Ibrexafungerp for the Treatment of Complicated Vulvovaginal Candidiasis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ibrexafungerp for the Treatment of Complicated Vulvovaginal Candidiasis (NCT05399641), a randomized phase 3 study. The primary outcome is Clinical Cure.

2. Clinical Question

3. Trial Design

This was a Phase 3, randomized, open-label, parallel-group study of ibrexafungerp for complicated vulvovaginal candidiasis in participants who had failed fluconazole therapy. The registry lists 150 as the enrollment and reports the study as completed. The recorded start date is 2022-05-01, and the primary completion date is 2023-05-16. Scynexis, Inc. is listed as the sponsor.

The intervention was oral ibrexafungerp. The record describes three groups: Group A received a single day of dosing; Group B received either 3-day or 7-day dosing. Group A was described as participants without underlying medical conditions and without isolates of C glabrata, C krusei, or C auris. Group B was described as participants with underlying medical conditions such as diabetes or immunocompromised conditions, recurrent vulvovaginal candidiasis, and/or one of the listed isolates. The record states 300 mg twice daily for the dosing regimens, although the descriptions of the longer regimens do not give a complete dosing sentence.

Masking is recorded as none. The registry does not report the allocation procedure, treatment assignment details, protocol deviations, or the trial's original sample-size assumptions. It also does not report whether the groups were intended as direct randomized comparisons or how participant characteristics informed assignment to the different durations. These details limit interpretation of the group comparisons as treatment effects. The main posted endpoint is clinical cure at the test-of-cure visit; secondary outcomes include clinical improvement, clinical success, mycological response, and other clinical measures.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Modified Intent-to-Treat (mITT): all treated participants who have a positive culture for candida species at screening

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: Intent- to Treat Set (ITT) - all ibrexafungerp-treated participants

6. Primary Endpoint

The registry lists the primary outcome as Clinical Cure, measured over 14 days post-Baseline - Test-Of-Cure (TOC).

The primary endpoint was clinical cure, measured as the number of participants meeting the registry's cure definition at 14 days post-baseline, at the test-of-cure assessment. Cure required complete resolution of signs and symptoms, a total vulvovaginal signs and symptom score of 0, and no additional antifungal therapy. The scale ranges from 0 to 18, with higher scores indicating worse signs and symptoms.

The endpoint therefore captures a defined clinical state at a specified assessment time, rather than a change in symptoms alone or a laboratory result alone. Requiring no additional antifungal therapy makes the endpoint dependent on both symptom resolution and the absence of further treatment during the relevant period. The registry specifies the modified intent-to-treat population: treated participants with a positive Candida species culture at screening.

Clinical cure is used to express the proportion of participants who met all parts of that definition at the assessment. The posted results give counts and denominators for each group, which allow the observed outcomes to be understood in relation to the number assessed. The record does not report the handling of missing test-of-cure assessments or a separate endpoint analysis plan, so the effect of missing data on the reported endpoint cannot be determined from the registry record.

7. Results Posted in the Registry

• Group B (3 Day Dosing): 23.8% (10/42) versus 53.8% (7/13) on control; risk difference -30.0 percentage points (95% CI -60.0 to -0.0), risk ratio 0.44 (0.21–0.93); unadjusted two-proportion z-test p = 0.041.
• Group B (7 Day Dosing): 50.0% (23/46) versus 53.8% (7/13) on control; risk difference -3.8 percentage points (95% CI -34.6 to 26.9), risk ratio 0.93 (0.52–1.66); unadjusted two-proportion z-test p = 0.807.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level: each person either met the clinical-cure definition or did not, based on the stated assessment criteria. The posted group results are counts of participants meeting the definition and the corresponding endpoint denominators. This is different from a continuous outcome, where each participant contributes a measured score and results might be summarized by a mean or median.

What does a risk difference describe?

A risk difference compares the observed event proportions in two groups by subtracting one from the other. Here, the event is clinical cure, and Group A is the reference. A negative estimate means the observed cure proportion was lower in the named Group B comparison than in Group A. The estimate does not adjust for other participant characteristics. Because the group sizes and observed event counts differ, the estimate should be read alongside its interval and the underlying counts rather than as a precise standalone quantity.

How should the intervals be read?

A confidence interval expresses uncertainty around an estimated difference under the statistical method used to construct it. A narrower interval indicates greater precision, while a wider interval indicates that a broader range of differences remains compatible with the data and method. The interval for 3-day dosing extends from -0.600 to -< 0.001; the interval for 7-day dosing extends from -0.346 to 0.269. The latter includes zero and values in both directions. The registry record does not report the confidence level or the interval-construction method, so those details cannot be specified from the posted record.

What do the p-values indicate?

The unadjusted p-value is a measure of how compatible the observed data are with a statistical null hypothesis of no difference, under the assumptions of the test used. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of a difference. The posted unadjusted p-values are 0.041 for 3-day dosing and 0.807 for 7-day dosing relative to Group A. The registry record does not report the test used, whether p-values were prespecified, or whether any multiplicity procedure was planned.

Why do denominators and group definitions matter?

Group A has 13 participants in the primary endpoint data, compared with 42 in the 3-day group and 46 in the 7-day group. When a group is small, each participant's outcome can have a substantial influence on the observed proportion and on a comparison. In addition, the registry defines Group A and Group B using different clinical or isolate characteristics. The posted estimates are not adjusted for those characteristics, and the record does not provide information that would allow their influence to be assessed.

The study is recorded as randomized, but the registry information does not explain how randomization was applied across these clinically differentiated groups. It is therefore important to distinguish the overall design label from the specific comparisons posted. The numerical comparisons describe observed differences between groups; the registry record alone does not show that the groups were exchangeable for those comparisons.

General statistical context: randomization can help balance measured and unmeasured characteristics when it applies to the comparison being analyzed. If assignment instead depends on participant characteristics, an unadjusted comparison may mix treatment-duration differences with those characteristics. This is a reason to examine the allocation description and analysis plan, neither of which is fully reported for these comparisons.

The registry lists several additional outcomes, including clinical improvement, clinical success, mycological response, and changes in symptom scores. Multiple outcomes create opportunities for chance findings when many comparisons are examined. Whether and how this issue was addressed is not reported in the registry record. No analysis records are posted, so adjusted results or a detailed model specification are not available for review.

10. Confidence Intervals and Precision

The estimates are not equally precise. The 3-day comparison has a risk difference of -0.300 and an interval from -0.600 to -< 0.001. This interval is wide in relation to the point estimate and reaches close to zero. It indicates considerable uncertainty about the magnitude of the observed difference, even though the interval's endpoints lie below zero.

The 7-day comparison has a risk difference of -0.038 and an interval from -0.346 to 0.269. It includes zero and substantial differences in either direction. The data therefore do not tightly determine the direction or size of the comparison. An unadjusted p-value of 0.807 should not be read as proof that the groups are equivalent; no equivalence margin or equivalence analysis is reported.

The endpoint denominators are 13 for Group A, 42 for Group B with 3-day dosing, and 46 for Group B with 7-day dosing. The relatively small reference group is important when considering the uncertainty of both comparisons. Confidence intervals describe sampling uncertainty under a method and assumptions; they do not account automatically for bias from group differences, missing outcomes, or unreported analysis choices. The registry record does not report the confidence level or interval method, limiting further assessment of precision.

The point estimates are based on observed counts, while the intervals show that the underlying differences remain uncertain. Neither a point estimate near zero nor an interval crossing zero demonstrates that two groups have identical outcomes. Likewise, an interval ending just below zero does not by itself resolve issues of clinical meaning, design, or multiplicity.

11. 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.

Read each planning row as a hypothetical target for a future two-group study based on a chosen fraction of the observed effect. The figures are participants per arm for 80% power and participants per arm for 90% power; they are not total sample sizes or observed participant counts. These are planning illustrations, not observed power.

The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is specified as a fraction of the observed effect. For the 3-day comparison, the 100% of observed effect row gives 41 participants per arm for 80% power and 54 participants per arm for 90% power. For the 7-day comparison, the same row gives 2,648 participants per arm for 80% power and 3,545 participants per arm for 90% power. These projections differ because the observed comparison estimates differ in size.

The 80% and 90% power columns represent different planning targets: under the stated assumptions, the higher target aims for a greater chance of detecting the specified effect if it is present, and requires a larger planned sample. Rows using 75% or 50% of the observed effect represent smaller effects to detect; smaller effects generally require more participants than larger effects under otherwise similar assumptions. These calculations use the observed estimates and are not the trial's original design justification. The registry record does not report the trial's own sample-size assumptions.

12. 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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.538; treatment proportion p₁ = 0.238; average p̄ = 0.388.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6892 = 1.3509.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6557 = 0.5518.
4. n = (1.3509 + 0.5518)² / (-0.3004)² = 40.1, rounded up to 41 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
p0 <- 0.538461538461538                          # control proportion
p1 <- 0.238095238095238                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(5399641)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 41 (80% power), 54 (90% power)
 75% of observed effect: n per arm = 75 (80% power), 100 (90% power)
 50% of observed effect: n per arm = 172 (80% power), 230 (90% power)
power.prop.test: 40.1 
Simulated power at n = 41 per arm: 0.821 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists 7 secondary outcomes in addition to the primary clinical-cure outcome. These include clinical improvement, clinical success, mycological response, clinical cure and mycological response, clinical cure at follow-up, and symptom-score measures. The registry also reports 8 outcome measures. Considering multiple outcomes can increase the chance of observing an apparently notable result by chance if many tests are conducted.

A multiplicity strategy might define a testing hierarchy, adjust significance thresholds, or identify outcomes as exploratory. Which approach, if any, was used is not reported in the registry record. The posted comparisons include unadjusted p-values, and no analysis records are posted. Thus, the p-values cannot be interpreted as multiplicity-adjusted results, and the record does not establish how the trial intended to control error across outcomes or comparisons.

The primary endpoint population is defined as treated participants with a positive Candida species culture at screening. The posted endpoint denominators are 13, 42, and 46 across the three groups. The registry record does not report how participants without an assessment at the test-of-cure visit were handled, whether missing outcomes were imputed, or whether sensitivity analyses were performed. It also does not report the number of missing primary endpoint assessments.

These omissions matter because an analysis limited to observed outcomes can differ from one that accounts for missing assessments, especially if outcome availability is related to treatment or clinical status. The record does not permit assessment of that possibility. It also does not report whether the analysis used an intention-to-treat, per-protocol, or other population beyond the stated modified intent-to-treat definition. The posted counts should therefore be interpreted according to that stated population, without assuming additional analysis procedures.

14. 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 non-serious adverse event terms

The registry reports serious adverse events affecting 0 participants in each group. The numbers at risk for serious adverse events were 27 for Group A, 62 for Group B with 3-day dosing, and 61 for Group B with 7-day dosing. Deaths were 0 in all three groups. No top serious adverse-event terms are listed.

For other adverse events, the record reports 12 affected participants among 27 at risk in Group A, 35 among 62 at risk in the 3-day group, and 39 among 61 at risk in the 7-day group. These safety denominators differ from the primary endpoint denominators. The registry does not explain the difference, so the safety counts should be read using their own reported at-risk groups rather than substituted for the clinical-cure population.

These figures are counts of affected participants, not counts of every adverse-event episode. They do not by themselves establish whether groups differ in risk, and the registry record does not report event severity details for the non-serious events, exposure-adjusted rates, or a statistical comparison. Zero reported serious events does not establish absence of risk; it describes the posted counts in the stated groups.

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

The posted primary results show that 7 of 13 participants in Group A, 10 of 42 in the 3-day group, and 23 of 46 in the 7-day group met the registry's clinical-cure definition at the test-of-cure assessment. The unadjusted comparison with Group A was -0.300 for 3-day dosing and -0.038 for 7-day dosing. The associated intervals indicate substantial uncertainty, particularly for determining the direction and size of the 7-day comparison.

These results describe the participants included in the endpoint population and the outcome definition used in the registry. They do not establish why the observed group counts differ. Group membership was described using clinical conditions and isolate characteristics, and the registry does not explain whether randomization applied directly to the comparisons. Consequently, differences in outcomes cannot be attributed to dosing duration alone from these posted comparisons.

The results also do not establish equivalence between groups. A comparison with a p-value of 0.807 and an interval spanning zero is not proof of no difference. Conversely, an unadjusted p-value of 0.041 for the 3-day comparison does not establish clinical importance or resolve uncertainty about design, multiplicity, and analysis populations.

The endpoint is a specific clinical measure at a defined visit, requiring complete resolution and no additional antifungal therapy. It does not capture every possible outcome or longer-term course. Several secondary measures are listed, but the registry record does not provide their posted results in the information described. The findings should therefore be understood as endpoint-specific observations, with limitations in precision and reporting, rather than as a complete account of all possible outcomes.

16. Why This Trial Matters Statistically

This trial raises several statistical questions that are important in clinical research. First, the three groups are not described as interchangeable populations: Group A and Group B differ by underlying conditions, recurrence, and/or isolate characteristics. Even though the study is labeled randomized, the registry does not describe how allocation operated across these groups or whether the specific comparisons were randomized. That distinction is central when interpreting an unadjusted contrast as a treatment-duration effect.

Second, the reference group is small in the primary endpoint data, with 13 participants, compared with 42 and 46 in the two Group B dosing groups. The resulting estimates have broad intervals. This illustrates why an observed difference should be interpreted together with its uncertainty and denominator, rather than from the point estimate or p-value alone.

Third, the study includes a primary clinical endpoint and multiple secondary outcomes. The registry record does not report how multiplicity was addressed, whether missing assessments were handled, or the full analysis plan. Those reporting details are necessary for readers to understand how results were selected and tested.

Finally, the sample-size illustrations vary substantially across comparisons because they are derived from observed effect estimates. They are useful for understanding how effect size and target power influence planning, but they do not reveal the study's original design rationale. Taken together, the record shows why transparent reporting of allocation, analysis populations, missing data, multiplicity, and precision is necessary for a careful statistical interpretation.

17. 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 registry record leaves important design and analysis details unreported. Although it identifies the study as randomized and parallel, it does not describe the allocation process or establish how randomization related to the three clinically defined groups. Group A was described differently from Group B, so the posted unadjusted comparisons may reflect differences in participant characteristics as well as treatment duration.

The primary endpoint denominators are 13, 42, and 46, while the safety denominators are 27, 62, and 61. Reasons for the differing counts are not reported. The record also does not state how missing endpoint data were handled, whether all randomized participants were included in an analysis, or whether additional sensitivity analyses were conducted.

No analysis records are posted. The test used for the comparisons, the confidence level and construction method for the intervals, covariate adjustment, and multiplicity handling are not reported in the registry record. The trial's original sample-size rationale and design assumptions are also not reported. The planning calculations based on observed effects cannot fill that gap.

Descriptions of the 3-day and 7-day dosing regimens do not provide complete dosing sentences, although the record states 300 mg twice daily and identifies the intended treatment durations. Finally, the posted primary results do not include detailed results for the listed secondary outcomes. These limitations restrict evaluation of the trial's full analysis, the comparability of the groups, and the broader outcome pattern.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Ibrexafungerp for the Treatment of Complicated Vulvovaginal Candidiasis — NCT05399641.
• Registry record last updated 2024-07-10; status last verified 2024-07.
• Results first posted 2024-07-10.
• 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.

21. Record Summary

The registry record describes a completed Phase 3 randomized, open-label, parallel study of oral ibrexafungerp for complicated vulvovaginal candidiasis after fluconazole failure. It lists 150 enrolled participants and identifies Scynexis, Inc. as sponsor. The study dates are 2022-05-01 for start and 2023-05-16 for primary completion.

The primary outcome was clinical cure at 14 days post-baseline in the modified intent-to-treat population. The posted counts were 7 of 13 for Group A, 10 of 42 for Group B with 3-day dosing, and 23 of 46 for Group B with 7-day dosing. The unadjusted risk differences relative to Group A were -0.300 and -0.038, respectively.

The record lists 7 secondary outcomes and 8 outcome measures, but no analysis records. It does not report the trial's original sample-size assumptions, missing-data procedures, multiplicity strategy, or the allocation details needed to understand the specific group comparisons.