Safety and Tolerability of Preservative-free Polyhexamethylene Biguanide (PHMB) Ophthalmic Solution in Healthy Subjects

Study Overview
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Brief Summary
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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
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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

Official Title
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Randomized, Double-Masked, Placebo-Controlled Multiple-Dose Phase 1 Study to Evaluate the Safety and Tolerability of Different Doses of Preservative-free Polyhexamethylene Biguanide (PHMB) Ophthalmic Solution in Healthy Subjects

Conditions
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Acanthamoeba Keratitis

Intervention / Treatment
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* Drug: 0.04% PHMB
* Drug: 0.06% PHMB
* Drug: 0.08% PHMB
* Drug: PHMB Vehicle


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.04% PHMB<br>0.04% PHMB eye drops, 1 drop 12 times daily for 7 days, followed by 1 drop 6 times daily for additional 7 days | Drug: 0.04% PHMB<br>* 0.04% PHMB eye drops, 1 drop 12 times daily for 7 days, followed by 1 drop 6 times daily for additional 7 days<br>* Other names: Polyhexamethylene Biguanide;|
| Experimental: 0.06% PHMB<br>0.06% PHMB eye drops, 1 drop 12 times daily for 7 days, followed by 1 drop 6 times daily for additional 7 days | Drug: 0.06% PHMB<br>* 0.06% PHMB eye drops, 1 drop 12 times daily for 7 days, followed by 1 drop 6 times daily for additional 7 days<br>* Other names: Polyhexamethylene Biguanide;|
| Experimental: 0.08% PHMB<br>0.08% PHMB eye drops, 1 drop 12 times daily for 7 days, followed by 1 drop 6 times daily for additional 7 days | Drug: 0.08% PHMB<br>* 0.08% PHMB eye drops, 1 drop 12 times daily for 7 days, followed by 1 drop 6 times daily for additional 7 days<br>* Other names: Polyhexamethylene Biguanide;|
| Placebo Comparator: PHMB Vehicle<br>PHMB vehicle eye drops, 1 drop 12 times daily for 7 days, followed by 1 drop 6 times daily for additional 7 days | Drug: PHMB Vehicle<br>* PHMB vehicle eye drops, 1 drop 12 times daily for 7 days, followed by 1 drop 6 times daily for additional 7 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Dose-limiting Adverse Events |  | up to 21 days from date of randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Concentration of PHMB |  | Day14 |