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6-Week Proof-of-Concept Study of Travoprost/Brinzolamide Ophthalmic Suspension in Subjects With Open-Angle Glaucoma or Ocular Hypertension

Sponsor
Alcon Research (Industry)
Overall Status
Completed
CT.gov ID
NCT02140060
Collaborator
(none)
327
Enrollment
6
Arms
5
Duration (Months)

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate Travoprost/Brinzolamide fixed combination (Trav/Brinz) administered twice daily as compared to each of its marketed components (TRAVATAN Z® solution and AZOPT® suspension) and to the unfixed combination of TRAVATAN Z® plus AZOPT® in lowering intraocular pressure (IOP).

Condition or Disease Intervention/Treatment Phase
  • Drug: Dose Level A / Brinzolamide 1% ophthalmic suspension
  • Drug: Dose Level B / Brinzolamide 1% ophthalmic suspension
  • Drug: Dose Level C / Brinzolamide 1% ophthalmic suspension
  • Drug: Brinzolamide 1% ophthalmic suspension AZOPT®
  • Drug: Travoprost 0.004% ophthalmic solution TRAVATAN Z®
  • Drug: Travoprost solution vehicle
  • Drug: Brinzolamide suspension vehicle
 Phase 2

Detailed Description

This study was divided into two phases conducted in sequence. Phase I was the Screening/Eligibility Phase, which included a Screening Visit, followed by two Eligibility Visits. Phase II was the randomized, double-masked, 6-week Treatment Phase which included on-therapy visits at Week 2 and Week 6. Travoprost was administered in 1 of 3 concentration levels (A-C), where A=lowest and C=highest.

Study Design

Study Type:
Interventional
Actual Enrollment :
327 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A 6-Week Proof-of-Concept Study Evaluating the Safety and IOP-Lowering Efficacy of Travoprost/Brinzolamide Fixed Combination Ophthalmic Suspension in Subjects With Open-Angle Glaucoma or Ocular Hypertension
Study Start Date :
Jun 1, 2014
Actual Primary Completion Date :
Nov 1, 2014
Actual Study Completion Date :
Nov 1, 2014

Arms and Interventions

Arm Intervention/Treatment
Experimental: TravA/Brinz

Dose Level A / Brinzolamide 1% ophthalmic suspension (fixed combination), 1 drop twice daily in the treated eye(s) morning and night, with travoprost solution vehicle, 1 drop once daily in the treated eye(s) at night, for 6 weeks

Drug: Dose Level A / Brinzolamide 1% ophthalmic suspension
Fixed combination

Drug: Travoprost solution vehicle
Inactive ingredients used for masking purposes
Experimental: TravB/Brinz

Dose Level B / Brinzolamide 1% ophthalmic suspension (fixed combination), 1 drop twice daily in the treated eye(s) morning and night, with travoprost solution vehicle, 1 drop once daily in the treated eye(s) at night, for 6 weeks

Drug: Dose Level B / Brinzolamide 1% ophthalmic suspension
Fixed combination

Drug: Travoprost solution vehicle
Inactive ingredients used for masking purposes
Experimental: TravC/Brinz

Dose Level C / Brinzolamide 1% ophthalmic suspension (fixed combination), 1 drop twice daily in the treated eye(s) morning and night, with travoprost solution vehicle, 1 drop once daily in the treated eye(s) at night, for 6 weeks

Drug: Dose Level C / Brinzolamide 1% ophthalmic suspension
Fixed combination

Drug: Travoprost solution vehicle
Inactive ingredients used for masking purposes
Active Comparator: AZOPT

Brinzolamide 1% ophthalmic suspension, 1 drop twice daily in the treated eye(s) morning and night, with travoprost solution vehicle, 1 drop once daily in the treated eye(s) at night for 6 weeks

Drug: Brinzolamide 1% ophthalmic suspension AZOPT®
Other Names:
  • AZOPT®

    • Drug: Travoprost solution vehicle
    Inactive ingredients used for masking purposes
    Active Comparator: TRAV Z

    Brinzolamide suspension vehicle, 1 drop twice daily in the treated eye(s) morning and night, with travoprost 0.004% ophthalmic solution, 1 drop once daily in the treated eye(s) at night, for 6 weeks

    Drug: Travoprost 0.004% ophthalmic solution TRAVATAN Z®
    Other Names:
  • TRAVATAN Z®

    • Drug: Brinzolamide suspension vehicle
    Inactive ingredients used for masking purposes
    Active Comparator: TRAV Z + AZOPT

    Brinzolamide 1% ophthalmic suspension, 1 drop twice daily in the treated eye(s) twice daily morning and night, with travoprost 0.004% ophthalmic solution, 1 drop once daily in the treated eye(s) at night, for 6 weeks

    Drug: Brinzolamide 1% ophthalmic suspension AZOPT®
    Other Names:
  • AZOPT®

    • Drug: Travoprost 0.004% ophthalmic solution TRAVATAN Z®
    Other Names:
  • TRAVATAN Z®

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Mean IOP at Week 6 [Week 6, 8 AM, 10 AM, 12 PM, 4 PM, and 8 PM]

      IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and measured in millimeters of mercury (mmHg). A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). One eye (study eye) was used for the analysis.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Diagnosed with open-angle glaucoma (including open-angle glaucoma with pseudoexfoliation or pigment dispersion) or ocular hypertension;

    • IOP within the protocol-specified range at both the Eligibility 1 and 2 Visits. Mean IOP must not be >36 mmHg at any time point;

    • Able to understand and sign an informed consent form;

    • Other protocol-specified inclusion criteria may apply.

    Exclusion Criteria:

    • Woman of childbearing potential who is currently pregnant, intends to become pregnant during the study period, breastfeeding, or not using adequate birth control methods to prevent pregnancy throughout the study;

    • Unable to discontinue all IOP-lowering ocular medication(s) per the appropriate washout schedule prior to the E1 Visit;

    • Chronic, recurrent or severe inflammatory eye disease;

    • Ocular trauma within the past 6 months prior to the Screening Visit;

    • Ocular infection or ocular inflammation within the past 3 months prior to the Screening Visit;

    • Clinically relevant or progressive retinal disease such as retinal degeneration, diabetic retinopathy, or retinal detachment;

    • Best-corrected visual acuity (BCVA) score worse than 55 ETDRS letters (equivalent to approximately 0.60 logMAR, 20/80 Snellen, or 0.25 decimal);

    • Other ocular pathology (including severe dry eye) that may, in the opinion of the Investigator, preclude the administration of a topical prostaglandin analogue or topical carbonic anhydrase inhibitor;

    • Intraocular surgery within the past 6 months prior to the Screening Visit;

    • Ocular laser surgery within the past 3 months prior to the Screening Visit;

    • Any abnormality preventing reliable applanation tonometry;

    • Any other conditions including severe illness which would make the subject, in the opinion of the Investigator, unsuitable for the study;

    • History of hepatic or renal disease that would preclude the safe administration of a carbonic anhydrase inhibitor (CAI) in the opinion of the Investigator;

    • Hypersensitivity to prostaglandin analogues, topical or oral CAIs, sulfonamide derivatives, or to any component of the study medications in the opinion of the Investigator;

    • Recent (within 4 weeks of the Eligibility 1 Visit) use of high dose (> 1 g daily) salicylate therapy;

    • Use of any additional topical or systemic ocular hypotensive medication during the study;

    • Concurrent use of glucocorticoids administered by any route;

    • Less than 30 days stable dosing regimen before the Screening Visit of any medications (excluding the IOP-lowering treatments) or substances administered by any route and used on a chronic basis that may affect IOP (ie, β adrenergic blocking agents);

    • Therapy with another investigational agent within 30 days prior to the Screening Visit;

    • Other protocol-specified exclusion criteria may apply.

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Alcon Research

    Investigators

    • Study Director: Sr. Clinical Manager, GCRA, Pharma, Alcon Research

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Alcon Research
    ClinicalTrials.gov Identifier:
    NCT02140060
    Other Study ID Numbers:
    • C-14-003
    First Posted:
    May 16, 2014
    Last Update Posted:
    Dec 29, 2015
    Last Verified:
    Nov 1, 2015
    Keywords provided by Alcon Research
    Glaucoma
    Ocular
    Hypertension
    OAG
    POAG
    OHT
    Additional relevant MeSH terms:
    Glaucoma
    Glaucoma, Open-Angle
    Ocular Hypertension
    Hypertension
    Travoprost
    Pharmaceutical Solutions
    Ophthalmic Solutions
    Brinzolamide

    Study Results

    Participant Flow

    Recruitment Details Subjects were recruited from 19 study centers located in the US.
    Pre-assignment Detail Of the 327 enrolled, 61 subjects were discontinued prior to randomization. This reporting group includes all randomized subjects (266).
    Arm/Group Title TravA/Brinz TravB/Brinz TravC/Brinz TRAV Z AZOPT TRAV Z + AZOPT
    Arm/Group Description Fixed combination, 1 drop twice daily in the treated eye(s) morning and night, with travoprost solution vehicle, 1 drop once daily in the treated eye(s) at night, for 6 weeks Fixed combination, 1 drop twice daily in the treated eye(s) morning and night, with travoprost solution vehicle, 1 drop once daily in the treated eye(s) at night, for 6 weeks Fixed combination, 1 drop twice daily in the treated eye(s) morning and night, with travoprost solution vehicle, 1 drop once daily in the treated eye(s) at night, for 6 weeks Suspension vehicle, 1 drop twice daily in the treated eye(s) morning and night, with travoprost 0.004% ophthalmic solution, 1 drop once daily in the treated eye(s) at night, for 6 weeks Ophthalmic suspension, 1 drop twice daily in the treated eye(s) morning and night, with travoprost solution vehicle, 1 drop once daily in the treated eye(s) at night for 6 weeks Ophthalmic suspension, 1 drop twice daily in the treated eye(s) twice daily morning and night, with travoprost 0.004% ophthalmic solution, 1 drop once daily in the treated eye(s) at night, for 6 weeks
    Period Title: Overall Study
    STARTED 44 44 44 45 45 44
    COMPLETED 44 44 44 43 44 43
    NOT COMPLETED 0 0 0 2 1 1

    Baseline Characteristics

    Arm/Group Title TravA/Brinz TravB/Brinz TravC/Brinz TRAV Z AZOPT TRAV Z + AZOPT Total
    Arm/Group Description Fixed combination, 1 drop twice daily in the treated eye(s) morning and night, with travoprost solution vehicle, 1 drop once daily in the treated eye(s) at night, for 6 weeks Fixed combination, 1 drop twice daily in the treated eye(s) morning and night, with travoprost solution vehicle, 1 drop once daily in the treated eye(s) at night, for 6 weeks Fixed combination, 1 drop twice daily in the treated eye(s) morning and night, with travoprost solution vehicle, 1 drop once daily in the treated eye(s) at night, for 6 weeks Suspension vehicle, 1 drop twice daily in the treated eye(s) morning and night, with travoprost 0.004% ophthalmic solution, 1 drop once daily in the treated eye(s) at night, for 6 weeks Ophthalmic suspension, 1 drop twice daily in the treated eye(s) morning and night, with travoprost solution vehicle, 1 drop once daily in the treated eye(s) at night for 6 weeks Ophthalmic suspension, 1 drop twice daily in the treated eye(s) twice daily morning and night, with travoprost 0.004% ophthalmic solution, 1 drop once daily in the treated eye(s) at night, for 6 weeks Total of all reporting groups
    Overall Participants 44 44 44 45 45 43 265
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    65.4
    (10.7)
    66.2
    (10.4)
    64.4
    (11.2)
    64.2
    (10.4)
    63.1
    (8.4)
    65.3
    (10.6)
    64.8
    (10.3)
    Sex: Female, Male (Count of Participants)
    Female
    29
    65.9%
    26
    59.1%
    30
    68.2%
    25
    55.6%
    23
    51.1%
    19
    44.2%
    152
    57.4%
    Male
    15
    34.1%
    18
    40.9%
    14
    31.8%
    20
    44.4%
    22
    48.9%
    24
    55.8%
    113
    42.6%

    Outcome Measures

    1. Primary Outcome
    Title Mean IOP at Week 6
    Description IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and measured in millimeters of mercury (mmHg). A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). One eye (study eye) was used for the analysis.
    Time Frame Week 6, 8 AM, 10 AM, 12 PM, 4 PM, and 8 PM

    Outcome Measure Data

    Analysis Population Description
    This analysis population includes all subjects who were randomized, received study medication, and completed at least 1 scheduled on-therapy study visit, based upon a last on-therapy carried forward (LOCF) analysis. Here, "n" is the number of subjects with non-missing values at the specific time point for each arm, respectively.
    Arm/Group Title TravA/Brinz TravB/Brinz TravC/Brinz TRAV Z AZOPT TRAV Z + AZOPT
    Arm/Group Description Fixed combination, 1 drop twice daily in the treated eye(s) morning and night, with travoprost solution vehicle, 1 drop once daily in the treated eye(s) at night, for 6 weeks Fixed combination, 1 drop twice daily in the treated eye(s) morning and night, with travoprost solution vehicle, 1 drop once daily in the treated eye(s) at night, for 6 weeks Fixed combination, 1 drop twice daily in the treated eye(s) morning and night, with travoprost solution vehicle, 1 drop once daily in the treated eye(s) at night, for 6 weeks Suspension vehicle, 1 drop twice daily in the treated eye(s) morning and night, with travoprost 0.004% ophthalmic solution, 1 drop once daily in the treated eye(s) at night, for 6 weeks Ophthalmic suspension, 1 drop twice daily in the treated eye(s) morning and night, with travoprost solution vehicle, 1 drop once daily in the treated eye(s) at night for 6 weeks Ophthalmic suspension, 1 drop twice daily in the treated eye(s) twice daily morning and night, with travoprost 0.004% ophthalmic solution, 1 drop once daily in the treated eye(s) at night, for 6 weeks
    Measure Participants 44 44 44 45 45 43
    8 AM
    20.2
    (0.52)
    18.7
    (0.48)
    19.9
    (0.58)
    19.3
    (0.48)
    22.0
    (0.45)
    20.3
    (0.72)
    10 AM
    18.9
    (0.47)
    17.2
    (0.35)
    18.2
    (0.55)
    17.4
    (0.47)
    19.7
    (0.50)
    18.2
    (0.59)
    12 PM
    18.9
    (0.47)
    17.3
    (0.50)
    17.7
    (0.51)
    17.2
    (0.50)
    19.5
    (0.53)
    18.0
    (0.57)
    4PM
    18.5
    (0.46)
    17.5
    (0.43)
    17.3
    (0.46)
    17.6
    (0.44)
    19.1
    (0.50)
    18.0
    (0.52)
    8 PM, n=44, 44, 44, 43, 45, 43
    18.4
    (0.43)
    17.5
    (0.39)
    17.2
    (0.40)
    17.3
    (0.43)
    19.3
    (0.48)
    18.1
    (0.49)

    Adverse Events

    Time Frame Adverse events (AEs) were collected for the duration of a subject's participation in the study (up to 11 weeks). AEs were reported as pre-treatment and treatment-emergent.
    Adverse Event Reporting Description 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. AEs were obtained through solicited and spontaneous comments from study subjects, and through observations by the study Investigator.
    Arm/Group Title TravA/Brinz TravB/Brinz TravC/Brinz TRAV Z AZOPT TRAV Z + AZOPT Pre-treatment
    Arm/Group Description Fixed combination, 1 drop twice daily in the treated eye(s) morning and night, with travoprost solution vehicle, 1 drop once daily in the treated eye(s) at night, for 6 weeks Fixed combination, 1 drop twice daily in the treated eye(s) morning and night, with travoprost solution vehicle, 1 drop once daily in the treated eye(s) at night, for 6 weeks Fixed combination, 1 drop twice daily in the treated eye(s) morning and night, with travoprost solution vehicle, 1 drop once daily in the treated eye(s) at night, for 6 weeks Suspension vehicle, 1 drop twice daily in the treated eye(s) morning and night, with travoprost 0.004% ophthalmic solution, 1 drop once daily in the treated eye(s) at night, for 6 weeks Ophthalmic suspension, 1 drop twice daily in the treated eye(s) morning and night, with travoprost solution vehicle, 1 drop once daily in the treated eye(s) at night for 6 weeks Ophthalmic suspension, 1 drop twice daily in the treated eye(s) twice daily morning and night, with travoprost 0.004% ophthalmic solution, 1 drop once daily in the treated eye(s) at night, for 6 weeks All subjects who signed an informed consent to participate in the study
    All Cause Mortality
    TravA/Brinz TravB/Brinz TravC/Brinz TRAV Z AZOPT TRAV Z + AZOPT Pre-treatment
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    TravA/Brinz TravB/Brinz TravC/Brinz TRAV Z AZOPT TRAV Z + AZOPT Pre-treatment
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/44 (0%) 0/44 (0%) 0/44 (0%) 1/45 (2.2%) 0/45 (0%) 0/44 (0%) 1/327 (0.3%)
    Cardiac disorders
    Angina unstable 0/44 (0%) 0/44 (0%) 0/44 (0%) 1/45 (2.2%) 0/45 (0%) 0/44 (0%) 0/327 (0%)
    Atrial fibrillation 0/44 (0%) 0/44 (0%) 0/44 (0%) 0/45 (0%) 0/45 (0%) 0/44 (0%) 1/327 (0.3%)
    Other (Not Including Serious) Adverse Events
    TravA/Brinz TravB/Brinz TravC/Brinz TRAV Z AZOPT TRAV Z + AZOPT Pre-treatment
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 7/44 (15.9%) 11/44 (25%) 15/44 (34.1%) 10/45 (22.2%) 9/45 (20%) 13/44 (29.5%) 1/327 (0.3%)
    Eye disorders
    Ocular hyperaemia 2/44 (4.5%) 8/44 (18.2%) 6/44 (13.6%) 7/45 (15.6%) 0/45 (0%) 8/44 (18.2%) 0/327 (0%)
    Conjunctival hyperaemia 0/44 (0%) 3/44 (6.8%) 3/44 (6.8%) 3/45 (6.7%) 3/45 (6.7%) 3/44 (6.8%) 1/327 (0.3%)
    Eye irritation 2/44 (4.5%) 2/44 (4.5%) 2/44 (4.5%) 2/45 (4.4%) 3/45 (6.7%) 1/44 (2.3%) 0/327 (0%)
    Eye pain 2/44 (4.5%) 2/44 (4.5%) 3/44 (6.8%) 0/45 (0%) 1/45 (2.2%) 1/44 (2.3%) 0/327 (0%)
    Nervous system disorders
    Dysgeusia 2/44 (4.5%) 0/44 (0%) 3/44 (6.8%) 1/45 (2.2%) 4/45 (8.9%) 3/44 (6.8%) 0/327 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Sponsor reserves the right of prior review of any publication or presentation of information related to the study.

    Results Point of Contact

    Name/Title Clinical Project Lead, GCRA, Pharma
    Organization Alcon Research, Ltd.
    Phone 1-888-451-3937
    Email alcon.medinfo@alcon.com
    Responsible Party:
    Alcon Research
    ClinicalTrials.gov Identifier:
    NCT02140060
    Other Study ID Numbers:
    • C-14-003
    First Posted:
    May 16, 2014
    Last Update Posted:
    Dec 29, 2015
    Last Verified:
    Nov 1, 2015