Study of the Safety and Efficacy of RVL-1201 in the Treatment of Acquired Blepharoptosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of the Safety and Efficacy of RVL-1201 in the Treatment of Acquired Blepharoptosis (NCT02436759), a randomized phase 3 study. The primary outcome is Mean Change in Number of Points Seen on the Leicester Peripheral Field Test (LPFT) in RVL-1201 Group vs. Vehicle Group.

2. Clinical Question

3. Trial Design

This was a randomized, quadruple-masked, parallel-group Phase 3 study of RVL-1201 for acquired blepharoptosis. The registry lists an enrollment of 140. It records the study as completed, with a start date of 2015-05 and primary completion in 2016-11. These dates describe the record’s study timeline; they do not establish when every participant was treated or followed.

The active arm received RVL-1201 Ophthalmic Solution 0.1%, one drop per eye once daily for 6 weeks. The comparator arm received the vehicle placebo on the same stated dosing schedule. A parallel-group design assigns participants to a treatment group and compares outcomes between groups rather than having each participant receive both assigned treatments. Randomization is intended to make treatment groups comparable on average, although the record does not report the sequence-generation or allocation-concealment procedures.

The registry describes the primary analysis population as the Intent-to-Treat population: randomized participants who received at least one dose, totaling 140 subjects. It also describes a Per-Protocol Population of 139 subjects, defined as the ITT population with no major protocol deviations. The record states that the primary endpoint was analyzed in the ITT population using Last Observation Carried Forward. Further details of the analysis, including how protocol deviations were classified, are not reported in the registry record.

The study’s stated purpose covered safety and efficacy, with additional assessment of safety and comfort during an extended dosing period of 6 weeks. The primary endpoint focused on change in Leicester Peripheral Field Test score. The registry also identifies mean change from baseline in Marginal Reflex Distance in the study eye as a secondary outcome, but numerical results for that outcome are not reported in the registry record. A sample-size justification, planned interim analyses, and a full statistical analysis plan are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-Treat (ITT) population: randomized who received at least one dose (total of 140 subjects). Per-Protocol Population (PPP): ITT population with no major protocol deviations (total of 139 subjects). ITT analysis was conducted for the primary endpoint, with Last Observation Carried Forward (LOCF) for missing data.

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.

Population: Intent to Treat (ITT) Population

6. Primary Endpoint

The registry lists the primary outcome as Mean Change in Number of Points Seen on the Leicester Peripheral Field Test (LPFT) in RVL-1201 Group vs. Vehicle Group, measured over Mean change from Baseline (Day 1, Hour 0) compared with Day 1, Hour 6 and Day 14, Hour 2.

The primary endpoint was mean change in the number of points seen on the Leicester Peripheral Field Test (LPFT), comparing RVL-1201 with vehicle. The record defines the LPFT Total Score as the number of points seen in the top 4 rows of the test. Its possible scores range from 0, meaning no points seen, to 35, meaning all points seen. The stated unit is points seen, and the endpoint is a continuous measure summarized by a mean and standard deviation.

The measurement is intended to quantify the portion of the visual field assessed by the test. A change from baseline expresses how the measured score at a follow-up assessment differs from a participant’s baseline score. Comparing change between randomized groups can describe whether the groups’ average trajectories differed during the measured period. That is a statistical description of the endpoint, not by itself an explanation of the cause or importance of a difference.

The record specifies baseline at Day 1, Hour 0, with comparisons to Day 1, Hour 6 and Day 14, Hour 2. Thus, the primary endpoint involves more than one post-baseline assessment. The registry record does not report numerical means, standard deviations, treatment contrasts, confidence intervals, or p-values for these comparisons. Without those results, the direction, magnitude, and precision of the observed changes cannot be described from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a continuous primary endpoint: change in LPFT points seen. Continuous outcomes are often summarized using a mean, which represents the arithmetic average, and a standard deviation, which describes the spread of observations around that average. Comparing group means can provide a concise summary, but interpretation also depends on the uncertainty of the estimated difference and on whether the analysis matches the study design. The numerical summaries and treatment contrast are not reported in the registry record.

What does a change-from-baseline comparison represent?

A change score is each participant’s follow-up measurement considered relative to that participant’s baseline measurement. A group’s mean change summarizes the average change within that group. The treatment comparison asks whether average changes differ between randomized groups. This is not the same as reporting a within-group change alone: improvement or decline within one arm does not by itself show that the arms differ. For the LPFT endpoint, the registry specifies baseline at Day 1, Hour 0 and assessments at Day 1, Hour 6 and Day 14, Hour 2.

When a study has multiple assessment times, each time-specific comparison addresses a distinct question. An analysis may estimate separate effects at each time, model measurements jointly, or designate one time as primary. The registry record names both follow-up times but does not report the precise statistical model, whether the comparisons were analyzed separately, or whether any time point was treated as more important than another. Those choices cannot be reconstructed from the endpoint title.

Why are both an estimate and its uncertainty needed?

An estimated difference indicates the direction and size of the observed contrast in the units of the outcome. A confidence interval conveys uncertainty around that estimate under the model and assumptions used. A narrow interval indicates greater precision than a wide interval, but neither width nor a point estimate alone establishes clinical importance. A p-value answers a different question about the compatibility of the data with a specified null hypothesis. General statistical practice treats these quantities as complementary rather than interchangeable. None of the primary comparison’s numerical estimates, confidence intervals, or p-values is reported in the registry record.

The endpoint is measured in points seen, with the LPFT Total Score defined as the number seen in the top 4 rows and a possible range from 0 to 35. The scale’s boundaries help explain what the measurement represents. They do not reveal where participants began, how scores changed, or how much the groups differed. Those require observed outcome data, which are not reported in the registry record.

What does the ITT population mean in this record?

The record defines the ITT population as randomized participants who received at least one dose, totaling 140 subjects, and says that the primary endpoint was analyzed in this population. In general, an intention-to-treat approach aims to preserve the comparison created by randomization by analyzing participants according to assigned group. However, the registry’s stated definition excludes randomized participants who received no dose, so readers should use the record’s exact population definition rather than assume a broader convention. Group-specific analysis counts are not reported in the registry record.

The registry also defines a Per-Protocol Population of 139 subjects, consisting of the ITT population with no major protocol deviations. A per-protocol analysis can describe outcomes among participants meeting protocol requirements, but it may no longer retain all the protections of randomization if exclusions are related to participant characteristics or outcomes. The record does not report a primary comparison for this population, the criteria used to identify major deviations, or whether results differed between populations.

How should Last Observation Carried Forward be understood?

The record states that the ITT primary analysis used Last Observation Carried Forward (LOCF), but the accompanying description ends before the full analysis details. In general, LOCF fills a missing follow-up value with that participant’s last observed value. This creates a complete analysis dataset under the method, but it does not make the missing measurement an actual observation. Its validity depends on assumptions about how outcomes would have evolved after the last measurement and why later data are missing. LOCF can misrepresent change when outcomes would otherwise continue to change, and it does not fully account for uncertainty due to imputation. The number and timing of missing observations, the reasons for missingness, and sensitivity analyses are not reported in the registry record.

What do planning calculations represent?

Planning sample sizes and observed study results answer different questions. A planning calculation estimates how many participants per arm might be needed under stated assumptions about the target effect, significance level, allocation, and statistical approximation. It is not a count of observed participants and is not a measure of the probability that a completed trial found an effect. The planning illustration associated with this trial is described as using a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect expressed as a fraction of the observed effect. Those are planning assumptions, not evidence that the original trial used them. The trial’s own sample-size justification is not reported in the registry record.

General statistical methods may also address multiplicity, meaning the increased chance of a false positive when several hypotheses are tested. The endpoint specifies more than one assessment time, and the record lists two outcome measures and two analyses. However, the registry record does not report a multiplicity adjustment or identify which comparisons, if any, were prespecified as confirmatory. It is therefore not possible to infer a statistical testing hierarchy from the listed outcomes alone.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint includes comparisons with baseline at two follow-up assessments: Day 1, Hour 6 and Day 14, Hour 2. The registry also lists a secondary outcome, mean change from baseline in Marginal Reflex Distance in the study eye, and records two outcome measures and two analyses. Testing multiple outcomes or times can raise multiplicity concerns because the chance of at least one apparently unusual result may increase as more comparisons are made. Whether and how that issue was handled is not reported in the registry record.

The record does not identify a testing hierarchy, adjustment procedure, or designation of a single primary time point among the listed comparisons. It would therefore be inappropriate to assume that a particular comparison was protected from multiplicity or that a nominal p-value, if encountered elsewhere, was adjusted. The numerical outcome findings themselves are not reported in the registry record.

For missing data, the registry states that the ITT primary analysis used Last Observation Carried Forward. In general, this procedure substitutes a participant’s last recorded value when a later measurement is missing. It relies on assumptions about the unobserved value and may not reflect the participant’s subsequent outcome. The available description does not report the amount or pattern of missingness, the reasons for missing measurements, or sensitivity analyses under alternative assumptions.

The analysis populations are defined as an ITT population of randomized participants who received at least one dose, totaling 140 subjects, and a Per-Protocol Population of 139 subjects without major protocol deviations. The record identifies ITT as the primary analysis population. Further detail about protocol deviations, exclusions, and population-specific results is not reported in the registry record.

11. 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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hyperparathyroidism (1.1%).

The registry lists serious adverse event counts by group, alongside the number at risk for those summaries. For RVL-1201, 94 were at risk and 1 was affected by a serious adverse event. For vehicle, 46 were at risk and 0 were affected. Deaths are listed as 0 in each group. The registry lists Hyperparathyroidism as a top serious term, with 1.1% shown alongside it.

These figures describe the recorded serious-event information; they do not by themselves establish whether an event was caused by treatment. The serious-event counts are small, and the record does not provide the event’s timing, clinical course, or assessment of relatedness. The listed percentage should be read as recorded, without inferring a denominator or recalculating it from the group counts.

The record also lists other adverse events: 20 affected in the RVL-1201 group, with 94 at risk, and 15 affected in the vehicle group, with 46 at risk. These counts are distinct from the serious adverse event counts. The registry record does not provide the full event-term breakdown, duration, severity distribution, or exposure-adjusted rates. Differences in the displayed counts should not be treated as a causal comparison without those details and an appropriate analysis.

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

This trial record establishes that RVL-1201 was compared with vehicle placebo in a randomized, quadruple-masked, parallel-group Phase 3 study of acquired blepharoptosis. It specifies a dosing schedule of one drop per eye once daily for 6 weeks and identifies change in LPFT points seen as the primary endpoint. It also identifies a secondary outcome involving Marginal Reflex Distance and records serious and other adverse-event counts.

Those design details do not supply the primary efficacy result. The registry record does not report the group mean changes, the between-group estimate, its confidence interval, or a p-value. The direction, magnitude, and precision of the primary comparison therefore cannot be determined from the registry record. The secondary outcome’s numerical result is likewise not reported in the registry record. No statement that a treatment did or did not work follows from the absence of those results.

The LPFT measures points seen in the top 4 rows, on a scale with possible scores from 0 to 35. A change on that measure is an observed score difference, and a group comparison would quantify the average contrast under the stated analysis. Whether a particular change is important to participants is a separate interpretation that requires context not reported in the registry record. Statistical evidence and practical importance are not interchangeable.

The safety counts indicate that serious adverse events were recorded in the RVL-1201 group and none in the vehicle group, with deaths listed as 0 in both groups. These counts alone do not establish cause, comparative risk, or the overall safety profile. The record’s adverse-event summary does not include all the context needed to interpret the events, including detail on timing and relatedness.

In general, a completed trial can still have incomplete registry results. Completion status, enrollment, and endpoint definitions do not substitute for effect estimates and uncertainty. The record supports a careful description of the design and the information it reports, while leaving the central numerical efficacy comparison unresolved.

13. Why This Trial Matters Statistically

Statistically, the record is useful for showing how the clinical question was framed: a randomized comparison of RVL-1201 and vehicle, with change in LPFT points seen as the primary endpoint. The endpoint definition and assessment times make clear what was intended to be measured and when. The record also identifies the populations used for analysis and names a missing-data method, which are important features for evaluating how a treatment comparison would be interpreted.

The record illustrates why endpoint definitions are not the same as results. A well-specified measure tells readers what an estimate would represent, but without the group summaries and treatment contrast it cannot show the observed direction or size of an effect. Precision also matters: a treatment estimate without an interval may leave substantial uncertainty, while a precise estimate can still require judgment about its relevance. For this trial, the primary numerical findings and their precision are not reported in the registry record.

The multiple assessment times and the presence of a secondary outcome make the analysis plan particularly relevant. When several outcomes or time points are examined, a stated approach to multiplicity helps readers understand how evidence was evaluated. The registry record does not report that approach, nor does it supply enough analysis detail to reconstruct it. This is a limitation of what can be interpreted from the record, rather than evidence that no such plan existed.

The population definitions and LOCF statement also demonstrate why missing-data and analysis-population choices deserve attention. ITT and per-protocol analyses can answer somewhat different questions, and imputation makes assumptions about unobserved measurements. The record gives some definitions but not enough detail to assess the impact of those choices.

Finally, the safety counts show why event summaries need context. Counts by group are descriptive, but event attribution, timing, and completeness affect how they should be understood. The statistical value of the registry record is thus both what it specifies and the boundaries it leaves: the design is described, while major efficacy and analysis details remain unreported.

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 most important limitation for interpreting the trial’s efficacy is that numerical primary outcome results are not reported in the registry record. Group means, standard deviations, treatment contrasts, confidence intervals, and p-values are absent from the record available for this analysis. The primary endpoint has two listed follow-up assessments, but no time-specific results or overall summary are reported. The secondary outcome’s numerical result is also not reported.

The analysis description is incomplete. The record says the primary endpoint was analyzed in the ITT population using Last Observation Carried Forward, but the population description ends mid-sentence and does not give a full statistical model. The amount and pattern of missing data, the reasons for missingness, and sensitivity analyses are not reported. Without those details, the implications of LOCF cannot be evaluated for this trial.

Although the record names an ITT population of 140 subjects and a Per-Protocol Population of 139 subjects, it does not report group-specific analysis counts or provide a primary result for the per-protocol population. It defines the latter by absence of major protocol deviations but does not give the criteria or identify the deviations. This limits assessment of exclusions and the relation between analysis populations.

The registry does not report the original sample-size justification, interim analyses, a full statistical analysis plan, or a multiplicity approach for the assessment times and listed outcomes. The planning illustration uses stated assumptions, but it should not be read as the original design rationale or as observed power. Safety results are also limited to summary counts and a listed serious-event term; timing, relatedness, severity detail, and a full event breakdown are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of the Safety and Efficacy of RVL-1201 in the Treatment of Acquired Blepharoptosis — NCT02436759.
• Registry record last updated 2021-10-28; status last verified 2021-10.
• Results first posted 2020-10-20.
• 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.

18. Record Summary

NCT02436759 is a completed randomized, quadruple-masked, parallel-group Phase 3 study of RVL-1201 versus vehicle placebo for acquired blepharoptosis. The registry lists enrollment of 140, a start date of 2015-05, and primary completion in 2016-11. The active and placebo regimens were one drop per eye once daily for 6 weeks.

The primary endpoint was change in LPFT points seen from baseline at Day 1, Hour 0, assessed at Day 1, Hour 6 and Day 14, Hour 2. The record defines the ITT population as randomized participants who received at least one dose, totaling 140 subjects, and the Per-Protocol Population as 139 subjects without major protocol deviations. The ITT primary analysis used Last Observation Carried Forward.

Primary and secondary numerical outcome results, the full statistical analysis plan, and the trial’s sample-size justification are not reported in the registry record. Serious adverse events were recorded for 1 of 94 at risk in the RVL-1201 group and 0 of 46 at risk in the vehicle group; deaths were listed as 0 in both groups.