Clinical Trial Results:
Additive Effect of Twice Daily Brinzolamide 1% /Brimonidine 0.2% Fixed Dose Combination as an Adjunctive Therapy to a Prostaglandin Analogue
Summary
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EudraCT number |
2015-000736-15 |
Trial protocol |
DE ES GB FR GR |
Global end of trial date |
27 Feb 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
01 Dec 2018
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First version publication date |
01 Dec 2018
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
GLH694-P001
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02419508 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Alcon Research Ltd
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Sponsor organisation address |
6201 S. Freeway, Fort Worth, TX, United States, 76134
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Public contact |
EMEA Regulatory Affairs, Alcon Eye Care (UK) Ltd, eurmea.ra@alcon.com
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Scientific contact |
EMEA Regulatory Affairs, Alcon Eye Care (UK) Ltd, eurmea.ra@alcon.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
27 Feb 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
27 Feb 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
27 Feb 2018
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The purpose of this study is to evaluate the additive intraocular pressure (IOP) lowering effect of brinzolamide 1%/brimonidine 0.2% (dosed twice per day (BID)) when added to a prostaglandin analogue (PGA) in subjects with open-angle glaucoma or ocular hypertension.
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Protection of trial subjects |
Prior to the start of the study, the study protocol, the informed consent and assent documents, patient
instruction sheets, the Investigator’s Brochure, as well as any advertising materials used to recruit patients were submitted to institutional review boards (IRBs) and independent ethics committees (IECs). The IRB/IECs reviewed all documents and approved required documents; copies of the approval letters were provided to Alcon. Consistent with both the IRB/IEC’s requirements and all applicable regulations, the Investigators periodically provided study updates to the IRB/IEC. A patient or parent/legal guardian (if necessary, a legally authorized representative) provided informed consent, and children signed an approved assent form when appropriate. This study was conducted in accordance with Good Clinical Practices (GCP) and the ethical principles that have their origins in the Declaration of Helsinki.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
07 Aug 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Spain: 28
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Country: Number of subjects enrolled |
United Kingdom: 18
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Country: Number of subjects enrolled |
France: 2
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Country: Number of subjects enrolled |
Germany: 14
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Country: Number of subjects enrolled |
Greece: 14
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Country: Number of subjects enrolled |
Australia: 6
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Country: Number of subjects enrolled |
Israel: 8
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Country: Number of subjects enrolled |
Argentina: 49
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Country: Number of subjects enrolled |
Canada: 47
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Country: Number of subjects enrolled |
Chile: 2
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Worldwide total number of subjects |
188
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EEA total number of subjects |
76
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
67
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From 65 to 84 years |
115
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85 years and over |
6
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Recruitment
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Recruitment details |
This study was conducted at 37 sites located in Argentina (3), Australia (4), Canada (12), Chile (3), France (1), Germany (3), Greece (2), Israel (3), Spain (3), and United Kingdom (3). | |||||||||||||||||||||
Pre-assignment
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Screening details |
Of the 290 subjects enrolled in the study, 102 were exited during the Screening/Eligibility period. This reporting group includes all randomized subjects. One randomized subject did not receive investigational product and is excluded from the Full Analysis Set and the Safety Analysis Set. | |||||||||||||||||||||
Period 1
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Period 1 title |
Overall (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||
Roles blinded |
Subject, Investigator | |||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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SIMBRINZA + PGA | |||||||||||||||||||||
Arm description |
Brinzolamide 1%/brimonidine 0.2% tartrate ophthalmic suspension, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Brinzolamide 1%/brimonidine 0.2% tartrate ophthalmic suspension
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Investigational medicinal product code |
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Other name |
SIMBRINZA® suspension
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Pharmaceutical forms |
Eye drops, suspension
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Routes of administration |
Ophthalmic use
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Dosage and administration details |
One drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) for 42 days
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Investigational medicinal product name |
Prostaglandin analogue
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Investigational medicinal product code |
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Other name |
TRAVATAN® PQ, LUMIGAN®, XALATAN®
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Pharmaceutical forms |
Eye drops, solution
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Routes of administration |
Ophthalmic use
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Dosage and administration details |
One drop of designated prostaglandin analogue instilled in each eye once per day in the evening for 42 days
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Arm title
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Vehicle + PGA | |||||||||||||||||||||
Arm description |
Brinz/brim vehicle, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days | |||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||
Investigational medicinal product name |
Brinz/brim vehicle
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Eye drops
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Routes of administration |
Ophthalmic use
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Dosage and administration details |
One drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) for 42 days
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Investigational medicinal product name |
Prostaglandin analogue
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Eye drops, solution
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Routes of administration |
Ophthalmic use
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Dosage and administration details |
One drop of designated prostaglandin analogue instilled in each eye once per day in the evening for 42 days
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Baseline characteristics reporting groups
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Reporting group title |
SIMBRINZA + PGA
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Reporting group description |
Brinzolamide 1%/brimonidine 0.2% tartrate ophthalmic suspension, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Vehicle + PGA
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Reporting group description |
Brinz/brim vehicle, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
SIMBRINZA + PGA
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Reporting group description |
Brinzolamide 1%/brimonidine 0.2% tartrate ophthalmic suspension, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days | ||
Reporting group title |
Vehicle + PGA
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Reporting group description |
Brinz/brim vehicle, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days | ||
Subject analysis set title |
SIMBRINZA + PGA
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subjects in FAS with values at both baseline and time point
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Subject analysis set title |
Vehicle + PGA
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subjects in FAS with values at both baseline and time point
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End point title |
Mean Change From Baseline (on PGA) in Diurnal IOP (Mean of 09:00 and 11:00 Time Points) at Week 6 | ||||||||||||||||||
End point description |
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. This analysis population includes all randomized subjects who received a dose of study medication and had at least 1 of the 2 scheduled on-treatment visits [Full Analysis Set (FAS)]. Only subjects with a value at both baseline and time point are included in the calculation of change. Here, "N" is the number of subjects at baseline for each arm group, respectively.
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End point type |
Primary
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End point timeframe |
Baseline (BL), Week 6
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Statistical analysis title |
Mean Change From Baseline (on PGA) in Diurnal IOP | ||||||||||||||||||
Statistical analysis description |
Mean of 09:00 and 11:00 Time Points at Week 6
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Comparison groups |
SIMBRINZA + PGA v Vehicle + PGA
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Number of subjects included in analysis |
174
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||
Confidence interval |
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End point title |
Mean Diurnal IOP at Week 6 | ||||||||||||
End point description |
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. FAS with data available.
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End point type |
Secondary
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End point timeframe |
Week 6
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Statistical analysis title |
Mean Diurnal IOP at Week 6 | ||||||||||||
Comparison groups |
Vehicle + PGA v SIMBRINZA + PGA
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Number of subjects included in analysis |
174
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Confidence interval |
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End point title |
Mean Percentage Change From Baseline in Diurnal IOP at Week 6 | ||||||||||||
End point description |
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. FAS. Only subjects with a value at both baseline and time point are included in the calculation of change. Here, "N" is the number of subjects at baseline for each arm group, respectively.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 6
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Statistical analysis title |
Mean Percent Change From Baseline in Diurnal IOP | ||||||||||||
Comparison groups |
SIMBRINZA + PGA v Vehicle + PGA
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Number of subjects included in analysis |
174
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Confidence interval |
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End point title |
Mean Change From Baseline in IOP at 11:00 at Week 6 | ||||||||||||||||||
End point description |
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. FAS. Only subjects with a value at both baseline and time point are included in the calculation of change. Here, "N" is the number of subjects at baseline for each arm group, respectively.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 6
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Statistical analysis title |
Mean Change From BL in IOP at 11:00 at Week 6 | ||||||||||||||||||
Comparison groups |
SIMBRINZA + PGA v Vehicle + PGA
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Number of subjects included in analysis |
174
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||
Confidence interval |
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End point title |
Mean Percentage Change From Baseline in IOP at 11:00 at Week 6 | ||||||||||||
End point description |
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. FAS. Only subjects with a value at both baseline and time point are included in the calculation of change. Here, "N" is the number of subjects at baseline for each arm group, respectively.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 6
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Statistical analysis title |
Mean Percent Change From BL in IOP at 11:00 | ||||||||||||
Comparison groups |
SIMBRINZA + PGA v Vehicle + PGA
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Number of subjects included in analysis |
174
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Confidence interval |
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End point title |
Mean Change From Baseline in IOP at 09:00 at Week 6 | ||||||||||||||||||
End point description |
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. FAS. Only subjects with a value at both baseline and time point are included in the calculation of change. Here, "N" is the number of subjects at baseline for each arm group, respectively.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 6
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Statistical analysis title |
Mean Change From BL in IOP at 09:00 at Week 6 | ||||||||||||||||||
Comparison groups |
SIMBRINZA + PGA v Vehicle + PGA
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Number of subjects included in analysis |
174
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||
Confidence interval |
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End point title |
Mean Percentage Change From Baseline at 09:00 at Week 6 | ||||||||||||
End point description |
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. FAS. Only subjects with a value at both baseline and time point are included in the calculation of change. Here, "N" is the number of subjects at baseline for each arm group, respectively.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 6
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Statistical analysis title |
Mean Percent Change From BL 09:00 at Week 6 | ||||||||||||
Comparison groups |
SIMBRINZA + PGA v Vehicle + PGA
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Number of subjects included in analysis |
174
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
Baseline through study completion, an average of 6 weeks.
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Adverse event reporting additional description |
Adverse Events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol.This analysis population includes all subjects who received a dose of study medication (Safety Analysis Set).
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||
Dictionary version |
17.0
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Reporting groups
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Reporting group title |
SIMBRINZA + PGA
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Reporting group description |
Subjects exposed to Brinz/brim + PGA | |||||||||||||||||||||||||||||||||
Reporting group title |
Vehicle + PGA
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Reporting group description |
Subjects exposed to brinz/brim vehicle + PGA | |||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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30 Mar 2017 |
Removed an IOP collection time point at all visits to reduce subject commitment and aid in recruitment.
Reduced the entry IOP, allowing more subjects to be eligible while maintaining an IOP baseline that was reasonable to observe the efficacy. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |