Oral Liquid 13-cis-retinoic Acid (13-CRA): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Oral Liquid 13-cis-retinoic Acid (13-CRA) (NCT03291080), a randomized phase 1, phase 2 study. The primary outcome is Relative Bioavailability.

2. Clinical Question

The clinical question is about the amount of 13-cis-retinoic acid measured in plasma over time after administration of the two formulations. The registry describes a randomized, open-label, multiple-dose crossover trial. In a crossover design, participants receive more than one treatment formulation, so the comparison is intended to examine the formulations within the same study population. The registry lists 20 participants and reports results for 20 participants under each formulation.

The primary outcome is relative bioavailability, expressed through area under the plasma concentration-time curve (AUC), with measurements on day 1 and day 14 of treatment. AUC is an exposure measure: it summarizes concentration across a period of time rather than describing a single concentration reading. The registry also lists secondary pharmacokinetic measures, including maximum plasma concentration, time to maximum concentration, and metabolite measures.

This question is narrower than whether the formulations have the same clinical effects or safety profile. The posted pharmacokinetic summaries describe measured exposure and related concentration features; they do not, by themselves, answer broader questions about clinical outcomes. The registry record does not report a clinical efficacy endpoint or a prespecified equivalence or non-inferiority margin.

3. Trial Design

The registry describes a randomized, open-label, multiple-dose crossover trial of oral liquid and extracted capsule 13-cis-retinoic acid. It lists the study as Phase 1 and Phase 2, with no masking. The condition is neuroblastoma, and the study summary describes patients aged from 0 months to <21 years who require treatment cycles of 13-cis-retinoic acid.

The liquid formulation was the test product. The reference product was isotretinoin capsules from which 13-cis-retinoic acid was extracted according to standard of care. Because the design is crossover, the comparison concerns the formulations administered within a trial in which participants were intended to receive more than one formulation. The registry record does not report the treatment sequence, the duration between treatment periods, or other details needed to assess how the crossover was implemented.

The registry lists an enrollment of 20. For the primary AUC outcome, it reports n=20 for each formulation. These arm-level counts should be read in the context of the crossover design rather than as evidence that the study enrolled separate groups of 20 people for each formulation. Participant flow, withdrawals, and the number completing each treatment period are not reported in the registry record.

The study began on 2018-04-17, had primary completion on 2019-09-12, and is listed as completed. The registry identifies Nova Laboratories Limited as the sponsor. The registry record does not report the trial’s original sample-size justification, detailed statistical analysis plan, treatment-period procedures, or analysis population definitions. Those omissions limit what can be inferred about how the posted comparisons relate to the intended crossover analysis.

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.

First Cycle (2 Weeks)

Washout (2 Weeks)

Second Cylcle (2 Weeks)

Analysis population for the primary outcome, as defined in the registry: Relative bioavailability - AUC (h.ng/mL)

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Relative Bioavailability, measured over On day 1 and 14 of treatment.

The primary endpoint is relative bioavailability measured by AUC for 13-cis-retinoic acid. AUC summarizes plasma concentration across time and is used in pharmacokinetic comparisons because it represents overall measured exposure over the specified sampling period. The registry gives the unit as (h.ng/mL) and the timeframe as day 1 and day 14 of treatment.

For this comparison, the AUC measure is used to assess how exposure after the oral liquid formulation compares with exposure after the extracted capsule formulation. It is a pharmacokinetic endpoint, not a direct measure of clinical benefit. An AUC difference can describe a difference in measured drug exposure, but interpretation also depends on the trial’s design, analysis method, sampling procedures, and prespecified criteria for judging similarity or acceptability. Those criteria and details of the analysis are not reported in the registry record.

The registry reports a mean and standard deviation for each formulation. The oral liquid mean is 10010.0 (h.ng/mL), with a standard deviation of 3673.0; the extracted capsule mean is 6076.0 (h.ng/mL), with a standard deviation of 2091.0. These summaries describe the posted measurements, but they do not give the participant-level concentration profiles or the within-participant covariance needed to reconstruct a crossover analysis. The AUC outcome therefore provides a focused comparison of exposure while leaving important analytical details unspecified.

7. Results Posted in the Registry

• 13-CRA Extracted Capsule: mean 6,076 versus 10,009 on control; difference -3,933 (95% CI -5,785 to -2,081), standardized effect d = -1.32; z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Maximum Plasma Concentration (Cmax)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • 13-CRA Extracted Capsule: mean 748.20 versus 1,238 on control; difference -489.40 (95% CI -824.03 to -154.77), standardized effect d = -0.91; z-test p = 0.004.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for 13-CRA Extracted Capsule than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Time to Maximum Concentration (Tmax)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • 13-CRA Extracted Capsule: mean 3.00 versus 3.20 on control; difference -0.20 (95% CI -0.67 to 0.27), standardized effect d = -0.26; z-test p = 0.405.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 13-CRA Extracted Capsule and the control. The interval gives the range of effects that remain compatible with the data.

Area Under Plasma Concentration Time Curve (AUC) Metabolite

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • 13-CRA Extracted Capsule: mean 23,313 versus 38,462 on control; difference -15,150 (95% CI -24,727 to -5,572), standardized effect d = -0.98; z-test p = 0.002.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for 13-CRA Extracted Capsule than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes extend the primary exposure question by describing peak plasma concentration, the time of that peak, and metabolite exposure. Taken together, the posted summaries generally show higher concentration or exposure measures for the oral liquid, while the time-to-peak measure does not show the same degree of separation. This broad pattern is directionally consistent with the primary AUC finding, but the measures describe different features of pharmacokinetics and should not be treated as interchangeable.

Secondary outcomes can help describe whether a primary result is accompanied by related changes in other aspects of concentration over time. They do not independently establish the primary finding, particularly when several outcomes are considered and no multiplicity adjustment or testing hierarchy is reported. The secondary p-values are unadjusted. When multiple comparisons are made, the chance of obtaining at least one apparently notable result by chance can increase; this is a general statistical concern, not a statement about a specific adjustment performed in this trial.

The registry lists five secondary outcome measures, but numerical comparative results are not reported for every listed measure. In particular, numerical results for metabolite maximum concentration and metabolite time to maximum concentration are not reported in the registry record. The available secondary summaries therefore provide an incomplete account of the full set of outcomes listed in the record.

As with the primary measure, the registry does not report whether secondary comparisons accounted for the crossover structure, how missing values were handled, or which analysis populations were used. These limitations make the secondary results best read as descriptive, supportive context rather than as a separate confirmatory analysis. Their relationship to the primary result is informative at the level of overall pattern, but does not resolve the absence of a reported analysis plan or multiplicity strategy.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Maximum Plasma Concentration (Cmax)
• Time to Maximum Concentration (Tmax)
• Area Under Plasma Concentration Time Curve (AUC) Metabolite
• Cmax (ng/mL)- Metabolite
• T Max of Metabolite

9. Statistical Interpretation

10. Statistical Methods Explained

The registry posts means and standard deviations for continuous pharmacokinetic measures, along with comparative estimates, confidence intervals, and unadjusted p-values for the primary outcome and several secondary outcomes. A mean describes the central value of the measurements; a standard deviation describes how spread out measurements are around that mean. Neither summary shows the shape of the participant-level data, and the same mean and standard deviation can arise from different underlying distributions.

What does a mean difference represent?

A mean difference is the contrast between the average measurement for the two formulations. For the primary outcome, the posted contrast is expressed as extracted capsule relative to oral liquid. A negative estimate therefore indicates a lower mean for the capsule under that ordering. The estimate is reported as -3933.0. Its interpretation depends on the contrast definition and on the method used to calculate it.

In a crossover trial, each participant may contribute measurements under both formulations. The statistical comparison can use the pairing of those measurements, which is information about how each participant’s response changes between treatments. The registry record does not report the model or test used for the crossover comparison, nor does it report a within-participant variance or a treatment-sequence analysis. As a result, the posted means and standard deviations do not fully describe the information required to reproduce a paired analysis.

What does a confidence interval add?

A confidence interval expresses the uncertainty around an estimated contrast under the method’s assumptions. The primary interval runs from -5785.0 to -2081.0. It gives a range of plausible values for the mean difference under the calculation used; it is not a range containing every participant’s response, nor does it describe the probability that a particular fixed value is true. The registry does not report enough detail to assess whether the interval comes from a crossover-specific analysis.

How should the p-value be read?

A p-value measures how incompatible the observed data are with a specified null hypothesis under the assumptions of the test. The primary unadjusted p-value is <0.001. This is not the probability that the null hypothesis is true, and it does not describe the size or clinical importance of the difference. The record does not report the precise test, the analysis model, or any adjustment for multiple outcomes. The p-value should therefore be understood as an unadjusted comparative summary, not as a complete account of the trial’s statistical evidence.

Why does the crossover structure matter?

Pairing can improve precision when measurements from the same participant are more alike than measurements from different participants. It can also make the treatment comparison sensitive to design features such as treatment order, period effects, and carryover. These are general considerations for crossover studies; the registry does not report whether or how these issues were assessed in this trial. The posted results do not identify the sequence in which participants received the formulations or the interval between treatment periods.

The interpretation also depends on who contributed data to each outcome. Although the registry reports n=20 for each primary formulation summary, the analysis population, participant flow, handling of missing measurements, and any exclusions are not reported in the registry record. The same limitations apply to the secondary summaries. Without these details, the reader cannot determine whether all enrolled participants contributed complete measurements on both treatment periods.

What does over-dispersion mean in general?

For continuous outcomes, variability is often described with a standard deviation. If outcome variability is greater than an analysis model assumes, the model may underestimate uncertainty and produce confidence intervals that are too narrow. This is a general concern when choosing a statistical model; the registry does not report whether over-dispersion was assessed or whether a model requiring such an assessment was used. The posted standard deviations describe observed spread but do not, on their own, establish which model is appropriate.

The registry record lists no reported analyses, and detailed statistical methods are not reported in the registry record. The comparative figures can be read as summaries of the results posted for each formulation, but they do not resolve whether the analysis appropriately accounted for pairing, period, sequence, or missing data. Those distinctions matter when moving from descriptive statistics to an estimate of the treatment effect intended by a crossover design.

11. Confidence Intervals and Precision

The primary mean difference is -3933.0, with a 95% confidence interval from -5785.0 to -2081.0. The interval’s placement below zero indicates that the posted estimate is lower for the extracted capsule under the stated contrast. Its width also shows that the estimate is not a single exact value: a range of differences remains compatible with the data and the calculation’s assumptions.

The two formulation means are based on n=20 in each treatment summary. The reported standard deviations are 3673.0 for the oral liquid and 2091.0 for the extracted capsule. These values describe the spread of measurements within each set of posted results. They do not give the variability of the within-participant difference, which is particularly relevant in a crossover trial.

Confidence intervals convey statistical precision, not clinical importance. Whether the interval is narrow enough to support a practical conclusion depends on a prespecified acceptable range or other decision criterion. A margin for equivalence or non-inferiority is not reported in the registry record. Consequently, the interval can be interpreted as a measure of uncertainty around the posted contrast, but not as evidence that the formulations meet a specific equivalence standard.

The registry does not report the model used to produce the interval or how the crossover pairing was handled. That limits assessment of its precision. The interval should be read alongside the design and the missing analytical details, rather than as a standalone description of all uncertainty in the trial.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning illustrations give participants per arm for 80% power and participants per arm for 90% power. They are based on a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The calculations use the observed effect or a stated fraction of that effect as the effect to detect. The trial’s own original sample-size assumptions are not reported in the registry record.

The 80% power column represents the number of participants per arm that the planning calculation estimates would be needed for an 80% chance of detecting the chosen effect under those assumptions, if that effect and the model assumptions were correct. The 90% column uses a higher target chance of detection and therefore generally calls for more participants. The rows for 100%, 75%, and 50% of the observed effect illustrate how the planned effect size changes the required sample size. Smaller effects need more participants to distinguish them from random variation at the same significance level.

These figures are planning illustrations, not observed power and not evidence about the trial’s actual probability of detecting an effect. They are calculated from the observed effect, which is uncertain, and use assumptions that may not match a crossover analysis. The stated assumptions describe the planning illustration only; the statistical design assumptions used by the trial itself are not reported in the registry record.

The planning description specifies participants per arm for these continuous outcomes, rather than total events. Because the trial is a crossover, the illustrations should not be mistaken for a reconstruction of the actual design or its enrollment plan. They do not account for unreported details such as pairing, incomplete treatment periods, or missing measurements.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -3933.100; pooled standard deviation σ = 2988.442.
2. n = 2 × (1.96 + 0.842)² × 2988.442² / -3933.100² = 9.1, rounded up to 10 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -3933.1                      # observed difference in means
sigma <- 2988.44172241153                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(3291080)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 10 (80% power), 13 (90% power)
 75% of observed effect: n per arm = 17 (80% power), 22 (90% power)
 50% of observed effect: n per arm = 37 (80% power), 49 (90% power)
power.t.test: 10.1 
Simulated power at n = 10 per arm: 0.796 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and multiple secondary pharmacokinetic outcomes. It does not report a statistical plan specifying how the primary and secondary tests were ordered, whether secondary outcomes were exploratory or confirmatory, or whether any multiplicity adjustment was planned or used. The posted secondary p-values are unadjusted. Without a stated strategy, they should not be interpreted as if the chance of false-positive findings across the set of outcomes had been controlled.

The registry record lists no reported analyses. Detailed definitions of the analysis populations, the primary analysis model, and the method for calculating comparative estimates are not reported in the registry record. It is therefore not possible to determine from the record whether the primary comparison was analyzed according to a prespecified plan, or whether the secondary outcomes followed the same analytical approach.

Missing-data handling is also not reported in the registry record. The record provides n=20 for each primary formulation summary, but does not explain whether all participants had complete measurements under both formulations, whether any values were excluded, or how incomplete treatment periods were handled. The reported sample counts alone do not answer those questions. This is especially relevant in a crossover trial, where an incomplete set of paired measurements can affect which participants contribute to the treatment comparison.

The record does not describe the analysis population, such as whether summaries include all enrolled participants or only those with evaluable measurements. Nor does it report sensitivity analyses for missing data, treatment sequence, period effects, or carryover. These are general features that may matter in a crossover analysis; whether they were addressed in this trial is not reported in the registry record.

These omissions do not invalidate the posted summaries, but they limit the ability to judge their confirmatory status and robustness. Readers can describe the reported means, confidence intervals, and unadjusted p-values, while recognizing that the registry does not document the multiplicity, missing-data, and analysis-population decisions needed for a fuller assessment.

15. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pyrexia (15.0%), febrile neutropenia (10.0%), haematemesis (5.0%), acute kidney injury (5.0%), diarrhoea (5.0%).

The registry reports serious adverse events in 10 of 20 participants in the oral liquid group and 5 of 20 in the extracted capsule group. Other adverse events are reported for 18 of 20 participants in the oral liquid group and 15 of 20 in the capsule group. No deaths are listed in either group. These are participant counts as recorded for each formulation; the registry does not provide a comparative statistical analysis of these figures.

The registry lists pyrexia (15.0%) and febrile neutropenia (10.0%) among the most frequent serious-event terms, along with haematemesis, acute kidney injury, diarrhoea, and vomiting (each 5.0%). The listed terms do not, in the record, establish which formulation caused an event or whether the event was related to treatment. Serious adverse events and other adverse events are distinct reporting categories, and the participant counts should not be added together.

These figures are descriptive safety summaries from a small trial. The registry does not report event timing, duration, severity grades, participant-level overlap, or a formal comparison between formulations. They therefore describe the posted adverse-event experience but do not establish a causal difference in safety.

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

The registry results describe a difference in measured pharmacokinetic exposure between the oral liquid and extracted capsule formulations in this trial. The oral liquid had a higher posted mean AUC, and the comparative estimate for capsule relative to liquid was negative with a confidence interval below zero. This is evidence about the recorded AUC measurements under the calculation reflected in the posted comparison.

That finding is not the same as evidence that one formulation produces better clinical outcomes. AUC is a pharmacokinetic measure, not a direct measure of disease response, symptom improvement, or survival. The registry does not report a clinical efficacy outcome or a prespecified threshold for what size of exposure difference would be clinically important.

The result also does not establish equivalence or interchangeability. Those conclusions ordinarily require an explicit decision framework, such as a prespecified equivalence range, as well as an analysis suited to the study design. Such a margin and the detailed analysis plan are not reported in the registry record. A statistically notable difference should not be recast as a claim that the formulations are clinically different in every relevant respect, just as a nonsignificant result in another measure would not establish equivalence.

Interpretation is further limited by the crossover design and the absence of reported details about treatment sequence, period effects, carryover, paired analysis, and missing measurements. The posted numerical summaries can be described, but those omissions prevent a complete evaluation of how closely the comparative estimate reflects the intended within-participant treatment contrast.

The safety counts are also descriptive. They provide the number of participants with reported serious and other adverse events, but do not establish that a formulation caused an event or that the groups differ in risk. Taken together, the registry provides useful pharmacokinetic and adverse-event summaries while leaving important questions about clinical meaning, analysis methods, and uncertainty unresolved.

17. Why This Trial Matters Statistically

This trial illustrates why pharmacokinetic endpoints need to be interpreted according to what they measure. AUC summarizes exposure over time, while maximum concentration and time to maximum concentration describe other features of the concentration profile. These measures can complement one another, but they answer different questions and should not be collapsed into a single claim about clinical effect.

The crossover design also makes the analysis structure consequential. When participants receive both formulations, the treatment contrast can use within-participant information. That can be informative, but the interpretation depends on details such as treatment order, period, and how paired observations are modeled. The registry gives arm-level summaries and comparative figures but does not document the crossover analysis. This makes the record a practical example of why design labels alone are not enough to assess a statistical result.

The primary confidence interval and unadjusted p-value tell different parts of the statistical story: the interval conveys uncertainty around the estimated contrast, while the p-value describes compatibility with a specified null under a test’s assumptions. Neither alone determines whether the difference is clinically meaningful. A decision threshold for interpreting AUC differences is not reported.

Finally, the secondary outcomes and planning illustrations highlight the distinction between exploratory description and confirmatory evidence. Multiple unadjusted comparisons require caution, and sample-size illustrations based on observed effects are not the same as the trial’s original design rationale. The registry record does not report that rationale or a multiplicity plan. These features show how transparent reporting of analysis methods and prespecified criteria is needed to connect numerical results to a defensible scientific interpretation.

18. 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 important trial-specific limitation for interpreting the primary comparison is the gap between the stated crossover design and the limited analytical detail in the registry record. Treatment sequence, period length, washout or interval details, and methods for addressing period or carryover effects are not reported in the registry record. The record also does not report whether the comparative estimate accounts for within-participant pairing, which is central to interpreting a crossover comparison.

Enrollment was 20, and the registry reports n=20 for each formulation’s primary summary. Participant flow, completion of both treatment periods, missing measurements, and analysis-population definitions are not reported in the registry record. It is therefore not possible to determine from the posted summaries whether all enrolled participants contributed complete paired data.

The registry does not report the original sample-size justification or the assumptions used to design the trial. The planning illustrations based on the observed effect are not a substitute for that information. Detailed statistical methods, the primary analysis plan, and procedures for handling multiple outcomes are also not reported in the registry record.

The outcome set is primarily pharmacokinetic. The registry does not report a clinical efficacy endpoint or a criterion for judging whether the observed exposure difference is meaningful. Numerical results are not available for every secondary outcome listed. Safety reporting is descriptive and does not include a comparative analysis or details such as event timing and severity grading.

These limitations do not change the values posted in the record, but they restrict assessment of precision, robustness, and clinical relevance. They also make it important to distinguish the descriptive formulation summaries from conclusions that would require fuller protocol and analysis information.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Oral Liquid 13-cis-retinoic Acid (13-CRA) — NCT03291080.
• Registry record last updated 2021-10-19; status last verified 2021-09.
• Results first posted 2021-10-19.
• 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.

22. Record Summary

NCT03291080 is a completed randomized, open-label, multiple-dose crossover trial comparing oral liquid 13-cis-retinoic acid with extracted capsule 13-cis-retinoic acid in patients with neuroblastoma. The registry lists Phase 1 and Phase 2, enrollment of 20, and the age range as 0 months to <21 years. The sponsor is Nova Laboratories Limited.

The primary outcome is relative bioavailability measured by AUC on day 1 and day 14 of treatment. The posted mean AUC is 10010.0 for oral liquid and 6076.0 for extracted capsule; the posted mean difference for capsule relative to liquid is -3933.0, with a 95% confidence interval from -5785.0 to -2081.0 and an unadjusted p-value of <0.001.

The record also includes selected secondary pharmacokinetic summaries and descriptive adverse-event counts. Detailed crossover analysis methods, missing-data procedures, multiplicity handling, and the original sample-size justification are not reported in the registry record.