This is a Study to Determine the Antidepressant Effects of AZD6765: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for This is a Study to Determine the Antidepressant Effects of AZD6765 (NCT00986479), a randomized phase 2 study. The primary outcome is Montgomery-Asberg Depression Rating Scale (MADRS) Total Score..

2. Clinical Question

The study’s stated purpose was to determine the antidepressant effects of AZD6765 compared with placebo. The primary outcome was the Montgomery-Asberg Depression Rating Scale (MADRS) total score. Since the design used two treatment periods, each participant’s assigned sequence determined whether AZD6765 or placebo was given first. The record describes a 7-day drug-free period between infusions.

The central statistical question is comparative: whether the pattern of MADRS scores following AZD6765 differed from the pattern following placebo. For a crossover comparison, interpretation depends not only on the treatment-period scores but also on how treatment order, period, and any residual effect are handled in the analysis. Those analysis details and a treatment comparison are not reported in the registry record. Therefore, the registered purpose and outcome can be described, but the posted information does not establish the direction or precision of a treatment effect.

3. Trial Design

This was a Phase 2 randomized, quadruple-masked crossover study with enrollment of 22 participants. The condition listed was treatment-resistant major depressive disorder. The study was sponsored by AstraZeneca and is recorded as completed. Its recorded start was 2009-12, and its primary completion was 2011-12.

Participants were assigned to one of two treatment sequences. In one sequence, participants received a single intravenous infusion of AZD6765 (150 mg) over 60 minutes in the first period, followed by a 7-day drug-free period and then a single placebo infusion over 60 minutes in the second period. In the other sequence, placebo was given first, followed by the same drug-free interval and then AZD6765. The crossover structure means the comparison was intended to include observations from both treatment periods, rather than only a parallel comparison of separate groups.

Randomization and masking are recorded as design features, but the registry record does not describe the randomization method, who was masked, or how masking was maintained. It also does not report the rationale for the 7-day interval or how period and carryover effects were addressed. These are relevant design and analysis details for interpreting crossover data, but their absence does not establish that any particular procedure was or was not used.

The primary outcome was MADRS total score, assessed before dosing and at multiple times after dosing. The record lists 13 outcome measures and several secondary measures, including remission and response definitions based on MADRS, as well as anxiety, depression, suicide-ideation, dissociation, psychiatric-rating, and visual-analogue assessments. No statistical analyses are listed in the registry record. A sample-size justification, interim-analysis plan, and full 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: Screening for eligibility and washout of restricted medications.

Period 1

Reasons for not completing this period:

Period 2

Analysis population for the primary outcome, as defined in the registry: ITT population including all randomized patients who were given study treatment.

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.

6. Primary Endpoint

The registry lists the primary outcome as Montgomery-Asberg Depression Rating Scale (MADRS) Total Score., measured over 60 minutes (min) prior to dosing (baseline); and 60 min, 80 min, 110 min, 230 min, 1 day, 2 days, 3 days and 7 days following dosing..

The primary endpoint was MADRS total score, a measure of depressive symptoms. The instrument has 10 items, each rated from 0 to 6; item scores are summed to a total from 0 to 60. The record states that higher scores indicate more severe depression, with 0 considered the best score and 60 the worst. The measure is reported in units on a scale.

The registry lists the endpoint as a least-squares mean with standard error. In general, a least-squares mean is an estimate from a statistical model, often adjusted for factors included in that model. The model and factors used for this trial are not reported in the registry record, and no least-squares mean estimates or standard errors are listed in the posted results.

MADRS is used to quantify symptom severity, so repeated assessments can describe how scores change over time and can support comparisons between treatment conditions. The record specifies a baseline assessment 60 minutes before dosing and follow-up assessments at 60, 80, 110, and 230 minutes, and 1, 2, 3, and 7 days following dosing. This is a set of time-specific assessments, not a single time point. The record does not identify one of these time points as the sole primary comparison, and it does not report an analysis that combines or contrasts them.

General: a rating scale provides a structured way to measure a construct that cannot be observed directly as a single physical quantity. Its scores can describe severity, but interpretation depends on the measurement context and the analysis used. A scale score alone does not establish a clinical benefit or explain why scores changed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the crossover design compare?

General: in a crossover trial, participants receive more than one treatment condition in an assigned order. Each participant can contribute observations under each condition, which permits a within-participant comparison. Such a comparison can account for stable differences between participants, but it requires attention to treatment sequence, period effects, and possible carryover from an earlier treatment. The registry record describes two treatment sequences and a 7-day drug-free period between infusions. It does not report the statistical method used to account for sequence, period, or carryover.

The distinction between a crossover design and a parallel-group design matters when reading results. A parallel-group estimate compares outcomes among different groups of participants. A crossover estimate may instead compare each participant’s outcomes across conditions, potentially while also including group-level design terms. The latter cannot be reconstructed from a simple comparison of group averages without participant-level data or the analysis method. No such analysis is listed in the registry record.

What does a least-squares mean represent?

The primary endpoint is specified as a least-squares mean. General: a least-squares mean is a model-based estimate of an average outcome, conditional on the terms included in a fitted model. For example, a model might account for design features or baseline measures, but whether it does so depends on the prespecified analysis. The registry record does not describe the model, its covariates, or the handling of repeated observations. It also does not post least-squares means or standard errors.

The listed dispersion measure is standard error. General: a standard error characterizes the sampling variability of an estimate under an assumed statistical model. It is not the same as the spread of individual participant scores. A standard error can be used to construct a confidence interval when the relevant estimate and inferential method are available. Neither a standard error nor a confidence interval for the primary treatment comparison is reported in the registry record.

Why do repeated time points require a clear analysis plan?

The primary outcome is measured at baseline and at multiple follow-up times after each dosing period. General: repeated measurements from the same participant are usually correlated; they are not independent observations. An analysis should account for this dependence if it uses multiple observations together. The selected time point or overall summary also matters: separate time-specific comparisons answer different questions from a single combined summary or a model of the full trajectory.

Because the record does not identify one time point as the sole primary comparison and does not list statistical analyses, it is not possible to determine how the repeated measurements were intended to be modeled. The record also does not report whether a treatment-by-time pattern was tested, whether any comparisons were adjusted, or how baseline scores entered the analysis.

How should standard errors and confidence intervals be read?

General: an estimate describes the effect or average supported by a particular analysis, while its standard error reflects uncertainty due to sampling under that analysis. A confidence interval combines the estimate and its uncertainty into a range. A narrow interval indicates greater precision than a wide interval, all else equal. Precision is separate from clinical importance: a precise estimate can still be small, and an imprecise estimate can cover effects in more than one direction. No treatment-effect estimate, standard error, or confidence interval is reported for the primary endpoint.

A p-value is also tied to a model and a specified null hypothesis. General: it measures how unusual data at least as incompatible with that null hypothesis would be, assuming the model and its assumptions. It is not an effect-size measure, and it does not quantify the probability that the null hypothesis is true. The registry record lists zero analyses, so no primary p-value or inferential result is available to interpret.

What does the registry say about sample size?

The record describes a planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. It states that the effect to detect is a specified fraction of the observed effect and that non-time-to-event illustrations are expressed as participants per arm. These are planning assumptions, not a sample-size justification for this trial. The record does not report the trial’s own sample-size calculation, the effect size used in that calculation, or its assumptions.

General: sample-size planning asks how many participants would be needed to target a chosen level of precision or probability of detecting an effect under stated assumptions. A planning illustration derived from an observed effect is not observed power and does not show that the completed study had adequate precision. Without an effect estimate and its uncertainty, the illustration should not be treated as evidence of a treatment effect.

What analysis details are absent?

The registry record does not report a full statistical analysis plan, model specification, handling of missing outcome data, analysis of treatment order, adjustment for multiple comparisons, or an interim-analysis plan. It identifies the primary population as randomized patients who received study treatment, but does not give participant counts contributing to each outcome assessment. These omissions limit assessment of the assumptions and decisions behind any treatment estimate. Since no analyses or primary estimates are listed, the posted information cannot be used to verify the analysis methods or reproduce a treatment comparison.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 13 outcome measures, including the primary MADRS total score, MADRS remission and response outcomes, and several other symptom and rating scales. The primary outcome itself is assessed at baseline and at multiple follow-up times. This creates several possible statistical comparisons. General: when many outcomes or time points are examined, the chance of at least one apparently unusual result can increase if each is tested separately. Prespecified priorities and a multiplicity strategy can help clarify how results should be interpreted.

The registry record does not report whether multiplicity was addressed, which outcomes or time points were designated for formal testing, or whether any adjustment was planned. It also lists zero analyses. No treatment estimates, p-values, or confidence intervals for the primary or secondary outcomes are reported. Therefore, there is no set of posted inferential results from which to assess either the impact of multiple comparisons or the consistency of findings across outcomes.

The stated primary population includes all randomized patients who received study treatment. Participant-level disposition, the number with observed outcomes at each time point, and the treatment of missing observations are not reported in the registry record. General: missing outcome data can affect both the precision and the potential bias of an estimate, particularly when the likelihood of missingness is related to participants’ outcomes or treatment experience. The appropriate interpretation depends on the reasons for missingness and the analysis assumptions; neither is documented.

The record does not report whether the analysis followed an intention-to-treat principle beyond its stated population description, or how participants without post-dose data were handled. These gaps mean the analysis population and completeness of outcome follow-up cannot be fully assessed from the registry record.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists serious adverse events in 0 of 22 participants at risk in the AZD6765 (150 mg) group and 0 of 20 participants at risk in the placebo group. The death counts are not reported in the registry record. The listed counts for other adverse events are 21 of 22 participants at risk for AZD6765 and 20 of 20 at risk for placebo.

These are participant counts, not measures of event severity beyond the serious-versus-other distinction recorded. The record does not provide event descriptions for serious adverse events; its serious-event terms list is empty. It also does not provide timing, duration, attribution, or the number of events per participant. The other-adverse-event counts alone do not describe the specific events or their clinical significance.

General: observing no serious adverse events in a study does not establish that the risk is absent. Safety counts are interpreted in light of the number of participants exposed, the observation period, event definitions, and completeness of reporting. In this crossover study, the risk denominators are listed separately for the two treatment conditions, and they differ. The counts should therefore be read as the registry reports them, rather than as a complete account of every possible safety outcome.

12. What the Result Does, and Does Not, Mean

The registry record documents a randomized, quadruple-masked Phase 2 crossover study designed to compare AZD6765 with placebo in treatment-resistant major depressive disorder. It identifies MADRS total score as the primary outcome and lists assessments from before dosing through 7 days after dosing. It also describes the two treatment sequences and a 7-day drug-free interval between periods.

Those design details explain what the study set out to compare, but they do not establish what the comparison found. The record does not report a primary treatment estimate, its precision, or a statistical test. It also does not report results for the listed secondary outcomes. Consequently, the posted information cannot establish whether scores differed between conditions, the direction of any difference, or whether any difference was large enough to matter clinically.

General: statistical evidence and clinical importance are related but distinct. An effect estimate describes the size and direction of a comparison; its uncertainty indicates how precisely it is estimated. Clinical interpretation also depends on the meaning of the scale and the context of the outcome. Without the estimate and its uncertainty, the study’s clinical implications cannot be evaluated from the registry record.

The safety entries record no serious adverse events among the listed participants at risk in either treatment condition and include counts for other adverse events. These entries do not provide detailed event descriptions, and the death counts are not reported in the registry record. They should not be read as a complete characterization of safety.

The appropriate conclusion is limited to what is documented: the study was designed to investigate an AZD6765-placebo comparison using repeated MADRS assessments, and the registry contains selected safety counts. It does not report the analyses needed to determine the estimated treatment effect or its uncertainty. This absence is not evidence that the treatments were equivalent, nor is it evidence of a beneficial or harmful effect.

13. Why This Trial Matters Statistically

This trial is statistically notable because its crossover design makes the treatment comparison dependent on more than the treatment labels alone. Participants were assigned to receive AZD6765 and placebo in opposite orders, with a 7-day drug-free period between treatments. General: crossover designs can make within-participant comparisons informative, but treatment order and period effects need to be considered because outcomes may vary over time or be affected by earlier treatment. The registry record does not report how these features were handled analytically.

The outcome schedule also matters. MADRS scores were planned before dosing and at several subsequent times, while the record does not identify a single time point as the only primary comparison. Multiple assessments can describe a time course, but they also create choices about which estimate answers the main question and how uncertainty across comparisons is interpreted. No analysis is listed to resolve those choices.

The record names a model-based summary, least-squares mean, and a standard error as its dispersion measure, but supplies no corresponding primary results. This makes the distinction between a planned outcome and an interpretable estimate especially important. An endpoint definition tells the reader what was measured; it does not substitute for a treatment contrast, uncertainty interval, or analysis description.

The registry also lists 13 outcome measures but no analyses. This gap prevents assessment of multiplicity, outcome consistency, and the relation between the stated primary and secondary measures. Statistically, the record is informative about design and measurement but insufficient to assess the treatment comparison itself. That distinction helps prevent a study’s stated purpose from being mistaken for a reported finding.

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.

Several trial-specific limitations of interpretation follow from what is and is not recorded. First, the primary outcome is measured at multiple times, but no single comparison or result is reported. The record notes that the outcome has several categories or time points and is not reduced to one comparison. Without a selected contrast and its estimate, the primary question cannot be answered from the posted results.

Second, although the design is crossover, the registry record does not report the model or explain how treatment sequence, period, or possible carryover were considered. The existence of a 7-day drug-free period is documented, but its adequacy or statistical role cannot be assessed from the record. These are potential considerations for interpreting a crossover comparison, not evidence that the design was improperly conducted.

Third, the record gives enrollment and a definition of the primary population but does not report participant flow or outcome completeness at each assessment. It does not describe missing-data handling. This prevents assessment of whether all enrolled participants contributed to each relevant analysis or whether missing observations could affect the estimates.

Fourth, the registry lists 13 outcome measures and no analyses. It does not report a multiplicity strategy, a detailed statistical analysis plan, or an interim-analysis plan. The trial’s sample-size justification is also not reported in the registry record. The listed planning illustration is not a substitute for the study’s own design rationale or for observed treatment-effect precision.

Finally, the available safety counts do not include serious-event descriptions, detailed other-event information, or reported death counts. These limitations constrain interpretation of the registry record; they do not establish that unreported procedures or results were absent from other records.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: This is a Study to Determine the Antidepressant Effects of AZD6765 — NCT00986479.
• Registry record last updated 2014-10-21; status last verified 2014-10.
• Results first posted 2014-10-21.
• 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.

18. Record Summary

NCT00986479 is a completed Phase 2 randomized, quadruple-masked crossover study sponsored by AstraZeneca. It enrolled 22 participants with treatment-resistant major depressive disorder. The two sequences used single 60-minute intravenous infusions of AZD6765 (150 mg) and placebo, separated by a 7-day drug-free period.

The primary outcome was MADRS total score, assessed before dosing and at multiple follow-up times through 7 days. The record lists 13 outcome measures and describes the primary population as randomized patients who received study treatment. It does not list statistical analyses or report a primary treatment-effect estimate, confidence interval, or p-value. Serious adverse events are listed for 0 of 22 participants at risk with AZD6765 and 0 of 20 at risk with placebo; death counts are not reported in the registry record.

The registry documents the study design and selected outcome and safety information, but does not report results sufficient to assess the primary treatment comparison.