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 Study Comparing 3 Dosage Levels Of SAM-531 In Outpatients With Mild To Moderate Alzheimer Disease (NCT00895895), a randomized phase 2 study. The primary outcome is Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog) Total Score at Week 24.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00895895 |
| Phase | Phase 2 |
| Condition | Alzheimer Disease |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 526 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Pfizer |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled outpatients with mild to moderate Alzheimer disease. The planned enrollment was 526 participants. The primary outcome population was defined as randomized participants who took at least one dose of study medication, had a baseline evaluation, and had at least one on-treatment post-baseline ADAS-Cog evaluation. The number analyzed for that outcome was the number of evaluable participants.
Intervention
During Period I, participants could receive SAM-531 at 1.5 mg, 3.0 mg, or 5.0 mg. The study evaluated each dosage level. The registry record describes continued treatment during Period II for participants assigned to a SAM-531 dosage level in Period I.
Comparator
Donepezil and placebo were the other Period I treatment groups. Participants assigned to placebo in Period I were assigned to SAM-531 5.0 mg for the remaining 28 weeks, while participants who received a SAM-531 dosage level or donepezil continued the same study drug in Period II. This planned transition means the placebo comparison applies to Period I, rather than an unchanged placebo group across the full study.
Primary question
The primary outcome was change from baseline in the ADAS-Cog total score at Week 24. The clinical question was whether the score changed differently across the treatment groups by that time point. The registry record does not report the primary outcome results, so it does not establish the size, direction, or precision of any between-group differences.
3. Trial Design
NCT00895895 was a Phase 2 randomized, parallel-group study with triple masking. It was described as a 52-week, two-period, multicenter study comparing three SAM-531 dosage levels with donepezil and placebo. The registry record lists Pfizer as the sponsor, an enrollment of 526, a start date of 2009-05, primary completion in 2011-05, and a status of terminated. The reason for termination is not reported in the registry record.
Period I lasted 24 weeks. Participants received placebo, SAM-531 1.5 mg, SAM-531 3.0 mg, SAM-531 5.0 mg, or donepezil. For Period II, which covered the remaining 28 weeks, participants who had received placebo were assigned to SAM-531 5.0 mg. Participants who had received one of the SAM-531 dosage levels or donepezil continued that study drug. Consequently, treatment assignment and treatment exposure did not remain the same for every group throughout the study.
The primary outcome was measured at Week 24, at the end of Period I. That timing is important when interpreting the planned placebo comparisons: the registry description places placebo in Period I, not in Period II. The record does not report the randomization ratio, details of the randomization procedure, or how masking was implemented. It also does not report the reason for ending the study or whether the planned follow-up was completed by all participants.
The study included multiple secondary outcomes assessing function, neuropsychiatric symptoms, global clinical change, and cognitive tasks. The registry record lists 20 outcome measures and 81 analyses. It does not explain how those analyses were prioritized or whether particular analyses were prespecified as confirmatory. The listed enrollment is a study-level figure; the number included in the primary analysis is 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.
Period 1
| Stage | Placebo, Then SAM-531 | SAM-531 (1.5 mg) | SAM-531 (3.0 mg) | SAM-531 (5.0 mg) | Donepezil |
|---|---|---|---|---|---|
| STARTED | 107 | 105 | 104 | 104 | 106 |
| Randomized But Not Treated | 1 | 3 | 1 | 1 | 2 |
| COMPLETED | 86 | 84 | 84 | 91 | 86 |
| NOT COMPLETED | 21 | 21 | 20 | 13 | 20 |
Reasons for not completing this period:
| Reason | Placebo, Then SAM-531 | SAM-531 (1.5 mg) | SAM-531 (3.0 mg) | SAM-531 (5.0 mg) | Donepezil |
|---|---|---|---|---|---|
| Adverse Event | 7 | 6 | 4 | 6 | 7 |
| Death | 0 | 0 | 0 | 0 | 1 |
| discontinued by sponsor | 2 | 1 | 2 | 1 | 1 |
| failed to return | 0 | 0 | 1 | 0 | 1 |
| investigator request | 0 | 1 | 0 | 0 | 0 |
| Lost to Follow-up | 2 | 1 | 3 | 2 | 3 |
| Other | 1 | 2 | 1 | 1 | 1 |
| Protocol Violation | 0 | 1 | 0 | 0 | 0 |
| Withdrawal by Subject | 6 | 6 | 8 | 2 | 4 |
| unsatisfactory response-efficacy | 2 | 0 | 0 | 0 | 0 |
| randomized and not treated | 1 | 3 | 1 | 1 | 2 |
After Period 1, Prior to Period 2
| Stage | Placebo, Then SAM-531 | SAM-531 (1.5 mg) | SAM-531 (3.0 mg) | SAM-531 (5.0 mg) | Donepezil |
|---|---|---|---|---|---|
| STARTED | 86 | 84 | 84 | 91 | 86 |
| COMPLETED | 86 | 84 | 82 | 91 | 84 |
| NOT COMPLETED | 0 | 0 | 2 | 0 | 2 |
Reasons for not completing this period:
| Reason | Placebo, Then SAM-531 | SAM-531 (1.5 mg) | SAM-531 (3.0 mg) | SAM-531 (5.0 mg) | Donepezil |
|---|---|---|---|---|---|
| Adverse Event | 0 | 0 | 1 | 0 | 0 |
| Other | 0 | 0 | 1 | 0 | 0 |
| Protocol Violation | 0 | 0 | 0 | 0 | 1 |
| Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 |
Period 2
| Stage | Placebo, Then SAM-531 | SAM-531 (1.5 mg) | SAM-531 (3.0 mg) | SAM-531 (5.0 mg) | Donepezil |
|---|---|---|---|---|---|
| STARTED | 86 | 84 | 82 | 91 | 84 |
| COMPLETED | 30 | 31 | 33 | 37 | 35 |
| NOT COMPLETED | 56 | 53 | 49 | 54 | 49 |
Reasons for not completing this period:
| Reason | Placebo, Then SAM-531 | SAM-531 (1.5 mg) | SAM-531 (3.0 mg) | SAM-531 (5.0 mg) | Donepezil |
|---|---|---|---|---|---|
| Adverse Event | 3 | 3 | 5 | 2 | 5 |
| Death | 0 | 0 | 1 | 0 | 0 |
| discontinued by sponsor | 44 | 44 | 38 | 46 | 37 |
| failed to return | 2 | 0 | 0 | 0 | 0 |
| investigator request | 2 | 0 | 0 | 0 | 0 |
| Lost to Follow-up | 1 | 2 | 1 | 1 | 0 |
| Other | 1 | 1 | 3 | 1 | 1 |
| Protocol Violation | 1 | 0 | 1 | 1 | 1 |
| Withdrawal by Subject | 0 | 2 | 0 | 3 | 5 |
| unsatisfactory response-efficacy | 2 | 1 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Intent to treat (ITT) population: randomized participants who took at least one dose of study medication, had a baseline evaluation and had at least one on-treatment post-baseline evaluation for the ADAS-Cog; Number of Participants Analyzed (N): number of evaluable participants
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, Then SAM-531 | SAM-531 (1.5 mg) | SAM-531 (3.0 mg) | SAM-531 (5.0 mg) | Donepezil | Total |
|---|---|---|---|---|---|---|---|
| Participants analysed | 106 | 102 | 103 | 103 | 104 | 518 | |
| Age, Customized: 50 to 65 years | participants | 22 | 17 | 19 | 18 | 20 | 96 |
| Age, Customized: 66 to 80 years | participants | 59 | 60 | 54 | 66 | 66 | 305 |
| Age, Customized: greater than 80 years | participants | 25 | 25 | 30 | 19 | 18 | 117 |
| Sex: Female, Male: Female | Participants | 72 | 70 | 71 | 73 | 70 | 356 |
| Sex: Female, Male: Male | Participants | 34 | 32 | 32 | 30 | 34 | 162 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog) Total Score at Week 24, measured over Baseline, Week 24.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | units on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was change from baseline in the total score on the Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog) at Week 24. It is a continuous measure intended to assess the severity of cognitive impairment in Alzheimer disease. The registry describes a 14-item scale covering tasks and abilities such as word recall, naming, following commands, orientation, word recognition, spoken language, concentration, and executive maze performance.
Each item was rated from 0 (not present) to 5 (severe). The total score was the sum of the scores for items 1-11 and ranged from 0 to 70, with higher scores indicating greater cognitive impairment. Change from baseline expresses how the measured score differed at follow-up relative to the participant's starting assessment. Comparing average changes between randomized groups can describe whether their observed score trajectories differed during Period I.
As a general statistical point, using a continuous score retains more gradation than reducing participants to categories such as improved or not improved. The mean summarizes the average score change, while the standard deviation describes variation among individual scores. Neither measure alone describes the full distribution of participant outcomes.
The primary assessment at Week 24 coincided with the end of the initial treatment period, before the registry-described switch from placebo to SAM-531 5.0 mg for Period II. The registry record gives the endpoint definition but not the group means, standard deviations, treatment contrasts, confidence intervals, or p-values. The observed primary outcome findings are therefore not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the planned comparison and defines the primary endpoint, but it does not provide primary outcome estimates. There are no reported group-specific ADAS-Cog changes, between-group contrasts, confidence intervals, or p-values in the record. Without those results, the size and direction of the observed changes and the precision of any comparison are not reported in the registry record. No conclusion about whether groups differed on the primary outcome can be drawn from the available record.
The endpoint is a continuous score, with higher total values indicating greater cognitive impairment. A comparison of change from baseline would ordinarily describe how the average score changed in each group and how those changes differed. The registry record does not show those values. It also does not report whether any estimate was adjusted for baseline score or other covariates, or how missing endpoint measurements were handled.
The Week 24 timing provides a defined period for the primary comparison: participants had been assigned to placebo, one of the three SAM-531 dosage levels, or donepezil in Period I. Period II differed because participants originally assigned to placebo moved to SAM-531 5.0 mg, whereas the other groups continued their assigned study drug. Thus, safety observations reported for Period II should not be treated as a continuation of the original placebo comparison. The registry record does not provide an overall primary-outcome interpretation for the two periods.
The record lists 20 outcome measures and 81 analyses, alongside secondary outcomes covering disability, neuropsychiatric symptoms, global clinical impression, and performance on cognitive tasks. Multiple outcomes and analyses create a general interpretive concern: when many comparisons are examined, some results may appear notable by chance. Whether the trial used a multiplicity adjustment, a hierarchy of outcomes, or another strategy is not reported in the registry record. No unadjusted or adjusted primary p-value is reported.
Selected adverse-event counts are reported by treatment-period group, including counts of participants with serious adverse events and with other adverse events. Those counts provide descriptive safety information, not an estimate of the primary cognitive treatment effect. The registry record does not report deaths for the listed groups. The listed serious-event terms and percentages are also not accompanied by treatment-group attribution in the information recorded, so they cannot be used to compare those terms across arms.
In general, an estimate and its confidence interval help distinguish the direction of a result from its precision. A confidence interval describes a range of values compatible with the data and the statistical method used; it does not guarantee that the true effect lies in that range. No confidence interval for the primary comparison is reported in the registry record. Any sample-size planning illustration based on an observed effect also depends on that effect estimate; the registry record does not provide the primary outcome estimate needed to interpret such a calculation.
9. Statistical Methods Explained
The registry describes a randomized, parallel-group, triple-masked Phase 2 study. Randomization is intended, in general, to make treatment groups comparable at the point of assignment by distributing measured and unmeasured participant characteristics across groups. It does not ensure that groups will be identical, especially when sample sizes are limited. The record does not report the randomization procedure or allocation ratio, so those details cannot be assessed.
Masking is a general design feature intended to reduce the influence of treatment knowledge on participant experience, clinical assessment, and study conduct. The registry labels the masking as triple, but does not identify which parties were masked or describe how masking was maintained. The study used a parallel-group structure, meaning the assigned treatment groups were followed as groups rather than every participant receiving each treatment in sequence. The Period II transition from placebo to SAM-531 5.0 mg is an exception to an unchanged treatment assignment over the full study, as described in the registry record.
The primary endpoint is a continuous measure, and its parameter is the mean. In general, the mean is the arithmetic average of observed values. The standard deviation describes how dispersed individual values are around that average. A mean change can summarize the average direction and magnitude of score movement in a group, but it does not show whether changes were similar for all participants. The registry record lists the standard deviation as the dispersion measure but does not report the actual means or standard deviations for the primary endpoint.
A treatment contrast for a continuous outcome can be expressed as a difference between group summaries, possibly adjusted for baseline measures or other factors. The interpretation depends on the analysis model and the definition of the contrast. The registry record does not report a primary treatment contrast, an analysis model, covariate adjustments, or standard errors. As a result, the posted information does not allow readers to assess the numerical effect estimate or its precision.
In general, a confidence interval conveys uncertainty around an estimate. A narrower interval indicates greater precision under the model and assumptions used, while a wider interval indicates less precision. The interval is not a measure of clinical importance, and it does not by itself resolve concerns about bias, missing data, or multiple comparisons. No primary confidence interval is reported in the registry record, so precision cannot be evaluated from the endpoint results.
A p-value, in general, quantifies how surprising data at least as incompatible with a specified null hypothesis would be if that hypothesis and the model assumptions were true. It is not the probability that the null hypothesis is true, and it does not measure the size or practical importance of an effect. The registry record does not report a primary p-value, and no significance conclusion can be made from the endpoint definition alone.
The sample-size assumptions described for planning illustrations are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power and not evidence that the trial was designed with those assumptions. The registry record does not report the trial's own sample-size justification, the effect used in any planning calculation, or a protocol-based power target. Because the primary observed effect is not reported, the numerical interpretation of an effect-based planning illustration is not reported in the registry record.
General sample-size planning asks how much information would be needed to detect a chosen effect under selected assumptions. It does not establish that an effect exists, and it does not turn a nonsignificant result into evidence of no effect. The assumptions matter: a different target effect, allocation, variability, significance level, or analysis approach can produce a different planning result. The sample-size assumptions recorded for the illustrations should therefore be distinguished from the trial's actual enrollment of 526 participants.
Over-dispersion is a general issue when outcome variability exceeds what a statistical model assumes. If ignored, standard errors can be too small and uncertainty can be understated. The primary endpoint is described with a mean and standard deviation, but the registry record does not report a model or diagnostics that would establish whether over-dispersion was relevant to its analysis. No particular over-dispersion correction can be inferred.
The registry lists 81 analyses across 20 outcome measures. In general, multiplicity matters because examining many outcomes, time points, or contrasts increases the chance of at least one apparently unusual result. Statistical approaches can control that risk by adjusting significance thresholds or by defining a prespecified testing sequence. Whether either approach was used is not reported in the registry record. The number of listed analyses does not by itself show which analyses were primary, exploratory, adjusted, or selected for reporting.
The primary analysis population is described as the intent-to-treat population, but its registry definition is more specific: randomized participants who took at least one dose, had a baseline evaluation, and had at least one on-treatment post-baseline ADAS-Cog evaluation. The number analyzed was defined as the number of evaluable participants. Because this definition requires post-baseline information and at least one dose, it does not mean every randomized participant necessarily contributed to the primary endpoint analysis. The number excluded and the reasons for exclusion are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 20 outcome measures and 81 analyses. The secondary outcomes include change in the Disability Assessment for Dementia total score, Neuropsychiatry Inventory, ADCS-CGIC scores, and several CANTAB task measures at Week 24. Multiple outcomes and analyses raise a general multiplicity issue: testing many hypotheses can increase the likelihood of at least one result appearing noteworthy by chance. The record does not report a testing hierarchy, multiplicity adjustment, or which secondary analyses were considered confirmatory.
The presence of multiple analyses does not establish that the reported findings were false or that any particular adjustment was required. It does mean that interpretation would benefit from knowing which outcomes and contrasts were prespecified, what inferential procedures were planned, and how selective reporting was addressed. Those details are not reported in the registry record. The primary outcome itself has several categories or time points and is not reduced to one comparison in the registry summary, so a single primary comparison is not available for interpretation.
The stated primary analysis population required randomization, at least one dose, a baseline evaluation, and at least one on-treatment post-baseline ADAS-Cog evaluation. The record does not report how many participants met each criterion, how many had missing Week 24 data, or how missing values were handled. It does not report whether the analysis used imputation, a likelihood-based method, or another approach. Those choices can affect estimates when missingness is related to participant characteristics or outcomes.
General missing-data reasoning distinguishes the amount of missing information from the assumptions used to analyze it. A complete-case analysis can be biased if the participants with observed outcomes differ systematically from those without observed outcomes. Methods that use available data also rely on assumptions about why measurements are missing. Without counts of missing endpoint data and the analysis method, the potential influence of missingness cannot be assessed from the registry record.
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/5.0 mg Period 1 | 7 | 106 | 6.6% |
| SAM-531 1.5 mg Period 1 | 7 | 102 | 6.9% |
| SAM-531 3.0 mg Period 1 | 8 | 103 | 7.8% |
| SAM-531 5.0 mg Period 1 | 4 | 103 | 3.9% |
| Donepezil Period 1 | 4 | 104 | 3.8% |
| SAM-531 5.0 mg Crossover Period 2 | 8 | 106 | 7.5% |
| SAM-531 1.5 mg Period 2 | 2 | 102 | 2.0% |
| SAM-531 3.0 mg Period 2 | 7 | 103 | 6.8% |
| SAM-531 5.0 mg Period 2 | 3 | 103 | 2.9% |
| Donepezil Period 2 | 7 | 104 | 6.7% |
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/5.0 mg Period 1 | 30 of 106 |
| SAM-531 1.5 mg Period 1 | 23 of 102 |
| SAM-531 3.0 mg Period 1 | 32 of 103 |
| SAM-531 5.0 mg Period 1 | 37 of 103 |
| Donepezil Period 1 | 24 of 104 |
| SAM-531 5.0 mg Crossover Period 2 | 13 of 106 |
Most frequent serious adverse event terms
| Event term | Organ system | Placebo/5.0 mg Period 1 | SAM-531 1.5 mg Period 1 | SAM-531 3.0 mg Period 1 | SAM-531 5.0 mg Period 1 | Donepezil Period 1 | SAM-531 5.0 mg Crossover Period 2 |
|---|---|---|---|---|---|---|---|
| Hip fracture | Injury, poisoning and procedural complications | 0 of 106 | 1 of 102 | 2 of 103 | 1 of 103 | 0 of 104 | 0 of 106 |
| Urinary tract infection | Infections and infestations | 1 of 106 | 1 of 102 | 1 of 103 | 0 of 103 | 0 of 104 | 0 of 106 |
| Angina pectoris | Cardiac disorders | 1 of 106 | 0 of 102 | 0 of 103 | 0 of 103 | 0 of 104 | 1 of 106 |
| Coronary artery disease | Cardiac disorders | 0 of 106 | 0 of 102 | 1 of 103 | 0 of 103 | 0 of 104 | 1 of 106 |
| Coronary artery stenosis | Cardiac disorders | 1 of 106 | 0 of 102 | 0 of 103 | 0 of 103 | 0 of 104 | 1 of 106 |
| Abdominal pain | Gastrointestinal disorders | 0 of 106 | 0 of 102 | 0 of 103 | 0 of 103 | 0 of 104 | 2 of 106 |
| Non-cardiac chest pain | General disorders | 0 of 106 | 1 of 102 | 1 of 103 | 0 of 103 | 0 of 104 | 0 of 106 |
| Chest pain | General disorders | 0 of 106 | 0 of 102 | 0 of 103 | 0 of 103 | 0 of 104 | 2 of 106 |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | 0 of 106 | 0 of 102 | 0 of 103 | 1 of 103 | 0 of 104 | 1 of 106 |
| Confusional state | Psychiatric disorders | 0 of 106 | 1 of 102 | 0 of 103 | 0 of 103 | 0 of 104 | 1 of 106 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Placebo/5.0 mg Period 1 | SAM-531 1.5 mg Period 1 | SAM-531 3.0 mg Period 1 | SAM-531 5.0 mg Period 1 | Donepezil Period 1 | SAM-531 5.0 mg Crossover Period 2 |
|---|---|---|---|---|---|---|---|
| Headache | Nervous system disorders | 6 of 106 | 6 of 102 | 8 of 103 | 11 of 103 | 4 of 104 | 2 of 106 |
| Urinary tract infection | Infections and infestations | 7 of 106 | 4 of 102 | 11 of 103 | 2 of 103 | 3 of 104 | 5 of 106 |
| Diarrhoea | Gastrointestinal disorders | 4 of 106 | 1 of 102 | 4 of 103 | 9 of 103 | 7 of 104 | 0 of 106 |
| Nasopharyngitis | Infections and infestations | 4 of 106 | 5 of 102 | 2 of 103 | 6 of 103 | 5 of 104 | 3 of 106 |
| Hypertension | Vascular disorders | 6 of 106 | 2 of 102 | 3 of 103 | 4 of 103 | 4 of 104 | 4 of 106 |
| Vomiting | Gastrointestinal disorders | 5 of 106 | 1 of 102 | 6 of 103 | 2 of 103 | 3 of 104 | 1 of 106 |
| Dizziness | Nervous system disorders | 0 of 106 | 5 of 102 | 7 of 103 | 3 of 103 | 2 of 104 | 0 of 106 |
| Insomnia | Psychiatric disorders | 3 of 106 | 1 of 102 | 2 of 103 | 8 of 103 | 1 of 104 | 1 of 106 |
Serious events with the highest arm-level rate: hip fracture (1.9%), abdominal pain (1.9%), chest pain (1.9%), cardiac arrest (1.0%), non-cardiac chest pain (1.0%).
The safety record reports participants at risk and participants affected by serious adverse events for treatment-period groups. In Period I, the serious-event counts were 7 of 106 for placebo/5.0 mg, 7 of 102 for SAM-531 1.5 mg, 8 of 103 for SAM-531 3.0 mg, 4 of 103 for SAM-531 5.0 mg, and 4 of 104 for donepezil. In Period II, the reported counts were 8 of 106 for SAM-531 5.0 mg crossover, 2 of 102 for SAM-531 1.5 mg, 7 of 103 for SAM-531 3.0 mg, 3 of 103 for SAM-531 5.0 mg, and 7 of 104 for donepezil.
These are participant counts within the listed groups, not event totals or adjusted comparisons. The Period I placebo/5.0 mg label and the Period II crossover label reflect the registry's treatment-period descriptions; they should not be read as the same fixed placebo group across both periods. Period-specific counts are descriptive and do not by themselves establish a treatment-related cause or support a formal comparison. The registry record does not report deaths for these groups.
The record lists hip fracture, abdominal pain, and chest pain at 1.9% each, and cardiac arrest, non-cardiac chest pain, and nasopharyngitis at 1.0% each among the top serious terms. The registry information does not assign these term percentages to particular treatment groups. Counts of participants with other adverse events are reported separately from serious events, so the two categories should not be conflated.
12. What the Result Does, and Does Not, Mean
The registry record describes a randomized comparison of three SAM-531 dosage levels, donepezil, and placebo, with a primary cognitive endpoint assessed at Week 24. It also identifies the population definition and scale used for that endpoint. Those details clarify what the study was designed to assess, but they are not outcome findings. The registry record does not report the primary ADAS-Cog results.
Without group-specific changes, contrasts, confidence intervals, and p-values, the available record does not establish whether the observed primary outcome differed among treatment groups, how large any difference was, or how precisely it was estimated. The absence of reported results is not evidence that the treatments had identical effects, nor does it show that any treatment caused a particular change. It means that the primary outcome comparison cannot be interpreted from the registry record.
The safety counts describe the number of participants with serious adverse events in each listed treatment-period group, and the record also lists selected serious-event terms. They do not establish that a treatment caused or prevented an event. The registry record does not report deaths for the listed groups, and it does not attribute the listed serious-term percentages to treatment groups. The available safety information is therefore descriptive rather than a complete comparative safety analysis.
The study's two-period structure also matters. Placebo participants moved to SAM-531 5.0 mg for Period II, while other participants continued their assigned study drug. As a result, Period II should not be interpreted as a continuing placebo-controlled comparison. The Week 24 primary outcome falls at the end of Period I, but the record does not provide the outcome estimates needed to interpret that comparison.
In general, statistical evidence and clinical importance are related but distinct. A precise estimate can still be small, and a sizeable estimate can be uncertain. The registry record does not report an effect estimate or its precision for the primary endpoint, so neither statistical nor clinical importance can be assessed. No treatment recommendation follows from the design description or adverse-event counts alone.
13. Why This Trial Matters Statistically
This study is statistically notable for its combination of a multi-arm Period I comparison and a treatment transition in Period II. The primary outcome is timed at Week 24, which aligns with the end of the initial placebo-controlled period described in the registry. The later switch from placebo to SAM-531 5.0 mg changes the interpretation of subsequent observations: Period II is not a continuation of the original placebo comparison.
The primary endpoint is a continuous cognitive score summarized by a mean and standard deviation. This makes the distinction between an average change and individual variation important. A group mean can conceal substantial differences in participant trajectories, while the standard deviation gives information about spread but not the full shape of the data. The registry record defines the measure and its scoring, but does not report results that would allow assessment of either group averages or variability.
The record lists 20 outcome measures and 81 analyses. This makes prespecification and multiplicity handling important questions for interpretation. The registry record does not report how outcomes were ranked, whether comparisons were adjusted, or which analyses were intended to support confirmatory conclusions. That absence limits interpretation of any analysis-specific findings, even where descriptive counts are available.
The safety information is organized by treatment period and includes participants at risk and participants affected. This organization can help distinguish the initial treatment assignments from the later crossover exposure, but it does not supply a causal comparison. The different exposure histories and the absence of reported group attribution for the listed serious-event terms should be kept in view.
Most importantly, design details and results are separate kinds of evidence. Randomization, masking, and a clearly defined primary endpoint describe how a comparison was intended to work. They do not reveal the observed treatment effect. Because the primary outcome results and their uncertainty are not reported in the registry record, the trial's main statistical question remains unresolved in the posted information.
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 primary limitation for interpreting this trial is that the registry record defines the primary endpoint but does not report its results. There are no group-specific ADAS-Cog changes, between-group estimates, confidence intervals, or p-values. Therefore, neither the direction nor the magnitude nor the precision of the primary comparison can be assessed.
The registry record also does not report why the study was terminated, whether the termination changed the planned analyses, or how many participants completed each period. The enrollment figure is 526, but the number included in the primary endpoint analysis is not reported. The record defines the analysis population by requiring at least one dose, a baseline evaluation, and at least one on-treatment post-baseline ADAS-Cog assessment; it does not give the number who met that definition.
Missing outcome information is another unresolved issue. The number of participants without a Week 24 score, reasons for missingness, and methods for handling missing values are not reported in the registry record. The analysis model, baseline adjustment, and any sensitivity analyses are also not reported. These details are needed to assess how robust a primary estimate would be, even if an estimate were available.
The record lists numerous outcome measures and analyses but does not report a multiplicity strategy or identify a testing hierarchy. This limits the ability to distinguish prespecified confirmatory analyses from exploratory analyses. The reason for termination and the trial's sample-size justification are also not reported in the registry record, so the planned statistical basis for enrollment cannot be evaluated.
Finally, the safety information is presented as counts by treatment-period group, with selected serious-event terms and percentages not attributed to specific groups. The record does not report deaths for the listed groups. These limitations prevent a complete assessment of comparative safety from the listed figures alone.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study Comparing 3 Dosage Levels Of SAM-531 In Outpatients With Mild To Moderate Alzheimer Disease — NCT00895895.
- Registry record last updated 2013-01-31; status last verified 2012-12.
- Results first posted 2013-01-31.
- 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
NCT00895895 was a Phase 2 randomized, parallel-group, triple-masked study in outpatients with mild to moderate Alzheimer disease. It compared SAM-531 1.5 mg, SAM-531 3.0 mg, and SAM-531 5.0 mg with donepezil and placebo during Period I. The registry describes a 52-week study with a 24-week first period and a 28-week second period; participants initially assigned to placebo moved to SAM-531 5.0 mg in Period II.
The primary endpoint was change from baseline in ADAS-Cog total score at Week 24. The registry record specifies the outcome scale and an analysis population definition, but does not report the primary outcome results, confidence intervals, or p-values. It lists 20 outcome measures and 81 analyses, without reporting a multiplicity strategy or the handling of missing endpoint data. Selected serious adverse-event counts are reported by treatment-period group. The study status is terminated; the reason is not reported in the registry record.