This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study Comparing Xalacom And Xalatan In Patients With Primary Open Angle Glaucoma (POAG) Or Ocular Hypertension (OH). (NCT00383019), a randomized phase 3 study. The primary outcome is Change of Intraocular Pressure (IOP) From Baseline to Week 8.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00383019 |
| Phase | Phase 3 |
| Condition | Glaucoma, Ocular Hypertension |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 300 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Pfizer's Upjohn has merged with Mylan to form Viatris Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Japanese patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH). The primary efficacy analysis population was the intent-to-treat population, defined in the registry record as all subjects treated with the study drug as randomized.
Intervention
The study aimed to compare Xalacom with Xalatan. The efficacy results label the intervention arm KP2035 Group; the arm description does not explain the relationship between that label and Xalacom.
Comparator
Xalatan, shown in the efficacy results as the Xalatan Group. The trial used randomized allocation and a parallel-group design, with double masking.
Primary question
How did intraocular pressure (IOP) change from baseline to Week 8 in each arm, and did the change differ between the groups? The registry’s stated aim was to show superiority of Xalacom over Xalatan for efficacy and similarity of safety. However, a primary between-group estimate or test is not reported in the registry record.
The primary outcome is a continuous measurement: change in IOP, expressed in mmHg. Its definition is the Week 8 value minus the baseline value, so a negative change represents a lower measured IOP at Week 8 than at baseline. The posted arm-level estimates are -2.59 mmHg for the KP2035 Group and -1.62 mmHg for the Xalatan Group. Each estimate is accompanied by a 95% confidence interval. These results describe the estimated within-arm changes; they are not, by themselves, an estimate of the difference between the arms.
The registry lists 300 participants as enrolled. The primary efficacy results include 144 participants in the KP2035 Group and 145 in the Xalatan Group. The record does not explain the difference between the enrollment count and the arm counts used for these results. The duration was 8 weeks, and the population was Japanese patients with POAG or OH. Interpretation therefore concerns the measured short-term IOP outcome in this study population, rather than other populations, durations, or outcomes.
3. Trial Design
This was a randomized, double-masked, parallel-group phase III study with an 8-week timeframe. The registry describes the comparison as Xalacom versus Xalatan in Japanese patients with primary open-angle glaucoma or ocular hypertension. The efficacy results identify the arms as KP2035 Group and Xalatan Group; the registry does not explain the KP2035 label in the arm description. The trial is marked completed.
Randomization is intended to allocate participants to treatment groups by chance, helping make groups comparable on average. Double masking means that masking was recorded at the double level, but the registry record does not specify which people were masked or describe the procedures used to maintain masking. The parallel-group model indicates that participants were assigned to a group and the groups were compared over the study period; details of visits and treatment administration are not reported in the registry record.
The primary outcome was change in IOP from baseline to Week 8, with results reported as least-squares means and 95% confidence intervals. The defined primary efficacy population was the intent-to-treat population, consisting of all subjects treated with the study drug as randomized. If a Week 8 IOP value was missing, the record says it was supplemented using the Week 4 value under last observation carried forward (LOCF). The record does not report the number of missing Week 8 values or the number of participants included in each analysis beyond the arm counts shown.
The registry lists eight secondary outcomes, including IOP changes at Week 4, percentage change at Week 8, and counts meeting IOP thresholds or specified reductions. It also records safety outcomes. A detailed statistical analysis plan, the planned sample-size justification, and interim-analysis procedures are not reported in the registry record. The registry lists 300 enrolled participants, but the rationale for that enrollment target is not reported.
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: 300 subjects were treated with Xalatan in Run-in period. (Run-in period: subjects treated with Xalatan\ (0.005% latanoprost eye drop), one drop, once daily in the evening (20:00-23:00).) Of these, 289 subjects were assigned to groups (144 in KP2035 group and 145 in Xalatan group).
Overall Study
| Stage | KP2035 Group | Xalatan Group |
|---|---|---|
| STARTED | 144 | 145 |
| COMPLETED | 139 | 143 |
| NOT COMPLETED | 5 | 2 |
Reasons for not completing this period:
| Reason | KP2035 Group | Xalatan Group |
|---|---|---|
| Adverse Event | 5 | 1 |
| Withdrawal by Subject | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: The primary efficacy analysis population was the Intent-to-treat population (ITT) which consisted of all subjects treated with the study drug as randomized. If there were any missing IOP values at Week 8, the data were supplemented by LOCF (Last Observation Carried Forward) using data at Week 4.
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.
| Characteristic | Unit | KP2035 Group | Xalatan Group | Total |
|---|---|---|---|---|
| Participants analysed | 144 | 145 | 289 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 78 | 77 | 155 |
| Age, Categorical: >=65 years | Participants | 66 | 68 | 134 |
| Sex: Female, Male: Female | Participants | 70 | 74 | 144 |
| Sex: Female, Male: Male | Participants | 74 | 71 | 145 |
| Region of Enrollment: Japan | Participants | 144 | 145 | 289 |
6. Primary Endpoint
The registry lists the primary outcome as Change of Intraocular Pressure (IOP) From Baseline to Week 8, measured over Baseline to Week 8.
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | mmHg |
| Endpoint classification | Continuous Endpoint |
The primary endpoint measures the difference between each participant’s IOP at Week 8 and their baseline IOP. The registry defines the calculation as Week 8 value minus baseline value and reports the group results as least-squares means in mmHg. A negative estimate therefore represents a reduction from baseline on this measurement. The posted estimates are -2.59 mmHg for the KP2035 Group and -1.62 mmHg for the Xalatan Group, with respective 95% confidence intervals of -2.92 to -2.25 and -1.96 to -1.28.
IOP is the measured clinical outcome selected for the study’s primary efficacy question. A continuous endpoint preserves information about the size of change rather than reducing the result to whether a participant did or did not cross a particular threshold. It can therefore describe the average change in the measured quantity across a group. The registry specifies least-squares means, but does not report the model details or covariates used to obtain them.
The arm-level changes do not answer the comparative question on their own. A direct between-group estimate, with its uncertainty and any associated test, would quantify how the average changes differ. Such a primary comparison is not reported in the registry record. Consequently, the posted arm estimates and their confidence intervals describe changes within each group, while the registry’s stated goal of demonstrating superiority cannot be assessed from a reported primary contrast.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
For the primary outcome, the estimated mean change from baseline to Week 8 was -2.59 mmHg in the KP2035 Group, with a 95% confidence interval from -2.92 to -2.25. In the Xalatan Group, the estimate was -1.62 mmHg, with a 95% confidence interval from -1.96 to -1.28. Both arm-level intervals lie on the negative side of zero, describing estimated decreases from baseline in both groups. The intervals quantify uncertainty around each arm’s estimated mean change, not uncertainty around a direct difference between groups.
The key limitation for the comparative primary question is that no primary between-group estimate, confidence interval, or p-value is reported in the registry record. The separate arm estimates cannot substitute for a direct comparison: evaluating whether each arm changed from baseline is a different statistical question from estimating whether the groups changed by different amounts. The registry’s stated objective was to show superiority in efficacy and similarity of safety, but the available primary results do not report a test of that superiority objective.
For selected secondary threshold outcomes, unadjusted comparisons were recalculated from the posted counts. At Week 8, 36 of 144 participants in the KP2035 Group and 13 of 145 in the Xalatan Group had an IOP of 15 mmHg or lower. The recalculated risk difference for Xalatan relative to KP2035 was -0.160, with a 95% confidence interval from -0.245 to -0.076, and p < 0.001. For the threshold of 16 mmHg or lower, the corresponding counts were 60 of 144 and 35 of 145; the recalculated risk difference was -0.175, with a 95% confidence interval from -0.282 to -0.069, and p = 0.002. These are secondary, unadjusted results, not the missing primary comparison.
For the threshold of 18 mmHg or lower, the counts were 105 of 144 and 91 of 145. The recalculated risk difference was -0.102, with a 95% confidence interval from -0.209 to 0.005, and p = 0.065. Its interval includes zero, so these data are compatible with a range of group differences that includes no difference. More generally, a confidence interval expresses the precision of an estimate under the analysis assumptions; it does not establish that the observed estimate will recur in another study.
The three secondary contrasts use different thresholds applied to the same clinical measurement. They are related outcomes, not independent replications of the primary finding. The unadjusted p-values do not account for the set of secondary outcomes or any multiplicity strategy. No multiplicity adjustment or prespecified hierarchy is reported in the registry record, so these results warrant more caution than a prespecified primary comparison with a reported analysis.
9. Statistical Methods Explained
The primary endpoint is continuous: each participant’s Week 8 IOP minus baseline IOP, measured in mmHg. The registry reports least-squares means and 95% confidence intervals for each arm. A least-squares mean is a model-based estimate of a group mean; the registry does not provide the model specification or identify any covariates. Accordingly, the estimates can be described as reported, but the details needed to reproduce the model are not available in the registry record.
A confidence interval conveys the uncertainty around an estimated quantity under the assumptions of the analysis. It is not a range containing every participant’s result, and the two arm-specific intervals are not a confidence interval for the difference between arms. Comparing whether two separate intervals overlap is not a replacement for a direct estimate and test of the treatment contrast. For the primary outcome, the registry reports the arm estimates and intervals but no direct contrast, contrast interval, or test. The stated primary comparison is therefore not fully quantified in the record.
The primary efficacy population is described as the intent-to-treat population consisting of all subjects treated with the study drug as randomized. That definition, as written, is narrower than a definition that explicitly includes every randomized participant regardless of whether treatment began. The registry states that missing Week 8 IOP values were supplemented using Week 4 data through last observation carried forward. LOCF carries a prior observed value forward to stand in for a missing later measurement. This is a specific missing-data procedure, not evidence that the carried-forward value equals the unobserved Week 8 value. The count of missing values and any sensitivity analysis are not reported.
Some secondary outcomes are binary counts: whether a participant met an IOP threshold or reduction criterion. For these, a risk difference expresses the difference between the proportions meeting the criterion in the two groups. In the recalculated results, the contrast is presented as Xalatan relative to the KP2035 Group; a negative estimate means the observed proportion was lower in the Xalatan Group. The confidence interval gives a range of values compatible with the data and method, while the p-value measures how unusual the observed data would be under a specified null hypothesis and assumptions. An unadjusted p-value does not account for testing multiple outcomes.
The p-values and contrast intervals for the listed threshold outcomes are recalculated unadjusted comparisons from the posted summary counts. They are not reported sponsor analyses. The registry lists no reported analyses for these secondary endpoints. A statistically small p-value, considered alone, does not give the magnitude or precision of an effect; the estimate and interval are also needed. Conversely, an interval that includes zero does not prove that the groups are identical. It indicates that the data and method do not rule out zero at the corresponding interval level.
The posted planning illustrations use a two-sided significance level of 0.05, equal allocation, and a normal approximation. They consider effects set at 100%, 75%, and 50% of the observed effect and give the number of participants per arm for 80% and 90% power. These values are illustrations based on observed effects, not the trial’s original sample-size plan and not observed power. The sample-size justification used when designing the trial is not reported in the registry record. Planning calculations based on an observed effect are sensitive to how large that observed effect is and should not be interpreted as evidence that the completed trial had a particular probability of detecting an effect.
Over-dispersion is a general concern when binary outcomes vary more than a simple model assumes: standard errors can then be too small and intervals too narrow if the model does not account for the extra variation. The registry’s listed binary comparison calculations do not report an over-dispersion model, and the arm-level counts alone do not establish whether extra variation was present. This is a general statistical consideration, not a reported feature or finding of this trial.
Multiplicity is the issue created when several hypotheses are tested. With multiple tests, the chance of at least one apparently notable result can increase if each test is interpreted without adjustment. The registry lists eight secondary outcomes, but does not report an adjustment, a testing hierarchy, or which secondary outcomes were confirmatory. Therefore, the secondary p-values should be read as unadjusted comparisons rather than as results that control an overall error rate. No interim analyses or stopping rules are reported in the registry record.
For adverse events, the record gives arm-level counts for serious adverse events, other adverse events, and deaths, along with several serious-event terms and percentages. Counts describe how many participants were recorded with an event in each group, not the probability of an event in a different population or over a different follow-up period. The registry record does not provide event-specific comparative tests or detailed definitions and ascertainment procedures for these categories.
10. Multiplicity, Missing Data and Analysis Populations
The registry record does not report a multiplicity strategy for the eight listed secondary outcomes. It does not identify a hierarchy of testing, say which secondary outcomes were confirmatory, or state whether p-values were adjusted. When multiple outcomes are tested, unadjusted results can produce apparently notable findings by chance more often than a single prespecified test. This general concern means the unadjusted secondary p-values should not be interpreted as if they controlled the overall false-positive risk across the full set of outcomes.
The record lists no reported analyses for the secondary outcomes, and the primary results do not include a between-group estimate or test. The presence of arm-level estimates and recalculated secondary contrasts does not establish what the sponsor’s prespecified statistical plan contained. The statistical plan, interim analyses, and stopping procedures are not reported in the registry record.
For the primary efficacy analysis, the record defines the intent-to-treat population as all subjects treated with the study drug as randomized. It also states that missing Week 8 IOP values were supplemented with Week 4 values using LOCF. This specifies how the registry says missing primary measurements were handled, but not how many were missing, why they were missing, or whether conclusions were examined under alternative assumptions. A carried-forward observation may not represent the unobserved Week 8 measurement; that is a general limitation of this approach.
The registry lists 300 participants enrolled, while the primary efficacy arms contain 144 and 145 participants. The reason for the difference is not reported in the registry record. The record also does not report a sample-size justification, so the enrollment count cannot be linked to a stated target power or assumed treatment effect. The planning illustrations based on observed effects are not the trial’s original design calculations.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| KP2035 Group | 1 | 144 | 0.7% |
| Xalatan Group | 2 | 145 | 1.4% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| KP2035 Group | 0 of 144 |
| Xalatan Group | 0 of 145 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| KP2035 Group | 51 of 144 |
| Xalatan Group | 29 of 145 |
Most frequent serious adverse event terms
| Event term | Organ system | KP2035 Group | Xalatan Group |
|---|---|---|---|
| Inflammatory bowel disease | Gastrointestinal disorders | 1 of 144 | 0 of 145 |
| Inguinal hernia | Gastrointestinal disorders | 0 of 144 | 1 of 145 |
| Pneumonia | Infections and infestations | 0 of 144 | 1 of 145 |
| Pyelitis | Infections and infestations | 0 of 144 | 1 of 145 |
Most frequent non-serious adverse event terms
| Event term | Organ system | KP2035 Group | Xalatan Group |
|---|---|---|---|
| Eye irritation | Eye disorders | 25 of 144 | 2 of 145 |
| Nasopharyngitis | Infections and infestations | 6 of 144 | 2 of 145 |
| Punctate keratitis | Eye disorders | 2 of 144 | 4 of 145 |
| Conjunctival hyperaemia | Eye disorders | 2 of 144 | 3 of 145 |
| Eczema | Skin and subcutaneous tissue disorders | 4 of 144 | 0 of 145 |
| Conjunctivitis | Eye disorders | 2 of 144 | 1 of 145 |
| Keratitis | Eye disorders | 3 of 144 | 0 of 145 |
| Abnormal sensation in eye | Eye disorders | 1 of 144 | 1 of 145 |
| Eye pain | Eye disorders | 0 of 144 | 2 of 145 |
| Headache | Nervous system disorders | 0 of 144 | 2 of 145 |
Serious events with the highest arm-level rate: inflammatory bowel disease (0.7%), inguinal hernia (0.7%), pneumonia (0.7%), pyelitis (0.7%).
The safety results list serious adverse events in 1 of 144 participants in the KP2035 Group and 2 of 145 in the Xalatan Group. No deaths are listed in either group. Other adverse events are recorded for 51 of 144 participants in the KP2035 Group and 29 of 145 in the Xalatan Group. These are counts of participants with recorded events; they are not adjusted comparisons and do not by themselves establish a difference between treatments.
The serious-event terms listed in the record are inflammatory bowel disease, inguinal hernia, pneumonia, and pyelitis, each reported as 0.7%. The record does not provide further event-level detail in these results, such as timing, recurrence, severity beyond the serious classification, or an assessment of whether events were related to treatment. It also does not report comparative statistical tests for the safety counts.
Safety observations apply to this study’s participants and 8-week timeframe. The small number of serious events means the counts offer limited precision for comparing uncommon events. The absence of recorded deaths in these groups is a description of this trial record, not evidence that risk is absent. Interpretation should remain focused on the counts, the short follow-up, and the lack of detailed comparative analyses.
12. What the Result Does, and Does Not, Mean
The primary results describe estimated changes in IOP from baseline to Week 8 within each arm. Both estimates are negative, and both arm-specific 95% confidence intervals lie below zero. This indicates that the reported mean change in each group was a decrease over the study period, with the uncertainty intervals given in the registry. It does not establish the comparative size of the change between groups.
The registry’s stated efficacy objective was to show superiority of Xalacom over Xalatan. The primary result needed to assess that objective—a direct between-group estimate with its uncertainty and test—is not reported in the registry record. The arm-level estimates cannot establish superiority merely because they differ numerically. A direct comparison is needed to estimate the difference and assess its precision under a specified analysis.
The secondary threshold outcomes offer additional descriptions of the Week 8 measurements, but their unadjusted comparisons are not a replacement for the missing primary contrast. The threshold results vary according to the cut-point, and the record does not report correction for testing multiple secondary outcomes. They should therefore be interpreted cautiously and in the context of the stated primary endpoint, rather than as definitive evidence on their own.
The findings do not establish what would happen outside the study’s Japanese POAG or OH population, beyond its 8-week duration, or for outcomes that were not reported. The registry record does not provide enough detail to assess the original sample-size rationale, the full analysis plan, or sensitivity to alternative missing-data assumptions. The safety counts likewise describe events recorded in these study groups and do not provide a precise estimate for uncommon outcomes.
Statistically, the record supports a description of the reported arm-level changes and selected secondary counts, with the uncertainty available for those results. It does not report the primary comparative analysis required to quantify the treatment difference against the trial’s stated superiority objective. That distinction is central to interpreting what the posted results can and cannot answer.
13. Why This Trial Matters Statistically
This trial illustrates why a clinical comparison needs more than two arm-specific outcome estimates. The primary endpoint results give a mean change and confidence interval for each group, but the question of comparative efficacy concerns the difference between those changes. Without a reported primary contrast, readers cannot see the estimated comparative effect or its precision directly. The distinction is important even when the arm estimates are individually clear.
The record also shows how continuous and threshold outcomes describe different features of the same measurement. Mean change summarizes magnitude across the group, while threshold counts describe how many participants meet a defined cut-point. Results can vary with the threshold, so several related outcomes should not be mistaken for several independent replications. The listed secondary p-values are unadjusted, and no multiplicity approach is reported.
Missing-data handling is another consequential part of interpretation. The primary analysis used LOCF for missing Week 8 measurements, carrying Week 4 data forward. This makes the rule explicit, but it does not remove uncertainty about the unobserved values. The registry does not report how many measurements were missing or whether results were tested under other assumptions.
Finally, the enrollment count and observed analysis-group counts do not come with a reported sample-size rationale. The planning illustrations based on the observed effect can help show how assumed effect size relates to planning requirements, but they cannot reveal the design assumptions used before the trial or establish observed power. These features make the record useful for understanding reported outcomes while also showing why a complete analysis plan and direct primary comparison matter.
14. 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 comparative result is not reported in the registry record. Although each arm has a least-squares mean change and a 95% confidence interval, there is no primary treatment difference, confidence interval for that difference, or primary p-value. This leaves the central superiority question without a reported direct statistical answer.
The efficacy arm is named KP2035 Group, while the study description names Xalacom. The arm description does not explain this label, so the relationship cannot be clarified from the registry record alone. The record also does not give detailed treatment administration, the full masking procedures, or the covariates and model specification for the least-squares means.
The primary analysis uses LOCF to replace missing Week 8 measurements with Week 4 values. The number of missing values, reasons for missingness, and sensitivity analyses are not reported. The listed enrollment is 300, but the primary arm counts are 144 and 145; the record does not explain the difference. A sample-size justification is also not reported.
The eight secondary outcomes cover related IOP measures, but no multiplicity adjustment or testing hierarchy is described. The unadjusted recalculated comparisons should therefore be regarded as limited evidence, particularly because the registry lists no reported secondary analyses. The record does not state whether the same missing-data handling was used for every secondary endpoint.
Safety information is limited to group counts, deaths, and a short list of serious-event terms. Follow-up was 8 weeks, and event-level detail and comparative safety analyses are not reported. These limitations constrain precision and scope; they do not establish that unreported procedures or analyses were or were not conducted.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study Comparing Xalacom And Xalatan In Patients With Primary Open Angle Glaucoma (POAG) Or Ocular Hypertension (OH). — NCT00383019.
- Registry record last updated 2021-09-08; status last verified 2021-08.
- Results first posted 2009-05-27.
- 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.
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18. Record Summary
This completed phase III study was randomized, double-masked, parallel-group, and lasted 8 weeks. It compared Xalacom and Xalatan in Japanese patients with primary open-angle glaucoma or ocular hypertension. The registry lists 300 enrolled participants.
The primary outcome was change in IOP from baseline to Week 8, reported as least-squares means with 95% confidence intervals. The KP2035 Group estimate was -2.59 mmHg and the Xalatan Group estimate was -1.62 mmHg. A direct primary comparison between groups is not reported in the registry record. Missing Week 8 primary measurements were handled using Week 4 values under LOCF.
Eight secondary outcomes are listed. Selected threshold comparisons were recalculated without adjustment for multiple testing; the registry does not report secondary analyses or a multiplicity strategy. Serious adverse events were recorded in 1 participant in the KP2035 Group and 2 in the Xalatan Group, with no deaths listed. The original sample-size justification, detailed statistical plan, and interim-analysis procedures are not reported in the registry record.