SIMBRINZA® Suspension BID as an Adjunctive to Prostaglandin Analogue (PGA)

This study consisted of 2 sequential phases: Screening/Eligibility Phase, followed by a Masked Treatment Phase (Phase II). Subjects were assigned into one of 3 PGA therapy groups for the duration of the study, based upon commercial availability.

• Brinzolamide 1%/brimonidine 0.2% tartrate ophthalmic suspension (Drug), also known as SIMBRINZA® suspension
• Brinz/brim vehicle (Drug): Inactive ingredients used as a placebo for masking purposes
• Prostaglandin analogue (Drug), also known as TRAVATAN® PQ (Travoprost ophthalmic solution with PQ, 0.004%), LUMIGAN® (Bimatoprost ophthalmic solution, 0.01%), XALATAN® (Latanoprost ophthalmic solution, 0.005%)

Primary outcomes

• Mean Change From Baseline (on PGA) in Diurnal IOP (Mean of 09:00 and 11:00 Time Points) at Week 6 [Baseline, Week 6]: IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry and averaged over the 09:00 AM and 11:00 AM time points. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. One eye (study eye) contributed to the analysis.

Secondary outcomes

• Mean Diurnal IOP at Week 6 [Week 6]: IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry and averaged over the 09:00 AM and 11:00 AM time points. A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). One eye (study eye) contributed to the analysis.
• Mean Percentage Change From Baseline in Diurnal IOP at Week 6 [Baseline, Week 6]: IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry and averaged over the 09:00 AM and 11:00 AM time points. A more negative percent change from baseline indicates a greater improvement, i.e., a reduction of IOP. One eye (study eye) contributed to the analysis.
• Mean Change From Baseline in IOP at 11:00 at Week 6 [Baseline, Week 6]: IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry at 11:00 AM. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. One eye (study eye) contributed to the analysis.
• Mean Percentage Change From Baseline in IOP at 11:00 at Week 6 [Baseline, Week 6]: IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry at 11:00 AM. A more negative percent change from baseline indicates a greater improvement, i.e., a reduction of IOP. One eye (study eye) contributed to the analysis.
• Mean Change From Baseline in IOP at 09:00 at Week 6 [Baseline, Week 6]: IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry at 09:00 AM. Baseline is defined as the average of the 9:00 hour values at both Eligibility visits. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. One eye (study eye) contributed to the analysis.
• Mean Percentage Change From Baseline at 09:00 at Week 6 [Baseline, Week 6]: IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry at 9:00 AM. Baseline is defined as the average of the 9:00 hour values at both Eligibility visits.A more negative percent change from baseline indicates a greater improvement, i.e., a reduction of IOP. One eye (study eye) contributed to the analysis.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Diagnosis of either open-angle glaucoma or ocular hypertension;
* Must sign an informed consent form;
* Mean IOP measurements at both the Eligibility 1 and 2 visits, in at least 1 eye (the same eye\[s\]) ≥ 19 and < 32 mmHg at 09:00.
* Willing and able to attend all study visits;
* Other protocol-specified inclusion criteria may apply.

Exclusion Criteria:

* Women of childbearing potential who are pregnant, breast-feeding, intend to become pregnant during the study, or not using adequate birth control methods to prevent pregnancy throughout the study;
* Any form of glaucoma other than open-angle glaucoma or ocular hypertension;
* Ocular disease, trauma, infection, inflammation, pathology, or surgery as specified in the protocol;
* Any other conditions including severe illness which would make the subject, in the opinion of the Investigator, unsuitable for the study;
* Other protocol-specified exclusion criteria may apply.

Participant flow

Outcome results

• Mean Change From Baseline (on PGA) in Diurnal IOP (Mean of 09:00 and 11:00 Time Points) at Week 6 (Primary), Mean, mmHg: SIMBRINZA + PGA -5.6 +/- 2.72; Vehicle + PGA -2.1 +/- 2.61 (p < 0.001)
• Mean Diurnal IOP at Week 6 (Secondary), Mean, mmHg: SIMBRINZA + PGA 17.2 +/- 3.49; Vehicle + PGA 20.9 +/- 3.59 (p <0.001)
• Mean Percentage Change From Baseline in Diurnal IOP at Week 6 (Secondary), Mean, percent change: SIMBRINZA + PGA -24.7 +/- 12.17; Vehicle + PGA -9.5 +/- 10.92 (p <0.001)
• Mean Change From Baseline in IOP at 11:00 at Week 6 (Secondary), Mean, mmHg: SIMBRINZA + PGA 22.4 +/- 2.70; Vehicle + PGA 22.6 +/- 2.69 (p <0.001)
• Mean Percentage Change From Baseline in IOP at 11:00 at Week 6 (Secondary), Mean, percent change: SIMBRINZA + PGA -31.3 +/- 14.81; Vehicle + PGA -10.8 +/- 11.86 (p <0.001)
• Mean Change From Baseline in IOP at 09:00 at Week 6 (Secondary), Mean, mmHg: SIMBRINZA + PGA 23.4 +/- 2.40; Vehicle + PGA 23.4 +/- 2.22 (p <0.001)
• Mean Percentage Change From Baseline at 09:00 at Week 6 (Secondary), Mean, percent change: SIMBRINZA + PGA -21.0 +/- 13.36; Vehicle + PGA -10.9 +/- 11.83 (p <0.001)

Adverse events

Time frame: Baseline through study completion, an average of 6 weeks.

Serious adverse events by term

Other adverse events by term

• Statistical Analysis Plan (PDF, 2018-03-12)
• Study Protocol (PDF, 2017-03-30)

• Clinical Manager, Ophtha, GCRA, Study director, Alcon, a Novartis Company

NIH grants: 2015