Ph2 Placebo-Controlled Study for Safety & Ocular Efficacy of SBI-100 Ophthalmic Emulsion in Pts w/ Elevated Eye Pressure: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ph2 Placebo-Controlled Study for Safety & Ocular Efficacy of SBI-100 Ophthalmic Emulsion in Pts w/ Elevated Eye Pressure (NCT06144918), a randomized phase 2 study. The primary outcome is Change From Baseline in Ocular Hypertension as Measured by Intraocular Pressure (IOP).

2. Clinical Question

The central outcome is change in intraocular pressure, measured in mmHg by Goldmann applanation tonometry. The registry describes the primary aim as evaluating diurnal ocular hypotensive efficacy at two dose levels compared with placebo. The posted results give mean changes for each group and comparisons of each active concentration with placebo. These comparisons describe the observed results in this trial; they do not, by themselves, establish that a treatment is effective or ineffective.

The record identifies the study as a phase 2, randomized, double-masked, placebo-controlled dose-response study. The trial included patients with elevated eye pressure and lists primary open angle glaucoma and ocular hypertension as conditions. Further eligibility details and a more specific definition of the primary analysis population are not reported in the registry record.

3. Trial Design

The registry identifies NCT06144918 as a completed phase 2, randomized, double-masked, parallel-group, placebo-controlled study. It lists an enrollment of 56. The study began on 2023-11-09, and primary completion was recorded on 2024-02-22. The sponsor is Skye Bioscience, Inc.

Participants were assigned to SBI-100 ophthalmic emulsion at 0.5%, SBI-100 ophthalmic emulsion at 1.0%, or placebo. The study summary describes a drop placed into each eye twice a day for 14 days, with administration by the site and by the patient. It describes measurements before treatment and comparison of change through the end of the study. The primary outcome timeframe is baseline and day 14.

Double masking and random assignment are design features intended to limit bias in treatment allocation and outcome assessment. A parallel-group design means the comparison is between groups assigned to different study arms, rather than a within-participant crossover comparison. These general design features do not establish how masking was implemented or maintained; further operational details are not reported in the registry record.

The posted primary endpoint results list 19 in each active arm and 18 in the placebo arm. The record does not report the trial’s original sample-size justification, the allocation ratio planned by the protocol, or whether the enrollment target changed during conduct. It also does not report interim analyses or a detailed statistical analysis plan. The posted group counts and outcome summaries should therefore be read as registry results, not as a complete account of the protocol or trial conduct.

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: There was a screening/washout period of up to 35 days to washout procedures and medications prohibited by the study protocol. At Visit 3 (Day 1), eligible patients were randomized 1:1:1 to IP in a double-masked fashion (SBI-100 0.5%, SBI-100 1.0% or placebo). Eleven (11) participants were screen failures and therefore, did not receive a treatment assigned. A total of 56 participants were screened and enrolled.

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 Change From Baseline in Ocular Hypertension as Measured by Intraocular Pressure (IOP), measured over baseline and day 14.

The primary endpoint is change from baseline in intraocular pressure (IOP), measured in mmHg, at baseline and day 14. The registry describes IOP measurement by Goldmann applanation tonometry and reports the group results as least-squares means with standard errors. A change score expresses how the measured pressure at the endpoint differs from the participant’s baseline measurement; the group mean summarizes those changes for the arm.

IOP is used in this trial because the study’s stated aim is to evaluate ocular hypotensive efficacy in patients with elevated IOP. In general, a continuous endpoint such as change in IOP retains information about the magnitude of measured change, rather than reducing results to a binary category. The diurnal assessment described in the registry is intended to evaluate pressure across the day, although the exact measurement schedule and the statistical handling of repeated measurements are not reported in the registry record.

The posted mean changes were -1.985 for the 0.5% arm, -1.118 for the 1.0% arm, and -0.827 for placebo. These are group summaries, not individual responses. The registry record does not report a distribution of participant-level changes or the number of participants with a particular direction or magnitude of change. The endpoint alone also does not capture all aspects of safety, which are reported separately as adverse-event counts.

7. Results Posted in the Registry

• SBI-100 Ophthalmic Emulsion, 0.5%: mean -1.99 versus -0.83 on control; difference -1.16 (95% CI -2.57 to 0.26), standardized effect d = -0.53; z-test p = 0.109.
• SBI-100 Ophthalmic Emulsion 1.0%: mean -1.12 versus -0.83 on control; difference -0.29 (95% CI -1.71 to 1.13), standardized effect d = -0.13; z-test p = 0.687.

8. Statistical Interpretation

9. Statistical Methods Explained

What does the mean change represent?

For a continuous outcome, a mean summarizes the observed values across a group. Here, the registry reports least-squares mean change in IOP, rather than a count of participants meeting a threshold. A negative change indicates that the measured group mean at follow-up was lower than its baseline value, according to the change measure used. The posted values are -1.985 for 0.5%, -1.118 for 1.0%, and -0.827 for placebo. Those summaries do not show how much individual participants varied around the group mean.

The registry gives standard errors of 0.504, 0.504, and 0.518 for the 0.5%, 1.0%, and placebo groups, respectively. In general, a standard error describes the precision of an estimated mean: smaller standard errors indicate less sampling uncertainty in the estimate, under the assumptions of the method. It is not the same as the spread of individual measurements. The registry does not provide the underlying participant-level outcome values.

How should the active-versus-placebo estimates be read?

The posted mean difference for 0.5% versus placebo is -1.158, and the posted mean difference for 1.0% versus placebo is -0.291. These estimates summarize the contrasts between each active group and placebo on the reported change measure. The signs and magnitudes describe the estimated contrasts; they do not establish a causal effect without considering the uncertainty and the trial’s analysis methods. The record lists pooled standard deviations and standardized effect estimates as well, but does not report a detailed explanation of how the comparison model was fitted.

The reported p-values are unadjusted: 0.109 for the 0.5% comparison and 0.687 for the 1.0% comparison. In general, a p-value measures how incompatible the observed data are with a specified null model, if that model and its assumptions hold. It is not the probability that the null hypothesis is true, nor does it measure the size or importance of an effect. The exact test and model used for the registry comparisons are not reported in the registry record.

What do the intervals add?

The interval for the 0.5% comparison is -2.574 to 0.258, and the interval for the 1.0% comparison is -1.707 to 1.125. In general, an interval estimate shows a range of values compatible with the data and the method’s assumptions. Its width conveys uncertainty: wider intervals leave more possible values consistent with the estimate. Because both intervals include zero, neither posted comparison rules out a zero mean difference using the reported interval method. The registry does not identify the confidence level or provide full details of the method used to construct these intervals.

Why can small group counts affect interpretation?

Each posted arm result is based on 19 in the 0.5% group, 19 in the 1.0% group, and 18 in placebo. In general, estimates based on fewer observations tend to be less precise, all else being equal. Precision also depends on variation in the outcome and on the analysis model. The observed standard errors and intervals give direct information about uncertainty for these results; no separate claim about a particular power level should be inferred from the observed group counts.

Over-dispersion is a general concern when a statistical model assumes less variability than the data contain. If present and unaddressed, it can make standard errors too small and intervals too narrow. It is not reported whether over-dispersion was assessed for this continuous endpoint, and the record does not report the model diagnostics or variance assumptions. The registry’s reported standard errors and intervals should be interpreted as calculated under methods that are not fully described in the record.

What analysis details are unavailable?

The endpoint is described as a least-squares mean, but the registry does not report the model specification, covariates, handling of repeated or diurnal measurements, or whether baseline IOP was included as a model term. It does not report the analysis population definition, missing-data approach, or how protocol deviations were handled. The statistical test behind the comparisons and the confidence-interval construction method are also not reported in the registry record. These omissions prevent a full reconstruction of the analysis from the posted summary statistics alone.

The record lists two outcome measures and no posted analysis entries. It lists no secondary outcomes posted. These registry entries indicate that the available numerical interpretation is concentrated on the primary change endpoint and the comparisons presented; they do not establish what analyses may have been specified or conducted outside the registry record.

10. Confidence Intervals and Precision

The posted comparisons give both a point estimate and an interval. For the 0.5% emulsion versus placebo, the estimate is -1.158, with an interval from -2.574 to 0.258. For the 1.0% emulsion versus placebo, it is -0.291, with an interval from -1.707 to 1.125. The intervals include zero and also include values on either side of zero, so the summaries leave uncertainty about the direction and magnitude of each difference.

In general, a confidence interval is a method-based range that conveys uncertainty around an estimate. It is not a guarantee that the true value lies in the displayed range, and it does not assign a probability to any particular value after the data have been observed. Its interpretation depends on the statistical method and assumptions. The registry record does not state the interval confidence level or fully describe the procedure used to calculate the intervals.

The group standard errors are 0.504 for 0.5%, 0.504 for 1.0%, and 0.518 for placebo. These quantify uncertainty in the reported group means, not the variation among individual participants. The intervals for the comparisons are more directly relevant to uncertainty in the active-versus-placebo contrasts.

Precision is limited by the breadth of the posted intervals: the data remain compatible with a range of possible mean differences. The estimates should therefore be read with their intervals, rather than as exact treatment effects. The record does not report an adjusted interval accounting for multiple comparisons.

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 the trial’s original design assumptions. The calculations use 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. These are participants per arm for 80% power and participants per arm for 90% power, not total event counts.

In plain language, the 80% power column gives the estimated number of participants in each arm for a planning scenario designed to detect the chosen effect with 80% power, under those assumptions. The 90% power column gives the corresponding per-arm planning number for 90% power. Power is the chance of detecting an effect of the specified size under the planning model if that effect is the true one. These figures are not observed power.

For the 0.5% comparison, planning for 100% of the observed effect gives 57 participants per arm for 80% power and 76 for 90% power. Planning for 75% of the observed effect gives 101 and 135 participants per arm; planning for 50% gives 226 and 303. For the 1.0% comparison, the corresponding figures are 895 and 1,198 for 100% of the observed effect, 1,591 and 2,130 for 75%, and 3,579 and 4,791 for 50%.

Smaller effects require more participants to detect under the same planning assumptions. These calculations use the observed estimates as their starting point, so they are sensitive to uncertainty in those estimates; they should not be treated as a recommended design or as evidence that the original trial was adequately or inadequately sized. The trial’s own design assumptions and sample-size justification are not reported in the registry record.

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, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -1.158; pooled standard deviation σ = 2.196.
2. n = 2 × (1.96 + 0.842)² × 2.196² / -1.158² = 56.5, rounded up to 57 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 <- -1.158                      # observed difference in means
sigma <- 2.19643261780812                     # 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(6144918)
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 = 57 (80% power), 76 (90% power)
 75% of observed effect: n per arm = 101 (80% power), 135 (90% power)
 50% of observed effect: n per arm = 226 (80% power), 303 (90% power)
power.t.test: 57.5 
Simulated power at n = 57 per arm: 0.797 (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.

13. Multiplicity, Missing Data and Analysis Populations

The posted results include two active-versus-placebo comparisons for the primary endpoint: one for 0.5% and one for 1.0%. The registry reports unadjusted p-values of 0.109 and 0.687. Unadjusted values treat each comparison without accounting for the fact that multiple comparisons are being considered. When multiple tests are conducted, the chance of at least one false-positive finding can increase; adjustment procedures are one way to address this general issue. The registry record does not report whether a multiplicity strategy was prespecified or used.

The available comparisons should therefore be read as unadjusted estimates and p-values, not as results with a documented family-wise error control procedure. The record does not state whether one comparison was considered primary among the active doses, whether a dose-response test was planned, or how the two dose comparisons were intended to be interpreted together.

The registry lists two outcome measures and no secondary outcomes posted. It does not give results for additional efficacy outcomes in the posted record. The exact handling of missing IOP measurements, withdrawals, protocol deviations, or participants who did not complete the assessment is not reported in the registry record. Nor does it define an intention-to-treat, modified intention-to-treat, per-protocol, or safety analysis population for the endpoint results.

These gaps matter because analysis populations and missing-data methods can affect the estimates and their uncertainty. The record also does not report whether any sensitivity analyses were performed to evaluate missing data or deviations from the planned treatment schedule. No assumptions about those procedures can be inferred from the arm summaries alone.

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 lists no serious adverse events in any arm: 0 among 19 at risk in the 0.5% group, 0 among 19 at risk in the 1.0% group, and 0 among 18 at risk in placebo. It also lists 0 deaths in each arm. These are the posted counts for the trial record and should not be read as evidence that serious events cannot occur.

For other adverse events, the registry lists 14 affected among 19 at risk in the 0.5% group, 19 among 19 at risk in the 1.0% group, and 8 among 18 at risk in placebo. These counts do not describe event severity, timing, duration, or whether an event was considered related to treatment. The record does not provide a list of the most frequent non-serious terms in the posted results.

Safety counts are descriptive and should be interpreted in light of the trial’s duration, group sizes, and the level of detail available in the registry record. The study summary describes dosing for 14 days; longer-term safety information is not reported in the registry record.

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

The registry results describe mean IOP changes from baseline to day 14 and the estimated differences between each active concentration and placebo. The 0.5% group mean change was -1.985, compared with -0.827 for placebo; the posted mean difference was -1.158. The 1.0% group mean change was -1.118; its posted difference from placebo was -0.291. The intervals for both comparisons include zero, and their unadjusted p-values are 0.109 and 0.687.

These findings do not establish that either concentration does or does not have an effect. The interval estimates show uncertainty around the comparisons, and the registry does not report a multiplicity adjustment, analysis model details, or the confidence level for the intervals. A failure to obtain a statistically significant unadjusted result is not evidence of equivalence, and no equivalence margin or non-inferiority analysis is reported.

The results also do not provide a definitive comparison between the two concentrations. The registry reports active-versus-placebo estimates, but does not report a direct 0.5%-versus-1.0% comparison or a formal dose-response test. Nor do the group means reveal individual participant responses or explain variation within each group.

The safety information is similarly bounded: no serious adverse events or deaths are listed, while other adverse events affected participants in each arm. The trial’s registry record describes a 14-day treatment period, so these counts do not characterize longer-term safety. Broader conclusions about outcomes beyond the posted endpoint and timeframe are not supported by these results alone.

16. Why This Trial Matters Statistically

This trial illustrates why a point estimate should be read together with its uncertainty. The posted group means differ, but the active-versus-placebo intervals extend across zero. The numerical estimates therefore do not settle the direction or size of the underlying differences. Looking only at the group means, or only at the unadjusted p-values, would omit important information about precision.

It also highlights the role of analysis choices. There are two active-versus-placebo comparisons, yet the registry does not report a multiplicity procedure or full statistical model. Without those details, the posted estimates can be described, but the analysis cannot be fully reconstructed or judged against a complete prespecified plan. Missing-data and analysis-population details are also absent from the registry record.

The planning illustrations show how sample-size requirements depend on the assumed effect. Smaller planning effects produce larger per-arm requirements under the stated calculation assumptions. Because these illustrations start from observed effects in a trial with limited group counts, they are best treated as sensitivity examples rather than definitive design targets.

Finally, the safety counts and IOP endpoint address different questions. The primary outcome summarizes pressure change, while adverse-event counts provide a limited view of safety over the recorded study period. Keeping those evidence types distinct helps prevent an efficacy estimate from being mistaken for a complete assessment of safety or longer-term outcomes.

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 gives concise outcome summaries but does not report the full statistical analysis plan, the model specification, the test used for the comparisons, or the confidence level and method for the reported intervals. Although the endpoint is described as a least-squares mean, the covariates and handling of baseline and diurnal measurements are not reported. This limits independent assessment of the analysis.

The record does not describe the analysis population, missing-data handling, withdrawals, or protocol deviations. It also does not report participant-level results or outcome distributions. The posted comparisons are unadjusted, and no multiplicity strategy is reported despite the two active-versus-placebo comparisons.

The efficacy results concern change from baseline to day 14. Longer-term outcomes, subgroup analyses, and secondary outcome results are not reported in the registry record. The record also does not report the original sample-size justification, so the planning illustrations based on observed effects should not be mistaken for the trial’s own design basis.

For safety, serious-event counts and other adverse-event affected counts are available, but detailed event terms, timing, severity, and attribution are not reported in the posted results. The study duration described in the summary limits what can be concluded about safety beyond the stated treatment period. These limitations call for a focused interpretation of the posted endpoint estimates and counts rather than broader conclusions.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Ph2 Placebo-Controlled Study for Safety & Ocular Efficacy of SBI-100 Ophthalmic Emulsion in Pts w/ Elevated Eye Pressure — NCT06144918.
• Registry record last updated 2026-01-14; status last verified 2025-05.
• Results first posted 2026-01-14.
• 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

NCT06144918 is a completed, randomized, double-masked, parallel-group, phase 2 placebo-controlled study sponsored by Skye Bioscience, Inc. The record lists 56 enrolled and conditions of primary open angle glaucoma and ocular hypertension. The study began on 2023-11-09, with primary completion on 2024-02-22.

The primary endpoint was change in IOP from baseline to day 14, measured in mmHg. The posted mean changes were -1.985 for SBI-100 at 0.5%, -1.118 for SBI-100 at 1.0%, and -0.827 for placebo. The comparisons with placebo had intervals that included zero. No serious adverse events or deaths were listed; other adverse events affected participants in all three arms.

The registry record does not report detailed analysis methods, multiplicity handling, missing-data procedures, or longer-term outcome results.