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 PTI-125 for Mild-to-moderate Alzheimer's Disease Patients (NCT03748706), a na phase 2 study. The primary outcome is Maximum Plasma Concentration (Cmax).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03748706 |
| Phase | Phase 2 |
| Condition | Alzheimer Disease |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 13 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Pain Therapeutics |
| Results posted | Yes |
2. Clinical Question
Population
Patients with mild-to-moderate Alzheimer's disease. The registry record lists enrollment of 13; further eligibility details are not reported in the registry record.
Intervention
Simufilam (PTI-125), given as 100 mg oral tablets twice daily.
Comparator
There is no comparator group. This is a single-group study, with allocation listed as NA and masking listed as none.
Primary question
What maximum plasma concentration of PTI-125 is observed, as assessed through scheduled blood sampling on Study Day 1 and Day 28?
The study is a Phase 2a, open-label investigation in people described as having mild-to-moderate Alzheimer's disease. Its primary endpoint is pharmacokinetic: it concerns the concentration of PTI-125 measured in plasma, rather than a direct measure of change in Alzheimer's disease symptoms or function. The planned assessment includes multiple blood-draw times after dosing on Study Day 1 and Day 28.
Because there is no control group and treatment masking is absent, the study does not directly compare PTI-125 with placebo, usual care, or another treatment. Its design can describe measurements collected during PTI-125 administration, but cannot by itself separate changes associated with treatment from other explanations. The registry record does not report numerical Cmax results, so the clinical question can be described from the endpoint definition, but its measured answer cannot be established from the posted record.
3. Trial Design
This is a Phase 2a, multicenter, open-label, single-group study of PTI-125 in patients with mild-to-moderate Alzheimer's disease. The registry record lists enrollment of 13 and a completed status. The recorded start date is 2019-03-07, and the primary completion date is 2019-05-08.
The intervention is named Simufilam (PTI-125) and is described as 100 mg oral tablets administered twice daily. Allocation is listed as NA, masking as none, and the model as single-group. There is therefore no concurrent control arm in the recorded design. The record does not describe random assignment or a blinded comparison.
The primary outcome is Maximum Plasma Concentration (Cmax), a continuous measure reported as a mean with standard deviation. Blood draws are specified on Study Day 1 and Day 28 at 20, 40, and 60 min and at 1.5, 2, 2.5, 3, 4, 6, 8, 10 and 12 h post-dose. The outcome description says PTI-125 plasma levels are to be evaluated using non-compartmental methods in WinNonlin.
SavaDx (Biomarker) and CSF Biomarkers are listed as secondary outcomes. The registry record also lists 8 outcome measures and 0 analyses. Details about the recruitment process, eligibility criteria, treatment adherence, and the analysis population are not reported in the registry record. The recorded design is suited to describing observations in the treated group, but does not provide a like-for-like control comparison.
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.
Overall Study
| Stage | PTI-125 |
|---|---|
| STARTED | 13 |
| COMPLETED | 12 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | PTI-125 |
|---|---|
| Lost to Follow-up | 1 |
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 | PTI-125 |
|---|---|---|
| Participants analysed | 13 | |
| Age, Continuous | Years | 67.8 (56 to 81) |
| Sex: Female, Male: Female | Participants | 9 |
| Sex: Female, Male: Male | Participants | 4 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 3 |
| Race (NIH/OMB): White | Participants | 10 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | Participants | 13 |
6. Primary Endpoint
The registry lists the primary outcome as Maximum Plasma Concentration (Cmax), measured over Study Day 1 and Day 28 at 20, 40, and 60 min and at 1.5, 2, 2.5, 3, 4, 6, 8, 10 and 12 h post-dose.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | ng/mL |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is Maximum Plasma Concentration (Cmax), measured in ng/mL. Cmax refers to the highest observed plasma concentration over the relevant concentration-time profile. The registry record specifies a mean and standard deviation as the summary measures and identifies blood sampling on Study Day 1 and Day 28 at multiple post-dose times.
General statistical and pharmacokinetic context: Measuring plasma concentrations over time helps characterize how much of a drug is present in the bloodstream after dosing and how that concentration changes during the sampling period. Cmax is used in pharmacokinetic assessment because it captures the peak concentration in the measured profile. It is one aspect of drug exposure; it is not, by itself, a measure of clinical benefit, disease progression, or safety.
The record describes non-compartmental evaluation in WinNonlin. In general, non-compartmental methods use the observed concentration-time data to characterize pharmacokinetic features without requiring a specified compartment structure. Interpretation depends on the sampling schedule and the quality and completeness of the concentration measurements.
The registry record does not report the observed Cmax mean, standard deviation, participant-level data, or a numerical estimate at either assessment day. It therefore establishes what the endpoint was intended to measure, but does not allow readers to quantify the observed plasma concentrations or their variability.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a completed, open-label, single-group study, but it does not report numerical results for the primary Cmax endpoint. In particular, there is no posted mean or standard deviation for plasma concentration, and no estimate or confidence interval is reported. The record therefore does not support a numerical interpretation of the primary endpoint.
The design matters when interpreting the observations. With no comparator group, any measured concentration describes participants receiving PTI-125 under the study conditions. There is no concurrent group against which to compare those observations. The open-label design means masking is absent, although Cmax is a laboratory-based pharmacokinetic measure rather than a subjective rating. The registry record does not describe procedures for sample handling, laboratory blinding, or quality control, so those details cannot be assessed.
The outcome description specifies repeated blood sampling on Study Day 1 and Day 28 at post-dose times extending through 12 h. Such sampling is intended to capture concentrations across the recorded period. In general, the observed maximum depends on the measured samples and their timing; the record does not provide actual concentration-time values or explain how missing samples would be handled.
The registry record lists 8 outcome measures and 0 analyses. SavaDx (Biomarker) and CSF Biomarkers are named as secondary outcomes, but numerical findings for those outcomes are not reported in the registry record. No statistical analysis plan, analysis population, or missing-data method is reported. Accordingly, the posted record does not show how endpoint estimates were calculated or whether all enrolled participants contributed to each analysis.
The safety information lists 0 participants affected by serious adverse events among 13 at risk, 1 affected in the other adverse-event category among 13 at risk, and 0 deaths. These are descriptive counts recorded for this study; they do not establish a comparative safety effect. The registry record does not provide serious adverse-event terms or additional detail about the other adverse event.
Planning illustrations based on an observed effect should not be confused with evidence from a randomized comparison. The stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between hypothetical arms, and a normal approximation. No numerical observed effect or planning estimates are reported in the registry record. More importantly, this study itself is not a two-arm comparison, so such illustrations do not represent its design or an observed power calculation.
9. Statistical Methods Explained
What does a mean describe?
General statistical explanation: A mean is a measure of the central location of a set of numerical observations. For a concentration endpoint, it provides a summary of the measured concentrations in the analysis group. Its interpretation depends on which observations are included and how the endpoint is defined. The registry record identifies the mean as the summary parameter for Cmax, but does not report the resulting estimate or specify the analysis population.
The mean alone does not show how similar or different individual observations are. The standard deviation is a measure of spread around the mean. A smaller standard deviation indicates observations closer to the mean, while a larger one indicates more spread. This is a general interpretation; the registry record does not give a Cmax standard deviation or participant-level measurements with which to assess variability.
What does Cmax capture?
General pharmacokinetic explanation: Cmax is the peak concentration observed in a concentration-time profile. Blood sampling at scheduled post-dose times creates the measurements used to characterize that profile. The registry record specifies sampling on Study Day 1 and Day 28 at 20, 40, and 60 min and at 1.5, 2, 2.5, 3, 4, 6, 8, 10 and 12 h post-dose. A measured peak is interpreted in relation to those observation times; the record does not provide the actual measurements or report when a peak occurred.
The endpoint description states that plasma levels will be evaluated using non-compartmental methods in WinNonlin. General explanation: Non-compartmental methods characterize drug concentration data using the observed profile and do not require the analyst to define a particular set of compartments for the body. The record does not report method settings, data handling decisions, or an analysis output. The endpoint definition alone therefore does not establish the resulting Cmax values.
Why does the design affect interpretation?
General statistical explanation: A single-group study can describe measurements among participants who receive the intervention, but it lacks a concurrent group for estimating a between-group contrast. The design lists allocation as NA, masking as none, and the model as single-group. It is therefore not appropriate to interpret the study as a randomized comparison or to attribute any change in a measurement to treatment by comparison with an unobserved control. For a pharmacokinetic endpoint, the measured plasma concentrations remain descriptive of the study observations; the registry record does not provide those results.
Open-label means that masking is absent. In general, masking can reduce the influence of knowledge of treatment assignment on some aspects of trial conduct and assessment. Cmax is a laboratory measurement, but the registry record does not state whether laboratory personnel were blinded to visit or treatment information, how samples were processed, or how assay performance was monitored. These details are not reported in the registry record and should not be assumed.
What can be inferred from the posted analysis information?
The registry record lists 8 outcome measures and 0 analyses. That metadata does not provide numerical endpoint estimates, confidence intervals, hypothesis tests, or a description of which participants were included in each analysis. The registry record does not report a statistical analysis plan, a sample-size justification, an interim analysis plan, or a method for handling missing measurements. These omissions prevent a reader from evaluating the precision of the primary estimate or reconstructing its analysis.
General explanation: A confidence interval expresses uncertainty around an estimated quantity under the assumptions of the statistical method. It is not reported for Cmax in the registry record. A p-value, if reported, would address a specified statistical hypothesis under its assumptions; no Cmax p-value or hypothesis test is reported. Without these quantities and the underlying estimate, the precision and statistical uncertainty of the primary result cannot be assessed from this record.
The separate planning illustration is described as a calculation based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes participants per arm for 80% or 90% power only if numerical outputs are posted; no such numerical outputs or observed effect are reported in the registry record. The illustration is not the trial's own design: the recorded study has a single group and no allocation to two arms. Sample-size illustrations are planning scenarios, not observed power, and cannot substitute for the missing endpoint results.
General explanation: Over-dispersion occurs when outcome variability exceeds what a chosen statistical model assumes. It can make standard errors and inferential results unreliable if the model does not account for the extra variation. The registry record does not identify an over-dispersion model or indicate that one was used. Since the primary outcome is continuous and the analysis details are not reported, no claim about over-dispersion or a particular distributional model can be made from the record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 8 outcome measures and 0 analyses. It names SavaDx (Biomarker) and CSF Biomarkers as secondary outcomes, in addition to the primary Cmax measure. Numerical results for the primary and secondary outcomes are not reported in the registry record.
When a study assesses multiple outcomes or conducts multiple statistical tests, the chance of at least one apparently notable finding can increase. General statistical explanation: Multiplicity methods can address that issue by adjusting inference or by defining a hierarchy of outcomes and tests in advance. The registry record does not report a multiplicity adjustment, a testing hierarchy, or a statistical analysis plan. It is therefore not possible to determine whether any adjustment was planned or how the multiple outcomes were to be interpreted together.
The record also does not report missing-data methods, the number of participants with usable measurements at each assessment, or the analysis population for Cmax. The enrollment count is 13, but that does not establish that all enrolled participants contributed data to each endpoint. In general, missing concentration measurements can affect the observed profile and the estimation of a peak; the consequences depend on which measurements are missing and the method used to handle them.
Rules for inclusion in analysis, protocol deviations, and treatment adherence are not reported in the registry record. Without those details, readers cannot determine how the analysis population was defined, whether the endpoint was available for every participant, or whether missingness could have influenced the posted results. No imputation or other missing-data approach should be presumed.
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 |
|---|---|---|---|
| PTI-125 | 0 | 13 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| PTI-125 | 0 of 13 |
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 |
|---|---|
| PTI-125 | 1 of 13 |
Most frequent non-serious adverse event terms
| Event term | Organ system | PTI-125 |
|---|---|---|
| Fall | General disorders | 1 of 13 |
| B12 deficiency | Metabolism and nutrition disorders | 1 of 13 |
| Hypercalcemia | Musculoskeletal and connective tissue disorders | 1 of 13 |
| Renal colic | Renal and urinary disorders | 1 of 13 |
| Dehydration | General disorders | 1 of 13 |
| Flu | Respiratory, thoracic and mediastinal disorders | 1 of 13 |
The registry record lists 0 participants affected by serious adverse events among 13 at risk. It lists 1 affected in the other adverse-event category among 13 at risk, and 0 deaths. These are the safety counts recorded for the PTI-125 group.
These counts are descriptive. The study has no comparator group, so the figures do not provide a direct comparison with another treatment or with an untreated group. A count of 0 serious adverse events in this study does not establish that serious adverse events cannot occur; it describes what is recorded for the study population. The registry record does not list serious adverse-event terms, and further details about the other adverse event are not reported in the registry record.
The counts should also be read in light of the limited information about safety follow-up and analysis. The registry record does not report event-level narratives, timing, severity details, or attribution assessments. It lists enrollment of 13 and 13 at risk for the safety categories, but does not provide additional information about individual follow-up or whether all events were captured in the same way. These figures alone cannot characterize comparative risk or support conclusions beyond the recorded counts.
12. What the Result Does, and Does Not, Mean
The record establishes that a completed Phase 2a, open-label, single-group study of PTI-125 was registered for patients with mild-to-moderate Alzheimer's disease. The intervention is described as 100 mg oral tablets administered twice daily. The primary endpoint was maximum plasma concentration, with blood sampling specified on Study Day 1 and Day 28. This information describes the study question and its measurement approach.
The posted registry record does not report the numerical Cmax results. It therefore does not show the measured mean, standard deviation, or uncertainty around the estimate. Without those results, readers cannot quantify the observed plasma concentration profile or assess how precisely the endpoint was estimated. Numerical findings for the listed secondary outcomes are also not reported in the registry record.
The design also sets limits on what the study can establish. A single-group, open-label study has no concurrent comparator. It can describe observations in participants receiving PTI-125, but does not provide a controlled estimate of a treatment difference. Cmax is a pharmacokinetic measure, not a direct measure of clinical change in Alzheimer's disease. The endpoint definition alone does not show whether participants experienced a clinical benefit or harm.
The safety counts recorded are 0 affected by serious adverse events among 13 at risk, 1 affected in the other adverse-event category among 13 at risk, and 0 deaths. These descriptive counts do not establish comparative safety, and the record does not provide further event detail. Overall, the registry information describes the design, endpoint, and selected safety counts, while leaving the primary numerical result and important analysis details unreported. No conclusion about clinical effectiveness can be drawn from the record as posted.
13. Why This Trial Matters Statistically
This trial is statistically notable for the distinction between a pharmacokinetic endpoint and a clinical outcome. Cmax describes the peak plasma concentration measured after dosing. It answers a question about drug concentration, not directly whether symptoms or function in Alzheimer's disease changed. Keeping that distinction clear prevents a concentration measure from being interpreted as evidence of clinical benefit.
The single-group, open-label design also makes the scope of inference important. Without a comparator, the study can describe recorded measurements during PTI-125 administration but cannot estimate a controlled treatment contrast. This is especially relevant when readers encounter a study title or intervention name and might otherwise assume a comparative efficacy evaluation.
The registry record specifies a detailed blood-sampling schedule on Study Day 1 and Day 28, and identifies non-compartmental methods in WinNonlin for evaluating plasma levels. Those design details show how the pharmacokinetic question was framed. However, the numerical Cmax findings and the analysis details are not reported in the registry record. A carefully specified measurement plan does not replace reporting the observed values and their uncertainty.
The posted safety counts are also best understood descriptively, rather than as comparative evidence. The record lists no participants affected by serious adverse events, one affected in the other adverse-event category, and no deaths. With no control group and limited event detail, those counts should not be extended into a comparative risk conclusion.
Finally, the record illustrates why transparency about analysis populations, missing measurements, and multiplicity matters. It lists multiple outcome measures but does not report an analysis plan or numerical outcome results. Those omissions constrain assessment of precision and interpretation. The statistical value of the record is therefore primarily in documenting the study design and intended endpoint, while making clear which results cannot be evaluated from 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 principal limitation for interpreting the primary endpoint is that its numerical results are not reported in the registry record. The Cmax mean and standard deviation are not available, and no confidence interval or statistical test is reported. Consequently, neither the observed concentration level nor the precision of an estimate can be assessed from the posted information.
The study is single-group and open-label, with allocation listed as NA and masking as none. It has no concurrent comparator, so it cannot provide a direct between-group treatment estimate. The design also does not support separating changes over time from other possible explanations. The registry record does not describe laboratory blinding, assay procedures, or quality control.
Although the record lists enrollment of 13 and specifies sampling on Study Day 1 and Day 28, it does not report how many participants contributed usable measurements at each time point. The analysis population, adherence information, protocol deviations, and approach to missing concentration data are not reported in the registry record. These omissions limit assessment of whether the planned sampling and analysis were completed as intended.
The registry record lists 8 outcome measures and 0 analyses, but does not report an analysis plan, multiplicity approach, interim analyses, or sample-size justification. The listed secondary outcomes do not have numerical results in the record. Serious adverse-event terms and further details about the other adverse event are also not reported. These limitations leave the posted information insufficient for assessing the primary endpoint's magnitude, variability, or comparative meaning.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: PTI-125 for Mild-to-moderate Alzheimer's Disease Patients — NCT03748706.
- Registry record last updated 2021-07-07; status last verified 2021-06.
- Results first posted 2021-04-01.
- 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
The registry record describes NCT03748706, a completed Phase 2a, multicenter, open-label, single-group study of PTI-125 in patients with mild-to-moderate Alzheimer's disease. Enrollment is listed as 13. The recorded start date is 2019-03-07, and primary completion is recorded as 2019-05-08.
The intervention is Simufilam (PTI-125), 100 mg oral tablets administered twice daily. The primary outcome is Maximum Plasma Concentration (Cmax), measured in ng/mL and summarized by mean and standard deviation, with scheduled sampling on Study Day 1 and Day 28. SavaDx (Biomarker) and CSF Biomarkers are listed as secondary outcomes.
Numerical primary and secondary outcome results are not reported in the registry record. The safety counts list 0 affected by serious adverse events among 13 at risk, 1 affected in the other adverse-event category among 13 at risk, and 0 deaths. Analysis methods, the analysis population, and missing-data procedures are not reported in the registry record.