A Study to Evaluate Oral VT-1161 in the Treatment of Patients With Recurrent Vaginal Candidiasis (Yeast Infection): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate Oral VT-1161 in the Treatment of Patients With Recurrent Vaginal Candidiasis (Yeast Infection) (NCT02267382), a randomized phase 2 study. The primary outcome is The Percentage of Subjects With 1 or More Culture-verified Acute VVC Episodes Through Week 48 of the Study in the Intent-to-treat Population..

2. Clinical Question

3. Trial Design

The registry describes a phase 2 randomized, double-blind, placebo-controlled, dose-ranging study of oral VT-1161 in recurrent vulvovaginal candidiasis. The sponsor is Viamet. The recorded start date is 2015-02-10, the primary completion date is 2016-11-09, and the study status is completed. Enrollment is listed as 254.

Listed VT-1161 regimens varied by dose and treatment duration. Each began with once-daily dosing for 7 days, followed by weekly dosing. The low-dose 3-month schedule used VT-1161 150mg tablets once weekly for 11 weeks and then placebo once weekly for 12 weeks. The high-dose 3-month schedule used two VT-1161 150mg tablets once weekly for 11 weeks and then placebo once weekly for 12 weeks. The low-dose 6-month and high-dose 24-week schedules continued weekly VT-1161 for 23 weeks after the initial daily dosing. The placebo schedule used placebo throughout its described dosing period.

The primary endpoint was assessed through Week 48 in the intent-to-treat population. Although the title and study description identify randomization and a placebo comparator, the registry model field is listed as SINGLE GROUP. That model label does not match the multiple regimen descriptions and placebo comparison recorded elsewhere. Further details about randomization procedures, allocation concealment, and the original statistical analysis plan are not reported in the registry record.

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 254 subjects were enrolled in the 14-day open-label Induction Phase of the study after providing consent. Those subjects whose acute VVC infections resolved during the Induction Phase (a total of 215) entered the Maintenance Phase of the study.

Overall Study

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 The Percentage of Subjects With 1 or More Culture-verified Acute VVC Episodes Through Week 48 of the Study in the Intent-to-treat Population., measured over 48 Weeks.

The primary endpoint counts participants with one or more culture-verified acute vulvovaginal candidiasis episodes through Week 48. The registry defines an episode as a positive fungal culture for Candida species together with a clinical signs-and-symptoms score of at least 3. The score combines three signs—erythema, edema, and excoriation—with three symptoms—itching, burning, and irritation. Each is scored from 0, none, to 3, severe, with higher scores indicating worse symptoms or signs.

Requiring both a positive culture and a clinical score ties the endpoint to a laboratory finding and a clinical presentation, rather than counting either alone. This definition is relevant to recurrence because it distinguishes the specified acute episodes from symptoms without a positive culture or a positive culture without the stated symptom threshold. The endpoint is reported as a participant count, although its title refers to a percentage. The registry record does not explain that presentation difference or provide event-level timing within the follow-up period.

7. Results Posted in the Registry

• VT-1161 Low-dose 3-month: 4.8% (2/42) versus 52.2% (24/46) on control; risk difference -47.4 percentage points (95% CI -63.2 to -31.6), risk ratio 0.09 (0.02–0.36); unadjusted two-proportion z-test p = <0.001.
• VT-1161 Low-dose 6-month: 7.0% (3/43) versus 52.2% (24/46) on control; risk difference -45.2 percentage points (95% CI -61.5 to -28.9), risk ratio 0.13 (0.04–0.41); unadjusted two-proportion z-test p = <0.001.
• VT-1161 High-dose 3-month: 0.0% (0/43) versus 52.2% (24/46) on control; risk difference -52.2 percentage points (95% CI -66.6 to -37.7); unadjusted two-proportion z-test p = <0.001.
• VT-1161 High-dose 24-week: 4.9% (2/41) versus 52.2% (24/46) on control; risk difference -47.3 percentage points (95% CI -63.2 to -31.4), risk ratio 0.09 (0.02–0.37); unadjusted two-proportion z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level: each participant either met the specified episode definition through Week 48 or did not. The registry reports counts rather than a continuous measurement. For each arm, the count is paired with the outcome denominator, and the risk difference compares the observed event proportions in a VT-1161 arm and placebo.

What does a risk difference describe?

A risk difference is the event proportion in the named treatment arm minus the event proportion in the comparator arm. A negative value therefore points toward a lower observed event proportion in the treatment arm in this comparison. Its scale is an absolute difference in proportions, not a relative change. The posted values are recalculated, simple unadjusted estimates from the arm-level summaries. They are not described as adjusted for baseline characteristics or other covariates.

The registry comparisons report unadjusted p-values of p < 0.001 for the treatment-versus-placebo comparisons. A p-value describes how compatible the observed data are with a specified null model, under the assumptions of the test. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The registry record does not describe the original sponsor test or a multiplicity procedure, so the posted unadjusted values should be read as unadjusted comparisons rather than as a documented confirmatory testing plan.

Why does the endpoint definition matter?

The episode definition requires both a positive fungal culture for Candida species and a signs-and-symptoms score of at least 3. The score combines the listed vulvovaginal signs and symptoms, each rated from 0 to 3. This rule makes the outcome more specific than a symptom report alone. It also means that participants with symptoms but without the culture criterion, or with a positive culture but a score below the threshold, would not meet the stated event definition. The registry does not report how often either situation occurred.

What are the limits of count-based results?

Counts are straightforward to read, but the number of participants meeting the endpoint does not capture the number of episodes per participant or when episodes occurred. The measure is whether a participant had one or more qualifying episodes during the specified follow-up, not a recurrent-event rate. The registry lists a timeframe of 48 Weeks, but it does not provide event timing or a time-to-event analysis for this outcome. No over-dispersion adjustment is relevant to interpreting this participant-level binary count as posted; over-dispersion is a concern for count models when variance exceeds the model's assumed variance, but no such model is described in the registry record.

The posted comparison estimates and confidence intervals are simple unadjusted recalculations from the summary counts. The registry lists no outcome analyses under its analyses count, even though arm-level results and comparisons are recorded. That distinction matters: the displayed comparisons can be described statistically, but the original analysis choices, including whether an adjusted analysis was planned, are not reported in the registry record. The record also does not specify how missing endpoint data were handled or whether the primary analysis used any additional covariate adjustment.

Randomization and masking are stated in the study description, but the registry gives no further procedural details. Randomization can reduce systematic differences between arms on average, while masking can reduce some forms of influence on assessment or reporting. Neither feature removes uncertainty from observed counts, nor do they address reporting gaps about adherence, outcome ascertainment, or missingness. The registry model field also says SINGLE GROUP despite the randomized, placebo-controlled description and multiple arm-level results. That inconsistency warrants care in treating the registry fields as a complete account of the design.

10. Confidence Intervals and Precision

A confidence interval gives a range of values compatible with the observed data under the method used. It communicates uncertainty around an estimate; it is not a guarantee that the true effect lies in the interval, nor does it describe variation among individual participants. For these comparisons, the intervals are for unadjusted risk differences.

For low-dose VT-1161 over 3 months, the risk difference is -0.474, with a confidence interval from -0.632 to -0.316. For low-dose treatment over 6 months, the estimate is -0.452, with an interval from -0.615 to -0.289. For high-dose treatment over 3 months, the estimate is -0.522, with an interval from -0.666 to -0.377. For high-dose treatment over 24 weeks, the estimate is -0.473, with an interval from -0.632 to -0.314.

All four posted intervals lie below zero, in keeping with the direction of the point estimates. Their width reflects the uncertainty associated with the observed arm counts and the unadjusted method. The interval for the high-dose 3-month comparison does not imply that its underlying event proportion is exactly zero; the observed count of zero is still subject to sampling uncertainty. These intervals do not address possible bias from missing data, differences in how outcomes were assessed, or multiple comparisons. The confidence level and precise interval method are not reported in the registry record.

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.

The sample-size figures are planning illustrations based on the observed effect, not sample sizes from the original trial design. They assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. The registry's own original design assumptions and sample-size justification are not reported in the registry record.

The listed figures are participants per arm for 80% power and participants per arm for 90% power. The 80% column gives the illustrative per-arm size for a design with an 80% chance of detecting the specified effect under the stated assumptions if that effect is real. The 90% column uses a higher target chance of detection. These planning figures are not observed power.

For low-dose treatment over 3 months, the listed per-arm figures for detecting 100% of the observed effect are 13 for 80% power and 17 for 90% power; for 75% of the observed effect, 27 and 36; and for 50%, 67 and 88. For low-dose treatment over 6 months, the corresponding figures are 15 and 20, 30 and 40, and 74 and 98. For high-dose treatment over 24 weeks, they are 14 and 17, 27 and 36, and 67 and 89. No planning rows are listed for the high-dose 3-month comparison.

Smaller effects require more participants under these assumptions, which is why the illustrative figures increase when the target moves from 100% to 50% of the observed effect. They should not be read as a recommendation or as evidence that the observed trial had a particular power. The original trial's own design assumptions are not reported.

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 = 0.522; treatment proportion p₁ = 0.048; average p̄ = 0.285.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6382 = 1.2508.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5430 = 0.4570.
4. n = (1.2508 + 0.4570)² / (-0.4741)² = 13.0, rounded up to 13 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 <- 0.521739130434783                          # control proportion
p1 <- 0.0476190476190476                          # 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(2267382)
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 = 13 (80% power), 17 (90% power)
 75% of observed effect: n per arm = 27 (80% power), 36 (90% power)
 50% of observed effect: n per arm = 67 (80% power), 88 (90% power)
power.prop.test: 13 
Simulated power at n = 13 per arm: 0.840 (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 records one primary outcome measure and no posted secondary outcomes. It lists no analyses under the analysis count, although it provides arm-level results and unadjusted comparisons for the primary endpoint. The treatment-versus-placebo comparisons cover several VT-1161 regimens. Whether the sponsor prespecified a multiplicity strategy, and whether any adjustment was performed, are not reported in the registry record.

Multiplicity matters because making several comparisons can increase the chance of at least one apparently unusual result under a collection of null hypotheses. The reported p-values are explicitly unadjusted, so they should not be treated as multiplicity-controlled evidence. The registry does not state whether one comparison was designated as the primary contrast or how the distinct dose and duration regimens were prioritized.

The primary endpoint is described for the intent-to-treat population, and arm denominators are posted. However, the registry does not describe the operational definition used for that analysis population, the number or reasons for missing endpoint assessments, or the method used to handle missing data. It also does not report whether every randomized participant was included in the endpoint analysis or how deviations from assigned treatment were handled. These details affect how fully the posted counts can be interpreted.

Further information about interim analyses, covariate adjustment, model choice, and the original statistical plan is not reported in the registry record. The endpoint's stated follow-up is through Week 48, but the record does not give the timing of individual qualifying events or explain how incomplete follow-up was treated. Consequently, the available results support description of the recorded counts and unadjusted comparisons, but not a reconstruction of the sponsor's full analysis process.

14. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: abdominal pain (2.4%), pancreatitis (2.4%), meningitis viral (2.4%), hypotension (2.4%), appendicitis (2.4%).

The registry reports serious adverse events and other adverse events as counts of affected participants alongside the number at risk in each group. For serious adverse events, the figures are 1 of 41 for low-dose 3-month treatment, 0 of 42 for low-dose 6-month treatment, 1 of 42 for high-dose 3-month treatment, 2 of 41 for high-dose 24-week treatment, and 1 of 45 for placebo. These are adverse-event counts, separate from the primary efficacy endpoint counts.

For other adverse events, the affected-participant counts are 26 of 41, 31 of 42, 30 of 42, 28 of 41, and 35 of 45, respectively, in the same group order. These counts do not by themselves establish that an event was caused by study treatment or permit a complete assessment of comparative safety. Death counts are not reported in the registry record.

The listed serious-event terms include Abdominal pain, Pancreatitis, Meningitis viral, Hypotension, and Appendicitis, each at 2.4%, and Herpes simplex at 2.2%. The registry does not provide enough detail in this listing to assign those terms to particular arms or interpret them as treatment-specific rates.

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

The posted results describe fewer participants meeting the culture-verified episode definition in each VT-1161 regimen than in placebo, with negative unadjusted risk differences and unadjusted p-values of p < 0.001. The estimates quantify the observed contrasts in this completed phase 2 trial. They do not by themselves establish how the regimens would perform in a different population, or whether the differences would be replicated.

The endpoint is specific to a positive Candida culture paired with a clinical score of at least 3, and it counts participants with one or more qualifying episodes through Week 48. It does not report the number of episodes per participant, symptom burden outside the qualifying definition, or the timing of each event. The findings therefore address the registry's defined binary endpoint, rather than every possible measure of recurrent illness.

The trial compared regimens that differ in dose and duration, including schedules that transition to placebo and schedules that continue active weekly dosing. The observed differences cannot isolate the contribution of dose from duration. The record also leaves important design and analysis details unreported, including missing-data handling, multiplicity procedures, and the confidence-interval method. Such gaps limit how much can be inferred beyond the posted arm counts and unadjusted comparisons.

The safety counts are descriptive and should be read separately from the primary endpoint. They do not establish causality or comparative safety, and the registry does not report deaths. Overall, the numerical results describe what was recorded for this trial; they are not medical advice and do not alone determine treatment decisions.

16. Why This Trial Matters Statistically

This trial illustrates why the endpoint definition is central to interpreting a clinical comparison. The primary measure requires both culture confirmation and a specified clinical score, so the result is not simply a count of reported symptoms or positive cultures. Knowing the rule clarifies what participants had to experience to be counted and what the result does not encompass.

It also shows the value of reading counts, denominators, and effect estimates together. The arm counts make the observed events concrete, while risk differences express the absolute contrast with placebo and confidence intervals show uncertainty around that contrast. A p-value alone would not communicate the size or precision of the observed difference. The reported estimates and intervals give a fuller statistical description, while remaining unadjusted.

The regimens make interpretation more complex than a single treatment-versus-placebo contrast. Dose and treatment duration vary, and the shorter schedules include placebo after active dosing. The registry model label also conflicts with the randomized, placebo-controlled description. Recognizing these features helps prevent treating all comparisons as equivalent or assuming a design detail that is not documented.

Finally, the record demonstrates the importance of distinguishing a registry's posted numerical results from a complete statistical analysis plan. The outcome and comparisons are available, but details about multiplicity, missing data, original sample-size planning, and analysis procedures are not reported. A statistically careful reading can describe the evidence in the record while keeping those uncertainties visible.

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.

Several limitations specific to the registry record affect interpretation. The study is described as randomized, double-blind, and placebo-controlled, but its model field is SINGLE GROUP. The record does not explain this mismatch. It also does not provide detailed randomization procedures, masking procedures, or baseline characteristics that would help readers assess the groups and conduct of the study.

The treatment arms differ in both dose and duration. The 3-month regimens include weekly placebo after the active phase, while the longer regimens continue weekly active treatment. Comparisons across these arms therefore do not isolate a single dosing feature. The primary endpoint is observed through Week 48, but the registry does not detail follow-up completeness, event timing, or handling of missing outcome data.

The registry lists unadjusted comparisons, but multiplicity procedures, the original statistical plan, and the confidence-interval method are not reported. It also does not provide posted secondary outcomes or analyses. The reported participant counts do not show episode frequency or time to recurrence. In addition, the serious-event term listing does not identify the treatment group associated with each term, and deaths are not reported in the registry record. These limitations do not negate the recorded results, but they constrain the scope of conclusions that can be drawn from them.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: A Study to Evaluate Oral VT-1161 in the Treatment of Patients With Recurrent Vaginal Candidiasis (Yeast Infection) — NCT02267382.
• Registry record last updated 2019-10-15; status last verified 2019-10.
• Results first posted 2019-10-04.
• 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

This completed phase 2 study evaluated oral VT-1161 regimens against placebo in participants with recurrent vulvovaginal candidiasis. The study is described as randomized, double-blind, and dose-ranging, with enrollment listed as 254. Its primary endpoint was the count of participants with one or more culture-verified acute episodes through Week 48 in the intent-to-treat population.

Each VT-1161 arm had fewer participants meeting the endpoint than placebo in the posted counts, and the unadjusted risk-difference comparisons were negative with p < 0.001. The registry does not report the original statistical plan, missing-data handling, multiplicity adjustments, or original sample-size assumptions. Safety results are posted as affected-participant counts; deaths are not reported in the registry record.