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 Non-inferiority of PRO-122 Ophthalmic Solution vs KRYTANTEK Ofteno® in Glaucoma or Ocular Hypertension (CONFORTK) (NCT03257813), a randomized phase 3 study. The primary outcome is Intraocular Pressure (IOP).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03257813 |
| Phase | Phase 3 |
| Condition | Primary Open Angle Glaucoma, Ocular Hypertension |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Double |
| Enrollment | 60 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Laboratorios Sophia S.A de C.V. |
| Results posted | Yes |
2. Clinical Question
Population
People with primary open-angle glaucoma or ocular hypertension. The registry lists an enrollment of 60. The primary-outcome description says each eye was treated as a case number, so one participant could contribute two cases to the analysis.
Intervention
PRO-122 ophthalmic solution, used as one drop twice daily for 30 days in the study description.
Comparator
Krytantek Ofteno® ophthalmic solution, described as timolol 0.5%/brimonidine 0.2%/dorzolamide 2%, used as one drop twice daily for 30 days.
Primary question
Whether PRO-122 is non-inferior to Krytantek Ofteno® for intraocular pressure, assessed by change from baseline at day 30 and day 60. The registry describes comparisons between the two treatment sequences using measurements at the end of each period.
The study is registered as a phase 3, randomized, double-blind, multicenter, prospective crossover trial. In a crossover design, participants receive both treatments in different periods, with the sequence determining which treatment comes first. This makes the comparison depend not only on treatment but also on how period, sequence, and possible carryover effects are handled.
The registry record describes the clinical question and endpoint, but numerical intraocular-pressure results and a non-inferiority margin are not reported in the registry record. Therefore, the record as described does not establish whether the non-inferiority criterion was met or how precisely the treatment comparison was estimated.
3. Trial Design
The registry describes a randomized, double-blind, multicenter, prospective 2x2 crossover study. It lists the study as phase 3 and completed. The listed start date is 2016-04-01, and the primary completion date is 2017-03-01. The registry enrollment is 60.
In a crossover trial, participants receive each treatment in separate periods rather than remaining on a single assigned treatment throughout. The brief summary describes two sequences: one begins with Krytantek Ofteno® and then switches to PRO-122, while the other begins with PRO-122 and then switches to Krytantek Ofteno®. Each treatment period is described as 30 days. A 20-hour washout period is specified. The group descriptions also refer to testing after the initial treatment and a final visit at day 60.
The brief summary describes a planned sample size of one hundred patients, whereas the registry enrollment is 60. These are different figures in the record; the reason for the difference is not reported in the registry record. The enrollment figure alone does not explain how many participants completed each period or contributed data to a particular endpoint analysis.
Because each participant can receive both treatments, the comparison may use within-participant information. This can account for stable differences between participants, but period effects, sequence effects, and carryover need appropriate consideration. How these features were handled in the analysis is not reported in the registry record. The record also does not report details of the randomization procedure or the specific measures used to maintain masking.
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
| Stage | Group A | Group B |
|---|---|---|
| STARTED | 30 | 30 |
| COMPLETED | 24 | 27 |
| NOT COMPLETED | 6 | 3 |
Reasons for not completing this period:
| Reason | Group A | Group B |
|---|---|---|
| Protocol Violation | 6 | 3 |
Analysis population for the primary outcome, as defined in the registry: the statistical analysis was carried out taking into account each eye as a case number, therefore, each research subject could provide 2 cases.
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 | Group A | Group B | Total |
|---|---|---|---|---|
| Participants analysed | 30 | 30 | 60 | |
| Age, Continuous | years | 68.43 (SD 8.86) | 64.37 (SD 12.84) | 66.44 (SD 11.17) |
| Sex: Female, Male: Female | Participants | 24 | 21 | 45 |
| Sex: Female, Male: Male | Participants | 6 | 9 | 15 |
| Race/Ethnicity, Customized: hispanic | Participants | 30 | 30 | 60 |
6. Primary Endpoint
The registry lists the primary outcome as Intraocular Pressure (IOP), measured over Change from Baseline intraocular pressure at day 30 and 60..
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | mmHg |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is intraocular pressure (IOP), measured in millimeters of mercury (mmHg). The registry describes IOP as a continuous measure, reports the mean and standard deviation as the summary form, and identifies Goldmann applanation tonometry as the measurement method. The endpoint timeframe is change from baseline at day 30 and day 60.
IOP is used in this trial as a measure of the pressure inside the eye and as the study’s stated indicator of the effect of the two ophthalmic treatments. The registry description gives 11-21 mmHg as the normal intraocular-pressure range. That reference does not, by itself, determine the trial’s non-inferiority criterion or indicate how the treatment comparison turned out.
The record says that changes in IOP were compared between sequence 1 and sequence 2 using data obtained at the end of each treatment period, day 30 and day 60. It also says each eye was counted as a case number, so a participant could contribute two cases. The endpoint results, including the estimated treatment contrast and its uncertainty, are not reported in the registry record. The non-inferiority margin and the exact analysis model are also not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies IOP change at day 30 and day 60 as the primary endpoint and describes comparisons of the two treatment sequences. However, numerical IOP outcomes are not reported in the registry record. Without the observed treatment contrast and a measure of its uncertainty, the size, direction, and precision of the difference cannot be described from this record. The record therefore does not support a conclusion about whether the non-inferiority objective was achieved.
General statistical context: a non-inferiority assessment asks whether the results exclude a prespecified amount of disadvantage for the treatment being evaluated, according to a defined margin. Interpreting such an assessment ordinarily requires the margin, the estimated contrast, and an appropriate confidence interval or test result. The margin and those numerical results are not reported in the registry record. A statement of the study aim is not itself evidence that the criterion was met.
The crossover structure also matters when interpreting an estimate. Each participant may receive both treatments, and the comparison can depend on within-participant measurements. For that approach to be interpretable, the analysis must account appropriately for the structure of repeated measurements and any relevant period or sequence effects. The record describes the sequences and treatment periods but does not report the statistical model or how those effects were handled.
The primary-outcome description treats each eye as a case, allowing one participant to contribute two cases. Measurements from two eyes of the same person may be correlated. General statistical context: treating correlated observations as independent can make uncertainty appear smaller than it is, so the analysis should account for the dependence or justify another approach. The registry record does not report whether or how within-participant correlation was handled.
The registry lists enrollment as 60, while the brief summary describes a planned sample size of one hundred patients. The record does not explain the difference, nor does it report how many participants or eye-level cases were included in each endpoint analysis. Enrollment should not be read as a completed-analysis denominator.
The posted safety counts describe adverse events by treatment, but they do not substitute for the missing IOP outcome results. They also do not establish the comparative efficacy finding. Taken together, the available record describes the study question, design, endpoint, and selected safety counts, while leaving the primary treatment-effect estimate and its precision unreported.
9. Statistical Methods Explained
What does non-inferiority mean?
General statistical context: non-inferiority is a prespecified type of comparison. It asks whether the evidence rules out a disadvantage larger than an agreed margin for one treatment relative to another. The margin defines what difference would count as too large for the non-inferiority claim. It needs to be chosen and justified before interpreting the result; it cannot be inferred from the observed outcomes alone.
The registry states that the study aimed to demonstrate non-inferiority of PRO-122 versus Krytantek Ofteno®. The margin, its justification, the direction used for the contrast, and the prespecified decision rule are not reported in the registry record. The study aim should therefore be distinguished from evidence that the aim was met.
How should an estimate and confidence interval be read?
General statistical context: an estimated treatment contrast describes the observed difference between treatments on the endpoint scale. A confidence interval expresses the uncertainty around that estimate under the assumptions of the analysis. For a non-inferiority assessment, the interval is interpreted relative to the prespecified margin and direction. A narrow interval can indicate greater precision than a wide interval, but precision alone does not determine whether a non-inferiority criterion is met.
Numerical IOP contrasts, confidence intervals, and test results are not reported in the registry record. Consequently, the treatment difference and its precision cannot be evaluated from the record. No non-inferiority conclusion can be reconstructed from the endpoint definition or study aim alone.
Why does the crossover design affect the analysis?
General statistical context: crossover studies compare treatments across periods in the same participants. This can reduce the influence of stable differences between participants because each participant receives both treatments. But outcomes may also vary with time or period, and the effect of an earlier treatment may persist into a later period. Such persistence is called carryover. Randomizing treatment sequence helps balance some systematic differences, but the statistical analysis still needs to address the design’s structure.
The registry describes two sequences, 30-day treatment periods, and a 20-hour washout. It does not report the analysis model, whether period or sequence effects were tested or adjusted, or how possible carryover was assessed. A washout duration is a design detail, not by itself evidence that carryover was absent.
What is the implication of counting each eye as a case?
The primary-outcome description says each eye was considered a case number and that each participant could provide two cases. General statistical context: two eyes from one participant are repeated or clustered observations, not necessarily independent observations. Their measurements can share participant-level influences. An analysis that accounts for this correlation can produce uncertainty estimates that better reflect the data structure; an analysis that assumes independence may not. The registry does not report how the eye-level observations were modeled, or whether the analysis instead used another approach to account for participants contributing more than one case.
What do the sample-size assumptions describe?
The sample-size material is identified as a planning illustration computed from the observed effect, not as the trial’s own design. It specifies a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. For time-to-event outcomes, the description says the illustrations use total events; for other outcomes, it says participants per arm.
General statistical context: a planning illustration estimates the sample size associated with a chosen set of assumptions. It is not an observed measure of power for the completed study, and it does not establish that the trial was adequately powered for its actual analysis. The observed IOP effect, numerical planning results, original sample-size justification, and the trial’s own statistical plan are not reported in the registry record.
What can be concluded from the available reporting?
The registry provides design and endpoint descriptions, but it does not report the numerical primary-outcome results or the statistical details needed to evaluate the non-inferiority claim. It also does not report a statistical analysis plan, confidence-interval method, treatment-contrast model, or analysis population definition. Those omissions limit interpretation of both the estimated effect and its uncertainty; they do not establish that the analyses were not conducted.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists eight outcome measures and 22 analyses. It identifies visual acuity as a secondary outcome and specifies IOP change at day 30 and day 60 as the primary endpoint timeframe. The primary-outcome description also refers to comparisons by sequence and period. How the multiple outcomes, timepoints, or analyses were prioritized or handled statistically is not reported in the registry record.
General statistical context: when several outcomes, timepoints, or comparisons are examined, the chance of at least one apparently notable result can increase if each is interpreted without regard to the others. A prespecified hierarchy, adjustment procedure, or other multiplicity strategy can help clarify which findings are confirmatory and how uncertainty should be interpreted. The registry record does not report whether such a strategy was used.
Missing-data methods are not reported in the registry record. The record does not describe how missing measurements, withdrawals, incomplete treatment periods, or other unavailable endpoint observations were handled. It also does not report an analysis population definition, such as which randomized participants were included in the primary analysis.
The endpoint description counts each eye as a case, with a participant potentially contributing two cases. The analysis method for accounting for dependence between eyes is not reported in the registry record. Nor does the record report the number of participants or eye-level cases contributing to each outcome analysis. These omissions make it difficult to assess how complete the endpoint data were and how the reported uncertainty, if available elsewhere, should be interpreted.
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 |
|---|---|---|---|
| PRO-122 | 0 | 60 | 0.0% |
| Krytantek Ofteno® | 1 | 60 | 1.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| PRO-122 | 0 of 60 |
| Krytantek Ofteno® | 0 of 60 |
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 |
|---|---|
| PRO-122 | 12 of 60 |
| Krytantek Ofteno® | 8 of 60 |
Most frequent serious adverse event terms
| Event term | Organ system | PRO-122 | Krytantek Ofteno® |
|---|---|---|---|
| acute gastritis | Gastrointestinal disorders | 0 of 60 | 1 of 60 |
Most frequent non-serious adverse event terms
| Event term | Organ system | PRO-122 | Krytantek Ofteno® |
|---|---|---|---|
| rhinopharyngitis | Respiratory, thoracic and mediastinal disorders | 4 of 60 | 1 of 60 |
| pharyngitis tonsillitis | Gastrointestinal disorders | 2 of 60 | 1 of 60 |
| Dotted Keratopathy | Eye disorders | 0 of 60 | 3 of 60 |
| headache | General disorders | 2 of 60 | 0 of 60 |
| allergic Blepharokeratoconjunctivitis | Eye disorders | 2 of 60 | 0 of 60 |
| bacterial conjunctivitis | Eye disorders | 1 of 60 | 1 of 60 |
| Meniere syndrome exacerbated | General disorders | 1 of 60 | 0 of 60 |
| vertigo | Ear and labyrinth disorders | 1 of 60 | 0 of 60 |
| atopic dermatitis | Skin and subcutaneous tissue disorders | 0 of 60 | 1 of 60 |
| maxillary traumatism | Musculoskeletal and connective tissue disorders | 1 of 60 | 0 of 60 |
Serious events with the highest arm-level rate: acute gastritis (1.7%).
The registry reports serious adverse events for PRO-122 as 0 among 60 at risk and for Krytantek Ofteno® as 1 among 60 at risk. It reports other adverse events as 12 among 60 at risk for PRO-122 and 8 among 60 at risk for Krytantek Ofteno®. Deaths are reported as 0 for each treatment. Acute gastritis is listed as the top serious adverse-event term, with 1.7% reported.
These counts are organized by treatment exposure in a crossover study, where participants may receive both treatments. The treatment-group counts should therefore not be treated automatically as independent groups of different participants. The record does not describe the event definitions, event ascertainment procedures, severity classifications beyond the serious-event category, or the timing of events relative to treatment periods.
The counts describe what the registry reports; they do not, on their own, establish that one treatment caused an event or that the treatments differ in safety. The record does not report a statistical comparison or uncertainty estimates for these adverse-event counts. Serious-event counts are also distinct from the broader “other adverse events” counts.
12. What the Result Does, and Does Not, Mean
The registry record establishes that CONFORTK was a phase 3, randomized, double-blind crossover study comparing PRO-122 and Krytantek Ofteno® for IOP in people with primary open-angle glaucoma or ocular hypertension. It describes the treatment sequences, treatment periods, washout, measurement method, and primary endpoint timeframe. It also reports selected adverse-event counts.
It does not report the numerical IOP results, an estimated treatment contrast, a confidence interval, a p-value, or the non-inferiority margin. Those omissions mean the record does not show whether the study met its non-inferiority objective, how large any difference was, or how precise the estimate was. The study’s stated aim is not a result.
General statistical context: a non-inferiority conclusion depends on both the size and uncertainty of the treatment comparison relative to the prespecified margin. A finding that is compatible with little difference is not automatically proof of non-inferiority, particularly if the estimate is imprecise or the margin is not known. The registry information is insufficient to make that assessment.
The safety entries give counts by treatment, but they do not demonstrate a causal relationship or establish a comparative safety conclusion. The crossover structure also means that the reported at-risk counts cannot be assumed to represent separate participant groups. The registry does not supply the analysis details needed to interpret the counts as a treatment-effect estimate.
Finally, the registry enrollment of 60 differs from the brief summary’s planned sample size of one hundred patients. The reason for the difference and the numbers included in the endpoint analyses are not reported in the registry record. As a result, the record supports a description of the intended comparison and some reported safety observations, but not a quantitative conclusion about the primary treatment effect.
13. Why This Trial Matters Statistically
This trial is statistically notable for using a crossover design to compare two ophthalmic treatments. Because participants are described as receiving both treatments in different periods, the design can make within-participant comparisons possible. That structure can be informative, but it also requires careful treatment of period, sequence, and potential carryover effects. The registry record gives the design framework without reporting how those features entered the analysis.
The endpoint is also described at the eye level: each eye was counted as a case, and a participant could contribute two cases. This creates an important unit-of-analysis question. General statistical context: observations from the same person may be correlated, and an analysis should account for that dependence when estimating uncertainty. The method used is not reported in the registry record.
The study’s stated non-inferiority aim makes the margin and confidence interval especially important. Without the margin and numerical IOP results, readers cannot evaluate the boundary used for the decision or the precision of the treatment comparison. The record shows why a clear question and design are only part of the evidence needed to interpret a non-inferiority trial.
The difference between the listed enrollment and the planned sample size in the summary is another relevant reporting detail. It does not explain why the figures differ or how many observations entered each analysis. Together, these design and reporting features illustrate why endpoint definitions, analysis populations, and uncertainty measures matter alongside headline trial aims.
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.
Several trial-specific details needed for a full statistical assessment are not reported in the registry record. These include numerical IOP outcomes, the non-inferiority margin, the treatment-effect estimate and its uncertainty, the primary analysis model, and the decision rule for non-inferiority. Without these items, the primary comparison cannot be independently interpreted from the registry information described.
The crossover design makes analysis of period, sequence, and possible carryover relevant, but the record does not say how these were handled. It lists a 20-hour washout between periods, but does not report evidence about whether that duration was sufficient or how possible carryover was evaluated.
The primary endpoint treats each eye as a case, with the possibility that one participant contributes two cases. The record does not report how dependence between a participant’s eyes was addressed. It also does not provide the number of participants or cases analyzed at each timepoint, or the method used to handle missing measurements and incomplete periods.
The registry enrollment is 60, whereas the brief summary describes a planned sample size of one hundred patients. The reason for the difference is not reported. The original sample-size justification and trial-specific statistical analysis plan are also not reported in the registry record. These gaps limit assessment of the study’s planned precision and the relationship between the stated design and the analyses conducted.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Non-inferiority of PRO-122 Ophthalmic Solution vs KRYTANTEK Ofteno® in Glaucoma or Ocular Hypertension (CONFORTK) — NCT03257813.
- Registry record last updated 2019-12-09; status last verified 2019-11.
- Results first posted 2019-12-09.
- 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
CONFORTK is registered as a completed, phase 3, randomized, double-blind, multicenter, prospective 2x2 crossover study of PRO-122 and Krytantek Ofteno® in people with primary open-angle glaucoma or ocular hypertension. The registry lists enrollment of 60. Its primary endpoint is change from baseline in IOP at day 30 and day 60, measured by Goldmann applanation tonometry. The study description specifies 30-day treatment periods and a 20-hour washout.
The record describes the study’s non-inferiority aim and reports selected adverse-event counts. Numerical primary-outcome results, the non-inferiority margin, analysis details, missing-data methods, and the reason the listed enrollment differs from the planned sample size in the summary are not reported in the registry record.