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

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

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

Study Overview

• Status: Completed
• Conditions: Acanthamoeba Keratitis
• Intervention / Treatment: Drug: 0.04% PHMB; Drug: 0.06% PHMB; Drug: 0.08% PHMB; Drug: PHMB Vehicle

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

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: 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; Other Names: Polyhexamethylene Biguanide
Experimental: 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	Drug: 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; Other Names: Polyhexamethylene Biguanide
Experimental: 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	Drug: 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; Other Names: Polyhexamethylene Biguanide
Placebo Comparator: 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	Drug: 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
Plasma Concentration of PHMB	Day14

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systolic Blood Pressure	Change from baseline systolic blood pressure	Baseline and Day 14
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.	Baseline and Day 14
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.	Baseline and Day 14
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	Baseline and Day 14

Collaborators and Investigators

• Sponsor: SIFI SpA
• Investigators: Principal Investigator: I JE van der meulen, MD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Publications and helpful links

General Publications

• Papa V, van der Meulen I, Rottey S, Sallet G, Overweel J, Asero N, Minassian DC, Dart JKG. Safety and tolerability of topical polyhexamethylene biguanide: a randomised clinical trial in healthy adult volunteers. Br J Ophthalmol. 2022 Feb;106(2):190-196. doi: 10.1136/bjophthalmol-2020-317848. Epub 2020 Nov 25.

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: July 20, 2015
• First Submitted That Met QC Criteria: July 22, 2015
• First Posted (Estimate): July 23, 2015

Study Record Updates

• Last Update Posted (Estimate): February 9, 2017
• Last Update Submitted That Met QC Criteria: December 15, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Eye Diseases; Parasitic Diseases; Protozoan Infections; Corneal Diseases; Eye Infections; Amebiasis; Eye Infections, Parasitic; Keratitis; Acanthamoeba Keratitis; Hypoglycemic Agents; Physiological Effects of Drugs; Anti-Infective Agents; Disinfectants; Polihexanide; Biguanides
• Other Study ID Numbers: 042SI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided