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 Open-label, Randomized, 2-way Crossover, Monocentric, Controlled Study to Evaluate the Effect on Daily PHE Fluctuation of PKU GOLIKE Versus SoC in Patients With PKU. (NCT05827536), a randomized na study. The primary outcome is Phe Blood Concentration With Dried Blood Spots (Umol/L) on the Second Test Day With Standard of Care Right Before Product Self-administration and Before Any Food Intake.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT05827536 |
| Phase | NA |
| Condition | Phenylketonurias |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | None (open label) |
| Enrollment | 21 |
| Arms in the primary outcome | 2 |
| Lead sponsor | APR Applied Pharma Research s.a. |
| Results posted | Yes |
2. Clinical Question
Population
Patients aged ≥ 16 years with phenylketonuria (PKU) were eligible according to the brief summary. The registry reports an enrollment of 21 participants. The number contributing to the posted primary outcome is 8 at each listed standard-of-care timepoint.
Intervention
PKU GOLIKE is described as a prolonged-release amino-acids mixture. Participants assigned to the sequence beginning with this product received 3 daily self-administrations for 2 consecutive days in the first period.
Comparator
The comparator was each participant’s usual standard of care (SoC). In the sequence beginning with SoC, participants received 3 daily self-administrations for 2 consecutive days in the first period, followed by PKU GOLIKE in the second period.
Primary question
The study set out to evaluate daily blood phenylalanine (Phe) fluctuation under PKU GOLIKE versus SoC. The posted primary endpoint is a Phe concentration measurement on the second test day before product self-administration and food intake. The registry reports two SoC means, but no estimable continuous two-arm comparison, so the posted primary data do not quantify a GOLIKE-versus-SoC difference.
3. Trial Design
This was a randomized, open-label, controlled, two-way crossover study conducted at a single center. The registry records the phase as NA and the study status as terminated. It lists an enrollment of 21, a start date of 2023-10-30, and a primary completion date of 2024-11-27. The reason for termination is not reported in the registry record.
In a crossover design, participants receive both study conditions in a planned sequence rather than remaining in only one treatment group. The registry describes two sequences: SoC followed by PKU GOLIKE, and PKU GOLIKE followed by SoC. Each period involved 3 daily self-administrations for 2 consecutive days. The study was open-label, meaning masking was not used.
General statistical context: a crossover can allow within-participant comparisons, because measurements from the same person may be more alike than measurements from different people. That design depends on having usable observations from both conditions and an analysis that accounts for the paired structure, period, and sequence. The registry record does not report a washout period, details of the randomization procedure, or how period and sequence effects were handled. It also does not report an analysis plan or an estimated treatment contrast.
The posted primary outcome is described as a mean Phe blood concentration on the second test day with SoC, measured at 8:00 am(±15 min). The registry presents two SoC labels, T2 and T4, each with 8 observations. These are not presented as the two randomized treatment conditions, and the posted results do not contain an estimable continuous comparison between GOLIKE and SoC. Enrollment and the number contributing to the endpoint therefore describe different quantities; the registry does not explain why the posted endpoint count is 8 at each timepoint.
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 21 participants signed the informed consent form and were assigned to a study arm (either AB or BA) as per protocol. Four participants did not receive any treatments, and one participant received the first assigned treatment only. These five participants were therefore excluded from the ITT population due to the absence of blood spot samples required for the determination of amino acid levels.
1st Period 3 Daily Administrations 2 Day
| Stage | AB =1st Usual SoC, 2nd PKU GOLIKE | BA =1st PKU GOLIKE 2nd Usual SoC |
|---|---|---|
| STARTED | 10 | 11 |
| COMPLETED | 6 | 7 |
| NOT COMPLETED | 4 | 4 |
Reasons for not completing this period:
| Reason | AB =1st Usual SoC, 2nd PKU GOLIKE | BA =1st PKU GOLIKE 2nd Usual SoC |
|---|---|---|
| Protocol Violation | 2 | 1 |
| Withdrawal by Subject | 2 | 3 |
2nd Period 3 Daily Administrations 2 Day
| Stage | AB =1st Usual SoC, 2nd PKU GOLIKE | BA =1st PKU GOLIKE 2nd Usual SoC |
|---|---|---|
| STARTED | 10 | 11 |
| COMPLETED | 5 | 7 |
| NOT COMPLETED | 5 | 4 |
Reasons for not completing this period:
| Reason | AB =1st Usual SoC, 2nd PKU GOLIKE | BA =1st PKU GOLIKE 2nd Usual SoC |
|---|---|---|
| Withdrawal by Subject | 3 | 3 |
| Protocol Violation | 2 | 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.
Population: Age distribution of all randomized patients (N = 21): The mean (SD) age was 29.8 (8.85) years. The median age was 31 years.
| Characteristic | Unit | AB =1st Usual SoC, 2nd PKU GOLIKE | BA =1st PKU GOLIKE 2nd Usual SoC | Total |
|---|---|---|---|---|
| Participants analysed | 10 | 11 | 21 | |
| Age, Continuous | years | 31.5 (SD 8.05) | 28.18 (SD 9.63) | 29.8 (SD 8.85) |
| Sex: Female, Male: Female | Participants | 6 | 3 | 9 |
| Sex: Female, Male: Male | Participants | 4 | 8 | 12 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 10 | 11 | 21 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Phe Blood Concentration With Dried Blood Spots (Umol/L) on the Second Test Day With Standard of Care Right Before Product Self-administration and Before Any Food Intake, measured over at 8:00 am(±15 min) on the second test day (T2; T4) with SoC.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | μmol/L |
| Endpoint classification | Continuous Endpoint |
The primary endpoint measures phenylalanine (Phe) concentration in blood using dried blood spots, with results expressed in μmol/L. The description identifies the measurement as a blood Phe level. The stated timeframe is 8:00 am(±15 min) on the second test day, with the endpoint title specifying measurement before product self-administration and before any food intake under SoC.
General context: a biochemical concentration is a direct measurement of the substance named in the endpoint. Repeated measurements at specified times can describe how that concentration varies over a day or across study conditions. Consistent timing and the stated pre-administration, pre-food conditions help define what a measurement represents. They do not, by themselves, establish that measurements from different timepoints or conditions are directly comparable; the design and analysis must also account for the crossover structure.
The registry’s primary endpoint description refers to daily Phe fluctuation, but the posted primary results contain means and standard deviations for SoC at T2 and SoC at T4. They do not provide a GOLIKE mean, a paired treatment contrast, or an uncertainty interval for a GOLIKE-versus-SoC effect. The registry does not report a clinical threshold or explain how a particular change in Phe concentration would be interpreted. The endpoint therefore describes a laboratory measure, rather than a reported clinical outcome.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
For SoC at T2, the posted mean Phe concentration is 620.2 μmol/L, with a standard deviation of 154.6, based on 8 observations. For SoC at T4, the posted mean is 554.2 μmol/L, with a standard deviation of 202.3, also based on 8 observations. These figures describe the two listed SoC measurements; they are not a reported estimate of the difference between PKU GOLIKE and SoC.
The standard deviation describes the spread of individual measurements around a mean. The posted values indicate variability among the observations at both timepoints, but they do not show the distribution of measurements or how the same participants’ values changed between timepoints. The registry does not report confidence intervals, standard errors, a test statistic, or a p-value for the primary endpoint. Consequently, the precision of either mean and the uncertainty around a treatment comparison cannot be determined from the posted summary statistics alone.
The endpoint counts are 8 at each SoC timepoint, whereas total enrollment is 21. The registry does not explain the difference between enrollment and the number with posted endpoint observations. It also does not report how missing observations were handled or whether the same participants contributed at T2 and T4. Without those details, the paired relationship that is central to a crossover comparison cannot be assessed from the listed summaries.
The study’s stated objective is to evaluate daily Phe fluctuation with PKU GOLIKE versus SoC. However, the primary results available in the registry are two SoC means, not results for both study conditions. The registry record explicitly indicates that values are missing or not estimable for a two-arm comparison of the continuous endpoint. It would therefore be inappropriate to interpret the two posted means as a treatment effect or to infer what the GOLIKE measurements were.
These results describe what is posted, not whether any difference is statistically distinguishable or clinically meaningful. A formal comparison would require an appropriate estimate for the crossover treatment contrast and its uncertainty, together with enough information to understand the analysis population and missing data. Those items are not reported in the registry record.
9. Statistical Methods Explained
General statistical context: the primary outcome is continuous, because it is a measured concentration rather than a count or a category. The registry reports the mean and standard deviation for each listed SoC timepoint. A mean gives the arithmetic center of a set of observations; the standard deviation describes how dispersed those observations are around that center. Neither summary alone indicates the full shape of the data, and neither is a treatment comparison.
What would a crossover comparison estimate?
In a crossover trial, each participant is intended to receive both conditions in a specified order. A treatment comparison can therefore be based on the within-participant difference between the measurements under the two conditions. This pairing matters: measurements from the same person may be correlated, so treating them as unrelated observations can misstate uncertainty. A suitable analysis generally needs to respect the paired design and consider whether measurements differ by period or sequence.
The registry record does not report a model, a paired analysis, an adjustment for period or sequence, or a treatment contrast. The posted primary results are labeled SoC at T2 and SoC at T4, with 8 observations for each. They do not give the corresponding GOLIKE endpoint summaries or a within-participant comparison. The record also states that values are missing or not estimable for a two-arm continuous comparison. As a result, an effect estimate and its precision cannot be reconstructed from these results.
How should the standard deviation be read?
General statistical context: a standard deviation is a measure of variation among observations, expressed in the same units as the outcome. It is not the uncertainty interval for the mean and does not provide a significance test. A confidence interval, when reported, gives a range of values compatible with the data and a specified statistical procedure. No confidence interval is reported for these primary results. It is therefore not possible to use the posted standard deviations as a substitute for an interval around the means or around a treatment effect.
The posted values are means of a continuous measure, as identified in the registry. The primary results list 620.2 with a standard deviation of 154.6 for SoC at T2, and 554.2 with a standard deviation of 202.3 for SoC at T4. The counts are 8 for both. These summaries do not indicate whether the observations are paired across timepoints, how many participants contributed to both, or whether the endpoint distribution was checked.
Why can over-dispersion matter?
General context: over-dispersion means the observed variability is greater than a statistical model assumes. When a model underestimates variability, its uncertainty estimates can be too narrow and statistical evidence can appear stronger than it is. This concept is relevant when choosing and checking a model for data, but the registry does not report a model or a diagnostic assessment for this endpoint. The posted standard deviations alone do not establish over-dispersion.
What do the planning illustrations mean?
General context: a sample-size planning illustration asks how many participants per arm might be needed under stated assumptions to detect a specified effect. The registry’s planning assumptions describe a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a stated fraction of the observed effect. These illustrations are explicitly not the trial’s own design. They should not be read as evidence that the study had a particular probability of detecting an effect, or as observed power. The registry does not report the trial’s sample-size justification.
Planning estimates depend on the assumptions used, including the effect size and variability. In a crossover study, planning also needs to reflect the paired structure and the analysis intended for the outcome. The registry’s stated illustration assumptions do not provide enough information to assess whether they match the study’s design or analysis. No computed planning values are described in the primary results, and they cannot replace an observed treatment estimate.
What can be concluded from the reported analysis information?
The record lists 20 outcome measures and reports 10 secondary outcomes. It lists 0 analyses. This does not provide a statistical analysis plan, details of model fitting, a multiplicity procedure, or an account of missing endpoint data. The absence of a posted analysis means that the registry’s descriptive means and standard deviations should be read as summaries, not as results from a documented inferential comparison.
General context: a complete treatment-effect report would ordinarily identify the population analyzed, the model or comparison method, the estimated contrast, and a measure of uncertainty. In a crossover trial, an explanation of how the repeated observations and periods were handled is especially important. These details are not reported in the registry record for the primary endpoint.
10. Confidence Intervals for Each Arm
No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.
| Arm | Participants | Mean | Standard deviation | 95% CI for the mean |
|---|---|---|---|---|
| SoC at T2 | 8 | 620.200 | 154.560 | 490.985 to 749.415 |
| SoC at T4 | 8 | 554.200 | 202.280 | 385.090 to 723.310 |
R code and output
arm <- c("SoC at T2", "SoC at T4")
n <- c(8, 8)
m <- c(620.2, 554.2)
sp <- c(154.56, 202.28)
sd <- sp # posted standard deviations
for (i in seq_along(n)) {
se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}
CARM SoC at T2 8 620.200 154.560 490.985 749.415
CARM SoC at T4 8 554.200 202.280 385.090 723.31011. Multiplicity, Missing Data and Analysis Populations
The registry lists 20 outcome measures and reports 10 secondary outcomes. Several secondary outcome descriptions concern tyrosine blood concentrations under SoC or GOLIKE at specified times on the second test day. The posted record does not describe a multiplicity strategy, such as a prespecified hierarchy or adjustment for testing multiple outcomes. Without that information, the relationship between any secondary findings and a primary confirmatory analysis is not reported.
The record lists 0 analyses. It does not describe a statistical analysis plan, an analysis population, or the rules used to include or exclude observations. The reason for termination is not reported in the registry record, and no explanation is given for the difference between enrollment of 21 and the primary endpoint count of 8 at each listed SoC timepoint.
Missing-data handling is not reported in the registry record. It is not stated whether the endpoint observations were missing, considered not estimable, or omitted for another reason. The record does not say whether participants with observations from only one period were included in any analysis, or whether an imputation method was used. The posted continuous two-arm comparison is identified as not estimable. No analysis population or sensitivity analysis is described.
General statistical context: missing observations can affect both the number of people contributing to an estimate and the interpretation of that estimate. In a crossover design, incomplete observations can also prevent some participants from contributing a within-person comparison. Without details about the missingness and analysis population, the extent and direction of any resulting uncertainty cannot be assessed.
12. 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 |
|---|---|---|---|
| A Where A=Standard of Care (SoC) | 0 | 21 | 0.0% |
| B Where B=PKU GOLIKE | 0 | 21 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| A Where A=Standard of Care (SoC) | 0 of 21 |
| B Where B=PKU GOLIKE | 0 of 21 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| A Where A=Standard of Care (SoC) | 0 of 21 |
| B Where B=PKU GOLIKE | 1 of 21 |
Most frequent non-serious adverse event terms
| Event term | Organ system | A Where A=Standard of Care (SoC) | B Where B=PKU GOLIKE |
|---|---|---|---|
| ASTHENIA | General disorders | 0 of 21 | 1 of 21 |
The registry reports serious adverse events for 21 participants at risk in each group: 0 affected in the group labeled A, SoC, and 0 affected in the group labeled B, PKU GOLIKE. It reports 0 deaths in both groups. No serious adverse event terms are listed among the top serious terms.
For other adverse events, the registry reports 21 participants at risk in each group, with 0 affected in group A and 1 affected in group B. These are the posted counts; the record does not provide further details about the event, its severity, timing, or relationship to either study product. The figures do not state whether the event was expected or related to treatment.
General context: a count of zero observed serious events means none are recorded for that group in the posted safety results. It does not establish that an event could not occur, and it does not by itself provide a precise estimate of event risk. Safety comparisons also require attention to how events were collected, how long participants were followed, and which participants contributed. Those details are not reported in the registry record. The study’s crossover design and the posted at-risk counts should not be taken to imply that the same people were counted only once or that exposures were of equal duration; the record does not explain the safety analysis structure.
13. What the Result Does, and Does Not, Mean
The posted primary endpoint results show two mean blood Phe concentrations under SoC: 620.2 μmol/L at T2 and 554.2 μmol/L at T4. Each is based on 8 observations, with standard deviations of 154.6 and 202.3, respectively. These figures describe the posted SoC measurements and their observed spread.
They do not show the primary treatment contrast in the study’s stated objective. No GOLIKE primary endpoint mean, paired treatment estimate, confidence interval, or statistical test is reported. The registry indicates that values are missing or not estimable for a two-arm comparison of this continuous outcome. Therefore, the posted results do not establish the size or direction of a GOLIKE-versus-SoC effect.
The results also do not show whether any difference would be clinically important. The registry does not state a clinical threshold for interpreting Phe concentration changes, and the endpoint is a laboratory measurement rather than a reported patient-centered outcome. Statistical precision and clinical meaning are separate questions; neither can be answered by comparing the two SoC means alone.
The record reports enrollment of 21, while the primary outcome summaries each have 8 observations. It does not explain this difference, describe missing-data handling, or identify an analysis population. It also does not report why the study was terminated. Those omissions limit interpretation of how representative the posted measurements are of the enrolled participants and how the planned crossover comparison was conducted.
General context: a trial’s design and stated objective explain the question it set out to address, while interpretation depends on the results and analysis actually reported. In this record, the objective concerns daily Phe fluctuation under two conditions, but the available primary summaries are limited to two SoC timepoints. No conclusion about comparative effects should be drawn from those summaries.
14. Why This Trial Matters Statistically
This study is statistically notable because it uses a randomized crossover design to examine a continuous biochemical measure. Such a design can make within-participant comparisons informative when each participant has usable measurements under both conditions and the analysis accounts for pairing. The trial’s sequence descriptions reflect that structure: participants were assigned to receive SoC then PKU GOLIKE, or PKU GOLIKE then SoC.
The posted results also illustrate why outcome labels and analysis structure matter. The primary objective concerns daily Phe fluctuation between PKU GOLIKE and SoC, but the available primary summaries are labeled SoC at T2 and SoC at T4. Those summaries do not constitute the intended two-condition comparison. Reporting means and standard deviations without a treatment contrast can describe observations while leaving the main comparative question unanswered.
The difference between 21 enrolled participants and 8 observations for each posted endpoint timepoint is another important reporting issue. The registry does not explain the endpoint counts or missing-data handling. In a crossover study, the number with measurements under both conditions is particularly relevant because it determines how many participants can contribute a paired comparison.
Finally, the record reports 0 analyses and does not report the statistical plan, a multiplicity approach, or an explanation for termination. These gaps make it difficult to evaluate how closely the posted outcomes and any intended analysis correspond to the study objective. The trial is therefore a useful example of the distinction between a well-defined design question and a reported statistical result: the latter requires a transparent estimate, uncertainty, and account of the data contributing to it.
15. 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 direct limitation is that the registry does not report an estimable two-arm continuous comparison for the primary endpoint. The posted results contain SoC means for T2 and T4, but no GOLIKE primary endpoint summary or treatment contrast. The objective of evaluating Phe fluctuation under the two conditions therefore cannot be assessed from the posted primary results.
The reported endpoint count is 8 for each timepoint, despite enrollment of 21. The registry does not explain the difference, identify the participants contributing to each timepoint, or say whether the same participants were observed at both. This is particularly important in a crossover design, where paired observations under both conditions are needed for a direct within-participant contrast.
The trial was open-label and monocentric. The registry does not report masking, and it does not provide details about the randomization procedure, washout, period effects, sequence effects, or carryover assessment. It also does not report the reason for termination. These omissions constrain evaluation of how the design was implemented and how possible period-related influences were handled.
For the primary endpoint, confidence intervals, inferential tests, the analysis population, a statistical model, and missing-data methods are not reported in the registry record. The record lists 0 analyses. It also does not report a multiplicity strategy for the outcomes. Thus, the precision, robustness, and confirmatory status of any comparative finding cannot be evaluated from the posted results.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Open-label, Randomized, 2-way Crossover, Monocentric, Controlled Study to Evaluate the Effect on Daily PHE Fluctuation of PKU GOLIKE Versus SoC in Patients With PKU. — NCT05827536.
- Registry record last updated 2026-03-11; status last verified 2026-03.
- Results first posted 2026-03-11.
- 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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19. Record Summary
NCT05827536 is a randomized, open-label, two-way crossover, monocentric controlled study of PKU GOLIKE versus standard of care in patients with phenylketonuria. The registry lists enrollment of 21 and status as terminated. The listed study start is 2023-10-30, and primary completion is dated 2024-11-27. The reason for termination is not reported in the registry record.
The primary outcome is blood Phe concentration measured from dried blood spots on the second test day. The posted primary summaries are SoC at T2 and SoC at T4, with 8 observations at each timepoint. A two-arm continuous comparison is not estimable in the posted results. The registry lists 20 outcome measures, 10 secondary outcomes, and 0 analyses. It does not report a statistical analysis plan, missing-data methods, or the reason for the difference between enrollment and the endpoint counts.