Hyperemia Eye
Conditions
Brief summary
Phase I Study to evaluate safety and tolerability of PRO-185 (naphazoline/hypromellose) ophthalmic solution through evaluation of vital signs, ocular signs such as intraocular pressure, hyperemia and mydriasis and adverse events.
Detailed description
A total of 22 healthy volunteers will apply PRO-185 ocular solution on both eyes QID (four times per day) for 8 days. The safety variables will include intraocular pressure, heart rate, systolic and diastolic blood pressure. Tolerability variables will include: hyperemia, mydriasis, and expected and unexpected adverse events. The presence of any of these in ≤ 20% will deem PRO-185 as safe and tolerable.
Interventions
DRUGNaphazoline / Hypromellose Ophthalmic
Naphazoline 0.03% / Hypromellose 0.2%
Sponsors
Laboratorios Sophia S.A de C.V.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Phase I, controlled, non-comparative, single-center, open study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Being clinically healthy * Having the ability to grant a signed informed consent * Being able and willing to comply with the programmed visits, treatment plan and other procedures of this study. * Age between 18 and 45 years * Women in child-bearing age must assure the continuation (start ≥ 30 days previous to the signing of the ICF) of a hormonal contraceptive method or a intrauterine device (IUD) during the period of the study. * Best corrected visual acuity equal of better than 20/30 in both eyes. * Vital signs within normal ranges. * Intraocular pressure ≥10 and ≤ 21 mmHg
Exclusion criteria
* Using any kind of topic ophthalmic products * Presenting allergies to naphazoline or the history of intolerance to nasal decongestants or ocular vasoconstrictive products. * History of diagnosis of suspicion of primary angle closure, primary angle closure or closed angle glaucoma. * History of iridotomies or waiting for this procedure to take place. * Conjunctival hyperemia grade 3 or 4 according to Efron scale. * Ocular surface staining equal or greater to 3 in the SICCA scale, for any eye. * Using medications or herbology products, through any route of administration. * Pregnant, breastfeeding or women who plan to get pregnant during the period of the study. * Previous participation in any clinical study 90 days prior to the inclusion in the present study. * Previous participation in this study. * Using contact lenses which cannot be suspended during the period of this study. * History of any chronic illness, including diabetes and hypertension. * Active inflammation or infection at the time of inclusion in this study. * Unresolved lesions or traumas at the moment of inclusion in this study. * History of any kind of ocular surgery. * History of any surgical procedure, non-ophthalmologic, within the previous 3 months to the inclusion in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Intraocular Pressure (IOP) Increment | Baseline visit (BV), day 1(pre and post pupil dilation); Visit 1 (V1), day 3 +1 (pre and post research product application); Visit 2 (V2), day 8 (pre and post research product application); Final Visit, day 10 (+1) | Safety evaluation through the incidence of subjects presenting an IOP elevation comparing Baseline Visit, Final Visit and before and after (20 minutes) research product administration (V1 and V2). Only right-eye values were analyzed. |
| Heart Rate Increment | Baseline visit, day 1(pre and post pupil dilation); Visit 1, day 3 +1 (pre and post research product application); Visit 2, day 8 (pre and post research product application); Final Visit, day 10 (+1) | Safety evaluation through the incidence of subjects presenting an elevation \> 15 beats per minute 20 minutes after administration, in comparison to baseline value. |
| Blood Pressure Increment (Systolic) | Baseline visit, day 1(pre and post pupil dilation); Visit 1, day 3 +1 (pre and post research product application); Visit 2, day 8 (pre and post research product application); Final Visit, day 10 (+1) | Safety evaluation through the incidence of subjects presenting an elevation \> 15 mmHg in systolic pressure or \> 10 mmHg in diastolic pressure 20 minutes after administration, in comparison to baseline value. |
| Incidence of Conjunctival Hyperemia | Trough Day 10 (+1) | Tolerability evaluation through the incidence of conjunctival hyperemia grades 3 and 4 (according to the Efron scale). A higher score (grades) in this scale translates into worse outcomes. Only right-eye values were analyzed. |
| Incidence of Pharmacological Mydriasis | Trough Day 10 (+1) | Incidence of pharmacological mydriasis measured through OPD III scan. If there was a change greater than 2 mm in pupil diameter between the baseline visit and any of the other measurements, pharmacological mydriasis was considered present, also if there was this change between the pre- and post-examination of the investigational product during visits 1 and 2. |
| Blood Pressure Increment (Diastolic) | Baseline visit, day 1(pre and post pupil dilation); Visit 1, day 3 +1 (pre and post research product application); Visit 2, day 8 (pre and post research product application); Final Visit, day 10 (+1) | Safety evaluation through the incidence of subjects presenting an elevation \> 15 mmHg in systolic pressure or \> 10 mmHg in diastolic pressure 20 minutes after administration, in comparison to baseline value. |
Countries
Mexico
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PRO-185 Healthy volunteers will apply one drop of PRO-185 ophthalmic solution (naphazoline / hypromellose) on both eyes, QID (four times per day) for 8 days.
Naphazoline / Hypromellose Ophthalmic: Naphazoline 0.03% / Hypromellose 0.2% | 22 |
| PRO-185 Healthy volunteers will apply one drop of PRO-185 ophthalmic solution (naphazoline / hypromellose) on both eyes, QID (four times per day) for 8 days.
Naphazoline / Hypromellose Ophthalmic: Naphazoline 0.03% / Hypromellose 0.2% | 44 |
| Total | 66 |
Baseline characteristics
| Characteristic | PRO-185 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants |
| Age, Continuous | 23.82 years STANDARD_DEVIATION 4.48 |
| Intraocular Pressure (IOP) | 14.00 mmhg STANDARD_DEVIATION 2.8 |
| Pupillary diameter | 6.50 millimeters STANDARD_DEVIATION 0.47 |
| Region of Enrollment Mexico | 22 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 22 |
| other Total, other adverse events | 9 / 22 |
| serious Total, serious adverse events | 0 / 22 |
Outcome results
Primary
Blood Pressure Increment (Diastolic)
Safety evaluation through the incidence of subjects presenting an elevation \> 15 mmHg in systolic pressure or \> 10 mmHg in diastolic pressure 20 minutes after administration, in comparison to baseline value.
Time frame: Baseline visit, day 1(pre and post pupil dilation); Visit 1, day 3 +1 (pre and post research product application); Visit 2, day 8 (pre and post research product application); Final Visit, day 10 (+1)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PRO-185 | Blood Pressure Increment (Diastolic) | BV Diastolic Blood Pressure | 68.36 mmHg | Standard Deviation 8.16 |
| PRO-185 | Blood Pressure Increment (Diastolic) | V1 Diastolic Blood Pressure (pre-instillation) | 68.40 mmHg | Standard Deviation 7.73 |
| PRO-185 | Blood Pressure Increment (Diastolic) | V1 Diastolic Blood Pressure (post-instillation) | 69.45 mmHg | Standard Deviation 7.2 |
| PRO-185 | Blood Pressure Increment (Diastolic) | V2 Diastolic Blood Pressure (pre-instillation) | 66.59 mmHg | Standard Deviation 6.54 |
| PRO-185 | Blood Pressure Increment (Diastolic) | V2 Diastolic Blood Pressure (post-instillation) | 67.31 mmHg | Standard Deviation 7.67 |
| PRO-185 | Blood Pressure Increment (Diastolic) | FV Diastolic Blood Pressure | 67.41 mmHg | Standard Deviation 7.76 |
Primary
Blood Pressure Increment (Systolic)
Safety evaluation through the incidence of subjects presenting an elevation \> 15 mmHg in systolic pressure or \> 10 mmHg in diastolic pressure 20 minutes after administration, in comparison to baseline value.
Time frame: Baseline visit, day 1(pre and post pupil dilation); Visit 1, day 3 +1 (pre and post research product application); Visit 2, day 8 (pre and post research product application); Final Visit, day 10 (+1)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PRO-185 | Blood Pressure Increment (Systolic) | BV Systolic Blood Pressure | 113.81 mmHg | Standard Deviation 9.09 |
| PRO-185 | Blood Pressure Increment (Systolic) | V1 Systolic Blood Pressure (pre-instillation) | 111.00 mmHg | Standard Deviation 12.07 |
| PRO-185 | Blood Pressure Increment (Systolic) | V1 Systolic Blood Pressure (post-instillation) | 111.22 mmHg | Standard Deviation 10.72 |
| PRO-185 | Blood Pressure Increment (Systolic) | V2 Systolic Blood Pressure (pre-instillation) | 107.50 mmHg | Standard Deviation 10.4 |
| PRO-185 | Blood Pressure Increment (Systolic) | V2 Systolic Blood Pressure (post-instillation) | 108.63 mmHg | Standard Deviation 9.21 |
| PRO-185 | Blood Pressure Increment (Systolic) | FV Systolic Blood Pressure | 113.90 mmHg | Standard Deviation 12.14 |
Primary
Heart Rate Increment
Safety evaluation through the incidence of subjects presenting an elevation \> 15 beats per minute 20 minutes after administration, in comparison to baseline value.
Time frame: Baseline visit, day 1(pre and post pupil dilation); Visit 1, day 3 +1 (pre and post research product application); Visit 2, day 8 (pre and post research product application); Final Visit, day 10 (+1)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PRO-185 | Heart Rate Increment | BV Heart Rate | 73.27 beats per minute | Standard Deviation 11.31 |
| PRO-185 | Heart Rate Increment | V1 Heart Rate (pre-instillation) | 70.54 beats per minute | Standard Deviation 7.49 |
| PRO-185 | Heart Rate Increment | V1 Heart Rate (post70.59-instillation) | 70.59 beats per minute | Standard Deviation 6.03 |
| PRO-185 | Heart Rate Increment | V2 Heart Rate (pre-instillation) | 70.68 beats per minute | Standard Deviation 5.33 |
| PRO-185 | Heart Rate Increment | V2 Heart Rate (post-instillation) | 69.90 beats per minute | Standard Deviation 4.61 |
| PRO-185 | Heart Rate Increment | FV Heart Rate | 73 beats per minute | Standard Deviation 9.19 |
Primary
Incidence of Conjunctival Hyperemia
Tolerability evaluation through the incidence of conjunctival hyperemia grades 3 and 4 (according to the Efron scale). A higher score (grades) in this scale translates into worse outcomes. Only right-eye values were analyzed.
Time frame: Trough Day 10 (+1)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PRO-185 | Incidence of Conjunctival Hyperemia | 2 Number of participants gde 3 or 4 Hypere |
Primary
Incidence of Pharmacological Mydriasis
Incidence of pharmacological mydriasis measured through OPD III scan. If there was a change greater than 2 mm in pupil diameter between the baseline visit and any of the other measurements, pharmacological mydriasis was considered present, also if there was this change between the pre- and post-examination of the investigational product during visits 1 and 2.
Time frame: Trough Day 10 (+1)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PRO-185 | Incidence of Pharmacological Mydriasis | 6.50 millimeters | Standard Deviation 0.6 |
Primary
Intraocular Pressure (IOP) Increment
Safety evaluation through the incidence of subjects presenting an IOP elevation comparing Baseline Visit, Final Visit and before and after (20 minutes) research product administration (V1 and V2). Only right-eye values were analyzed.
Time frame: Baseline visit (BV), day 1(pre and post pupil dilation); Visit 1 (V1), day 3 +1 (pre and post research product application); Visit 2 (V2), day 8 (pre and post research product application); Final Visit, day 10 (+1)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PRO-185 | Intraocular Pressure (IOP) Increment | VB IOP (pre-pupil dilation) | 14.00 mmhg | Standard Deviation 2.17 |
| PRO-185 | Intraocular Pressure (IOP) Increment | VB IOP (post-pupil dilation) | 13.57 mmhg | Standard Deviation 2.75 |
| PRO-185 | Intraocular Pressure (IOP) Increment | V1 IOP (pre-research product application) | 13.47 mmhg | Standard Deviation 2.21 |
| PRO-185 | Intraocular Pressure (IOP) Increment | V1 IOP (post-research product application) | 13.25 mmhg | Standard Deviation 1.9 |
| PRO-185 | Intraocular Pressure (IOP) Increment | V2 IOP (pre-research product application) | 13.02 mmhg | Standard Deviation 2.09 |
| PRO-185 | Intraocular Pressure (IOP) Increment | V2 IOP (post-research product application) | 13.65 mmhg | Standard Deviation 2.63 |
| PRO-185 | Intraocular Pressure (IOP) Increment | FV IOP | 12.79 mmhg | Standard Deviation 2.17 |