Trial Outcomes & Findings for Comparison of Intraocular Pressure (IOP)-Lowering Efficacy and Safety of AZORGA® Ophthalmic Suspension and COSOPT® Ophthalmic Solution (NCT NCT02325518)

NCT ID: NCT02325518

Last Updated: 2016-12-08

Results Overview

IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and measured in millimeters of mercury (mmHg). Data from 4 and 8 weeks at 11 AM were pooled, and a negative change indicates an improvement. One eye (target eye) was used for the analysis.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 218 participants
• Primary outcome timeframe: Baseline (Day 0), Week 4, Week 8 at 11 AM
• Results posted on: 2016-12-08

Participant Flow

Subjects were recruited from 26 study sites in Japan.

Of the 218 enrolled, 6 subjects withdrew informed consent and 11 were exited as screen failures prior to randomization. This reporting group includes all randomized subjects (201).

Participant milestones

Measure	BRI/TIM Brinzolamide 1%/Timolol maleate 0.5% fixed combination ophthalmic suspension, 1 drop in each eye twice daily, and habitual prostaglandin-analog (PGA) monotherapy, 1 drop in each eye once daily for 8 weeks.	DOR/TIM Dorzolamide hydrochloride 1%/Timolol maleate 0.5% ophthalmic solution, 1 drop in each eye twice daily, and habitual PGA monotherapy, 1 drop in each eye once daily for 8 weeks.
Overall Study STARTED	98	103
Overall Study Safety Set	98	103
Overall Study Full Analysis Set (FAS)	98	101
Overall Study Per Protocol Set (PPS)	92	97
Overall Study COMPLETED	94	100
Overall Study NOT COMPLETED	4	3

Reasons for withdrawal

Measure	BRI/TIM Brinzolamide 1%/Timolol maleate 0.5% fixed combination ophthalmic suspension, 1 drop in each eye twice daily, and habitual prostaglandin-analog (PGA) monotherapy, 1 drop in each eye once daily for 8 weeks.	DOR/TIM Dorzolamide hydrochloride 1%/Timolol maleate 0.5% ophthalmic solution, 1 drop in each eye twice daily, and habitual PGA monotherapy, 1 drop in each eye once daily for 8 weeks.
Overall Study Adverse Event	4	1
Overall Study Physician Decision	0	1
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Comparison of Intraocular Pressure (IOP)-Lowering Efficacy and Safety of AZORGA® Ophthalmic Suspension and COSOPT® Ophthalmic Solution

Baseline characteristics by cohort

Measure	BRI/TIM n=98 Participants Brinzolamide 1%/Timolol maleate 0.5% fixed combination ophthalmic suspension, 1 drop in each eye twice daily, and habitual PGA monotherapy, 1 drop in each eye once daily for 8 weeks.	DOR/TIM n=101 Participants Dorzolamide hydrochloride 1%/Timolol maleate 0.5% ophthalmic solution, 1 drop in each eye twice daily, and habitual PGA monotherapy, 1 drop in each eye once daily for 8 weeks.	Total n=199 Participants Total of all reporting groups
Age, Continuous	63.1 years STANDARD_DEVIATION 11.8 • n=5 Participants	64.4 years STANDARD_DEVIATION 12.3 • n=7 Participants	63.7 years STANDARD_DEVIATION 12.0 • n=5 Participants
Sex: Female, Male Female	52 Participants n=5 Participants	53 Participants n=7 Participants	105 Participants n=5 Participants
Sex: Female, Male Male	46 Participants n=5 Participants	48 Participants n=7 Participants	94 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 0), Week 4, Week 8 at 11 AM

Population: This analysis population includes all subjects who received study medication and met inclusion/exclusion criteria prior to randomization (Per Protocol Set).

IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and measured in millimeters of mercury (mmHg). Data from 4 and 8 weeks at 11 AM were pooled, and a negative change indicates an improvement. One eye (target eye) was used for the analysis.

Outcome measures

Measure	BRI/TIM n=92 Participants Brinzolamide 1%/Timolol maleate 0.5% fixed combination ophthalmic suspension, 1 drop in each eye twice daily, and habitual PGA monotherapy, 1 drop in each eye once daily for 8 weeks.	DOR/TIM n=97 Participants Dorzolamide hydrochloride 1%/Timolol maleate 0.5% ophthalmic solution, 1 drop in each eye twice daily, and habitual PGA monotherapy, 1 drop in each eye once daily for 8 weeks.
Least Squares Mean Change From Baseline in Intraocular Pressure (IOP) at 11 AM Baseline	17.0 mmHg Interval 16.6 to 17.3	17.0 mmHg Interval 16.6 to 17.3
Least Squares Mean Change From Baseline in Intraocular Pressure (IOP) at 11 AM Mean change pooled over Week 4 and Week 8	-3.3 mmHg Interval -3.6 to -2.9	-3.4 mmHg Interval -3.7 to -3.0

SECONDARY outcome

Timeframe: Baseline (Day 0), Week 4, Week 8 at 9 AM

Population: Per Protocol Set (PPS)

IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and measured in millimeters of mercury (mmHg). Data from 4 and 8 weeks at 9 AM were pooled, and a negative change indicates an improvement. One eye (target eye) was used for the analysis.

Outcome measures

Measure	BRI/TIM n=92 Participants Brinzolamide 1%/Timolol maleate 0.5% fixed combination ophthalmic suspension, 1 drop in each eye twice daily, and habitual PGA monotherapy, 1 drop in each eye once daily for 8 weeks.	DOR/TIM n=97 Participants Dorzolamide hydrochloride 1%/Timolol maleate 0.5% ophthalmic solution, 1 drop in each eye twice daily, and habitual PGA monotherapy, 1 drop in each eye once daily for 8 weeks.
Least Squares Mean Change From Baseline in IOP at 9 AM Change at Pool (Week 4, Week 8)	-3.3 mmHg Interval -3.6 to -2.9	-2.9 mmHg Interval -3.2 to -2.5
Least Squares Mean Change From Baseline in IOP at 9 AM Baseline	17.4 mmHg Interval 17.1 to 17.8	17.3 mmHg Interval 17.0 to 17.7

Adverse Events

Pretreatment

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

BRI/TIM

Serious events: 1 serious events

Other events: 21 other events

Deaths: 0 deaths

DOR/TIM

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Measure	Pretreatment n=218 participants at risk All subjects who consented to participate in the study prior to the initiation of study treatment	BRI/TIM n=98 participants at risk Brinzolamide 1%/Timolol maleate 0.5% fixed combination ophthalmic suspension, 1 drop in each eye twice daily, and habitual PGA monotherapy, 1 drop in each eye once daily for 8 weeks.	DOR/TIM n=103 participants at risk Dorzolamide hydrochloride 1%/Timolol maleate 0.5% ophthalmic solution, 1 drop in each eye twice daily, and habitual PGA monotherapy, 1 drop in each eye once daily for 8 weeks.
Infections and infestations Appendicitis	0.46% 1/218 • Adverse events (AEs) were collected from time of informed consent throughout the duration of a subject's participation in the study (up to 8 weeks). Ocular adverse events are presented for both study eye and non-study eye combined. AEs are reported as pretreatment and treatment-emergent. This analysis population includes all subjects who received study medication (Safety Analysis Set). An AE was defined as all medically undesirable or unintended diseases or symptoms that occur in subjects who receive study medication regardless of the causal relationship. Reports of AEs were obtained through solicited and spontaneous comments from the subjects and through observations by the Investigator as outlined in the study protocol.	1.0% 1/98 • Adverse events (AEs) were collected from time of informed consent throughout the duration of a subject's participation in the study (up to 8 weeks). Ocular adverse events are presented for both study eye and non-study eye combined. AEs are reported as pretreatment and treatment-emergent. This analysis population includes all subjects who received study medication (Safety Analysis Set). An AE was defined as all medically undesirable or unintended diseases or symptoms that occur in subjects who receive study medication regardless of the causal relationship. Reports of AEs were obtained through solicited and spontaneous comments from the subjects and through observations by the Investigator as outlined in the study protocol.	0.00% 0/103 • Adverse events (AEs) were collected from time of informed consent throughout the duration of a subject's participation in the study (up to 8 weeks). Ocular adverse events are presented for both study eye and non-study eye combined. AEs are reported as pretreatment and treatment-emergent. This analysis population includes all subjects who received study medication (Safety Analysis Set). An AE was defined as all medically undesirable or unintended diseases or symptoms that occur in subjects who receive study medication regardless of the causal relationship. Reports of AEs were obtained through solicited and spontaneous comments from the subjects and through observations by the Investigator as outlined in the study protocol.

Other adverse events

Measure	Pretreatment n=218 participants at risk All subjects who consented to participate in the study prior to the initiation of study treatment	BRI/TIM n=98 participants at risk Brinzolamide 1%/Timolol maleate 0.5% fixed combination ophthalmic suspension, 1 drop in each eye twice daily, and habitual PGA monotherapy, 1 drop in each eye once daily for 8 weeks.	DOR/TIM n=103 participants at risk Dorzolamide hydrochloride 1%/Timolol maleate 0.5% ophthalmic solution, 1 drop in each eye twice daily, and habitual PGA monotherapy, 1 drop in each eye once daily for 8 weeks.
Eye disorders Blurred vision	0.00% 0/218 • Adverse events (AEs) were collected from time of informed consent throughout the duration of a subject's participation in the study (up to 8 weeks). Ocular adverse events are presented for both study eye and non-study eye combined. AEs are reported as pretreatment and treatment-emergent. This analysis population includes all subjects who received study medication (Safety Analysis Set). An AE was defined as all medically undesirable or unintended diseases or symptoms that occur in subjects who receive study medication regardless of the causal relationship. Reports of AEs were obtained through solicited and spontaneous comments from the subjects and through observations by the Investigator as outlined in the study protocol.	20.4% 20/98 • Adverse events (AEs) were collected from time of informed consent throughout the duration of a subject's participation in the study (up to 8 weeks). Ocular adverse events are presented for both study eye and non-study eye combined. AEs are reported as pretreatment and treatment-emergent. This analysis population includes all subjects who received study medication (Safety Analysis Set). An AE was defined as all medically undesirable or unintended diseases or symptoms that occur in subjects who receive study medication regardless of the causal relationship. Reports of AEs were obtained through solicited and spontaneous comments from the subjects and through observations by the Investigator as outlined in the study protocol.	8.7% 9/103 • Adverse events (AEs) were collected from time of informed consent throughout the duration of a subject's participation in the study (up to 8 weeks). Ocular adverse events are presented for both study eye and non-study eye combined. AEs are reported as pretreatment and treatment-emergent. This analysis population includes all subjects who received study medication (Safety Analysis Set). An AE was defined as all medically undesirable or unintended diseases or symptoms that occur in subjects who receive study medication regardless of the causal relationship. Reports of AEs were obtained through solicited and spontaneous comments from the subjects and through observations by the Investigator as outlined in the study protocol.
Eye disorders Eye irritation	0.00% 0/218 • Adverse events (AEs) were collected from time of informed consent throughout the duration of a subject's participation in the study (up to 8 weeks). Ocular adverse events are presented for both study eye and non-study eye combined. AEs are reported as pretreatment and treatment-emergent. This analysis population includes all subjects who received study medication (Safety Analysis Set). An AE was defined as all medically undesirable or unintended diseases or symptoms that occur in subjects who receive study medication regardless of the causal relationship. Reports of AEs were obtained through solicited and spontaneous comments from the subjects and through observations by the Investigator as outlined in the study protocol.	2.0% 2/98 • Adverse events (AEs) were collected from time of informed consent throughout the duration of a subject's participation in the study (up to 8 weeks). Ocular adverse events are presented for both study eye and non-study eye combined. AEs are reported as pretreatment and treatment-emergent. This analysis population includes all subjects who received study medication (Safety Analysis Set). An AE was defined as all medically undesirable or unintended diseases or symptoms that occur in subjects who receive study medication regardless of the causal relationship. Reports of AEs were obtained through solicited and spontaneous comments from the subjects and through observations by the Investigator as outlined in the study protocol.	9.7% 10/103 • Adverse events (AEs) were collected from time of informed consent throughout the duration of a subject's participation in the study (up to 8 weeks). Ocular adverse events are presented for both study eye and non-study eye combined. AEs are reported as pretreatment and treatment-emergent. This analysis population includes all subjects who received study medication (Safety Analysis Set). An AE was defined as all medically undesirable or unintended diseases or symptoms that occur in subjects who receive study medication regardless of the causal relationship. Reports of AEs were obtained through solicited and spontaneous comments from the subjects and through observations by the Investigator as outlined in the study protocol.

Additional Information

Novartis Pharma KK

Alcon, A Novartis Division

Phone: 1-888-451-3937

Email: alcon.medinfo@alcon.com

Results disclosure agreements

• Principal investigator is a sponsor employee Sponsor reserves the right of prior review of any publication or presentation of information related to the study.
• Publication restrictions are in place

Restriction type: OTHER