Comparing Efficacy and Safety of Combigan With Timolol Adjunctive to Xalatan in Glaucoma or Ocular Hypertension Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparing Efficacy and Safety of Combigan With Timolol Adjunctive to Xalatan in Glaucoma or Ocular Hypertension Subjects (NCT00735449), a randomized phase 4 study. The primary outcome is Mean Intraocular Pressure (IOP) at 10 AM at Week 12.

2. Clinical Question

The question is about a continuous pressure measurement at a specified visit and time of day, rather than a count of participants reaching a threshold. The comparison therefore describes the difference between group averages, alongside uncertainty about that difference. The endpoint description identifies intraocular pressure as a measurement of fluid pressure in the eye. The record also lists measurements at Week 6 and at 8 AM, which provide related observations but do not replace the designated primary endpoint.

The registry record does not report a threshold for clinically meaningful change or a decision rule linking the measured difference to a clinical outcome. The statistical comparison should therefore be read as evidence about the reported pressure measurement, not as a complete assessment of symptoms, longer-term outcomes, or the overall balance of benefits and harms.

3. Trial Design

The registry record identifies this as a Phase 4, randomized, single-masked, parallel-group trial. The study status is completed. Enrollment is listed as 204. The recorded study start is 2008-07, and primary completion is recorded as 2009-12. The sponsor is Allergan.

The two parallel regimens were Combigan® adjunctive to Xalatan® and timolol maleate 0.5% adjunctive to Xalatan®. Randomization means assignment was described as randomized in the registry. The record labels masking as single, but does not report which people were masked or how masking was maintained. It also does not report the allocation procedure or a planned allocation ratio. The observed endpoint groups have the participant counts shown with the results; those counts should not be taken as a description of the original allocation procedure.

The primary outcome was mean intraocular pressure at 10 AM at Week 12, measured in millimeters of mercury. The primary analysis population was per-protocol, defined in the record as randomized participants who started the study, had at least one follow-up visit, and were assessed for that outcome at the Week 12 visit. The registry lists four secondary outcomes: pressure at 10 AM at Week 6, pressure at 8 AM at Week 12, pressure at 8 AM at Week 6, and the number of participants with adverse events.

The registry record does not report the original sample-size justification, the planned statistical model, the planned handling of missing data, or whether interim analyses were planned or conducted. It lists no reported analyses. These omissions limit what can be inferred about the investigators’ prespecified analysis strategy; the posted summary statistics can still be described on their own terms.

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

Analysis population for the primary outcome, as defined in the registry: Per-protocol, which included all patients who started the study (randomized) and had at least one follow-up visit and who were assessed for this outcome measure at the Week 12 visit.

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 Mean Intraocular Pressure (IOP) at 10 AM at Week 12, measured over Week 12.

The primary endpoint is mean intraocular pressure at 10 AM at Week 12, reported in millimeters of mercury (mmHg). Intraocular pressure is described in the registry as a measurement of the fluid pressure in the eye. The endpoint summarizes a continuous measurement across participants in each analysis group, rather than recording only whether an individual did or did not meet a threshold.

A continuous endpoint can retain information about the level of the measured outcome across the group. Comparing group means gives a direct description of how their average recorded pressure differed at the specified visit and measurement time. The registry reports a mean of 15.1 mmHg for Combigan adjunctive to Xalatan and 16.9 mmHg for timolol adjunctive to Xalatan. The comparison is expressed as timolol minus Combigan, so a positive difference means the reported mean was higher in the timolol group.

Specifying both the visit and time of day matters to interpretation: the primary result concerns the 10 AM measurement at Week 12, not every measurement or time point in the trial. The record also includes pressure measurements at other scheduled times, which are secondary outcomes. The registry does not report a threshold for a clinically meaningful difference or a link between this endpoint and outcomes beyond the measured pressure. Accordingly, the endpoint supports interpretation of the recorded group averages and their statistical precision, but does not by itself establish the importance of the difference for every participant or for other outcomes.

7. Results Posted in the Registry

• Timolol Maleate 0.5%: mean 16.90 versus 15.10 on control; difference 1.80 (95% CI 1.08 to 2.52), standardized effect d = 0.71; 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.

Mean Intraocular Pressure (IOP) at 10 AM at Week 6

• 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:
  • Timolol Maleate 0.5%: mean 16.70 versus 15.90 on control; difference 0.80 (95% CI -0.03 to 1.63), standardized effect d = 0.27; z-test p = 0.058.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Timolol Maleate 0.5% and the control. The interval gives the range of effects that remain compatible with the data.

Mean Intraocular Pressure (IOP) at 8 AM at Week 12

• 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:
  • Timolol Maleate 0.5%: mean 17.70 versus 17.00 on control; difference 0.70 (95% CI -0.03 to 1.43), standardized effect d = 0.27; z-test p = 0.060.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Timolol Maleate 0.5% and the control. The interval gives the range of effects that remain compatible with the data.

Mean Intraocular Pressure (IOP) at 8 AM at Week 6

• 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:
  • Timolol Maleate 0.5%: mean 17.80 versus 17.30 on control; difference 0.50 (95% CI -0.35 to 1.35), standardized effect d = 0.17; z-test p = 0.248.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Timolol Maleate 0.5% and the control. The interval gives the range of effects that remain compatible with the data.

Across the secondary pressure endpoints, the estimated mean differences favor a higher recorded pressure in the timolol group, but the confidence intervals include zero at each reported secondary time point. The estimates are smaller than the primary endpoint estimate. Taken together, these results give a broadly similar direction to the primary comparison, but they are less precise evidence for a nonzero difference at their respective measurements.

The secondary outcomes measure pressure at different combinations of visit and time of day. They are related to the primary endpoint because they assess the same general continuous measure, but they are not interchangeable: a measurement at Week 6 or at 8 AM is not the same endpoint as the primary Week 12 measurement at 10 AM. Similar direction across measurements can be informative about pattern, but does not establish that the primary result applies identically to every time point.

The registry reports unadjusted p-values for these comparisons and no reported analyses. When several outcomes or time points are examined, the chance of seeing at least one small p-value by chance can increase. Multiplicity methods can address that issue when prespecified, but the record does not report whether such methods were planned or applied. Consequently, the secondary results carry less confirmatory weight than the designated primary endpoint and should be treated as supportive or exploratory evidence rather than as independent proof.

The number of participants with adverse events is also listed as a secondary outcome, but it addresses safety reporting rather than the pressure comparison. It should be interpreted separately. The registry does not provide a reported analysis combining pressure outcomes and adverse events into a single overall measure, so the two types of results should not be collapsed into one conclusion.

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

• Mean Intraocular Pressure (IOP) at 10 AM at Week 6
• Mean Intraocular Pressure (IOP) at 8 AM at Week 12
• Mean Intraocular Pressure (IOP) at 8 AM at Week 6
• Number of Subjects With Adverse Events

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is a continuous variable summarized by a mean and standard deviation for each group. The posted comparison is a mean difference, with the direction defined by subtracting the Combigan group mean from the timolol group mean. This direction is important: a positive difference indicates a higher mean in the timolol group, while a negative difference would indicate a higher mean in the Combigan group. The comparison is unadjusted and is recalculated from the posted group summaries; the registry lists no reported analyses.

What does the mean difference describe?

A mean difference places the group contrast in the same units as the outcome. Here, those units are millimeters of mercury. At the primary endpoint, the difference is 1.8 mmHg, with the timolol mean higher than the Combigan mean. This is an estimate of a contrast between group averages. It is not a measure of the range of individual outcomes, and it does not mean that every participant’s result differs by that amount.

The group standard deviations describe how dispersed individual measurements were around each group mean. They are not confidence intervals and do not directly express the precision of the difference. Precision of the contrast also depends on the amount of information in each group. The primary outcome summaries report 94 participants in each arm, while the stated analysis population requires an endpoint assessment at Week 12.

How should the confidence interval be read?

A confidence interval describes a range of values compatible with the observed data under the assumptions of the calculation. For the primary contrast, the 95% confidence interval is 1.078 to 2.522 mmHg. Because the interval does not include zero, it is consistent with a positive mean difference for timolol minus Combigan. The interval also shows that the estimate is not known exactly: values across the interval remain compatible with the data under the interval’s statistical assumptions. It does not give the probability that the true difference lies inside this particular interval.

The unadjusted p-value is <0.001. A p-value measures how unusual data at least as incompatible with a zero difference would be under a statistical model that assumes no difference and the other calculation assumptions. It is not the probability that the null hypothesis is true, nor does it quantify clinical importance. The p-value and confidence interval express related information about statistical evidence and uncertainty, but neither substitutes for judging the scale and relevance of the measured outcome.

Why does the analysis population matter?

The registry defines the primary population as per-protocol: randomized participants who started the study, had at least one follow-up visit, and were assessed for the endpoint at Week 12. This definition means the primary summary pertains to those meeting the stated assessment criteria, not necessarily every participant originally randomized. The record does not report an intention-to-treat analysis, reasons participants may not have been assessed, or methods for handling missing measurements. These details matter because the interpretation of a randomized comparison can depend on which participants contribute to the analysis and how unavailable outcomes are handled.

What can be inferred from the other measurements?

The three secondary pressure comparisons are also differences between group means at specified times. Their confidence intervals include zero, unlike the primary interval. This does not establish that the groups are identical at those secondary time points; rather, the posted estimates are compatible with a range that includes no difference. The registry supplies unadjusted p-values for these comparisons and does not report analyses addressing multiplicity. They should therefore be considered less definitive than a prespecified primary result, and the statistical evidence across several measurements should not be interpreted as though each were an isolated confirmatory test.

In general, repeated outcomes and measurement times can create multiple opportunities to observe an apparently notable result. Adjusting for multiplicity is one way a statistical plan may account for that broader set of comparisons, but the registry record does not report whether an adjustment was planned or used. No adjusted secondary inference should be assumed.

Why can over-dispersion matter?

Over-dispersion is a general concern when observed variability is greater than a model expects. It can make standard errors too small if a model does not account for the extra variability, which in turn can make intervals too narrow and p-values too small. The endpoint is continuous, and the posted summaries give standard deviations. The registry does not report a model-based analysis, an over-dispersion assessment, or a concern of this kind. The general concept should not be read as evidence that over-dispersion occurred in this trial.

Because no sponsor analyses are listed, the displayed mean differences, intervals, and p-values are best understood as unadjusted calculations based on the posted summaries, rather than as a documented sponsor model. The registry record does not report the original statistical analysis plan, prespecified tests, or covariate adjustments. This leaves uncertainty about whether the posted summaries reflect the full planned inferential approach.

11. Confidence Intervals and Precision

Precision concerns how narrowly the data estimate the group difference. At the primary endpoint, the mean difference is 1.8 mmHg, and its 95% confidence interval extends from 1.078 to 2.522 mmHg. The interval excludes zero, so the unadjusted comparison is statistically inconsistent with an exactly zero mean difference under the calculation assumptions. Its span also reminds readers that the estimated contrast is uncertain: the point estimate is not an exact value for the underlying group difference.

The confidence interval is about the difference between means, not the spread of individual measurements. The group standard deviations are 2.59 mmHg for Combigan and 2.46 mmHg for timolol. Those standard deviations describe participant-level variability within each arm; they do not indicate how precisely the group difference is estimated by themselves.

The secondary pressure intervals are wider relative to their estimated differences and include zero. The Week 6 10 AM interval ranges from -0.026 to 1.626 mmHg; the Week 12 8 AM interval ranges from -0.029 to 1.43 mmHg; and the Week 6 8 AM interval ranges from -0.349 to 1.349 mmHg. These intervals leave room for no difference as well as differences in either direction. They therefore support less decisive conclusions than the primary interval.

Confidence intervals depend on the analysis and assumptions used to calculate them. The registry does not report sponsor analyses or a detailed statistical plan, so the posted intervals should be read as unadjusted re-calculations from the summary statistics, not as confirmation of a particular adjusted model. The intervals also do not account for the broader set of outcomes unless a multiplicity procedure is specified; none is reported in the registry record.

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 sample-size figures are planning illustrations based on the observed effect, not the trial’s original design calculations. For these continuous outcomes, the entries are participants per arm, not total events. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each scenario uses the stated fraction of the observed effect as the effect to detect.

The 80% power column gives the number of participants per arm estimated to provide an 80% chance of detecting the specified effect under those planning assumptions, if that effect is present. The 90% power column gives the corresponding per-arm planning figure for a 90% chance. These are conditional planning calculations, not guarantees that a future study will detect an effect or that the estimated effect is correct.

Rows describing planning for 100% of the observed effect use the observed difference as the target. Rows for 75% and 50% use progressively smaller target effects. Smaller effects are harder to distinguish from random variation, so they require more participants per arm to reach the same stated power under otherwise unchanged assumptions. The figures therefore vary across both the effect scenario and the desired power.

These calculations are not observed power. They do not measure the probability that the completed trial’s result is true, and they do not explain why the trial was designed with its actual enrollment. The registry record does not report the original sample-size justification or its design assumptions. The planning figures are best used to understand how sample-size requirements depend on the assumed effect, rather than as a retrospective verdict on trial quality.

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 = 1.800; pooled standard deviation σ = 2.526.
2. n = 2 × (1.96 + 0.842)² × 2.526² / 1.800² = 30.9, rounded up to 31 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 <- 1.8                      # observed difference in means
sigma <- 2.52583649510415                     # 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(735449)
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 = 31 (80% power), 42 (90% power)
 75% of observed effect: n per arm = 55 (80% power), 74 (90% power)
 50% of observed effect: n per arm = 124 (80% power), 166 (90% power)
power.t.test: 31.9 
Simulated power at n = 31 per arm: 0.787 (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

Multiplicity arises when an analysis examines several outcomes, time points, or statistical contrasts. Each additional test creates another opportunity for a result to appear noteworthy by chance, even if no underlying difference exists. A prespecified hierarchy or a statistical adjustment can help control this issue, but the registry record does not report a multiplicity strategy, a testing hierarchy, or whether secondary endpoints were intended to be confirmatory.

The primary endpoint is clearly identified as mean intraocular pressure at 10 AM at Week 12. Its result should be distinguished from the secondary pressure measurements at Week 6 and at 8 AM. The secondary comparisons are unadjusted, and their p-values should not be read as if each were the only outcome examined. No adjusted estimates or multiplicity-corrected p-values are reported.

Missing-data handling is also not reported in the registry record. The primary population is described as per-protocol and includes randomized participants who started the study, had at least one follow-up visit, and were assessed for the primary outcome at Week 12. The record does not report how many randomized participants were excluded from this analysis, why any participant lacked an outcome assessment, or how missing measurements were handled. It does not report an intention-to-treat analysis.

These limitations do not change the arithmetic of the posted group summaries, but they constrain interpretation of the comparison. If assessment availability is related to outcomes or group assignment, a per-protocol estimate may differ from an estimate based on all randomized participants. The registry record does not provide information to evaluate whether that occurred.

The record also lists no reported analyses and does not report the original statistical analysis plan. The planned model, any covariate adjustment, interim analyses, and the trial’s original sample-size justification are not reported in the registry record. Readers therefore cannot determine from the registry whether the posted unadjusted summaries correspond to every prespecified analysis or whether additional analyses were conducted but not reported there.

15. 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 5% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: acute exacerbation of copd (1.0%), bacterial bronchitis (1.0%).

The registry reports serious adverse-event figures for the safety groups, with 102 participants at risk in each group. The serious-event count is 0 in the Combigan group and 2 in the timolol group. The listed serious-event terms are Acute exacerbation of COPD and Bacterial bronchitis, each reported as 1.0%. The record does not assign those terms to an arm in the listed terms, so they should not be attributed to a particular group from this information alone.

These are counts reported as serious adverse events, not a complete description of every possible harm or every participant’s experience. The record reports 0 other adverse events in each group in the corresponding summary. Death counts are not reported in the registry record. The registry information does not establish whether an event was caused by a study treatment, and the small number of reported serious events does not support broad conclusions about comparative safety. Safety counts should be read separately from the pressure endpoint and alongside the limitations of the reported follow-up and analysis information.

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

The primary result describes a difference in average intraocular pressure at a specific visit and time of day. In the per-protocol endpoint population, the mean was 15.1 mmHg for Combigan adjunctive to Xalatan and 16.9 mmHg for timolol adjunctive to Xalatan. The unadjusted mean difference, timolol minus Combigan, was 1.8 mmHg, with a 95% confidence interval of 1.078 to 2.522 and an unadjusted p-value of <0.001. This is evidence of a difference in the posted group means at that measurement under the calculation assumptions.

The result does not describe the outcome of every individual participant. Group averages can conceal variation in individual measurements, and the standard deviations indicate that measurements varied within each group. The registry does not report a threshold for what would count as a clinically meaningful pressure difference. Statistical evidence for a nonzero group contrast is not, by itself, a measure of clinical importance.

The result also does not establish what would happen at other visits, measurement times, or on outcomes not listed in the registry. The secondary pressure comparisons have confidence intervals that include zero, and the record does not report multiplicity adjustments. Nor does the primary endpoint alone characterize the overall balance of efficacy and harms. Serious adverse-event counts are a separate piece of information, and the registry does not establish that reported events were caused by treatment.

Randomization is part of the study design, but the primary analysis is per-protocol. The registry does not report a full analysis plan, missing-data procedures, or an intention-to-treat result. Those omissions limit assessment of how exclusions or unavailable measurements might affect the estimated contrast. The findings should therefore be interpreted as the posted comparison for the defined endpoint population, rather than as a complete account of every randomized participant or a guarantee of effects beyond the measured outcome.

17. Why This Trial Matters Statistically

This trial illustrates why a statistical result is more than a p-value. The primary comparison includes a group difference in the outcome’s own units, a confidence interval describing uncertainty, and a p-value testing compatibility with a zero difference under the calculation assumptions. Reading these together distinguishes the estimated scale of the contrast from the evidence against a null difference.

It also shows why the endpoint and its timing must be kept precise. The primary result concerns mean pressure at 10 AM at Week 12. Related measurements at other times and visits point in a similar direction, but their confidence intervals include zero. Treating all those measurements as interchangeable, or treating every unadjusted test as independently confirmatory, would overstate what the registry establishes.

The choice of analysis population is another statistical issue with practical consequences for interpretation. The primary endpoint uses a per-protocol population, and the registry does not report an intention-to-treat analysis or missing-data methods. Even with randomization in the design, those details matter when judging how closely the posted estimate represents the randomized comparison.

Finally, planning calculations based on an observed effect are not the same as the original trial design justification and are not observed power. Separating retrospective planning illustrations from the actual design assumptions helps avoid misleading conclusions about whether a trial was adequately planned. The registry record does not report those original assumptions, so the planning figures serve as illustrations of how assumed effects and desired power relate to participant requirements, not as a reconstruction of the study’s design.

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 primary endpoint analysis is per-protocol, with the registry defining eligibility for that analysis by study start, follow-up, and assessment at the Week 12 visit. The record does not report how many randomized participants were not included, why any assessment was unavailable, or how missing values were handled. There is no reported intention-to-treat analysis to compare with the per-protocol result.

The statistical comparisons are unadjusted re-calculations from summary statistics, and the registry lists no reported analyses. The original analysis plan, model, covariate adjustments, and multiplicity strategy are not reported. This makes it difficult to judge whether the posted comparisons reproduce the prespecified analysis or how the multiple secondary measurements were intended to be interpreted.

The masking is labeled single, but the registry does not identify who was masked or describe the masking procedures. The randomization method and planned allocation ratio are also not reported. The recorded enrollment and endpoint-specific group counts do not fill in those design details.

The endpoint is a pressure measurement at a particular time and visit. The registry does not report a threshold for clinical importance or outcomes that would establish how the measured difference relates to broader patient outcomes. The posted pressure results therefore address a limited, specified measurement rather than every aspect of efficacy.

Safety information is also limited to the adverse-event summaries reported in the record. The serious-event terms are not assigned to an arm in the listed terms, death counts are not reported, and the record does not establish causation. The trial’s original sample-size justification and interim-analysis plans are not reported, so neither the planning illustrations nor the posted results can resolve those omissions.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Comparing Efficacy and Safety of Combigan With Timolol Adjunctive to Xalatan in Glaucoma or Ocular Hypertension Subjects — NCT00735449.
• Registry record last updated 2019-04-23; status last verified 2019-04.
• Results first posted 2011-11-24.
• 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

The registry describes a completed, randomized, single-masked, parallel Phase 4 trial sponsored by Allergan, with enrollment listed as 204. It compared Combigan® adjunctive to Xalatan® with timolol maleate 0.5% adjunctive to Xalatan® in participants with glaucoma or ocular hypertension.

The primary outcome was mean intraocular pressure at 10 AM at Week 12. The posted means were 15.1 mmHg for Combigan and 16.9 mmHg for timolol; the unadjusted mean difference was 1.8 mmHg, with a 95% confidence interval of 1.078 to 2.522 and an unadjusted p-value of <0.001. Secondary pressure comparisons had confidence intervals that included zero. Serious adverse-event counts were 0 for Combigan and 2 for timolol; the registry does not establish causation.

The primary result uses a per-protocol population. The registry record does not report the original sample-size justification, missing-data procedures, multiplicity strategy, or a detailed statistical analysis plan.