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 Study to Evaluate Safety, Tolerability and Pharmacokinetics of rhNGF Eye Drops in Healthy Volunteers (NCT01744704), a randomized phase 1 study. The primary outcome is Changes in VAS Ocular Tolerability.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01744704 |
| Phase | Phase 1 |
| Condition | Healthy |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 74 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Dompé Farmaceutici S.p.A |
| Results posted | Yes |
2. Clinical Question
Population
Healthy male and female volunteers were eligible for this study. The primary outcome defines the safety population as subjects randomized and receiving a dose of study medication. The registry record does not report further eligibility details.
Intervention
The study assessed rhNGF eye drops at several concentrations, from 0.5 µg/mL through 180 µg/mL, in sentinel groups and in Part A or Part B. The descriptions include single-dose regimens and repeated dosing over 5 consecutive days.
Comparator
Placebo groups are listed for Part A and Part B. The registry record does not report a single pooled comparison or the allocation ratio for each part.
Primary question
The primary objective was to assess safety and tolerability after single and multiple ascending doses. The primary outcome was change in a global ocular discomfort VAS score. Its numerical results are not reported in the registry record, so the magnitude and precision of any differences between rhNGF and placebo cannot be described.
3. Trial Design
This was a Phase I, randomized, quadruple-masked, parallel study of rhNGF eye drops in healthy male and female volunteers. The registry lists enrollment of 74 and identifies Dompé Farmaceutici S.p.A as the sponsor. The study started in 2012-07, reached primary completion in 2013-02, and is recorded as completed.
The official title describes a combined single and multiple ascending dose study. The intervention descriptions distinguish sentinel groups, Part A, and Part B. Sentinel regimens list one 35 µL drop at 0.5 µg/mL, 5 µg/mL, or 20 µg/mL. Part A descriptions list three 35 µL drops at 4 h intervals at 20 µg/mL, 60 µg/mL, or 180 µg/mL, alongside placebo. Part B descriptions list three 35 µL drops at 4 h intervals per day during 5 consecutive days at 20 µg/mL, 60 µg/mL, or 180 µg/mL, alongside placebo.
The registry lists group descriptions and group sizes for the safety results, but it does not report the allocation ratio, randomization procedure, or operational details of masking. It also does not report the protocol for dose escalation or how decisions about moving between dose levels were made. The overall enrollment figure should not be treated as a substitute for the group-specific counts or for information about the population included in each outcome analysis.
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.
Only the first 6 of 12 groups are shown.
Overall Study
| Stage | rhNGF 0.5 µg/mL Sentinel | rhNGF 5 µg/mL Sentinel | rhNGF 20 µg/mL Sentinel | rhNGF 60 µg/mL Part A | rhNGF 20 µg/mL Part A | rhNGF 180 µg/mL Part A |
|---|---|---|---|---|---|---|
| STARTED | 3 | 3 | 3 | 6 | 6 | 7 |
| COMPLETED | 3 | 3 | 3 | 6 | 6 | 7 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Safety population: consisted of all subjects randomised into the study and receiving a dose of study medication.
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.
Only the first 6 of 12 groups are shown.
| Characteristic | Unit | rhNGF 0.5 µg/mL Sentinel | rhNGF 5 µg/mL Sentinel | rhNGF 20 µg/mL Sentinel | rhNGF 20 µg/mL Part A | rhNGF 60 µg/mL Part A | rhNGF 180 µg/mL Part A |
|---|---|---|---|---|---|---|---|
| Participants analysed | 3 | 3 | 3 | 6 | 6 | 7 | |
| Age, Continuous | years | 30 (SD 7) | 47 (SD 9.2) | 29 (SD 11.9) | 46 (SD 10) | 36 (SD 9.4) | 42 (SD 17.8) |
| Sex: Female, Male: Female | Participants | 2 | 2 | 1 | 1 | 1 | 3 |
| Sex: Female, Male: Male | Participants | 1 | 1 | 2 | 5 | 5 | 4 |
| Region of Enrollment: United Kingdom | participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Region of Enrollment: Switzerland | participants | 3 | 3 | 3 | 6 | 6 | 7 |
6. Primary Endpoint
The registry lists the primary outcome as Changes in VAS Ocular Tolerability, measured over Day -1, Day 1, Day 5, Day 15 (FU).
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | units on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was change in ocular tolerability measured with a visual analogue scale. The scale runs from 0, meaning no symptoms, to 100, meaning the worst possible discomfort. The global score covered foreign body sensation, burning or stinging, itching, pain, sticky feeling, blurred vision, and photophobia. The assessment was performed before any ophthalmic assessment at a study visit.
The registry describes the outcome as a mean with standard deviation and gives the unit as units on a scale. It lists Day -1, Day 1, Day 5, and Day 15 (FU) as the outcome timeframe, while its detailed description distinguishes assessment schedules across the study parts. Part 0 and Part A used Day -1, Day 1, Day 3, and Day 10 (FU); Part B used Day -1, Day 1, Day 5, and Day 15 (FU). The record says the outcome measure time points and data table refer to Part B. Follow-up refers to the participants’ last available assessment.
A patient-reported symptom score can capture discomfort that may not be represented by an examination finding. General statistical context: a mean describes the average score in a group, while a standard deviation describes variability among scores. Numerical mean and standard deviation results for this endpoint are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies ocular tolerability as the primary outcome but does not report numerical outcome results for the VAS scores. It therefore does not support a description of the observed mean scores, changes over time, or differences between rhNGF and placebo. No confidence intervals, p-values, or other numerical estimates for this endpoint are reported in the registry record. The record lists 6 outcome measures and 0 analyses.
The listed assessment schedule is not uniform across all study parts. The detailed description gives different visits for Part 0, Part A, and Part B, and notes that the outcome time points and data table refer to Part B. The general timeframe field separately lists Day -1, Day 1, Day 5, and Day 15 (FU). These schedule details matter when interpreting a change score: a comparison must refer to the same visit and study part, and a score at follow-up is not interchangeable with one at an earlier visit.
The safety results are presented by group. The record reports zero serious adverse events in every listed group, while non-serious adverse-event counts differ among groups. Those counts are descriptive. The registry record does not provide an inferential comparison of adverse-event rates, and the small group sizes mean that the counts alone do not precisely establish how common an event would be in a broader population. The record also does not report serious-event terms, and death counts are not reported in the registry record.
General statistical context: an estimate describes the observed data, and a confidence interval conveys how uncertain that estimate is under the analysis assumptions. Without numerical endpoint estimates and their uncertainty, it is not possible to judge whether apparent score changes are large or small relative to variation. Nor can a claim about statistical significance or comparative effect be drawn from the endpoint description alone.
The registry’s planning illustration is described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a stated fraction of the observed effect. Those assumptions describe a planning calculation, not evidence that the study had a particular achieved power. A trial’s enrollment and its observed outcome are different quantities; no sample-size justification for the original trial is reported in the registry record.
9. Statistical Methods Explained
The statistical information in the registry is limited. It identifies the primary endpoint as a continuous score summarized by a mean and standard deviation, gives the assessment schedule, and lists no analyses. Numerical primary-outcome results and an inferential analysis are not reported in the registry record. The concepts below explain how such data are generally interpreted; they do not describe an unreported analysis from this study.
What does a mean and standard deviation describe?
General statistical context: a mean is the arithmetic average of observed scores in a group. A standard deviation describes the spread of individual scores around that average. Two groups can have similar means but different variability, or different means with substantial overlap in their score distributions. The mean and standard deviation are descriptive summaries; on their own they do not establish whether a group difference is statistically distinguishable from random variation.
For a repeated symptom score, the assessment time matters. Comparing scores at the same scheduled visit preserves a like-for-like interpretation. The registry describes several schedules across study parts and says follow-up is each participant’s last available assessment. That definition does not give a single fixed follow-up time shared by everyone. Numerical results by visit and study part are not reported in the registry record.
What would an uncertainty interval add?
General statistical context: a confidence interval gives a range of estimates compatible with the observed data under a statistical model and its assumptions. It is useful because it conveys precision as well as the direction and size of an estimate. A narrow interval generally indicates greater precision than a wide one, but the interval still depends on the design, analysis, and assumptions. No confidence intervals for the primary outcome are reported in the registry record.
A p-value, if reported, would address how compatible the data are with a specified null hypothesis under the analysis assumptions. It would not measure the probability that a treatment is effective, nor would it describe the size or clinical importance of an effect. No p-value or test result for the primary endpoint is reported in the registry record. General statistical context: an analysis plan normally specifies the comparison, outcome time point, model, and handling of repeated measurements before results are examined. Those details are not reported in the registry record.
How should the planning illustration be understood?
The registry describes sample-size planning illustrations based on an observed effect, with two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. The illustration considers detecting a stated fraction of the observed effect. For outcomes other than time-to-event outcomes, the stated convention is participants per arm for 80% power or another displayed power target. These are planning illustrations, not observed trial results or observed power. The original study’s sample-size justification is not reported in the registry record.
General statistical context: a planning calculation asks what sample size might be needed under stated assumptions to detect a target effect with a chosen error rate and power. Its result depends on the target effect, variability, design, and analysis. It does not show that a completed study had that power, and it cannot replace an estimate with an uncertainty interval. The registry record’s description of the calculation does not supply an original protocol rationale.
Why does over-dispersion matter?
General statistical context: over-dispersion means that observed variability is greater than a statistical model expects. For count outcomes, this can make standard errors too small if a model assumes less variability than the data contain. The primary endpoint in this study is a continuous VAS score, and the registry describes it with a mean and standard deviation. The record does not report a model or an over-dispersion assessment; such an assessment should not be inferred from the endpoint description.
For a continuous outcome, the distribution of scores, missing observations, repeated measurements, and any baseline adjustment can affect the analysis and its uncertainty. The registry record does not report these analytic details. It is therefore not possible to determine whether the posted analysis used a particular model or adjustment. The listed outcome definition and summary measure explain what was intended to be assessed, but do not specify all methods needed to reproduce an analysis.
10. Multiplicity, Missing Data and Analysis Populations
The study assessed the primary VAS outcome at multiple time points, with schedules that differ by study part. Several dose levels and placebo groups are also listed. When many outcomes, visits, or comparisons are examined, the chance of at least one apparently unusual result can increase. General statistical context: multiplicity procedures can control this risk, but the method depends on which comparisons are considered confirmatory and how they are organized.
The registry record does not report a multiplicity adjustment, a hierarchy of comparisons, a prespecified primary visit, or an approach to repeated measurements. It lists 6 outcome measures and 0 analyses. The numerical primary-outcome results are not reported in the registry record, so it is not possible to assess how multiple visits or dose comparisons were handled in an analysis.
The primary outcome defines a safety population as all subjects randomized into the study and receiving a dose of study medication. The registry record does not report how many participants contributed VAS measurements at each visit, whether that population definition was applied to every outcome, or how missing observations were handled. Follow-up is defined as each participant’s last available assessment, but this does not describe a general missing-data method. No imputation strategy, sensitivity analysis, or reason for missingness is reported in the registry record.
These omissions limit reproducibility and make it difficult to judge whether reported summaries, if available elsewhere, would reflect all relevant participants and comparisons. They do not establish that a particular method was or was not used outside the registry record.
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 |
|---|---|---|---|
| rhNGF 0.5 µg/mL Sentinel | 0 | 3 | 0.0% |
| rhNGF 5 µg/mL Sentinel | 0 | 3 | 0.0% |
| rhNGF 20 µg/mL Sentinel | 0 | 3 | 0.0% |
| rhNGF 20 µg/mL Part A | 0 | 6 | 0.0% |
| rhNGF 60 µg/mL Part A | 0 | 6 | 0.0% |
| rhNGF 180 µg/mL Part A | 0 | 7 | 0.0% |
| Placebo Part A | 0 | 6 | 0.0% |
| rhNGF 20 µg/mL Part B | 0 | 12 | 0.0% |
| rhNGF 60 µg/mL Part B | 0 | 9 | 0.0% |
| rhNGF 180 µg/mL Part B | 0 | 9 | 0.0% |
| Placebo Part B | 0 | 10 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| rhNGF 0.5 µg/mL Sentinel | 0 of 3 |
| rhNGF 5 µg/mL Sentinel | 1 of 3 |
| rhNGF 20 µg/mL Sentinel | 1 of 3 |
| rhNGF 20 µg/mL Part A | 1 of 6 |
| rhNGF 60 µg/mL Part A | 0 of 6 |
| rhNGF 180 µg/mL Part A | 2 of 7 |
Most frequent non-serious adverse event terms
| Event term | Organ system | rhNGF 0.5 µg/mL Sentinel | rhNGF 5 µg/mL Sentinel | rhNGF 20 µg/mL Sentinel | rhNGF 20 µg/mL Part A | rhNGF 60 µg/mL Part A | rhNGF 180 µg/mL Part A |
|---|---|---|---|---|---|---|---|
| Abnormals sensation in eye | Eye disorders | 0 of 3 | 1 of 3 | 1 of 3 | 1 of 6 | 0 of 6 | 0 of 7 |
| Vision Blurred | Eye disorders | 0 of 3 | 0 of 3 | 0 of 3 | 1 of 6 | 0 of 6 | 0 of 7 |
| Conjunctivitis | Eye disorders | 0 of 3 | 0 of 3 | 0 of 3 | 1 of 6 | 0 of 6 | 0 of 7 |
| Eye irritation | Eye disorders | 0 of 3 | 0 of 3 | 0 of 3 | 0 of 6 | 0 of 6 | 1 of 7 |
| Photophobia | Eye disorders | 0 of 3 | 0 of 3 | 0 of 3 | 0 of 6 | 0 of 6 | 1 of 7 |
| Nasopharyngitis | Infections and infestations | 0 of 3 | 0 of 3 | 1 of 3 | 0 of 6 | 0 of 6 | 0 of 7 |
| Corneal staining | Investigations | 0 of 3 | 0 of 3 | 0 of 3 | 1 of 6 | 0 of 6 | 0 of 7 |
| Ligament sprain | Injury, poisoning and procedural complications | 0 of 3 | 0 of 3 | 0 of 3 | 0 of 6 | 0 of 6 | 1 of 7 |
| Eyelid irritation | Eye disorders | 0 of 3 | 0 of 3 | 0 of 3 | 0 of 6 | 0 of 6 | 0 of 7 |
| Eye pain | Eye disorders | 0 of 3 | 0 of 3 | 0 of 3 | 0 of 6 | 0 of 6 | 0 of 7 |
The registry lists serious and other adverse-event counts separately for each study group. Each listed group reports zero participants affected by serious adverse events. The registry does not list serious adverse-event terms. Death counts are not reported in the registry record.
The other adverse-event counts are not all zero. In Part B, the listed numbers of participants affected are 8 at 20 µg/mL, 6 at 60 µg/mL, 7 at 180 µg/mL, and 6 in the placebo group. In Part A, the corresponding counts are 1 at 20 µg/mL, 0 at 60 µg/mL, 2 at 180 µg/mL, and 3 in the placebo group. Sentinel groups report 0 at 0.5 µg/mL, 1 at 5 µg/mL, and 1 at 20 µg/mL.
These are descriptive counts of participants affected, not a statistical comparison or an estimate of risk beyond the listed groups. The group sizes are small, and the registry record does not report a comparative analysis of these counts. Zero reported serious events should be read as the observed registry count in each group, not as proof that serious events cannot occur.
12. What the Result Does, and Does Not, Mean
This record describes a Phase I study designed to assess safety, tolerability, and pharmacokinetics of single and multiple ascending doses of rhNGF eye drops in healthy volunteers. Its primary outcome was a global ocular discomfort score measured on a 100 mm VAS. The registry also reports adverse-event counts by group.
The primary endpoint’s numerical results are not reported in the registry record. There are no reported means, standard deviations, confidence intervals, or p-values for the VAS outcome in the information available for this record. As a result, the posted information does not establish the size, direction, or precision of change in ocular discomfort, or how scores compared between rhNGF and placebo groups.
The adverse-event entries show zero serious adverse events in each listed group, alongside non-serious adverse-event counts that vary by group. These descriptive data do not establish a comparative safety effect. The record does not report serious-event terms or death counts, and the group sizes are limited. The absence of a reported serious event in a group is not the same as evidence that an event is impossible or that a broader population would have the same experience.
General statistical context: results from an early-phase study can characterize observations under the study conditions, but an estimate should be interpreted alongside its uncertainty and the study population. The record concerns healthy volunteers, not a population defined by an eye condition. The registry entries do not support conclusions about effectiveness for treating a disease or about use outside the study setting. A complete interpretation of the primary outcome would require numerical results and information about the analysis, missing data, and comparison strategy, which are not reported in the registry record.
13. Why This Trial Matters Statistically
Early-phase clinical studies raise statistical questions that differ from those of a single, large comparative trial. This study combines sentinel dosing, Part A, and Part B, with several rhNGF concentrations and placebo groups. The registry describes both single-dose and repeated-dose regimens. These features make it important to know which groups and visits are being compared rather than treating every dose and time point as one common contrast.
The primary outcome is a symptom score measured repeatedly, and the assessment schedule differs across study parts. Reporting a mean and standard deviation can describe scores, but interpretation also depends on the visit, the study part, and uncertainty around any comparison. The record does not report numerical VAS results or analyses, making it impossible to assess those aspects from the registry record.
The adverse-event results illustrate why group-specific counts should be read with their group sizes and with caution. Zero serious events are recorded in each listed group, while other events are reported in both rhNGF and placebo groups. Such small-group descriptive counts are not a substitute for a precise comparative estimate.
The record’s planning description also highlights an important distinction: sample-size illustrations based on an observed effect are not evidence of observed power and are not the same as the original sample-size rationale. The registry does not report that original rationale or the statistical plan. Taken together, the trial is statistically informative as a record of an early-phase design and its stated measurement approach, while the missing primary-outcome results and analytic details constrain what can be concluded from the posted information.
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 limitation for interpreting the main outcome is that numerical VAS results are not reported in the registry record. Although the endpoint definition includes a mean and standard deviation, no values are available for the listed visits. The record also lists 0 analyses, so it does not provide a reported inferential comparison, uncertainty interval, or p-value for the primary outcome.
Assessment times differ among Part 0, Part A, and Part B. The general timeframe lists Day -1, Day 1, Day 5, and Day 15 (FU), while the detailed description gives Day -1, Day 1, Day 3, and Day 10 (FU) for Part 0 and Part A, and Day -1, Day 1, Day 5, and Day 15 (FU) for Part B. The record says the outcome time points and data table refer to Part B. This makes it especially important to identify the study part and visit when interpreting any result.
The registry does not report the randomization procedure, allocation ratio, dose-escalation decision process, analysis plan, multiplicity approach, or missing-data methods. It does not report the original sample-size justification. Although adverse-event counts are listed by group, serious-event terms are absent and death counts are not reported in the registry record. The study population consists of healthy volunteers, which also limits direct generalization to other populations.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study to Evaluate Safety, Tolerability and Pharmacokinetics of rhNGF Eye Drops in Healthy Volunteers — NCT01744704.
- Registry record last updated 2024-04-19; status last verified 2023-12.
- Results first posted 2019-09-09.
- 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
NCT01744704 is a completed Phase I, randomized, quadruple-masked, parallel study sponsored by Dompé Farmaceutici S.p.A. It enrolled 74 healthy male and female volunteers and assessed single and multiple ascending doses of rhNGF eye drops. The listed groups include sentinel regimens, Part A and Part B dose groups, and placebo groups.
The primary outcome was change in ocular tolerability measured with a VAS, described as a mean and standard deviation. Numerical VAS results and statistical analyses are not reported in the registry record. The safety listings report zero serious adverse events in each listed group, along with other adverse-event counts. Serious-event terms and death counts are not reported in the registry record.