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 on Sapropterin Dihydrochloride Oral Suspension in Healthy Subjects Under Fed Conditions (NCT06987773), a randomized phase 1 study. The primary outcome is Uncorrected and Baseline-corrected Sapropterin AUCt.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT06987773 |
| Phase | Phase 1 |
| Condition | Bioequivalence |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | None (open label) |
| Enrollment | 42 |
| Arms in the primary outcome | n/a |
| Lead sponsor | APR Applied Pharma Research s.a. |
| Results posted | Yes |
2. Clinical Question
Population
Healthy participants enrolled in a Phase 1 study. The registry record lists an enrollment of 42. The study was described as single center; further eligibility details are not reported in the registry record.
Intervention
RLF-OD032, a 100 mg/mL sapropterin dihydrochloride oral suspension. The registered treatment was a single 10 mg/kg dose under fed conditions, administered without water.
Comparator
Kuvan, sapropterin dihydrochloride 100 mg powder for oral solution. The registered treatment was a single 10 mg/kg dose under fed conditions, dissolved in water.
Primary question
The study was designed to compare the pharmacokinetics of sapropterin after the test suspension and reference powder. Its primary outcome is uncorrected and baseline-corrected AUCt, the area under the concentration curve through the last measurable concentration. The registry record does not report an estimate of the treatment comparison or a conclusion about bioequivalence.
The comparison is about drug exposure measured over time in healthy participants, rather than a clinical health outcome. The crossover arrangement means participants were assigned to one of two treatment sequences: test followed by reference, or reference followed by test. The question is whether the measured exposure differs between formulations under the study conditions. A formal bioequivalence conclusion depends on specified statistical criteria and the results of the treatment comparison; those criteria and results are not reported in the registry record. The study description therefore identifies the intended comparison, but it does not by itself establish how similar the formulations were in this sample.
3. Trial Design
This was a randomized, open-label, Phase 1, single-dose, two-treatment, two-period, two-sequence crossover study in healthy participants under fed conditions. The registry record lists 42 enrolled participants and marks the study completed. Treatment A was RLF-OD032, a 100 mg/mL oral suspension of sapropterin dihydrochloride; treatment B was Kuvan, a 100 mg powder for oral solution. Each treatment was described as a single 10 mg/kg dose. The suspension was administered without water, while the powder was dissolved in water.
In the AB sequence, participants received treatment A followed by treatment B; in the BA sequence, they received treatment B followed by treatment A. Randomization assigns participants to sequences to reduce systematic differences between sequence groups. In a crossover design, each participant can contribute observations under both treatments, so a treatment comparison can account for within-participant variation. The registry record does not report the allocation ratio, the interval between periods, or the detailed timing of treatment administration beyond the fed-condition descriptions.
The study was open-label, meaning masking was not used. The primary outcome concerns sapropterin concentration over time and includes both uncorrected and baseline-corrected AUCt. Concentrations were scheduled from pre-dose measurements through 24 hours after dosing. Secondary outcomes include uncorrected and baseline-corrected Tmax and Tlag. The registry record lists 11 outcome measures but no posted analyses. It does not report the statistical analysis plan, the analysis populations, or the prespecified criteria for assessing bioequivalence. These omissions limit how fully the planned design and the intended interpretation of the pharmacokinetic comparison can be reconstructed.
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 | Sequence AB | Sequence BA |
|---|---|---|
| STARTED | 21 | 21 |
| COMPLETED | 20 | 20 |
| NOT COMPLETED | 1 | 1 |
Reasons for not completing this period:
| Reason | Sequence AB | Sequence BA |
|---|---|---|
| Withdrawal by Subject | 1 | 0 |
| Non Compliance | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: One (1) subject exhibited a pre-dose concentration for uncorrected sapropterin greater than 5% of their corresponding Cmax (9.17%) in Period 1 (Treatment A) and was excluded from the statistical dataset.
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 | All Patients Included in the 2 Sequences (AB,BA) |
|---|---|---|
| Participants analysed | 42 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 42 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age, Continuous | years | 36 (SD 9) |
| Sex: Female, Male: Female | Participants | 22 |
| Sex: Female, Male: Male | Participants | 20 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 8 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 34 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 8 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 16 |
| Race (NIH/OMB): White | Participants | 17 |
| Race (NIH/OMB): More than one race | Participants | 1 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: Canada | participants | 42 |
6. Primary Endpoint
The registry lists the primary outcome as Uncorrected and Baseline-corrected Sapropterin AUCt, measured over Pre-dose (-1, -0.5, and 0-hour) and at 0.333, 0.667, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 16, 20, and 24 hours post-dose (22 time points).
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Error |
| Unit | hr*ng/mL |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is uncorrected and baseline-corrected sapropterin AUCt, measured in hr*ng/mL. AUCt represents the area under the analyte concentration-versus-time curve from time zero through the time of the last measurable concentration. It combines concentration information across the sampling period into a measure of exposure, rather than relying on a single concentration measurement. For this study, scheduled sampling included pre-dose measurements at -1, -0.5, and 0 hours, followed by post-dose measurements from 0.333 through 24 hours.
Uncorrected AUCt uses the measured concentrations as recorded. Baseline correction accounts for concentration present before dosing when deriving the post-dose exposure measure. Considering both versions can help describe how pre-dose concentration affects the exposure calculation. The registry record notes that one participant had a pre-dose uncorrected sapropterin concentration greater than 5% of their corresponding Cmax (9.17%) in Period 1 for treatment A and was excluded from the statistical dataset.
AUCt is used in pharmacokinetic comparisons because it reflects exposure across multiple sampling times. It is not itself a clinical benefit or harm outcome. The registry record specifies the endpoint as a mean with standard error, but does not report the treatment-specific means, their uncertainty, or a comparison estimate. The reason this endpoint was selected and the rules for interpreting it as evidence of bioequivalence are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a planned pharmacokinetic comparison, but does not provide a single result that can be interpreted as the estimated difference or ratio between treatments. The primary outcome includes uncorrected and baseline-corrected AUCt, and the posted outcome information spans multiple categories or time points rather than one reduced comparison. No analysis is listed in the record. Accordingly, there is no reported treatment estimate, confidence interval, or p-value from which to judge the magnitude or precision of a difference in exposure.
The outcome description identifies the measure and its units, and specifies that it is reported as a mean with standard error. Those details explain the intended summary but do not supply the observed means. A standard error describes the precision of an estimated mean; it is not the spread of individual observations. A confidence interval, when reported, would show a range of estimates compatible with the data under the analysis assumptions. Neither the standard errors nor confidence intervals for the treatment comparison are reported in the registry record, so the precision of the comparison cannot be assessed from the posted information.
The crossover design is relevant to interpretation because the treatments were assigned in sequences and each sequence includes both formulations. In general, a crossover analysis can use within-participant comparisons, which may reduce the influence of stable differences between participants. However, the statistical model, the handling of period or sequence effects, and any assessment of carryover are not reported in the registry record. The presence of a crossover design alone does not show how those features were addressed in analysis.
The study title identifies bioequivalence as its purpose. That purpose should not be confused with a reported finding. A bioequivalence assessment ordinarily depends on a prespecified comparison and decision criteria, together with an estimate and its uncertainty. The criteria, estimates, and conclusion are not reported in the registry record. The available description therefore supports identifying what was compared and how exposure was measured, but not deciding whether the products met a bioequivalence standard.
One participant was excluded from the statistical dataset because of a pre-dose concentration criterion for uncorrected sapropterin in Period 1 under treatment A. The registry record gives the individual concentration as 9.17% of corresponding Cmax and states the criterion as greater than 5%. This is a documented analysis-population detail, not a treatment-effect result. Other exclusions, missing measurements, and sensitivity analyses are not reported. The safety counts describe one other adverse event in each treatment group, with no serious adverse events or deaths reported; these counts do not resolve the pharmacokinetic question.
9. Statistical Methods Explained
The registry record names the outcome summaries and study structure, but does not report the statistical analysis plan or treatment-comparison results. The explanations below describe general statistical concepts and distinguish them from methods documented for this study.
What does AUCt summarize?
As a general concept, an area under a concentration-time curve combines measurements taken across time into an exposure summary. AUCt in this study is defined from time zero to the last measurable analyte concentration. This approach uses the concentration profile rather than treating a single time point as the entire exposure. The registry record lists pre-dose sampling at -1, -0.5, and 0 hours, as well as post-dose measurements at 0.333, 0.667, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 16, 20, and 24 hours.
The primary outcome includes uncorrected and baseline-corrected forms. In general, baseline correction adjusts for analyte concentration already present before dosing. The registry record does not describe the exact calculation used for correction, nor how the last measurable concentration was identified when measurements were missing or below a measurement threshold. It does state that one participant meeting the recorded pre-dose concentration condition was excluded from the statistical dataset.
Why use a crossover design?
In general, a crossover design compares treatments within participants across different periods. This can make each participant their own reference and reduce the effect of stable participant-to-participant differences. Random assignment to sequences helps distribute order across the study. The two sequences are AB and BA, with treatment A and treatment B each given once in a sequence. Interpretation still depends on the analysis accounting appropriately for the design. The statistical model, period handling, sequence effects, and any carryover assessment are not reported in the registry record. The interval between periods is also not reported.
The study was open-label, so masking was not used. For a laboratory concentration endpoint, whether knowledge of treatment could affect collection, processing, or other procedures depends on conduct and safeguards not described in the registry record. No further detail on those procedures is reported.
What do mean and standard error tell readers?
The primary outcome is identified as a mean with standard error. In general, the mean is a summary of the observations, while the standard error expresses the uncertainty of the estimated mean under the analysis approach. It is not interchangeable with a standard deviation, which describes variation among observations. A confidence interval is another way to express estimation uncertainty, giving a range of values compatible with the observed data and the method's assumptions. No means, standard errors, confidence intervals, or treatment contrast are reported in the registry record, so these concepts cannot be applied to quantify this study's comparison.
The registry record's title and design describe a bioequivalence study, but the statistical decision rule is not reported. In general, bioequivalence is evaluated using a prespecified comparison and acceptance criteria. Without the criteria and the estimated comparison with its uncertainty, the study's intended objective should not be treated as a demonstrated conclusion.
What do the other pharmacokinetic measures add?
The listed secondary outcomes include uncorrected and baseline-corrected Tmax and Tlag. In general, Tmax is the time at which the maximum measured concentration occurs, and Tlag represents a lag before measurable or modeled appearance, depending on the definition used. The registry record does not give a detailed calculation or analysis definition for either measure. These timing measures describe a different aspect of the concentration profile from AUCt, which summarizes exposure over the observation period. The record lists 11 outcome measures, but does not report the results for those measures or how they relate to any primary analysis.
What can planning calculations establish?
In general, sample-size planning calculations illustrate how many participants might be needed under stated assumptions; they do not describe the number actually analyzed or provide evidence that a study had a particular probability of detecting an effect after results are known. The planning assumptions described for this record use a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects expressed as fractions of the observed effect. The resulting planning participant counts are not reported in the registry record. The registry record also does not report the trial's own sample-size justification. Any planning illustration based on an observed effect should not be read as observed power or as a substitute for the estimate and uncertainty from the treatment comparison.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 11 outcome measures. The primary outcome itself includes uncorrected and baseline-corrected AUCt, and the secondary outcomes include uncorrected and baseline-corrected Tmax and Tlag. Concentration sampling also occurs at multiple scheduled times. When several outcomes or analysis choices are examined, the chance of at least one apparently notable finding can increase if the analyses are treated as independent opportunities to test a hypothesis. In general, multiplicity procedures or a clear hierarchy of outcomes can help define how such findings should be interpreted.
The registry record does not report a multiplicity adjustment, testing hierarchy, or a complete statistical analysis plan. It does not report a treatment estimate or p-value for the primary endpoint. The outcome information is not reduced to one primary comparison, and no analysis is listed. It is therefore not possible to determine which comparisons were prespecified, whether any multiplicity control was planned, or how conclusions were to be based on the multiple measures.
Some analysis-population information is available: one participant with a pre-dose uncorrected sapropterin concentration greater than 5% of their corresponding Cmax (9.17%) in Period 1 for treatment A was excluded from the statistical dataset. The registry record does not report whether additional participants or measurements were excluded, how missing concentration values were handled, or whether sensitivity analyses were performed. It does not specify the precise populations used for efficacy or safety summaries. Those details matter because exclusions and missing-data handling can affect the data contributing to a crossover comparison. No assumptions about the analysis population or missing-data method can be made from the information reported.
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 |
|---|---|---|---|
| Treatment A | 0 | 41 | 0.0% |
| Treatment B | 0 | 41 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Treatment A | 0 of 41 |
| Treatment B | 0 of 41 |
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 |
|---|---|
| Treatment A | 1 of 41 |
| Treatment B | 1 of 41 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Treatment A | Treatment B |
|---|---|---|---|
| Thermal burn | Injury, poisoning and procedural complications | 0 of 41 | 1 of 41 |
| Neutrophil count decreased | Investigations | 0 of 41 | 1 of 41 |
| White blood cell count decreased | Investigations | 0 of 41 | 1 of 41 |
| Headache | Nervous system disorders | 0 of 41 | 1 of 41 |
| Somnolence | Nervous system disorders | 1 of 41 | 0 of 41 |
The registry record lists 41 participants at risk in each treatment group. Treatment A had 0 serious adverse events, 1 other adverse event, and 0 deaths; treatment B had 0 serious adverse events, 1 other adverse event, and 0 deaths. No serious adverse event terms are listed. These figures are counts in the registry safety summary and should be read separately from the pharmacokinetic outcomes.
The counts do not identify whether the other adverse event in each treatment group involved the same participant, nor do they provide event descriptions, timing, severity, or an assessment of relationship to treatment. The registry record does not give additional details on adverse-event collection or follow-up. Because this was a crossover study, the treatment groups refer to the treatment exposures; the counts do not by themselves show how events were attributed across periods or whether an event occurred after both exposures.
Zero serious adverse events and zero deaths in the posted groups mean none were recorded in those categories in this summary. They do not establish that no adverse events of any kind occurred: one other adverse event is listed for each treatment. These safety counts also do not answer whether the formulations had comparable pharmacokinetic exposure. They should not be interpreted as evidence of a treatment effect or as a complete assessment of safety beyond the registry record.
12. What the Result Does, and Does Not, Mean
The record establishes the study's intended comparison: a sapropterin oral suspension versus a powder for oral solution, administered as single doses under fed conditions to healthy participants. It also identifies the randomized, open-label crossover design, the primary pharmacokinetic endpoint, the sampling schedule, and the documented exclusion of one participant from the statistical dataset. These details describe the question and some of the methods used to address it.
The record does not report the treatment-specific AUCt means, the comparison estimate, a confidence interval, or a statistical test. It therefore does not show the size or precision of any difference between formulations. Although the study is described as a bioequivalence study, the registry record does not state the prespecified acceptance criteria or report whether they were met. The study title and objective should not be treated as a result.
In general, interpreting a bioequivalence comparison requires both an estimate and its uncertainty, assessed against prespecified criteria. A nonsignificant test alone, if one were available, would not establish equivalence; failure to detect a difference and evidence that values fall within an accepted range are different statistical claims. For this record, neither a test result nor the relevant acceptance range is reported, so neither claim can be evaluated.
The safety summary reports no serious adverse events or deaths, and one other adverse event in each treatment group. Those observations are limited to the recorded counts and do not describe event details or establish whether an event was caused by treatment. They are separate from the pharmacokinetic evidence and cannot fill the gap in the primary outcome results.
Accordingly, the registry information supports a description of the trial design and its planned measurement strategy, but not a conclusion about comparative exposure, bioequivalence, or clinical effect. Those conclusions would require the analyses and supporting results, which are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically informative as a design example because a randomized crossover arrangement is used for a pharmacokinetic comparison. In general, crossover studies can compare treatments within participants, which can help separate treatment-related variation from stable differences across individuals. Sequence randomization is an important feature of that design. At the same time, the interpretation depends on the period structure, sufficient separation between treatments, and an analysis that reflects the repeated observations. The registry record does not report the interval between periods or the analysis model, so those aspects cannot be evaluated.
The endpoint also illustrates why the measurement schedule matters. AUCt summarizes concentrations over time, and this study lists sampling from pre-dose through 24 hours after dosing. The record distinguishes uncorrected from baseline-corrected exposure and identifies a participant excluded under a pre-dose concentration rule. That makes the handling of baseline concentrations and analysis-population decisions relevant to interpreting a treatment comparison.
However, design detail is not a substitute for results. There are no posted primary comparison estimates, uncertainty measures, or analyses in the registry record. As a result, readers can identify the intended statistical question but cannot assess how large or precise the observed treatment comparison was, or whether a stated bioequivalence criterion was satisfied. This distinction is central to reading registry records: a study objective tells readers what investigators sought to evaluate, while outcome estimates and prespecified decision rules are needed to evaluate what the data show.
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 main limitation of the registry information is the absence of reported primary outcome estimates and analyses. Although AUCt is identified as the primary outcome and the record specifies its unit, summary type, and sampling schedule, it does not give treatment-specific values or a comparison with uncertainty. No formal conclusion about bioequivalence can be assessed because the decision criteria and result are not reported in the registry record.
The study enrolled 42 participants, while the safety summaries list 41 at risk for each treatment. The record does not explain the difference between the enrollment figure and the safety counts. It states that one participant was excluded from the statistical dataset after a pre-dose uncorrected concentration in Period 1 for treatment A exceeded the stated criterion, and reports that value as 9.17% of corresponding Cmax against a criterion greater than 5%. The effect of this exclusion on the treatment comparison cannot be assessed without results or sensitivity analyses.
Further design and analysis details are not reported in the registry record, including the period interval, analysis model, handling of period or sequence effects, carryover assessment, missing-data methods, analysis populations, and multiplicity strategy. The open-label design is documented, but safeguards for concentration measurement and analysis are not described. The outcome list includes multiple endpoint forms and timing measures, without results for those measures. Together, these gaps restrict assessment of the precision, robustness, and prespecification of any treatment comparison. These are limitations of what the registry record reports; they do not establish that the procedures were absent from study conduct.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study on Sapropterin Dihydrochloride Oral Suspension in Healthy Subjects Under Fed Conditions — NCT06987773.
- Registry record last updated 2026-04-28; status last verified 2026-02.
- Results first posted 2026-04-28.
- 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
NCT06987773 is a completed Phase 1 randomized, open-label, single-dose crossover study of sapropterin dihydrochloride formulations in healthy participants under fed conditions. It lists enrollment of 42 and a single-center design. The study compared RLF-OD032 100 mg/mL oral suspension with Kuvan 100 mg powder for oral solution, with each treatment described as a single 10 mg/kg dose and participants assigned to AB or BA sequences.
The primary outcome is uncorrected and baseline-corrected sapropterin AUCt, measured in hr*ng/mL, with concentrations scheduled from pre-dose through 24 hours post-dose. Secondary outcomes include uncorrected and baseline-corrected Tmax and Tlag. One participant was excluded from the statistical dataset under the stated pre-dose concentration rule. Safety summaries list 0 serious adverse events and 0 deaths in each treatment group, with 1 other adverse event in each group.
The registry record does not report a primary treatment comparison, outcome estimates, or a statistical analysis. It therefore describes the intended bioequivalence question but does not provide results sufficient to determine the comparative exposure or whether bioequivalence criteria were met.