Bacterial Conjunctivitis, Ophthalmological Agent Toxicity
Conditions
Brief summary
This is a phase I clinical study evaluating the safety and tolerability of PRO-231 ophthalmic solution through the incidence of unexpected adverse events, incidence of conjunctival hyperemia and chemosis, changes in Best Corrected Visual Acuity (BCVA), changes in ocular surface integrity, compared to VIGAMOXI®.
Detailed description
This is a Phase I, controlled, comparative, parallel-group, single-blind, single-center, controlled clinical trial. The variables to be evaluated include: Primary (safety): * Incidence of unexpected adverse events related to the interventions * Incidence of conjunctival hyperemia and chemosis * Changes in Best Corrected Visual Acuity (BCVA) assessed with Snellen chart * Changes in ocular surface integrity using fluorescein staining, using the standard Oxford scale. Primary (tolerability): \- Changes in the ocular comfort index (OCI) score Secondary (safety): \- Incidence of unexpected adverse events related to the interventions(excluding conjunctival hyperemia and/or chemosis). Secondary (tolerability): \- Presence of other ocular symptoms (burning, foreign body sensation, pruritus and lacrimation).
Interventions
DRUGPRO-231
Moxifloxacin 0.5% Ophthalmic solution.
DRUGVIGAMOXI®
Moxifloxacin 0.5% Ophthalmic solution.
Sponsors
Laboratorios Sophia S.A de C.V.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Single-blind
Intervention model description
Phase I, controlled, comparative, parallel-group, single-blind, single-center, controlled clinical trial.
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Having the ability to voluntarily give their signed informed consent. * Ophthalmologically and clinically healthy subjects. * Being able to and willing to comply with scheduled visits, treatment plan, and other study procedures. * Age between 18 to 45 years. * Male or female gender. * Women of childbearing potential who have not undergone Bilateral Tubal Occlusion (BTO \[Tubal Ligation\]), hysterectomy, or bilateral oophorectomy must ensure continuation (initiated ≥ 30 days prior to signing the informed consent form \[ICF\]) of the use of a hormonal contraceptive method or intrauterine device (IUD) during the study period. * Best corrected visual acuity (BCVA) of 20/30 or better in both eyes. * Corneal staining ≤ grade I on the Oxford Scale. * Having an intraocular pressure ≥ 10 and ≤ 21 mmHg.
Exclusion criteria
* History of hypersensitivity to fluoroquinolones, steroid anti-inflammatories, or any of the components of the drugs under investigation. * Use of ophthalmic medications from any pharmacological group. * Use of medications by any other route of administration. * Use of non-steroidal anti-inflammatory drugs, steroid anti-inflammatory drugs, or antibiotics by any route of administration in the last 30 days. * History of eye surgery in the last 6 months. * Use of contact lenses for a period less than two weeks prior to the start of the study, and during the intervention period of this study. * In the case of women: being pregnant, breastfeeding, or planning to become pregnant within the study period. * Having participated in any clinical research study 30 days prior to inclusion in this study. * Having previously participated in this same study. * History of any chronic-degenerative disease, including Diabetes Mellitus or Systemic Arterial Hypertension. * Diagnosis of glaucoma or ocular hypertension. * Known diagnosis of liver or heart disease. * Presenting active inflammatory or infectious disease at the time of entry into the study. * Presenting unresolved lesions or traumas at the time of entry into the study. * Having been subjected to non-ophthalmological surgical procedures in the last 3 months. * Being or having an immediate family member (e.g., spouse, parent/legal guardian, sibling, or child) who is an employee of the research site or the sponsor, and who directly participates in this study. * Active smoking (specified as the consumption of cigarettes regardless of the amount and frequency, 4 weeks prior to study inclusion and during the intervention period of this study). * Active alcoholism (specified as the consumption of alcoholic beverages, regardless of the amount and frequency, 72 hours prior to study inclusion and during the intervention period of this study). Elimination Criteria * Withdrawal of their consent to participate in the study (informed consent form). * Occurrence of a serious adverse event, whether related or not to the interventions, that in the opinion of the principal investigator (PI) and/or the sponsor, could affect the patient's fitness to safely continue with the study procedures. * Non-tolerability or hypersensitivity to any of the compounds used during the tests -(fluorescein, tetracaine). * Non-tolerability or hypersensitivity to any of the drugs under investigation. * Adherence \< 80% determined by the subject's diary and corroborated by the final weight of the research products (RP) compared to the initial weight.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Conjunctival Hyperemia | Days 0 (Basal Visit), 3 (Visit 1), and 8 (Final Visit) | Any signs of conjunctival hyperemia in between interventions. |
| Number of Patients With Any Changes in Grade Measurement of the Integrity of the Ocular Surface (Fluorescein Staining) | Days 0 (Basal Visit), Days 3 (Visit 1) and 8 (Final Visit) | Number of patients with any changes in the integrity of the ocular surface using fluorescein staining and evaluated through the Oxford scale compared to baseline. The standard Oxford scale for fluorescein staining has the following criteria: Grade 0- Equal to or less than panel A; Grade I- Equal to or less than panel B, greater than panel A; Grade II- Equal to or less than panel C, greater than panel B; Grade III- Equal or less than panel D, greater than panel C; Grade IV- Equal or less than panel E, greater than panel D; Grade V- Greater than panel E. |
| Changes in the Ocular Comfort Index (OCI) Score Between Interventions. | Days 0 (Basal Visit), and 8 (Final Visit) | The Ocular Comfort Index is a questionnaire designed to measure ocular surface irritation. It assesses symptoms related to comfort in cases of ocular surface disorders. The Ocular Comfort Index is composed of 12 items that assess the frequency and intensity symptoms. Each item is scored on a scale from 0 to 6 (never to always, or absent to severe). The total score becomes a linear continuous interval scale, which ranges from 0 (least symptomatic) to 100 (most symptomatic). The questionnaire was administered to each research subject, allowing them to respond calmly without any pressure and/or coercion. The results were collected using the Ocular Comfort Index calculator \[1\], obtaining a logit score and a 0-100 scale score for each subject. \[1\].- M. E. Johnson, Measurement of Ocular Surface Irritation on a Linear Interval Scale with the Ocular Comfort Index, Investigative Ophthalmology & Visual Science, vol. 48, nº 10, 2007. |
| Incidence of Unexpected Adverse Events Related to the Interventions | Days 0 (Basal Visit), 3 (Visit 1), 8 (Final Visit) and 12 (Safety Call) | Any unfavorable medical condition affecting the subject after the administration of the investigation product, related to such intervention. Adverse events where inquired and evaluated in every time point specified in the time frame, however, the final number of adverse events reported throught the entire study was evaluated for each group. |
| Changes in Best Corrected Visual Acuity (BCVA) | Days 0 (Basal Visit), Days 3 (Visit 1) and 8 (Final Visit) | The BCVA will be evaluated through Snellen chart. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Assess the Tolerability of PRO-231 Ophthalmic Solution | Days 3 (Visit 1), 8 (Final Visit) | To assess the tolerability of PRO-231 ophthalmic solution applied to the ocular surface, in healthy volunteers, versus VIGAMOXI®, by means of: Presence of ocular symptoms (burning, foreign body sensation, pruritus and lacrimation) between interventions. |
| Incidence of Unexpected Adverse Events (Excluding Conjunctival Hyperemia and Chemosis) | Days 3 (Visit 1), 8 (Final Visit) and 12 (Safety Call) | Any unfavorable medical condition affecting the subject after the administration of the investigation product, related to such intervention, excluding conjunctival hyperemia and chemosis. Unexpected adverse events where inquired and evaluated in every time point specified in the time frame, however, the final number of adverse events reported throught the entire study was evaluated for each group. |
Countries
Mexico
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PRO-231 * PRO-231: Moxifloxacin 0.5% Ophthalmic solution.
* Dosage: 1 drop every 6 hours (3 daily applications \[TID\], in the right eye).
* Route of administration: Topical ophthalmic.
PRO-231: Moxifloxacin 0.5% Ophthalmic solution. | 18 |
| VIGAMOXI® * VIGAMOXI® :Moxifloxacin 0.5% Ophthalmic Solution.
* Dosage: 1 drop every 6 hours (3 daily applications \[TID\], in the right eye).
* Route of administration: Topical ophthalmic.
VIGAMOXI®: Moxifloxacin 0.5% Ophthalmic solution. | 19 |
| Total | 37 |
Baseline characteristics
| Characteristic | PRO-231 | VIGAMOXI® | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants | 19 Participants | 37 Participants |
| Age, Continuous | 23.55 years STANDARD_DEVIATION 4.89 | 25.79 years STANDARD_DEVIATION 6.21 | 24.76 years STANDARD_DEVIATION 5.69 |
| Race/Ethnicity, Customized Hispanic | 18 Participants | 19 Participants | 37 Participants |
| Region of Enrollment Mexico | 18 Participants | 19 Participants | 37 Participants |
| Sex: Female, Male Female | 6 Participants | 11 Participants | 17 Participants |
| Sex: Female, Male Male | 12 Participants | 8 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 19 |
| other Total, other adverse events | 3 / 18 | 9 / 19 |
| serious Total, serious adverse events | 0 / 18 | 0 / 19 |
Outcome results
Primary
Changes in Best Corrected Visual Acuity (BCVA)
The BCVA will be evaluated through Snellen chart.
Time frame: Days 0 (Basal Visit), Days 3 (Visit 1) and 8 (Final Visit)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PRO-231 | Changes in Best Corrected Visual Acuity (BCVA) | Day 0 (Basal Visit) | -0.03 Best Corrected Visual Acuity (LogMar) | Standard Deviation 0.06 |
| PRO-231 | Changes in Best Corrected Visual Acuity (BCVA) | Day 3 (Visit 1) | -0.02 Best Corrected Visual Acuity (LogMar) | Standard Deviation 0.05 |
| PRO-231 | Changes in Best Corrected Visual Acuity (BCVA) | Day 8 (Final Visit) | -0.04 Best Corrected Visual Acuity (LogMar) | Standard Deviation 0.06 |
| VIGAMOXI® | Changes in Best Corrected Visual Acuity (BCVA) | Day 0 (Basal Visit) | -0.02 Best Corrected Visual Acuity (LogMar) | Standard Deviation 0.07 |
| VIGAMOXI® | Changes in Best Corrected Visual Acuity (BCVA) | Day 3 (Visit 1) | -0.03 Best Corrected Visual Acuity (LogMar) | Standard Deviation 0.05 |
| VIGAMOXI® | Changes in Best Corrected Visual Acuity (BCVA) | Day 8 (Final Visit) | -0.03 Best Corrected Visual Acuity (LogMar) | Standard Deviation 0.07 |
Primary
Changes in the Ocular Comfort Index (OCI) Score Between Interventions.
The Ocular Comfort Index is a questionnaire designed to measure ocular surface irritation. It assesses symptoms related to comfort in cases of ocular surface disorders. The Ocular Comfort Index is composed of 12 items that assess the frequency and intensity symptoms. Each item is scored on a scale from 0 to 6 (never to always, or absent to severe). The total score becomes a linear continuous interval scale, which ranges from 0 (least symptomatic) to 100 (most symptomatic). The questionnaire was administered to each research subject, allowing them to respond calmly without any pressure and/or coercion. The results were collected using the Ocular Comfort Index calculator \[1\], obtaining a logit score and a 0-100 scale score for each subject. \[1\].- M. E. Johnson, Measurement of Ocular Surface Irritation on a Linear Interval Scale with the Ocular Comfort Index, Investigative Ophthalmology & Visual Science, vol. 48, nº 10, 2007.
Time frame: Days 0 (Basal Visit), and 8 (Final Visit)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PRO-231 | Changes in the Ocular Comfort Index (OCI) Score Between Interventions. | Day 0 (Basal Visit) | 25.91 score on a scale | Standard Deviation 8.17 |
| PRO-231 | Changes in the Ocular Comfort Index (OCI) Score Between Interventions. | Day 8 (Final Visit) | 19.78 score on a scale | Standard Deviation 11.86 |
| VIGAMOXI® | Changes in the Ocular Comfort Index (OCI) Score Between Interventions. | Day 0 (Basal Visit) | 28.01 score on a scale | Standard Deviation 8.6 |
| VIGAMOXI® | Changes in the Ocular Comfort Index (OCI) Score Between Interventions. | Day 8 (Final Visit) | 27.14 score on a scale | Standard Deviation 10.22 |
Primary
Incidence of Conjunctival Hyperemia
Any signs of conjunctival hyperemia in between interventions.
Time frame: Days 0 (Basal Visit), 3 (Visit 1), and 8 (Final Visit)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PRO-231 | Incidence of Conjunctival Hyperemia | Day 3 (Visit 1) | 3 number of patients |
| PRO-231 | Incidence of Conjunctival Hyperemia | Day 8 (Final Visit) | 4 number of patients |
| PRO-231 | Incidence of Conjunctival Hyperemia | Day 0 (Basal Visit) | 5 number of patients |
| VIGAMOXI® | Incidence of Conjunctival Hyperemia | Day 0 (Basal Visit) | 4 number of patients |
| VIGAMOXI® | Incidence of Conjunctival Hyperemia | Day 3 (Visit 1) | 4 number of patients |
| VIGAMOXI® | Incidence of Conjunctival Hyperemia | Day 8 (Final Visit) | 3 number of patients |
Primary
Incidence of Unexpected Adverse Events Related to the Interventions
Any unfavorable medical condition affecting the subject after the administration of the investigation product, related to such intervention. Adverse events where inquired and evaluated in every time point specified in the time frame, however, the final number of adverse events reported throught the entire study was evaluated for each group.
Time frame: Days 0 (Basal Visit), 3 (Visit 1), 8 (Final Visit) and 12 (Safety Call)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PRO-231 | Incidence of Unexpected Adverse Events Related to the Interventions | 1 number of related adverse events |
| VIGAMOXI® | Incidence of Unexpected Adverse Events Related to the Interventions | 4 number of related adverse events |
Primary
Number of Patients With Any Changes in Grade Measurement of the Integrity of the Ocular Surface (Fluorescein Staining)
Number of patients with any changes in the integrity of the ocular surface using fluorescein staining and evaluated through the Oxford scale compared to baseline. The standard Oxford scale for fluorescein staining has the following criteria: Grade 0- Equal to or less than panel A; Grade I- Equal to or less than panel B, greater than panel A; Grade II- Equal to or less than panel C, greater than panel B; Grade III- Equal or less than panel D, greater than panel C; Grade IV- Equal or less than panel E, greater than panel D; Grade V- Greater than panel E.
Time frame: Days 0 (Basal Visit), Days 3 (Visit 1) and 8 (Final Visit)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PRO-231 | Number of Patients With Any Changes in Grade Measurement of the Integrity of the Ocular Surface (Fluorescein Staining) | Days 0 (Basal Visit) | 0 Participants |
| PRO-231 | Number of Patients With Any Changes in Grade Measurement of the Integrity of the Ocular Surface (Fluorescein Staining) | Days 3 (Visit 1) | 0 Participants |
| PRO-231 | Number of Patients With Any Changes in Grade Measurement of the Integrity of the Ocular Surface (Fluorescein Staining) | Day 8 (Final Visit) | 0 Participants |
| VIGAMOXI® | Number of Patients With Any Changes in Grade Measurement of the Integrity of the Ocular Surface (Fluorescein Staining) | Days 0 (Basal Visit) | 0 Participants |
| VIGAMOXI® | Number of Patients With Any Changes in Grade Measurement of the Integrity of the Ocular Surface (Fluorescein Staining) | Days 3 (Visit 1) | 1 Participants |
| VIGAMOXI® | Number of Patients With Any Changes in Grade Measurement of the Integrity of the Ocular Surface (Fluorescein Staining) | Day 8 (Final Visit) | 0 Participants |
Secondary
Incidence of Unexpected Adverse Events (Excluding Conjunctival Hyperemia and Chemosis)
Any unfavorable medical condition affecting the subject after the administration of the investigation product, related to such intervention, excluding conjunctival hyperemia and chemosis. Unexpected adverse events where inquired and evaluated in every time point specified in the time frame, however, the final number of adverse events reported throught the entire study was evaluated for each group.
Time frame: Days 3 (Visit 1), 8 (Final Visit) and 12 (Safety Call)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PRO-231 | Incidence of Unexpected Adverse Events (Excluding Conjunctival Hyperemia and Chemosis) | 1 number of unexpected adverse events |
| VIGAMOXI® | Incidence of Unexpected Adverse Events (Excluding Conjunctival Hyperemia and Chemosis) | 4 number of unexpected adverse events |
Secondary
To Assess the Tolerability of PRO-231 Ophthalmic Solution
To assess the tolerability of PRO-231 ophthalmic solution applied to the ocular surface, in healthy volunteers, versus VIGAMOXI®, by means of: Presence of ocular symptoms (burning, foreign body sensation, pruritus and lacrimation) between interventions.
Time frame: Days 3 (Visit 1), 8 (Final Visit)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PRO-231 | To Assess the Tolerability of PRO-231 Ophthalmic Solution | Burning Day 0 (Basal Visit) | 0 ocular symptom events |
| PRO-231 | To Assess the Tolerability of PRO-231 Ophthalmic Solution | Burning Day 3 (Visit 1) | 4 ocular symptom events |
| PRO-231 | To Assess the Tolerability of PRO-231 Ophthalmic Solution | Burning Day 8 (Final Visit) | 3 ocular symptom events |
| PRO-231 | To Assess the Tolerability of PRO-231 Ophthalmic Solution | Foreign Body Sensation Day 0 (Basal Visit) | 0 ocular symptom events |
| PRO-231 | To Assess the Tolerability of PRO-231 Ophthalmic Solution | Foreign Body Sensation Day 3 (Visit 1) | 1 ocular symptom events |
| PRO-231 | To Assess the Tolerability of PRO-231 Ophthalmic Solution | Foreign Body Sensation Day 8 (Final Visit) | 1 ocular symptom events |
| PRO-231 | To Assess the Tolerability of PRO-231 Ophthalmic Solution | Pruritus Day 0 (Basal Visit) | 0 ocular symptom events |
| PRO-231 | To Assess the Tolerability of PRO-231 Ophthalmic Solution | Pruritus Day 3 (Visit 1) | 3 ocular symptom events |
| PRO-231 | To Assess the Tolerability of PRO-231 Ophthalmic Solution | Pruitus Day 8 (Final Visit) | 2 ocular symptom events |
| PRO-231 | To Assess the Tolerability of PRO-231 Ophthalmic Solution | Lacrimation Day 0 (Basal Visit) | 0 ocular symptom events |
| PRO-231 | To Assess the Tolerability of PRO-231 Ophthalmic Solution | Lacrimation Day 3 (Visit 1) | 0 ocular symptom events |
| PRO-231 | To Assess the Tolerability of PRO-231 Ophthalmic Solution | Lacrimation Day 8 (Final Visit) | 0 ocular symptom events |
| VIGAMOXI® | To Assess the Tolerability of PRO-231 Ophthalmic Solution | Lacrimation Day 0 (Basal Visit) | 0 ocular symptom events |
| VIGAMOXI® | To Assess the Tolerability of PRO-231 Ophthalmic Solution | Burning Day 0 (Basal Visit) | 0 ocular symptom events |
| VIGAMOXI® | To Assess the Tolerability of PRO-231 Ophthalmic Solution | Lacrimation Day 8 (Final Visit) | 0 ocular symptom events |
| VIGAMOXI® | To Assess the Tolerability of PRO-231 Ophthalmic Solution | Burning Day 3 (Visit 1) | 5 ocular symptom events |
| VIGAMOXI® | To Assess the Tolerability of PRO-231 Ophthalmic Solution | Pruritus Day 3 (Visit 1) | 2 ocular symptom events |
| VIGAMOXI® | To Assess the Tolerability of PRO-231 Ophthalmic Solution | Burning Day 8 (Final Visit) | 2 ocular symptom events |
| VIGAMOXI® | To Assess the Tolerability of PRO-231 Ophthalmic Solution | Lacrimation Day 3 (Visit 1) | 0 ocular symptom events |
| VIGAMOXI® | To Assess the Tolerability of PRO-231 Ophthalmic Solution | Foreign Body Sensation Day 0 (Basal Visit) | 0 ocular symptom events |
| VIGAMOXI® | To Assess the Tolerability of PRO-231 Ophthalmic Solution | Pruitus Day 8 (Final Visit) | 2 ocular symptom events |
| VIGAMOXI® | To Assess the Tolerability of PRO-231 Ophthalmic Solution | Foreign Body Sensation Day 3 (Visit 1) | 0 ocular symptom events |
| VIGAMOXI® | To Assess the Tolerability of PRO-231 Ophthalmic Solution | Pruritus Day 0 (Basal Visit) | 0 ocular symptom events |
| VIGAMOXI® | To Assess the Tolerability of PRO-231 Ophthalmic Solution | Foreign Body Sensation Day 8 (Final Visit) | 0 ocular symptom events |