Trial Outcomes & Findings for Clinical Investigation on the Use of Ophthalmic Solution Based on Sodium Hyaluronate in Treatment of Eye Discomfort (NCT NCT05777798)

Last Updated: 2026-01-07

Results Overview

The TFBUT will be performed after instillation of 5 microliters of 2% preservative-free sodium fluorescein solution into the inferior conjunctival cul-de-sac of each eye. The patient will be instructed to blink several times to thoroughly mix the fluorescein with the tear film. To achieve maximum fluorescence, the examiner should wait approximately 30 seconds after instillation before evaluating TFBUT. The TFBUT was measured by determining the time in seconds to tear break-up within 10 seconds maximum, and it was measured three time during the first minute after the instillation of fluorescein solution. The TFBUT value will be the average of 3 measurements.

Recruitment status

COMPLETED

Target enrollment

28 participants

Primary outcome timeframe

Evaluated at Visit 1 (baseline) and Visit 3 (day 35 ± 4 - study termination)

Results posted on

2026-01-07

Participant Flow

Subjects with signs and symptoms of ocular discomfort and ocular irritation resulting from ocular dryness / tear film alterations

Unit of analysis: one eye (the worst eye)

Participant milestones

Participant milestones
Measure	Hyalistil Bio PF 28 subjects were treated for 30 days with 4 daily instillations of Hyalistil Bio PF.
Overall Study STARTED	28 28
Overall Study COMPLETED	28 28
Overall Study NOT COMPLETED	0 0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Clinical Investigation on the Use of Ophthalmic Solution Based on Sodium Hyaluronate in Treatment of Eye Discomfort

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Hyalistil Bio PF n=28 worst eye 28 male and female subjects with signs and symptoms of ocular discomfort were treated for 30 days with 4 daily instillations of Hyalistil Bio PF.
Age, Categorical <=18 years	0 Participants n=37 Participants
Age, Categorical Between 18 and 65 years	18 Participants n=37 Participants
Age, Categorical >=65 years	10 Participants n=37 Participants
Age, Continuous	58.46 years STANDARD_DEVIATION 55.50 • n=37 Participants
Sex: Female, Male Female	20 Participants n=37 Participants
Sex: Female, Male Male	8 Participants n=37 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=37 Participants
Race (NIH/OMB) Asian	0 Participants n=37 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=37 Participants
Race (NIH/OMB) Black or African American	0 Participants n=37 Participants
Race (NIH/OMB) White	28 Participants n=37 Participants
Race (NIH/OMB) More than one race	0 Participants n=37 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=37 Participants
Region of Enrollment Italy	28 participants n=37 Participants
TFBUT (Tear Film Break Up Time)	5 Second STANDARD_DEVIATION 2.03 • n=37 Participants

PRIMARY outcome

Timeframe: Evaluated at Visit 1 (baseline) and Visit 3 (day 35 ± 4 - study termination)

Population: A total of 28 patients were screened and included in the FAS (ITT analysis) and in the Safety population. Three out of 28 patients had a major protocol deviation, one patient did not show up for the study termination visit, two patients did not meet the exclusion criteria "Taking drugs that may interfere with tear gland secretion (beta -blockers)". Thus, the PP population consisted of 25 patients.

Outcome measures

Outcome measures
Measure	Hyalistil Bio PF n=28 the worst eye 28 male and female subjects with signs and symptoms of ocular discomfort were treated for 30 days with 4 daily instillations of Hyalistil Bio PF.
Tear Film Break-up Time With Fluorescein (TFBUT) TFBUT at Visit 1 (Baseline)	5.00 Second Standard Deviation 2.03
Tear Film Break-up Time With Fluorescein (TFBUT) TFBUT at Visit 3 (Study termination)	13.46 Second Standard Deviation 5.83

SECONDARY outcome

Timeframe: Evaluated at Visit 1 (baseline), Visit 2 (day 14± 2) and Visit3 (day 35 ± 4 - study termination visit)

The NEI/Industry Workshop scale (1995) is an ophthalmological rating scale developed by the National Eye Institute (NEI, USA) to measure the degree of corneal and conjunctival staining after instillation of fluorescein or rose bengal/lissamine green. * The cornea is divided into 5 zones: Central, Superior, Inferior, Nasal, Temporal. Each zone is assigned a score from 0 to 3: 0 = no staining; 1 = mild; 2 = moderate; 3 = severe (Lower values=better outcomes - Total maximum cornea staining = 15). * The bulbar conjunctiva is divided into 6 areas: Superior nasal, Inferior nasal, Superior temporal, Inferior temporal, Superior (under the upper eyelid, less frequently assessed), Inferior (above the inferior fornix). The total maximum conjunctiva staing is 18. The total staining score is given by the sum of the corneal and conjunctival staining (Lower values=better outcomes - Min=0, Max=33).

Outcome measures

Outcome measures
Measure	Hyalistil Bio PF n=28 Participants 28 male and female subjects with signs and symptoms of ocular discomfort were treated for 30 days with 4 daily instillations of Hyalistil Bio PF.
Fluorescein Staining Total NEI Score at Visit 1 (baseline)	16.82 score on a scale Standard Deviation 5.48
Fluorescein Staining Total NEI Score at Visit 2	9.79 score on a scale Standard Deviation 3.45
Fluorescein Staining Total NEI Score at Visit 3 (Study Termination Visit)	5.18 score on a scale Standard Deviation 2.46

SECONDARY outcome

Timeframe: Evaluated at Visit 1 (baseline), Visit2 (day 14± 2) and Visit3 (35 ± 4 - study termination)

The SANDE questionnaire (Symptom Assessment in Dry Eye) is a very simple, validated tool to assess dry eye symptoms. It's based on two visual analog scale (VAS) questions that measure: 1) Frequency of symptoms (dry and irritated); 2) Severity of symptoms (dryness and irritation). Each question is scored by the patients on a 0-100 mm VAS line (0 = no symptoms, 100 = maximum symptoms), marking the point that they feel represents their perception of their current state. Data collected from the SANDE questionnaire were calculated by multiplying the frequency score by the severity score and obtaining the square root.

Outcome measures

Outcome measures
Measure	Hyalistil Bio PF n=28 Participants 28 male and female subjects with signs and symptoms of ocular discomfort were treated for 30 days with 4 daily instillations of Hyalistil Bio PF.
SANDE Total score severity: Visit 1 (baseline)	67.32 score on scale (millimeters) Standard Deviation 16.53
SANDE Total score severity: Study termination	26.43 score on scale (millimeters) Standard Deviation 22.15
SANDE Total score frequency: Visit 1 (baseline)	67.68 score on scale (millimeters) Standard Deviation 17.08
SANDE Total score frequency: Study termination	27.14 score on scale (millimeters) Standard Deviation 25.07

SECONDARY outcome

Timeframe: Evaluated at day 35 ± 4 of treatment

Population: Frequency missing = 1

To evaluate the degree of satisfaction of patients to the treatment we used the visual analogue scale (VAS) ranging from 0 to 100 mm in a horizontal line. Patients will be asked to place a vertical mark (on the horizontal line, from 0 to100 mm) to indicate the degree of satisfaction to the treatment, where: 0-10 mm=no: 1-30 mm=very mild; 31-50 mm=mild; 51-70 mm=moderate; 71-90 mm=strong; 91-100 mm=very strong. Patients were asked to rate their level of satisfaction answering each of these questions: 1) "I feel satisfied using this treatment? ''; 2) "With this treatment, I have a feeling of freshness?"; 3) "With this treatment, I have a feeling of relief?"; 4) "This treatment contributed to reduce my pain due to eye dryness?''; 5) "This treatment is comfortable? '' The response results are expressed in frequency and percentage of the total for each of the questions in the categories "very mild", "mild", "moderate", "strong" and "very strong".

Outcome measures

Outcome measures
Measure	Hyalistil Bio PF n=27 Participants 28 male and female subjects with signs and symptoms of ocular discomfort were treated for 30 days with 4 daily instillations of Hyalistil Bio PF.
Evaluation of the Degree of Satisfaction to the Treatment Reported by Patients Through the Use of the Visual Analogue Scale (VAS). 1) "I feel satisfied using this treatment?" · very mild	0 Participants
Evaluation of the Degree of Satisfaction to the Treatment Reported by Patients Through the Use of the Visual Analogue Scale (VAS). 1) "I feel satisfied using this treatment?" · mild	4 Participants
Evaluation of the Degree of Satisfaction to the Treatment Reported by Patients Through the Use of the Visual Analogue Scale (VAS). 1) "I feel satisfied using this treatment?" · moderate	3 Participants
Evaluation of the Degree of Satisfaction to the Treatment Reported by Patients Through the Use of the Visual Analogue Scale (VAS). 1) "I feel satisfied using this treatment?" · strong	12 Participants
Evaluation of the Degree of Satisfaction to the Treatment Reported by Patients Through the Use of the Visual Analogue Scale (VAS). 1) "I feel satisfied using this treatment?" · very strong	8 Participants
Evaluation of the Degree of Satisfaction to the Treatment Reported by Patients Through the Use of the Visual Analogue Scale (VAS). 2) "With this treatment, I have a feeling of freshness?" · very mild	2 Participants
Evaluation of the Degree of Satisfaction to the Treatment Reported by Patients Through the Use of the Visual Analogue Scale (VAS). 2) "With this treatment, I have a feeling of freshness?" · mild	1 Participants
Evaluation of the Degree of Satisfaction to the Treatment Reported by Patients Through the Use of the Visual Analogue Scale (VAS). 2) "With this treatment, I have a feeling of freshness?" · moderate	3 Participants
Evaluation of the Degree of Satisfaction to the Treatment Reported by Patients Through the Use of the Visual Analogue Scale (VAS). 2) "With this treatment, I have a feeling of freshness?" · strong	14 Participants
Evaluation of the Degree of Satisfaction to the Treatment Reported by Patients Through the Use of the Visual Analogue Scale (VAS). 2) "With this treatment, I have a feeling of freshness?" · very strong	7 Participants
Evaluation of the Degree of Satisfaction to the Treatment Reported by Patients Through the Use of the Visual Analogue Scale (VAS). 3) "With this treatment, I have a feeling of relief?" · very mild	1 Participants
Evaluation of the Degree of Satisfaction to the Treatment Reported by Patients Through the Use of the Visual Analogue Scale (VAS). 3) "With this treatment, I have a feeling of relief?" · mild	2 Participants
Evaluation of the Degree of Satisfaction to the Treatment Reported by Patients Through the Use of the Visual Analogue Scale (VAS). 3) "With this treatment, I have a feeling of relief?" · moderate	2 Participants
Evaluation of the Degree of Satisfaction to the Treatment Reported by Patients Through the Use of the Visual Analogue Scale (VAS). 3) "With this treatment, I have a feeling of relief?" · strong	15 Participants
Evaluation of the Degree of Satisfaction to the Treatment Reported by Patients Through the Use of the Visual Analogue Scale (VAS). 3) "With this treatment, I have a feeling of relief?" · very strong	7 Participants
Evaluation of the Degree of Satisfaction to the Treatment Reported by Patients Through the Use of the Visual Analogue Scale (VAS). 4) "This treatment contributed to reduce my pain due to eye dryness?'' · very mild	0 Participants
Evaluation of the Degree of Satisfaction to the Treatment Reported by Patients Through the Use of the Visual Analogue Scale (VAS). 4) "This treatment contributed to reduce my pain due to eye dryness?'' · mild	2 Participants
Evaluation of the Degree of Satisfaction to the Treatment Reported by Patients Through the Use of the Visual Analogue Scale (VAS). 4) "This treatment contributed to reduce my pain due to eye dryness?'' · moderate	4 Participants
Evaluation of the Degree of Satisfaction to the Treatment Reported by Patients Through the Use of the Visual Analogue Scale (VAS). 4) "This treatment contributed to reduce my pain due to eye dryness?'' · strong	14 Participants
Evaluation of the Degree of Satisfaction to the Treatment Reported by Patients Through the Use of the Visual Analogue Scale (VAS). 4) "This treatment contributed to reduce my pain due to eye dryness?'' · very strong	7 Participants
Evaluation of the Degree of Satisfaction to the Treatment Reported by Patients Through the Use of the Visual Analogue Scale (VAS). 5) "This treatment is comfortable? '' · very mild	0 Participants
Evaluation of the Degree of Satisfaction to the Treatment Reported by Patients Through the Use of the Visual Analogue Scale (VAS). 5) "This treatment is comfortable? '' · mild	2 Participants
Evaluation of the Degree of Satisfaction to the Treatment Reported by Patients Through the Use of the Visual Analogue Scale (VAS). 5) "This treatment is comfortable? '' · moderate	2 Participants
Evaluation of the Degree of Satisfaction to the Treatment Reported by Patients Through the Use of the Visual Analogue Scale (VAS). 5) "This treatment is comfortable? '' · strong	11 Participants
Evaluation of the Degree of Satisfaction to the Treatment Reported by Patients Through the Use of the Visual Analogue Scale (VAS). 5) "This treatment is comfortable? '' · very strong	12 Participants

SECONDARY outcome

Timeframe: Baseline (Visit 1) and Study Termination Visit (Day 35 ± 4)

Quality of life was assessed using the Dry Eye-Related Quality of Life Score (DEQS) questionnaire, which includes 15 items grouped into two subscales: Symptom Burden (6 items) and Impact on Daily Life (9 items). Each item is scored on a 0 to 4 scale, with higher scores indicating worse symptoms. Subscale scores range from 0 to 24 and 0 to 36, respectively. A total DEQS score was calculated by summing all item scores and converting the raw total to a 0-100 scale, where lower scores indicate better quality of life.

Outcome measures

Outcome measures
Measure	Hyalistil Bio PF n=28 Participants 28 male and female subjects with signs and symptoms of ocular discomfort were treated for 30 days with 4 daily instillations of Hyalistil Bio PF.
Dry Eye-Related Quality of Life (DEQS Total Score) DEQS Summary score - Visit 1 baseline	53.87 score on a scale Standard Deviation 13.44
Dry Eye-Related Quality of Life (DEQS Total Score) DEQS Summary score - Study Termination V	24.08 score on a scale Standard Deviation 17.13
Dry Eye-Related Quality of Life (DEQS Total Score) DEQS Bothersome Ocular Symptoms subscale Visit 1 baseline	56.37 score on a scale Standard Deviation 13.72
Dry Eye-Related Quality of Life (DEQS Total Score) DEQS Bothersome Ocular Symptoms subscale Study Termination Visit	23.25 score on a scale Standard Deviation 16.70
Dry Eye-Related Quality of Life (DEQS Total Score) DEQS Impact on Daily Life subscale Visit 1 baseline	51.96 score on a scale Standard Deviation 17.26
Dry Eye-Related Quality of Life (DEQS Total Score) DEQS Impact on Daily Life subscale Study Termination Visit	23.81 score on a scale Standard Deviation 19.31

SECONDARY outcome

Timeframe: Evaluated at day 14 ± 2 of treatment (Visit 2) and day 35 ± 4 of treatment (Visit 3 - Study termination)

Outcome measures

Outcome measures
Measure	Hyalistil Bio PF n=28 the worst eye 28 male and female subjects with signs and symptoms of ocular discomfort were treated for 30 days with 4 daily instillations of Hyalistil Bio PF.
Tear Film Break-up Time With Fluorescein (TFBUT) TFBUT at Visit 2	10.27 Second Standard Deviation 5.01
Tear Film Break-up Time With Fluorescein (TFBUT) TFBUT at Visit 3 (Study termination)	13.46 Second Standard Deviation 5.83

SECONDARY outcome

Timeframe: Evaluated at day 14± 2 and 35 ± 4 of treatment versus baseline

The ETDRS chart uses a standardized, logarithmic letter chart (Sloan letters, 5 per line). Results can be reported as either logMAR values or letter scores, in our study we used the "Line method" (the smallest line where at least 3 of 5 letters are correctly read), while Visual Acuity was expressed as Snellen Distance Equivalent (meters); in the Italian decimal system, 10/10 corresponds to 6/6" or 0.0 logMAR. To maintain consistency across clinics and trials, the examination conditions were standardized as follow: Test distance 4 meters, Chart uniformly illuminated (\~85 cd/m² luminance), with a white, high contrast (≥ 90%) background, the Best corrected visual acuity (BCVA) was measured with trial frame lenses. The BCVA was testing monocularly, while the patient was encouraged to read as many letters as possible, even if guessing. When the patient misses a prespecified number (3 or more errors in a row), testing stops.

Outcome measures

Outcome measures
Measure	Hyalistil Bio PF n=28 Participants 28 male and female subjects with signs and symptoms of ocular discomfort were treated for 30 days with 4 daily instillations of Hyalistil Bio PF.
Best Corrected Visual Acuity (BCVA) BCVA Visit 1 (Baseline) · BCVA = 0.6/10 (logMAR 1.2)	1 Participants
Best Corrected Visual Acuity (BCVA) BCVA Visit 1 (Baseline) · BCVA = 6/10 (logMAR 0.2)	2 Participants
Best Corrected Visual Acuity (BCVA) BCVA Visit 1 (Baseline) · BCVA = 9/10 (logMAR 0.05)	2 Participants
Best Corrected Visual Acuity (BCVA) BCVA Visit 1 (Baseline) · BCVA = 10/10 (logMAR 0.0)	23 Participants
Best Corrected Visual Acuity (BCVA) BCVA Visit 2 · BCVA = 0.6/10 (logMAR 1.2)	1 Participants
Best Corrected Visual Acuity (BCVA) BCVA Visit 2 · BCVA = 6/10 (logMAR 0.2)	2 Participants
Best Corrected Visual Acuity (BCVA) BCVA Visit 2 · BCVA = 9/10 (logMAR 0.05)	2 Participants
Best Corrected Visual Acuity (BCVA) BCVA Visit 2 · BCVA = 10/10 (logMAR 0.0)	23 Participants
Best Corrected Visual Acuity (BCVA) BCVA Study Termination Visit · BCVA = 0.6/10 (logMAR 1.2)	1 Participants
Best Corrected Visual Acuity (BCVA) BCVA Study Termination Visit · BCVA = 6/10 (logMAR 0.2)	2 Participants
Best Corrected Visual Acuity (BCVA) BCVA Study Termination Visit · BCVA = 9/10 (logMAR 0.05)	1 Participants
Best Corrected Visual Acuity (BCVA) BCVA Study Termination Visit · BCVA = 10/10 (logMAR 0.0)	24 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Study Termination Visit (Day 35 ± 4)

Population: One patient did not show up to study termination visit

Safety was assessed using the Investigator Global Assessment of Safety (IGAS), a 4-point categorical scale where 1 = very good safety, 2 = good safety, 3 = moderate safety, and 4 = poor safety. IGAS was evaluated at the Study Termination Visit and summarized by reporting the number and percentage of participants in each category.

Outcome measures

Outcome measures
Measure	Hyalistil Bio PF n=27 Participants 28 male and female subjects with signs and symptoms of ocular discomfort were treated for 30 days with 4 daily instillations of Hyalistil Bio PF.
Investigator Global Assessment of Safety (IGAS) Point scale 1 (very good safety)	27 Participants
Investigator Global Assessment of Safety (IGAS) Point scale 2 (good safety)	0 Participants
Investigator Global Assessment of Safety (IGAS) Point scale 3 (moderate safety)	0 Participants
Investigator Global Assessment of Safety (IGAS) Point scale 4 (poor safety)	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (Visit 1), Visit 2 (Day 14 ± 2), and Study Termination Visit (Day 35 ± 4)

Intraocular pressure (IOP) was measured in mmHg using Goldmann applanation tonometry after topical anesthesia with unpreserved 0.4 percent oxybuprocaine hydrochloride. IOP was assessed at three pre-specified study visits: baseline (Visit 1), Visit 2 during treatment, and the Study Termination Visit. Results were summarized by visit for all participants included in the intention-to-treat population.

Outcome measures

Outcome measures
Measure	Hyalistil Bio PF n=28 Participants 28 male and female subjects with signs and symptoms of ocular discomfort were treated for 30 days with 4 daily instillations of Hyalistil Bio PF.
Change in Intraocular Pressure (IOP) IOP - Visit 1	12.86 millimeters of mercury Standard Deviation 2.00
Change in Intraocular Pressure (IOP) IOP - Visit 2	12.82 millimeters of mercury Standard Deviation 1.44
Change in Intraocular Pressure (IOP) IOP - Visit 3 Study termination Visit	12.61 millimeters of mercury Standard Deviation 1.32

OTHER_PRE_SPECIFIED outcome

Timeframe: During the treatment period, assessed at Study Termination Visit (Day 35 ± 4)

Treatment compliance was assessed during the treatment period by counting returned single-dose containers and boxes at the Study Termination Visit. Compliance was calculated as the percentage of prescribed doses administered relative to planned doses for each participant. Participants were categorized into predefined compliance categories (\<50%, 50-80%, \>80%) for reporting purposes.

Outcome measures

Outcome measures
Measure	Hyalistil Bio PF n=28 Participants 28 male and female subjects with signs and symptoms of ocular discomfort were treated for 30 days with 4 daily instillations of Hyalistil Bio PF.
Treatment Compliance Rate < 50% = Poor Compliance	1 Participants
Treatment Compliance Rate 50-80% = Moderate Compliance	2 Participants
Treatment Compliance Rate > 80% = Good Compliance	25 Participants

Adverse Events

Hyalistil Bio PF

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Clinical Development

SIFI SpA

Phone: 00390957922111

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60