Open Label, Sequential-dose Study of PA5108 Latanoprost FA SR Ocular Implant for Mild-moderate Glaucoma

This is a multi-centre, open label, interventional, comparative, phase Ib dose ranging study to identify a safe and efficacious dose (within the range of 14.7 to 35.5 microgram) of PA5108 Latanoprost FA SR Ocular Implant in adults who have Primary Open Angle Glaucoma (POAG).

The proposed study is a single ascending dose design to determine the minimum effective dose that provides the target of \>20% IOP lowering effect at 12 weeks with minimal adverse events.

Up to three single-dose cohorts will be assessed from the following implant strengths:

* 35.5 microgram * 26.6 microgram * 14.7 microgram

In addition, a repeat-dose cohort will be assessed from the following implant strength:

o 14.7 microgram

A first cohort of participants will be recruited and dosed with the 14.7 mcg PA5108 Latanoprost FA SR Ocular Implant. A second cohort of participants will be recruited after SMC review of 6-week data of the first cohort and dosed with the 26.6 mcg PA5108 Latanoprost FA SR Ocular Implant. A third cohort of participants will be recruited after SMC review of 6-week data of the second cohort and repeat-dosed with 14.7 mcg PA5108 Latanoprost FA SR Ocular Implant. A fourth cohort of participants will be recruited and dosed with the 35.5 mcg PA5108 Latanoprost FA SR Ocular Implant

Prior to study registration, participants will have been medicated with intraocular pressure (IOP) lowering drop therapy, including a prostaglandin analogue, to manage their POAG. The IOP lowering drops will be stopped in the intent to treat eye within 29 to 43 days prior to the date of implant administration. Participants will be required to have an unmedicated (post wash-out) 8:00am IOP ≥ 24 mmHg and ≤ 36mmHg in the intent to treat eye at either of two screening visits 2-weeks apart. Additionally, the IOP at 12:00 noon and 4:00 pm must be ≥ 20mmHg and ≤ 36mmHg on the same screening visit where the 8:00am IOP was ≥ 24 mmHg and ≤ 36mmHg.

The PA5108 Latanoprost FA SR Ocular Implant will be administered to one eye (unilateral) of each participant.

IOP will be monitored and if after implant administration is found to rise ≥30% over baseline in the study eye, IOP lowering eye drops will be restarted.

The study will recruit up to 10 participants per cohort/dose level. After screening, eligible participants enrolled in the single-dose cohorts will be administered a single PA5108 Latanoprost FA SR Ocular Implant by clear corneal injection to the anterior chamber of the eye, by means of a custom-built injector fitted with a 27G pre-loaded needle at Day 0. Whereas eligible participants enrolled in the repeat-dose cohort will be administered a single PA5108 Latanoprost FA SR Ocular Implant by clear corneal injection to the anterior chamber of the eye, by means of a custom-built injector fitted with a 27G pre-loaded needle at Day 0, and again at Week 21.