Acanthamoeba Keratitis
Conditions
Brief summary
Randomized, double-masked, placebo-controlled, multiple center, parallel-group Phase 1 study to evaluate the safety and tolerability of 3 doses of preservative-free PHMB ophthalmic solution compared to placebo in healthy subjects
Detailed description
The primary objective of the study is to establish the ocular safety and tolerability, and systemic safety of 3 different concentrations of preservative-free PHMB in healthy subjects. Safety and tolerability will be compared to those of a placebo.The PHMB bioavailability in plasma will also be assessed
Interventions
DRUG0.04% PHMB
0.04% PHMB eye drops, 1 drop 12 times daily for 7 days, followed by 1 drop 6 times daily for additional 7 days
DRUG0.06% PHMB
0.06% PHMB eye drops, 1 drop 12 times daily for 7 days, followed by 1 drop 6 times daily for additional 7 days
DRUG0.08% PHMB
0.08% PHMB eye drops, 1 drop 12 times daily for 7 days, followed by 1 drop 6 times daily for additional 7 days
DRUGPHMB Vehicle
PHMB vehicle eye drops, 1 drop 12 times daily for 7 days, followed by 1 drop 6 times daily for additional 7 days
Sponsors
SIFI SpA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* able and willing to give informed consent. * man or woman of any race and 18 to 55 years of age, inclusive. * Body Mass Index of 20-30 kg/m2 * willing and able to attend required study visits. * bilateral visual acuity \>6/10. * intraocular pressure (IOP) of 14-21 mmHg. * ophthalmologic examination without abnormalities. * medical history without major pathology. * laboratory test results without deviations from the normal range. * female subjects of childbearing potential with negative urine pregnancy test and using effective contraception during the study.
Exclusion criteria
* presence of bacterial ocular infections. * presence of any concomitant ocular pathology. * performing activities likely to result in an irritated conjunctiva during the study (including heavy alcohol intake, swimming in chlorinated water and heavy smoking). * contact lenses wearing . * ocular surface fluorescein staining score \>3. * use of topical or systemic antibiotics, antihistamines, decongestants and non-steroidal anti-inflammatory agents as well as steroids within 7 days before screening. * known or suspected allergy to biguanides or intolerance to any other ingredient of the test treatments. * ocular surgery performed within 12 months before screening. * participation in another clinical study in the preceding 30 days. * one functional eye. * pregnancy or breastfeeding. * use of recreational drugs.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Subjects With Dose-limiting Adverse Events | up to 21 days from date of randomization |
Secondary
| Measure | Time frame |
|---|---|
| Plasma Concentration of PHMB | Day14 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Systolic Blood Pressure | Baseline and Day 14 | Change from baseline systolic blood pressure |
| Visual Acuity | Baseline and Day 14 | Change from baseline Visual acuity. Best corrected visual acuity was reported in decimal fraction. A decrease of visual acuity during treatment was considered a negative safety outcome. |
| Ocular Surface Disease Index-OSDI | Baseline and Day 14 | Change from baseline OSDI at D 14. Score range was betwwen 0-100. An increase of OSDI values with treatment represent a negative outcome. |
| Conjunctival Examination | Baseline and Day 14 | Change from baseline conjunctival staining at Day 14. Staining with lissamine green was used. The density of staining was graded with the Oxford Score. Score range was between 0-15. An increase in the score after treatment represent a negative outcome |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 0.04% PHMB 0.04% PHMB eye drops, 1 drop 12 times daily for 7 days, followed by 1 drop 6 times daily for additional 7 days
0.04% PHMB: 0.04% PHMB eye drops, 1 drop 12 times daily for 7 days, followed by 1 drop 6 times daily for additional 7 days | 26 |
| 0.06% PHMB 0.06% PHMB eye drops, 1 drop 12 times daily for 7 days, followed by 1 drop 6 times daily for additional 7 days
0.06% PHMB: 0.06% PHMB eye drops, 1 drop 12 times daily for 7 days, followed by 1 drop 6 times daily for additional 7 days | 28 |
| 0.08% PHMB 0.08% PHMB eye drops, 1 drop 12 times daily for 7 days, followed by 1 drop 6 times daily for additional 7 days
0.08% PHMB: 0.08% PHMB eye drops, 1 drop 12 times daily for 7 days, followed by 1 drop 6 times daily for additional 7 days | 27 |
| PHMB Vehicle PHMB vehicle eye drops, 1 drop 12 times daily for 7 days, followed by 1 drop 6 times daily for additional 7 days
PHMB Vehicle: PHMB vehicle eye drops, 1 drop 12 times daily for 7 days, followed by 1 drop 6 times daily for additional 7 days | 9 |
| Total | 90 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 3 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | 0.04% PHMB | 0.06% PHMB | 0.08% PHMB | PHMB Vehicle | Total |
|---|---|---|---|---|---|
| Age, Continuous | 30.5 years STANDARD_DEVIATION 12.5 | 29.4 years STANDARD_DEVIATION 8.7 | 30.4 years STANDARD_DEVIATION 10.3 | 25.7 years STANDARD_DEVIATION 4.6 | 29.6 years STANDARD_DEVIATION 10.1 |
| Gender Female | 14 Participants | 15 Participants | 17 Participants | 2 Participants | 48 Participants |
| Gender Male | 12 Participants | 13 Participants | 10 Participants | 7 Participants | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 11 / 26 | 23 / 28 | 16 / 27 | 5 / 9 |
| serious Total, serious adverse events | 0 / 26 | 0 / 28 | 0 / 27 | 0 / 9 |
Outcome results
Primary
Number of Subjects With Dose-limiting Adverse Events
Time frame: up to 21 days from date of randomization
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 0.04% PHMB | Number of Subjects With Dose-limiting Adverse Events | 0 participants |
| 0.06% PHMB | Number of Subjects With Dose-limiting Adverse Events | 2 participants |
| 0.08% PHMB | Number of Subjects With Dose-limiting Adverse Events | 3 participants |
| PHMB Vehicle | Number of Subjects With Dose-limiting Adverse Events | 0 participants |
Secondary
Plasma Concentration of PHMB
Time frame: Day14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.04% PHMB | Plasma Concentration of PHMB | 0 micrograms/ml | Standard Deviation 0 |
| 0.06% PHMB | Plasma Concentration of PHMB | 0 micrograms/ml | Standard Deviation 0 |
| 0.08% PHMB | Plasma Concentration of PHMB | 0 micrograms/ml | Standard Deviation 0 |
| PHMB Vehicle | Plasma Concentration of PHMB | 0 micrograms/ml | Standard Deviation 0 |
Other Pre-specified
Conjunctival Examination
Change from baseline conjunctival staining at Day 14. Staining with lissamine green was used. The density of staining was graded with the Oxford Score. Score range was between 0-15. An increase in the score after treatment represent a negative outcome
Time frame: Baseline and Day 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.04% PHMB | Conjunctival Examination | 0.7 scores on a scale | Standard Deviation 1.3 |
| 0.06% PHMB | Conjunctival Examination | 1.2 scores on a scale | Standard Deviation 1.9 |
| 0.08% PHMB | Conjunctival Examination | 1.7 scores on a scale | Standard Deviation 1.8 |
| PHMB Vehicle | Conjunctival Examination | 1.0 scores on a scale | Standard Deviation 1.7 |
Other Pre-specified
Ocular Surface Disease Index-OSDI
Change from baseline OSDI at D 14. Score range was betwwen 0-100. An increase of OSDI values with treatment represent a negative outcome.
Time frame: Baseline and Day 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.04% PHMB | Ocular Surface Disease Index-OSDI | 1.5 scores on a scale | Standard Deviation 3.6 |
| 0.06% PHMB | Ocular Surface Disease Index-OSDI | 1.3 scores on a scale | Standard Deviation 4.1 |
| 0.08% PHMB | Ocular Surface Disease Index-OSDI | 4.2 scores on a scale | Standard Deviation 5.8 |
| PHMB Vehicle | Ocular Surface Disease Index-OSDI | -2.2 scores on a scale | Standard Deviation 4.9 |
Other Pre-specified
Systolic Blood Pressure
Change from baseline systolic blood pressure
Time frame: Baseline and Day 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.04% PHMB | Systolic Blood Pressure | -0.7 mmHg | Standard Deviation 9.6 |
| 0.06% PHMB | Systolic Blood Pressure | 0.6 mmHg | Standard Deviation 8.3 |
| 0.08% PHMB | Systolic Blood Pressure | -0.9 mmHg | Standard Deviation 8.6 |
| PHMB Vehicle | Systolic Blood Pressure | 1.0 mmHg | Standard Deviation 8.6 |
Other Pre-specified
Visual Acuity
Change from baseline Visual acuity. Best corrected visual acuity was reported in decimal fraction. A decrease of visual acuity during treatment was considered a negative safety outcome.
Time frame: Baseline and Day 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.04% PHMB | Visual Acuity | 0.3 decimals | Standard Deviation 1.4 |
| 0.06% PHMB | Visual Acuity | 0.3 decimals | Standard Deviation 1.3 |
| 0.08% PHMB | Visual Acuity | 0.3 decimals | Standard Deviation 0.1 |
| PHMB Vehicle | Visual Acuity | 0.3 decimals | Standard Deviation 0.1 |