70 | 214 |
| Sex: Female, Male: Male | Participants | 32 | 45 | 37 | 114 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 1 | 1 | 2 | 4 |
| Race (NIH/OMB): Asian | Participants | 4 | 2 | 3 | 9 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 16 | 17 | 21 | 54 |
| Race (NIH/OMB): White | Participants | 86 | 92 | 79 | 257 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 1 | 1 | 2 | 4 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in the 17-item Hamilton Depression Rating Scale (HAM-D) Total Score, measured over Baseline (Day 1) to Week 6.
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | Standard Error |
| Unit | Scores on a Scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was change from baseline in the 17-item HAM-D total score between Day 1 and Week 6. The HAM-D is a symptom-rating scale intended to measure the severity of depressive symptoms in participants with primary depressive illness. Its items cover areas including mood, guilt, suicidal thoughts, sleep, work and activities, anxiety, and physical symptoms. Item responses are summed to produce a total score.
The registry describes possible total scores from 0 to 52, with 0 representing no depression and 52 representing the most severe measure of depression. Change was calculated by subtracting the baseline score from the post-baseline score. A change score therefore expresses how the measured symptom total differed from the participant’s baseline; it is not itself a diagnosis or a direct account of every aspect of a participant’s experience.
The primary outcome is reported as a least-squares mean, with standard error as the stated dispersion measure. A mean provides a group-level summary, while a standard error describes the precision of an estimated mean. The record does not report the resulting estimates, standard errors, confidence intervals, or treatment comparisons. It therefore does not permit assessment of the magnitude or precision of the primary endpoint results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a randomized comparison of orvepitant 30 mg/day, orvepitant 60 mg/day, and placebo, with the primary assessment at Week 6. However, it does not report the primary outcome values or the contrasts between the treatment groups. No direction, magnitude, or precision of a HAM-D effect can be established from the record’s reported primary endpoint information. In particular, the stated endpoint and its measurement schedule are not substitutes for outcome estimates.
The record identifies the primary measure as change from baseline in HAM-D total score and specifies least-squares means and standard errors. It does not report a standard error, confidence interval, test statistic, or p-value for either orvepitant comparison. Without these results, readers cannot assess how compatible the data are with a range of possible treatment effects, or distinguish a small uncertain estimate from a larger, more precise one. A missing result should not be interpreted as evidence that groups were equivalent or that there was no effect.
The registry lists additional efficacy outcomes, including response measures, other symptom scales, and global-impression measures. The record reports 17 outcome measures and 122 analyses, but does not provide enough information in the listed details to reconstruct the full set of group estimates or determine which comparisons were emphasized. The registry record does not report a multiplicity adjustment or a prespecified hierarchy for interpreting the many outcomes and analyses.
Safety information is reported as counts of participants affected. Serious adverse events were reported for 1 participant in the placebo group, 0 in the orvepitant 30 mg group, and 1 in the orvepitant 60 mg group. Other adverse events were reported for 27, 40, and 34 participants, respectively. No deaths were reported in any group. These counts describe the registry’s reported safety outcomes; they do not supply a comparison adjusted for exposure, event duration, or other factors.
The study’s terminated status is relevant to understanding the record, but the reason for termination is not reported in the registry record. It should not be used to infer why the study ended or to interpret unreported efficacy results. The posted information supports description of the design, endpoint, and reported safety counts, but not a conclusion about the comparative efficacy of the study groups.
9. Statistical Methods Explained
Randomization assigns participants to study groups by chance. In general, this is intended to reduce systematic differences between groups at the point of assignment, although it does not guarantee that every characteristic will be balanced. The study description states that assignment was in a 1:1:1 ratio across orvepitant 30 mg/day, orvepitant 60 mg/day, and placebo. The record does not report the sequence-generation method or the procedure used to conceal allocation before assignment.
What does the parallel-group design mean?
In a parallel-group study, participants are assigned to one group and receive that group’s assigned treatment during the study. The registry describes three groups and a six-week treatment period. This differs from a design in which participants cross over between treatments. The placebo was described as matching the orvepitant dosage forms in appearance, which is one element intended to support masking. The design metadata records quadruple masking, while the brief description calls the study double-blind. The registry record does not clarify the roles included in the masking designation or reconcile the terminology.
What does change from baseline measure?
For each participant, a change score is formed by comparing a post-baseline score with the baseline score. The registry states that baseline was Day 1 and defines change as the post-baseline value minus the baseline value. The group-level primary endpoint was a least-squares mean change in HAM-D total score at Week 6. A least-squares mean is a model-based estimate of a group mean; the details of the model used for the primary analysis are not reported in the registry record.
A standard error describes the sampling precision of an estimated quantity. It is not the same as the spread of individual participants’ scores. A confidence interval, when reported, gives a range of values compatible with the data and the method used to calculate it. The primary endpoint’s stated dispersion measure is standard error, but the registry record does not report its numerical value or a confidence interval. Therefore the precision of the endpoint estimate cannot be evaluated from the record.
Why does over-dispersion matter?
General: for count outcomes, over-dispersion means that observed variability is greater than a statistical model assumes. If present and not handled appropriately, uncertainty estimates and tests from a model may be misleading. This is a general consideration for count data; the primary endpoint in this study is a continuous score, and the registry record does not report an over-dispersion analysis or identify over-dispersion as an issue in the primary analysis.
How should p-values and multiple analyses be considered?
General: a p-value summarizes how unusual data would be under a specified null model and analysis. It does not quantify the size or clinical importance of an effect. When many outcomes, time points, or comparisons are analyzed, the chance of finding at least one apparently notable result can increase unless the analysis plan accounts for multiplicity. The registry lists 17 outcome measures and 122 analyses, but the posted record does not report the complete analysis strategy, any multiplicity adjustment, or a hierarchy of confirmatory comparisons. It also does not report a p-value for the primary endpoint in the registry record for this account.
What is the role of a sample-size illustration?
A planning illustration based on an observed effect is different from the original trial’s design justification. The stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a fraction of the observed effect. Such calculations are planning illustrations, not observed power. The registry record does not report the trial’s sample-size justification or the planning assumptions used to select its enrollment. Since the primary treatment estimates are not reported, the illustration should not be treated as evidence about the probability that this study detected an effect.
The enrollment of 328 is the number recorded for the study, not a statement that every enrolled participant contributed to every endpoint analysis. The endpoint population definition requires randomization, receipt of at least one dose, and at least one post-randomization assessment. The record further states that only participants available at specified time points were analyzed. These details matter when interpreting group summaries because the analyzed set may differ by outcome or time point. The record does not describe imputation methods or sensitivity analyses for missing assessments.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies 17 outcome measures and 122 analyses. That breadth makes the analysis plan important: multiple outcomes, time points, and comparisons can create several opportunities for apparently notable findings. General statistical practice may address this through a prespecified hierarchy, an adjustment for multiple comparisons, or a clear distinction between confirmatory and exploratory analyses. Whether any such approach was used in this study is not reported in the registry record.
The primary endpoint is specified as change from baseline to Week 6 in HAM-D total score. The registry record does not report its group estimates, treatment contrasts, confidence intervals, standard errors, or p-values. It also does not report which of the listed analyses were prespecified, how any repeated measurements were modeled, or whether the analysis used adjustments for baseline characteristics. The reason for termination is not reported in the registry record, and no inference about its consequences for the analysis should be made from status alone.
The defined endpoint population included randomized participants who received at least one dose and had at least one post-randomization assessment. The record says only participants available at each specified time point were analyzed. This indicates that the number contributing to an analysis could depend on availability, but the missing-data mechanism, amount of missingness, imputation procedures, and sensitivity analyses are not reported in the registry record. As a result, the potential effect of unavailable assessments on the estimates cannot be judged.
The registry’s population definition is not identical to an unrestricted all-randomized population, because it includes receipt of medication and availability of a post-randomization assessment. The record does not provide participant flow counts by group to show how many randomized participants met the endpoint analysis criteria. These omissions limit assessment of the analysis population and the robustness of any efficacy interpretation.
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 |
|---|---|---|---|
| Placebo | 1 | 108 | 0.9% |
| Orvepitant 30 mg | 0 | 113 | 0.0% |
| Orvepitant 60 mg | 1 | 107 | 0.9% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Placebo | 0 of 108 |
| Orvepitant 30 mg | 0 of 113 |
| Orvepitant 60 mg | 0 of 107 |
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 |
|---|---|
| Placebo | 27 of 108 |
| Orvepitant 30 mg | 40 of 113 |
| Orvepitant 60 mg | 34 of 107 |
Most frequent serious adverse event terms
| Event term | Organ system | Placebo | Orvepitant 30 mg | Orvepitant 60 mg |
|---|---|---|---|---|
| Abdominal pain lower | Gastrointestinal disorders | 0 of 108 | 0 of 113 | 1 of 107 |
| Pelvic fracture | Injury, poisoning and procedural complications | 1 of 108 | 0 of 113 | 0 of 107 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Placebo | Orvepitant 30 mg | Orvepitant 60 mg |
|---|---|---|---|---|
| Headache | Nervous system disorders | 10 of 108 | 11 of 113 | 5 of 107 |
| Diarrhoea | Gastrointestinal disorders | 7 of 108 | 9 of 113 | 7 of 107 |
| Somnolence | Nervous system disorders | 2 of 108 | 9 of 113 | 9 of 107 |
| Nausea | Gastrointestinal disorders | 6 of 108 | 9 of 113 | 5 of 107 |
| Dry mouth | Gastrointestinal disorders | 6 of 108 | 8 of 113 | 4 of 107 |
| Upper respiratory tract infection | Infections and infestations | 6 of 108 | 3 of 113 | 5 of 107 |
| Dizziness | Nervous system disorders | 3 of 108 | 7 of 113 | 2 of 107 |
| Fatigue | General disorders | 2 of 108 | 0 of 113 | 9 of 107 |
Serious events with the highest arm-level rate: abdominal pain lower (0.9%), pelvic fracture (0.9%).
The safety record reports participant counts for serious adverse events, other adverse events, and deaths by study group. The denominators listed at risk were 108 for placebo, 113 for orvepitant 30 mg, and 107 for orvepitant 60 mg. Serious adverse events affected 1 participant in the placebo group, 0 in the orvepitant 30 mg group, and 1 in the orvepitant 60 mg group. Other adverse events affected 27, 40, and 34 participants, respectively. The reported death count was 0 in each group.
The serious-event terms listed in the record are abdominal pain lower and pelvic fracture, each reported as 0.9%. The record does not specify in the listed details which group or groups these terms correspond to, or provide further event-level detail. These terms should therefore be read as the registry’s reported serious-event entries, not assigned to a particular treatment group.
Counts do not by themselves show whether differences between groups are meaningful. They do not describe timing, duration, severity beyond the serious-event classification, or exposure-adjusted rates. The record does not report a statistical comparison of safety outcomes. The counts also do not establish that an event was caused by study treatment. They are descriptive registry data, not a complete assessment of individual risk.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a randomized, placebo-controlled study compared orvepitant 30 mg/day and 60 mg/day with placebo over a six-week treatment phase in participants with major depressive disorder. It identifies change in HAM-D total score from baseline to Week 6 as the primary endpoint and describes the scale’s purpose and scoring. These are important features for understanding the intended comparison, but they do not reveal the observed efficacy results.
The primary outcome estimates and treatment contrasts are not reported in the registry record. Consequently, the record does not show how much scores changed in each group, how different those changes were, or how precise the estimates were. It cannot support a conclusion that one group had a larger or smaller change than another, or that the groups were similar. Lack of reported results is not equivalent to a finding of no difference.
The registry reports safety counts, including serious adverse events, other adverse events, and deaths. Those figures describe the counts recorded for the groups, but do not establish causation or provide a complete comparison of safety. They should be interpreted alongside the limits of the registry entries, including the absence of event timing, fuller event descriptions, and a reported statistical analysis of safety outcomes.
General: an estimate and its uncertainty are both needed for a balanced interpretation. A point estimate alone can be compatible with a range of plausible effects, and a significance test alone does not describe the size or practical importance of a difference. Here, the absence of the primary estimates and uncertainty measures means that neither the magnitude nor the precision of the treatment contrast can be assessed from the registry record.
The study is recorded as terminated, but the reason is not reported. That status does not, by itself, establish whether the planned analysis was completed, why enrollment or follow-up ended, or what the results would have been. The record supports a description of the study design and the outcomes it intended to assess; it does not support a treatment recommendation or a definitive comparative efficacy conclusion.
13. Why This Trial Matters Statistically
This study is statistically notable for having three randomized groups and a prespecified continuous primary endpoint, while also listing many outcomes and analyses. The design description states equal chance of assignment across orvepitant 30 mg/day, orvepitant 60 mg/day, and placebo. The primary outcome was change in HAM-D total score from baseline to Week 6, summarized as a least-squares mean with standard error. These features indicate the kinds of estimates that would be needed to evaluate the primary comparison: group-level changes, between-group contrasts, and measures of uncertainty.
The record lists 17 outcome measures and 122 analyses. With multiple measures and analyses, interpretation depends on knowing which comparisons were planned as primary, how other comparisons were classified, and whether multiplicity was addressed. Those details are not reported in the registry record. Without them, readers cannot distinguish a focused confirmatory analysis from a broader set of exploratory analyses based on the registry entries.
Missing outcome estimates are also a statistical limitation, not a result in themselves. The record provides the endpoint definition but not the numerical findings needed to judge effect size or precision. It gives an analysis-population definition and says participants available at each time point were analyzed, but does not report missingness by group or methods for handling missing assessments. Those omissions prevent assessment of how the analysis population and missing data might affect interpretation.
The safety counts add descriptive information, while leaving comparative inference uncertain. In combination, the record shows why transparent reporting needs more than study design and outcome definitions: estimates, uncertainty, participant flow, and analysis choices are necessary to understand what the data indicate. The terminated status makes the missing explanation of study completion relevant, but does not itself explain the absent efficacy 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 most important limitation for interpreting efficacy is that the registry record does not report the primary outcome values or treatment comparisons. It identifies the endpoint and its timing but gives no group means, contrasts, standard errors, confidence intervals, or p-values. The size and precision of any difference therefore cannot be assessed.
The record lists 17 outcome measures and 122 analyses, but does not report a complete statistical analysis plan, the status of individual analyses as confirmatory or exploratory, or any multiplicity procedure. It also does not report the trial’s sample-size justification, interim analyses, or the reason the study was terminated. None of these details should be inferred from the enrollment or status.
The endpoint population required participants to be randomized, to receive at least one dose, and to have at least one post-randomization assessment. The record says only participants available at the specified time points were analyzed. It does not give participant flow by group, the number contributing to the primary endpoint, the amount or pattern of missing data, or any imputation or sensitivity analyses. As a result, the impact of missing assessments and exclusions from the defined analysis population cannot be evaluated.
The registry metadata lists quadruple masking, whereas the study description calls the trial double-blind. It does not explain the difference or identify the roles involved in masking. The safety information is also limited to counts and selected serious-event terms, without detailed timing, exposure adjustment, or a reported between-group safety analysis. These limitations restrict how fully the record can support judgments about efficacy, precision, and safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Fixed Dose Study Evaluating the Efficacy and Safety of Orvepitant in Subjects With Major Depressive Disorder — NCT00880399.
- Registry record last updated 2017-09-12; status last verified 2017-04.
- Results first posted 2017-09-12.
- 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
NCT00880399 was a randomized, parallel-group, phase 2, placebo-controlled study of orvepitant in participants with major depressive disorder. It enrolled 328 participants, according to the registry record, and compared orvepitant 30 mg/day and 60 mg/day with placebo over a six-week treatment phase. The record lists a start date of 2009-03-01, primary completion on 2010-06-01, and status as terminated.
The primary endpoint was change from baseline to Week 6 in 17-item HAM-D total score. Although the record describes the endpoint and its analysis population, it does not report primary outcome results or the reason for termination. Safety counts include serious adverse events in 1 placebo participant, 0 participants receiving orvepitant 30 mg, and 1 receiving orvepitant 60 mg; no deaths were reported in any group.