Trial Outcomes & Findings for Effect of SIMBRINZA® Suspension as an Added Therapy to TRAVATAN Z® (NCT NCT01937299)

NCT ID: NCT01937299

Last Updated: 2015-05-14

Results Overview

Diurnal IOP was defined as the average of the four timepoints measured (8 AM, 10 AM, 3 PM, and 5 PM). IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and reported in millimeters mercury (mmHg). One eye was chosen as the study eye and only data for the study eye were used for the analyses. A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage).

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 307 participants
• Primary outcome timeframe: Week 6
• Results posted on: 2015-05-14

Participant Flow

Participants were recruited from 32 investigational centers located in the US.

Of the 307 enrolled, 74 participants were exited as screen failures prior to randomization. This reporting group includes all randomized participants (233).

Participant milestones

Measure	SIMBRINZA 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with travoprost 0.004% ophthalmic solution, 1 drop in each eye at bedtime, for 6 weeks	Vehicle 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with travoprost 0.004% ophthalmic solution, 1 drop in each eye at bedtime, for 6 weeks
Overall Study STARTED	117	116
Overall Study COMPLETED	103	112
Overall Study NOT COMPLETED	14	4

Reasons for withdrawal

Measure	SIMBRINZA 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with travoprost 0.004% ophthalmic solution, 1 drop in each eye at bedtime, for 6 weeks	Vehicle 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with travoprost 0.004% ophthalmic solution, 1 drop in each eye at bedtime, for 6 weeks
Overall Study Adverse Event	13	0
Overall Study Lack of Efficacy	0	4
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

Effect of SIMBRINZA® Suspension as an Added Therapy to TRAVATAN Z®

Baseline characteristics by cohort

Measure	SIMBRINZA n=113 Participants 1 drop instilled 3 times a day in each eye for 6 weeks as adjunctive therapy to travoprost ophthalmic solution 0.004%	Vehicle n=116 Participants 1 drop instilled 3 times a day in each eye for 6 weeks in conjunction with travoprost ophthalmic solution 0.004%	Total n=229 Participants Total of all reporting groups
Age, Continuous	67.5 years STANDARD_DEVIATION 10.3 • n=5 Participants	66.0 years STANDARD_DEVIATION 10.6 • n=7 Participants	66.8 years STANDARD_DEVIATION 10.5 • n=5 Participants
Sex: Female, Male Female	69 Participants n=5 Participants	67 Participants n=7 Participants	136 Participants n=5 Participants
Sex: Female, Male Male	44 Participants n=5 Participants	49 Participants n=7 Participants	93 Participants n=5 Participants
Mean Diurnal Intraocular Pressure (IOP) at Baseline	22.48 mmHg STANDARD_DEVIATION 2.507 • n=5 Participants	22.66 mmHg STANDARD_DEVIATION 2.407 • n=7 Participants	22.57 mmHg STANDARD_DEVIATION 2.453 • n=5 Participants

PRIMARY outcome

Timeframe: Week 6

Population: This analysis population includes all subjects who received study medication and completed at least 1 scheduled on-therapy study visit. Last observation carried forward (LOCF) was not utilized; therefore results report subjects present at Week 6 with no imputation for missingness.

Diurnal IOP was defined as the average of the four timepoints measured (8 AM, 10 AM, 3 PM, and 5 PM). IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and reported in millimeters mercury (mmHg). One eye was chosen as the study eye and only data for the study eye were used for the analyses. A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage).

Outcome measures

Measure	SIMBRINZA n=103 Participants 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with travoprost 0.004% ophthalmic solution, 1 drop in each eye at bedtime, for 6 weeks	Vehicle n=112 Participants 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with travoprost 0.004% ophthalmic solution, 1 drop in each eye at bedtime, for 6 weeks
Mean Diurnal Intraocular Pressure (IOP) at Week 6	17.44 mmHg Standard Deviation 2.838	20.34 mmHg Standard Deviation 3.702

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: This analysis population includes all subjects who received study medication and completed at least 1 scheduled on-therapy study visit. Last observation carried forward (LOCF) was not utilized; therefore results report subjects present at Week 6 with no imputation for missingness.

Baseline IOP was defined as the average of the timepoint-matched IOP measurements at Eligibility 1 and Eligibility 2 Visits. Diurnal IOP change was defined as the average of the four changes from baseline (timepoints 8 AM, 10 AM, 3 PM, and 5 PM). IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and reported in millimeters mercury (mmHg). One eye was chosen as the study eye and only data for the study eye were used for the analyses. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP.

Outcome measures

Measure	SIMBRINZA n=103 Participants 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with travoprost 0.004% ophthalmic solution, 1 drop in each eye at bedtime, for 6 weeks	Vehicle n=112 Participants 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with travoprost 0.004% ophthalmic solution, 1 drop in each eye at bedtime, for 6 weeks
Mean Diurnal IOP Change From Baseline to Week 6	-5.10 mmHg Standard Deviation 2.637	-2.22 mmHg Standard Deviation 2.925

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: This analysis population includes all subjects who received study medication and completed at least 1 scheduled on-therapy study visit. Last observation carried forward (LOCF) was not utilized; therefore results report subjects present at Week 6 with no imputation for missingness.

Baseline IOP was defined as the average of the timepoint-matched IOP measurements at Eligibility 1 and Eligibility 2 Visits. Diurnal IOP Percentage Change was defined as the average of the four percent changes from baseline (timepoints 8 AM, 10 AM, 3 PM, and 5 PM). IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and reported in millimeters mercury (mmHg). One eye was chosen as the study eye and only data for the study eye were used for the analyses. A more negative percent change from baseline indicates a greater amount of improvement, i.e., a reduction of IOP.

Outcome measures

Measure	SIMBRINZA n=103 Participants 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with travoprost 0.004% ophthalmic solution, 1 drop in each eye at bedtime, for 6 weeks	Vehicle n=112 Participants 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with travoprost 0.004% ophthalmic solution, 1 drop in each eye at bedtime, for 6 weeks
Mean Diurnal IOP Percentage Change From Baseline to Week 6	-22.27 percent change Standard Deviation 10.842	-9.57 percent change Standard Deviation 12.923

Adverse Events

Pre-Treatment

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

SIMBRINZA

Serious events: 0 serious events

Other events: 26 other events

Deaths: 0 deaths

Vehicle

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Measure	Pre-Treatment n=307 participants at risk Travoprost 0.004% ophthalmic solution, 1 drop in each eye at bedtime for a 4-week run-in period	SIMBRINZA n=117 participants at risk 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with travoprost 0.004% ophthalmic solution, 1 drop in each eye at bedtime for a 6-week treatment period	Vehicle n=116 participants at risk 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with travoprost 0.004% ophthalmic solution, 1 drop in each eye at bedtime for a 6-week treatment period
Nervous system disorders Syncope	0.33% 1/307 • Adverse events (AEs) were collected for the duration of the study, Oct 2013-Apr 2014. This analysis population includes all consented subjects. Adverse events are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a subject who was administered a study medication, regardless of whether or not the event had a causal relationship with the medication. All AEs were obtained as solicited and spontaneous comments from the subjects, and as observations by the Investigator, as outlined in the study protocol.	0.00% 0/117 • Adverse events (AEs) were collected for the duration of the study, Oct 2013-Apr 2014. This analysis population includes all consented subjects. Adverse events are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a subject who was administered a study medication, regardless of whether or not the event had a causal relationship with the medication. All AEs were obtained as solicited and spontaneous comments from the subjects, and as observations by the Investigator, as outlined in the study protocol.	0.00% 0/116 • Adverse events (AEs) were collected for the duration of the study, Oct 2013-Apr 2014. This analysis population includes all consented subjects. Adverse events are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a subject who was administered a study medication, regardless of whether or not the event had a causal relationship with the medication. All AEs were obtained as solicited and spontaneous comments from the subjects, and as observations by the Investigator, as outlined in the study protocol.

Other adverse events

Measure	Pre-Treatment n=307 participants at risk Travoprost 0.004% ophthalmic solution, 1 drop in each eye at bedtime for a 4-week run-in period	SIMBRINZA n=117 participants at risk 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with travoprost 0.004% ophthalmic solution, 1 drop in each eye at bedtime for a 6-week treatment period	Vehicle n=116 participants at risk 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with travoprost 0.004% ophthalmic solution, 1 drop in each eye at bedtime for a 6-week treatment period
Eye disorders Conjunctival hyperaemia	0.65% 2/307 • Adverse events (AEs) were collected for the duration of the study, Oct 2013-Apr 2014. This analysis population includes all consented subjects. Adverse events are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a subject who was administered a study medication, regardless of whether or not the event had a causal relationship with the medication. All AEs were obtained as solicited and spontaneous comments from the subjects, and as observations by the Investigator, as outlined in the study protocol.	13.7% 16/117 • Adverse events (AEs) were collected for the duration of the study, Oct 2013-Apr 2014. This analysis population includes all consented subjects. Adverse events are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a subject who was administered a study medication, regardless of whether or not the event had a causal relationship with the medication. All AEs were obtained as solicited and spontaneous comments from the subjects, and as observations by the Investigator, as outlined in the study protocol.	6.0% 7/116 • Adverse events (AEs) were collected for the duration of the study, Oct 2013-Apr 2014. This analysis population includes all consented subjects. Adverse events are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a subject who was administered a study medication, regardless of whether or not the event had a causal relationship with the medication. All AEs were obtained as solicited and spontaneous comments from the subjects, and as observations by the Investigator, as outlined in the study protocol.
Eye disorders Vision blurred	0.00% 0/307 • Adverse events (AEs) were collected for the duration of the study, Oct 2013-Apr 2014. This analysis population includes all consented subjects. Adverse events are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a subject who was administered a study medication, regardless of whether or not the event had a causal relationship with the medication. All AEs were obtained as solicited and spontaneous comments from the subjects, and as observations by the Investigator, as outlined in the study protocol.	6.0% 7/117 • Adverse events (AEs) were collected for the duration of the study, Oct 2013-Apr 2014. This analysis population includes all consented subjects. Adverse events are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a subject who was administered a study medication, regardless of whether or not the event had a causal relationship with the medication. All AEs were obtained as solicited and spontaneous comments from the subjects, and as observations by the Investigator, as outlined in the study protocol.	4.3% 5/116 • Adverse events (AEs) were collected for the duration of the study, Oct 2013-Apr 2014. This analysis population includes all consented subjects. Adverse events are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a subject who was administered a study medication, regardless of whether or not the event had a causal relationship with the medication. All AEs were obtained as solicited and spontaneous comments from the subjects, and as observations by the Investigator, as outlined in the study protocol.
Gastrointestinal disorders Dry mouth	0.33% 1/307 • Adverse events (AEs) were collected for the duration of the study, Oct 2013-Apr 2014. This analysis population includes all consented subjects. Adverse events are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a subject who was administered a study medication, regardless of whether or not the event had a causal relationship with the medication. All AEs were obtained as solicited and spontaneous comments from the subjects, and as observations by the Investigator, as outlined in the study protocol.	7.7% 9/117 • Adverse events (AEs) were collected for the duration of the study, Oct 2013-Apr 2014. This analysis population includes all consented subjects. Adverse events are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a subject who was administered a study medication, regardless of whether or not the event had a causal relationship with the medication. All AEs were obtained as solicited and spontaneous comments from the subjects, and as observations by the Investigator, as outlined in the study protocol.	1.7% 2/116 • Adverse events (AEs) were collected for the duration of the study, Oct 2013-Apr 2014. This analysis population includes all consented subjects. Adverse events are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a subject who was administered a study medication, regardless of whether or not the event had a causal relationship with the medication. All AEs were obtained as solicited and spontaneous comments from the subjects, and as observations by the Investigator, as outlined in the study protocol.

Additional Information

Doug Hubatsch, Global Brand Leader, Medical Affairs, Glaucoma

Alcon Research, Ltd.

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