Trial Outcomes & Findings for Effect of SIMBRINZA® Suspension as an Added Therapy to a Prostaglandin Analogue (NCT NCT01937312)

NCT ID: NCT01937312

Last Updated: 2015-07-28

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 analysis. 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: 282 participants
• Primary outcome timeframe: Week 6
• Results posted on: 2015-07-28

Participant Flow

Participants were recruited and enrolled from 30 investigative sites located in the US.

Of the 282 enrolled, 93 participants were exited from the study as screen failures prior to randomization. This reporting group includes all randomized participants (189). Note: One subject randomized to SIMBRINZA® Suspension was not exposed to investigational product.

Participant milestones

Measure	SIMBRINZA 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with prostaglandin analogue, 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 prostaglandin analogue, 1 drop in each eye at bedtime, for 6 weeks
Overall Study STARTED	94	95
Overall Study Treated	93	95
Overall Study COMPLETED	83	92
Overall Study NOT COMPLETED	11	3

Reasons for withdrawal

Measure	SIMBRINZA 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with prostaglandin analogue, 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 prostaglandin analogue, 1 drop in each eye at bedtime, for 6 weeks
Overall Study Adverse Event	10	1
Overall Study Lack of Efficacy	0	1
Overall Study Withdrawal of subject prior to treatment	1	1

Baseline Characteristics

Effect of SIMBRINZA® Suspension as an Added Therapy to a Prostaglandin Analogue

Baseline characteristics by cohort

Measure	SIMBRINZA n=88 Participants 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with prostaglandin analogue, 1 drop in each eye at bedtime, for 6 weeks	Vehicle n=94 Participants 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with prostaglandin analogue, 1 drop in each eye at bedtime, for 6 weeks	Total n=182 Participants Total of all reporting groups
Age, Continuous	65.5 years STANDARD_DEVIATION 9.4 • n=93 Participants	64.7 years STANDARD_DEVIATION 9.6 • n=4 Participants	65.1 years STANDARD_DEVIATION 9.5 • n=27 Participants
Sex: Female, Male Female	53 Participants n=93 Participants	63 Participants n=4 Participants	116 Participants n=27 Participants
Sex: Female, Male Male	35 Participants n=93 Participants	31 Participants n=4 Participants	66 Participants n=27 Participants
Mean Diurnal Intraocular Pressure (IOP) at Baseline	22.68 mmHg STANDARD_DEVIATION 2.123 • n=93 Participants	22.39 mmHg STANDARD_DEVIATION 2.774 • n=4 Participants	22.53 mmHg STANDARD_DEVIATION 2.478 • n=27 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 visit (intent-to-treat). 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 analysis. 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=83 Participants 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with prostaglandin analogue, 1 drop in each eye at bedtime, for 6 weeks	Vehicle n=92 Participants 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with prostaglandin analogue, 1 drop in each eye at bedtime, for 6 weeks
Mean Diurnal Intraocular Pressure (IOP) at Week 6	17.01 mmHg Standard Deviation 2.897	20.37 mmHg Standard Deviation 3.914

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 visit (intent-to-treat). 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 analysis. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP.

Outcome measures

Measure	SIMBRINZA n=83 Participants 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with prostaglandin analogue, 1 drop in each eye at bedtime, for 6 weeks	Vehicle n=92 Participants 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with prostaglandin analogue, 1 drop in each eye at bedtime, for 6 weeks
Mean Diurnal IOP Change From Baseline to Week 6	-5.69 mmHg Standard Deviation 2.571	-1.99 mmHg Standard Deviation 2.865

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 visit (intent-to-treat). 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 analysis. A more negative percent change from baseline indicates a greater amount of improvement, i.e., a reduction of IOP.

Outcome measures

Measure	SIMBRINZA n=83 Participants 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with prostaglandin analogue, 1 drop in each eye at bedtime, for 6 weeks	Vehicle n=92 Participants 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with prostaglandin analogue, 1 drop in each eye at bedtime, for 6 weeks
Mean Diurnal IOP Percentage Change From Baseline to Week 6	-24.88 percent change Standard Deviation 10.818	-8.50 percent change Standard Deviation 12.396

SECONDARY outcome

Timeframe: Week 6

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

IOP was assessed using Goldmann applanation tonometry and reported in mmHg. One eye was chosen as the study eye and only data for the study eye were used for the analysis. 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=83 Participants 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with prostaglandin analogue, 1 drop in each eye at bedtime, for 6 weeks	Vehicle n=92 Participants 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with prostaglandin analogue, 1 drop in each eye at bedtime, for 6 weeks
Mean IOP at Week 6 for Each Time Point (8 AM, 10 AM, 3 PM, 5 PM) 8 AM	19.4 mmHg Standard Deviation 3.53	21.4 mmHg Standard Deviation 4.33
Mean IOP at Week 6 for Each Time Point (8 AM, 10 AM, 3 PM, 5 PM) 10 AM	15.8 mmHg Standard Deviation 3.54	20.2 mmHg Standard Deviation 4.17
Mean IOP at Week 6 for Each Time Point (8 AM, 10 AM, 3 PM, 5 PM) 3 PM	17.2 mmHg Standard Deviation 3.15	19.9 mmHg Standard Deviation 4.28
Mean IOP at Week 6 for Each Time Point (8 AM, 10 AM, 3 PM, 5 PM) 5 PM	15.6 mmHg Standard Deviation 3.14	19.9 mmHg Standard Deviation 4.41

Adverse Events

Pre-Treatment

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

SIMBRINZA

Serious events: 1 serious events

Other events: 16 other events

Deaths: 0 deaths

Vehicle

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Measure	Pre-Treatment n=282 participants at risk Prostaglandin analogue, 1 drop in each eye at bedtime for a 4-week run-in period	SIMBRINZA n=93 participants at risk 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with prostaglandin analogue, 1 drop in each eye at bedtime, for 6 weeks	Vehicle n=95 participants at risk 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with prostaglandin analogue, 1 drop in each eye at bedtime, for 6 weeks
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/282 • Adverse events (AEs) were collected for the duration of the study, Oct 2013-May 2014. Adverse events are reported as pre-treatment and treatment-emergent. The treatment-emergent analysis set included all subjects exposed to investigational product. 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.	1.1% 1/93 • Adverse events (AEs) were collected for the duration of the study, Oct 2013-May 2014. Adverse events are reported as pre-treatment and treatment-emergent. The treatment-emergent analysis set included all subjects exposed to investigational product. 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% 0/95 • Adverse events (AEs) were collected for the duration of the study, Oct 2013-May 2014. Adverse events are reported as pre-treatment and treatment-emergent. The treatment-emergent analysis set included all subjects exposed to investigational product. 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic malignant melanoma	0.00% 0/282 • Adverse events (AEs) were collected for the duration of the study, Oct 2013-May 2014. Adverse events are reported as pre-treatment and treatment-emergent. The treatment-emergent analysis set included all subjects exposed to investigational product. 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.	1.1% 1/93 • Adverse events (AEs) were collected for the duration of the study, Oct 2013-May 2014. Adverse events are reported as pre-treatment and treatment-emergent. The treatment-emergent analysis set included all subjects exposed to investigational product. 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% 0/95 • Adverse events (AEs) were collected for the duration of the study, Oct 2013-May 2014. Adverse events are reported as pre-treatment and treatment-emergent. The treatment-emergent analysis set included all subjects exposed to investigational product. 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=282 participants at risk Prostaglandin analogue, 1 drop in each eye at bedtime for a 4-week run-in period	SIMBRINZA n=93 participants at risk 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with prostaglandin analogue, 1 drop in each eye at bedtime, for 6 weeks	Vehicle n=95 participants at risk 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with prostaglandin analogue, 1 drop in each eye at bedtime, for 6 weeks
Eye disorders Vision Blurred	0.00% 0/282 • Adverse events (AEs) were collected for the duration of the study, Oct 2013-May 2014. Adverse events are reported as pre-treatment and treatment-emergent. The treatment-emergent analysis set included all subjects exposed to investigational product. 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.	9.7% 9/93 • Adverse events (AEs) were collected for the duration of the study, Oct 2013-May 2014. Adverse events are reported as pre-treatment and treatment-emergent. The treatment-emergent analysis set included all subjects exposed to investigational product. 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.	6.3% 6/95 • Adverse events (AEs) were collected for the duration of the study, Oct 2013-May 2014. Adverse events are reported as pre-treatment and treatment-emergent. The treatment-emergent analysis set included all subjects exposed to investigational product. 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 Eye irritation	0.35% 1/282 • Adverse events (AEs) were collected for the duration of the study, Oct 2013-May 2014. Adverse events are reported as pre-treatment and treatment-emergent. The treatment-emergent analysis set included all subjects exposed to investigational product. 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.	6.5% 6/93 • Adverse events (AEs) were collected for the duration of the study, Oct 2013-May 2014. Adverse events are reported as pre-treatment and treatment-emergent. The treatment-emergent analysis set included all subjects exposed to investigational product. 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.	1.1% 1/95 • Adverse events (AEs) were collected for the duration of the study, Oct 2013-May 2014. Adverse events are reported as pre-treatment and treatment-emergent. The treatment-emergent analysis set included all subjects exposed to investigational product. 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 Eye Pruritus	0.00% 0/282 • Adverse events (AEs) were collected for the duration of the study, Oct 2013-May 2014. Adverse events are reported as pre-treatment and treatment-emergent. The treatment-emergent analysis set included all subjects exposed to investigational product. 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.	6.5% 6/93 • Adverse events (AEs) were collected for the duration of the study, Oct 2013-May 2014. Adverse events are reported as pre-treatment and treatment-emergent. The treatment-emergent analysis set included all subjects exposed to investigational product. 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% 0/95 • Adverse events (AEs) were collected for the duration of the study, Oct 2013-May 2014. Adverse events are reported as pre-treatment and treatment-emergent. The treatment-emergent analysis set included all subjects exposed to investigational product. 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 Ocular hyperaemia	0.71% 2/282 • Adverse events (AEs) were collected for the duration of the study, Oct 2013-May 2014. Adverse events are reported as pre-treatment and treatment-emergent. The treatment-emergent analysis set included all subjects exposed to investigational product. 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.	5.4% 5/93 • Adverse events (AEs) were collected for the duration of the study, Oct 2013-May 2014. Adverse events are reported as pre-treatment and treatment-emergent. The treatment-emergent analysis set included all subjects exposed to investigational product. 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.	2.1% 2/95 • Adverse events (AEs) were collected for the duration of the study, Oct 2013-May 2014. Adverse events are reported as pre-treatment and treatment-emergent. The treatment-emergent analysis set included all subjects exposed to investigational product. 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

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