ORIGINAL STUDY
`
`Travoprost 0.004% With and Without Benzalkonium
`Chloride: A Comparison of Safety and Efficacy
`Richard A. Lewis, MD,* Gregory J. Katz, MD,w Mark J. Weiss, MD,zTheresa A. Landry, PhD,y
`Jaime E. Dickerson, PhD,yJohn E. James, MS,ySteven Y. Hua, PhD,yE. Kenneth Sullivan, PhD,y
`Dawnelle B. Montgomery, PharmD,yDavid T. Wells, RN,y and Michael V. W. Bergamini, PhD,y
`for the Travoprost BAC-free Study Group
`
`Purpose: To compare the safety and efficacy of travoprost
`0.004% without benzalkonium chloride (BAC) to that of the
`marketed formulation of travoprost 0.004% in patients with
`open-angle glaucoma or ocular hypertension.
`
`Methods: The study was a double-masked, randomized, parallel
`group, multicenter, noninferiority design. Adult patients with
`open-angle glaucoma or ocular hypertension with qualifying
`intraocular pressure (IOP) on 2 eligibility visits received either
`travoprost 0.004% with BAC (n = 346), or travoprost 0.004%
`without BAC (n = 344) dosed once-daily each evening. Patients
`were followed for a period of 3 months. IOP measurements at 8
`AM, 10 AM, and 4 PM were taken at study visits on week 2, week 6,
`and month 3.
`
`Results: Mean IOP reductions, across all 9 study visits and times
`ranged from 7.3 to 8.5 mm Hg for travoprost 0.004% without
`BAC and from 7.4 to 8.4 mm Hg for travoprost 0.004% with
`BAC. Statistical equivalence was also demonstrated for the
`comparison of mean IOP changes; 95% confidence limits were
`within ± 0.8 mm Hg at 9 of 9 study visits and times in both the
`per protocol and intent-to-treat data sets. Adverse events and
`the number of patients discontinued owing to adverse events
`were similar for both treatment groups. Adverse events due to
`hyperemia occurred in 6.4% and 9.0% of patients treated with
`travoprost 0.004% without BAC and travoprost 0.004% with
`BAC, respectively.
`
`Conclusion: Travoprost 0.004% without BAC is equivalent to
`travoprost 0.004% with BAC in both safety and efficacy.
`
`Key Words: glaucoma, travoprost, benzalkonium chloride
`
`(J Glaucoma 2007;16:98–103)
`
`Received for publication May 2, 2006; accepted July 19, 2006.
`From the *Grutzmacher and Lewis, Inc, Sacramento, CA; wHuron
`Ophthalmology, Ypsilanti, MI; zThe Eye Institute, Tulsa, OK; and
`yAlcon Research, Ltd, Fort Worth, TX.
`Support for this study was provided by Alcon Research, Ltd, Fort
`Worth, TX.
`Reprints: Jaime E. Dickerson, PhD, Alcon Research, Ltd., Fort Worth,
`TX (e-mail: jaime.dickerson@alconlabs.com).
`Copyright r 2007 by Lippincott Williams & Wilkins
`
`98
`
`B enzalkonium chloride (BAC) is an important and
`
`widely used preservative in topical ocular prepara-
`tions and in contact lens cleaning solutions. Although
`BAC has been employed as a preservative for many years,
`numerous reports have demonstrated that prolonged use
`of topical ocular medications preserved with BAC may
`exacerbate sequelae associated with ocular surface disease
`and have adverse effects on the conjunctiva and cornea.
`These
`effects
`include
`the
`induction of
`subclinical
`inflammation,1,2 reduction of corneal epithelial barrier
`function,3,4 destabilization of the tear film,4 cataract
`formation,5 and an overall higher incidence of patient
`complaints of dryness and irritation.6–8 Potentially
`more serious is the possibility that chronic use of eye
`drops preserved with BAC could negatively impact
`rate for glaucoma filtration surgery9–12
`the success
`(cf, Johnson et al13).
`Travoprost is a selective full agonist for the FP
`prostanoid receptor.14–16 In 3 large, multicenter, double-
`masked, randomized, controlled pivotal clinical studies,
`travoprost 0.004% given as monotherapy was shown to
`provide safe and effective intraocular pressure (IOP)
`control for patients with open-angle glaucoma (OAG) or
`ocular hypertension (OHT).17–19 Travoprost 0.004%
`(TRAVATAN, Alcon Laboratories, Fort Worth, TX) is
`preserved with 0.015% BAC. Although travoprost
`0.004% has proved to be a safe and well-tolerated
`therapy since its introduction in 2001, the development
`of a formulation without BAC might prove to be
`beneficial for patients having concomitant ocular surface
`disease and for those with a sensitivity to this preserva-
`tive. This formulation might also decrease the risk of
`developing some of the conjunctival, corneal, and lens
`side effects thought
`to be caused by chronic BAC
`exposure. The objective of this study was to demonstrate
`that an alternative formulation for travoprost 0.004%,
`without BAC, has equivalent efficacy and safety to the
`current marketed formulation.
`
`MATERIALS AND METHODS
`
`Test Article
`Study patients received either travoprost 0.004%
`(marketed as TRAVATAN Ophthalmic Solution), or
`
`J Glaucoma  Volume 16, Number 1, January 2007
`
`ALCON 2019
`Apotex Corp. v. Alcon Research, Ltd.
`Case IPR2013-00428
`
`

`
`J Glaucoma  Volume 16, Number 1, January 2007
`
`Travoprost BAC-free
`
`solution formulated
`travoprost 0.004% ophthalmic
`without BAC. Both formulations meet United States
`Pharmacopeia (USP) standards for preservative efficacy.
`
`Patients
`This was a multicenter study conducted at 47 sites
`throughout the United States in accordance with the
`principles set forth in the Declaration of Helsinki. This
`double-masked, randomized, parallel-group study was
`designed to demonstrate
`equivalence of
`travoprost
`0.004% preserved with BAC (travoprost 0.004%) and
`travoprost 0.004% without BAC (travoprost BAC-free)
`in IOP-lowering efficacy. Patients were required to have
`an IOP of 24 to 36 mm Hg (inclusive) at 8 AM, and 21 to
`36 mm Hg at 10 AM and 4 PM, on 2 eligibility visits, after
`washout of previous ocular hypotensive medications. At
`least 1 eye must have qualified at each of the 6 time points
`(the same eye for all time points). The minimum period
`between the screening visit and the first eligibility visit was
`3 days for patients who were not being treated with ocular
`hypotensive agents at the time of screening, up to 28 days
`for those patients treated with b-blocking agents or
`prostaglandin analogues.
`The study was approved for each study site by the
`appropriate Institutional Review Boards and all patients
`or their legal representatives read, signed, and dated an
`Institutional Review Board-approved consent form be-
`fore undergoing a screening examination and participa-
`tion in the study.
`The study population consisted of patients of any
`race and of either sex, diagnosed with OAG (with or
`without pseudoexfoliation or pigment dispersion compo-
`nents) or OHT. Women of childbearing potential were
`allowed to participate in the study provided they were not
`pregnant or breast-feeding, had no intention of becoming
`pregnant, were using highly effective birth control
`measures, and consented to a urine pregnancy test at
`screening and upon exiting the study. Contact lens use
`was allowed, provided lenses were removed before and for
`15 minutes after instillation of drops.
`Patients were excluded from the study for any of the
`following criteria: best-corrected visual acuity worse than
`0.6 logarithm of minimal angle of resolution (logMAR) in
`either eye (20/80 Snellen equivalent); history of chronic or
`recurrent severe inflammatory eye disease; ocular trauma
`or intraocular surgery within the past 6 months in either
`eye; ocular infection, ocular inflammation, or ocular laser
`surgery within the past 3 months in either eye; clinically
`significant or progressive retinal disease; ocular disease
`precluding topical prostaglandin analogues (eg, patients
`at risk for cystoid macular edema or in patients with
`chronic or recurrent intraocular inflammation); severe
`hypersensitivity to study medications or vehicle; any
`abnormality preventing reliable applanation tonometry;
`anterior chamber angle less than 10 degrees in either eye
`as measured by gonioscopy; severe central visual field loss
`in either eye; cup-to-disc ratio greater than 0.80 in either
`eye; contraindications to pupil dilation; chronic gluco-
`corticoid use within 1 month of and during the eligibility
`
`phase or intermittent glucocorticoid use within 2 weeks of
`the eligibility phase;
`less than 30 days stable dosing
`regimen before screening of any medications that may
`affect IOP; any type of glaucoma other than OAG or
`OHT; therapy with another investigational agent within
`30 days of study start; use of any other topical or systemic
`ocular hypotensive medication during the study.
`
`Procedures
`Patients meeting inclusion and exclusion criteria at
`the screening visit discontinued the use of any ocular
`hypotensive medications for a washout of appropriate
`duration before returning for the 2 prerandomization
`eligibility visits. These washout periods were 5 days for
`carbonic anhydrase inhibitors or miotics, 2 weeks for
`a-agonists, and 4 weeks for b-blockers or prostaglandin
`analogues. Patients were considered eligible when they
`met the IOP criteria for both eligibility visits. Eligible
`patients were randomized in a 1:1 ratio to either
`travoprost 0.004% preserved with BAC (travoprost
`0.004%), or to travoprost 0.004% without BAC (travo-
`prost BAC-free). Study drugs were supplied in identical
`plastic dropper bottles, each labeled with a unique patient
`number. Patients were instructed to instill a drop in each
`study eye at approximately 8 PM each evening.
`Concomitant medications were allowed except glucocor-
`ticoids or other treatments listed in the exclusion criteria.
`Changes in concomitant medications known to affect IOP
`(eg, b-blockers) were not allowed.
`IOP was measured by Goldmann applanation
`tonometry at the screening visit and at 8 AM, 10 AM, and
`4 PM at both eligibility visits and at week 2, week 6, and
`month 3.
`Gonioscopy was performed at the screening visit.
`A slit lamp examination and logMAR visual acuity were
`performed at 8 AM on all visits. Dilated fundus examina-
`tion (including retina, macula, choroid, optic nerve head,
`vitreous, and cup-to-disc ratios), automated perimetry,
`corneal endothelial cell density, and pachymetry were all
`evaluated before randomization and at exit from the
`study.
`
`Statistical Methods
`Hypothesis tests were performed using repeated
`measures analysis of variance. For the test of equivalence,
`95% 2-sided confidence intervals for the treatment group
`difference were constructed at each visit and time point
`based on the analysis of variance. Analysis of other
`parameters was conducted using analysis of variance,
`t tests, w2 tests, or Fisher exact tests, as appropriate,
`depending on the variable being analyzed.
`Analyses were conducted using 2 data sets, intent-
`to-treat
`(ITT) and per protocol. The ITT data set
`included all patients who received study medication and
`had at least 1 on-therapy visit. The per protocol data set
`included all patients who received study medication, had
`at least 1 on-therapy visit, and satisfied all inclusion/ex-
`clusion criteria. In addition, only those data points that
`satisfied protocol criteria were included in the per
`
`r 2007 Lippincott Williams & Wilkins
`
`99
`
`

`
`Lewis et al
`
`J Glaucoma  Volume 16, Number 1, January 2007
`
`TABLE 1. Patient Demographics by Treatment Group (Per Protocol Data Set)
`
`Age group (y)
`<65
`Z65
`Mean ± SD
`Sex
`Male
`Female
`Race
`White
`Black
`Hispanic
`Asian
`Other
`Iris color
`Brown
`Hazel
`Green
`Blue
`Grey
`Diagnosis
`OHT
`OAG
`Pigmentary glaucoma
`Psuedoexfoliation glaucoma
`
`n = 332 (52.0%)
`n = 329 (48.0%)
`63.1 ± 11.0
`
`n = 307 (46.4%)
`n = 354 (53.6%)
`
`n = 446 (67.5%)
`n = 126 (19.1%)
`n = 80 (12.1%)
`n = 6 (0.9%)
`n = 3 (0.5%)
`
`n = 359 (54.3%)
`n = 102 (15.4%)
`n = 32 (4.8%)
`n = 161 (24.4%)
`n = 7 (1.1%)
`
`n = 256 (38.7%)
`n = 392 (59.3%)
`n = 11 (1.7%)
`n = 2 (0.3%)
`
`Treatment (N = 661)
`
`Travoprost BAC-free
`
`Travoprost 0.004%
`
`n (322)
`
`% (48.7)
`
`n (339)
`
`% (51.3)
`
`P*
`
`170
`152
`
`146
`176
`
`211
`63
`43
`4
`1
`
`181
`51
`20
`65
`5
`
`124
`191
`6
`1
`
`52.8
`47.2
`62.9 ± 10.7
`
`45.3
`54.7
`
`65.5
`19.6
`13.4
`1.2
`0.3
`
`56.2
`15.8
`6.2
`20.2
`1.6
`
`38.5
`59.3
`1.9
`0.3
`
`162
`177
`
`161
`178
`
`235
`63
`37
`2
`2
`
`178
`51
`12
`96
`2
`
`132
`201
`5
`1
`
`0.198
`
`0.579
`
`0.692
`
`0.065
`
`0.971
`
`47.8
`52.2
`63.3 ± 11.3
`
`47.5
`52.5
`
`69.3
`18.6
`10.9
`0.6
`0.6
`
`52.5
`15.0
`3.5
`28.3
`0.6
`
`38.9
`59.3
`1.5
`0.3
`
`*P value from w2 or Fisher exact test.
`SD indicates standard deviation; Travoprost BAC-free, travoprost 0.004% without BAC; Travoprost 0.004%, travoprost 0.004% preserved with BAC.
`
`protocol data set. In the ITT data set, last observation
`was carried forward to impute missing values.
`The primary statistical objective of this study was to
`demonstrate that the IOP-lowering efficacy of travoprost
`0.004% was equivalent to travoprost BAC-free. Equiva-
`lence was to be declared if the 95% confidence interval
`about
`the
`treatment difference
`lay entirely with-
`in ± 1.5 mm Hg. This tolerance criterion is commonly
`used and accepted in noninferiority glaucoma studies to
`compare a test medication to an active control.
`A target enrollment of 700 patients was selected to
`ensure that at least 600 evaluable patients (300 per
`treatment group) would be followed for 3 months. With
`300 patients per group, there was at least 99% coverage
`probability that a 95% 2-sided confidence interval would
`fall within ± 1.5 mm Hg, and at least 87% coverage
`probability that a 95% 2-sided confidence interval would
`fall within ± 1 mm Hg. The sample size estimate was
`based on a standard deviation for IOP of 3.5 mm Hg and
`a 5% chance of a type I error.
`
`RESULTS
`
`Demographics
`Six hundred ninety patients were randomized to
`treatment. All patients were evaluable for safety. Eleven
`patients (5 from travoprost 0.004%, 6 from travoprost
`BAC-free) discontinued the study before the collection of
`any on-therapy data and were excluded from the ITT
`
`data set, resulting in 679 patients in the ITT data set.
`Twenty-nine patients were excluded from the per protocol
`data set (travoprost 0.004%, n = 7; travoprost BAC-free,
`n = 22). These included the 11 patients with no on-
`therapy study visit data and an additional 18 patients
`because of protocol violations. These violations included
`nonqualifying IOP (n = 4), contraindicated concomitant
`medication (n = 6), entry criteria violations (n = 7), and
`an errant repeat of
`the first eligibility visit
`(n = 1),
`resulting in 661 patients in the per protocol data set.
`There were no statistically significant differences between
`treatment groups for mean age (P = 0.616), age distribu-
`tion (elderly vs. nonelderly, P = 0.198), sex (P = 0.579),
`(P = 0.692),
`(P = 0.065), or ocular
`race
`iris
`color
`diagnosis (P = 0.971). The demographic data for the
`per protocol data set are shown in Table 1. Demographic
`results were similar
`in the ITT analysis, with no
`significant differences observed.
`
`Equivalence Analysis
`The primary efficacy analysis was planned and
`carried out as a test of equivalence. In accordance with
`International Conference on Harmonisation of Technical
`Requirements for Registration of Pharmaceuticals for
`Human Use (ICH) guidance (ICH Topic E9, Statistical
`Principles for Clinical Trials), the per protocol data set
`was evaluated first to test the hypothesis of equivalence
`and the ITT data set was then used to confirm the per
`
`100
`
`r 2007 Lippincott Williams & Wilkins
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`

`
`J Glaucoma  Volume 16, Number 1, January 2007
`
`Travoprost BAC-free
`
`CIindicatesconfidenceinterval;TRAVBAC-free,travoprostBAC-free;TRAV0.004%,travoprost0.004%.
`Estimatesbasedonleastsquaresmeansusingrepeatedmeasuresanalysisofvariance.Baselineestimatesobtainedfromseparatemodel.
`*Pooleddatafromweek2,week6,andmonth3visits.
`
`0.2
`0.8
`0.2648
`0.3
`328
`7.7
`310
`7.4
`
`0.4
`0.6
`0.6085
`0.1
`329
`7.9
`308
`7.8
`
`0.4
`0.5
`0.8461
`0.0
`328
`8.4
`309
`8.3
`
`0.5
`0.5
`0.8795
`0.0
`330
`7.5
`309
`7.5
`
`0.5
`0.5
`0.9184
`
`0.0
`333
`7.6
`313
`7.7
`
`0.4
`0.6
`0.7064
`0.1
`333
`8.4
`313
`8.3
`
`0.6
`0.4
`0.7563
`
`0.6
`0.4
`0.7977
`
`0.5
`0.4
`0.8373
`
`0.1
`331
`7.4
`319
`7.5
`
`0.1
`332
`7.7
`320
`7.8
`
`0.1
`333
`8.4
`320
`8.5
`
`0.3
`0.5
`0.7003
`0.1
`337
`7.5
`322
`7.4
`
`0.4
`0.4
`0.9501
`0.0
`337
`7.7
`322
`7.7
`
`0.4
`0.4
`0.8831
`0.0
`338
`8.4
`322
`8.4
`
`0.5
`0.3
`0.6341
`
`0.6
`0.3
`0.4440
`
`0.6
`0.2
`0.2721
`
`0.1
`339
`24.9
`
`322
`24.8
`
`0.2
`339
`25.6
`
`322
`25.5
`
`0.2
`339
`27.2
`
`322
`27.0
`
`Lower95%CI
`Upper95%CI
`
`P
`
`Difference
`
`N
`
`Mean
`
`TRAV0.004%
`
`N
`
`Mean
`
`TRAVBAC-free
`
`4PM
`
`10AM
`
`8AM
`
`4PM
`
`10AM
`
`8AM
`
`4PM
`
`10AM
`
`8AM
`
`4PM
`
`10AM
`
`8AM
`
`4PM
`
`10AM
`
`8AM
`
`Treatment
`
`Month3
`
`Week6
`
`Week2
`
`Combined*
`
`Baseline
`
`TABLE2.MeanIOPChangeFromBaselineComparisonofTravoprostBAC-freeandTravoprost0.004%(PerProtocolData)
`
`protocol result. The equivalence criterion used was
`1.5 mm Hg.
`There were no statistically significant differences
`in mean IOP at baseline between treatment groups.
`Differences in on-therapy mean IOP between travoprost
`BAC-free and travoprost 0.004% ranged from 0.3 to
`+0.2 mm Hg in both the per protocol and ITT analyses.
`The study results demonstrate that
`travoprost
`BAC-free, and travoprost 0.004%, both dosed once-daily
`in the evening, maintained IOP similarly throughout
`the day and provided significant IOP reductions. Study
`results demonstrate that travoprost BAC-free and travo-
`prost 0.004% produced statistically equivalent IOP-
`lowering efficacy. The 95% 2-sided confidence limits
`for the differences in mean IOP between the 2 treatment
`groups were <1.5 mm Hg at 9 of 9 study visits and times
`in both the ITT and per protocol analyses. Moreover, the
`magnitude of
`the largest observed value across all
`confidence limits was 0.8 mm Hg in both analyses. Per
`protocol results are presented in Table 2.
`
`Changes From Baseline
`Mean IOP reductions from baseline for travoprost
`0.004% and travoprost BAC-free were clinically relevant
`and statistically significant at all measurement
`times.
`The IOP reductions ranged from 7.3 to 8.5 mm Hg for
`travoprost BAC-free
`and from 7.4
`to 8.4 mm Hg
`for travoprost 0.004%. Mean IOP at baseline was similar
`for the 2 treatment groups. Per protocol results are provided
`in Figure 1. The ITT analysis yielded similar results.
`
`Safety Evaluation
`All of the 690 patients enrolled were evaluable for
`safety. No treatment-related serious adverse events were
`reported during the study. In both the travoprost BAC-
`free and the travoprost 0.004% treatment groups, the
`most frequently reported, treatment-related adverse event
`was ocular hyperemia, occurring at incidences of 6.4%
`and 9.0%, respectively. No safety concerns were identified
`based on an analysis of change from baseline for visual
`acuity (best-corrected logMAR), ocular signs (cornea,
`iris/anterior chamber, lens, aqueous flare, and inflamma-
`tory cells), ocular hyperemia, dilated fundus parameters
`(retina/macula/choroid, vitreous, optic nerve, cup/disc
`ratio), visual fields, and endothelial cell density measure-
`ments in either treatment group in the overall safety
`population, adult population, or elderly population. Five
`patients (four [1.2%] in the travoprost 0.004% group and
`one [0.3%] in the travoprost BAC-free group) experi-
`enced mild corneal staining. Only one of the five was
`considered to be related to treatment (travoprost 0.004%
`treatment group), none resulted in patient discontinua-
`tion, three resolved prior to exit, and two (one in each
`treatment group) reported corneal staining post-exit after
`treatment with a different prostaglandin analogue. Nine
`patients (1.3%) discontinued study participation because
`of an adverse event assessed as treatment-related, which
`included 5 patients (1.5%) with exposure to travoprost
`BAC-free and 4 patients
`(1.2%) with exposure to
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`
`Lewis et al
`
`J Glaucoma  Volume 16, Number 1, January 2007
`
`Travoprost BAC-free
`Travoprost 0.004%
`
`30
`
`28
`
`26
`
`24
`
`22
`
`20
`
`18
`
`16
`
`14
`
`12
`
`10
`
`Mean IOP (mmHg)
`
`8AM 10AM 4PM 8AM 10AM 4PM
`
`8AM 10AM 4PM 8AM 10AM 4PM
`
`Baseline
`
`Week 2
`
`Week 6
`
`Month 3
`
`FIGURE 1. Mean IOP for travoprost BAC-free and travoprost 0.004%.
`
`IOP = intraocular pressure
`
`travoprost 0.004%. Adverse events in the overall safety
`population were predominately nonserious, generally
`mild to moderate in intensity, usually resolved with or
`without treatment, and generally did not interrupt patient
`continuation in the study.
`
`DISCUSSION
`This study demonstrates that travoprost BAC-free
`and travoprost 0.004% (both dosed once-daily in the
`evening) produce equivalent IOP-lowering efficacy in
`patients with OAG or OHT. Both formulations were
`found to be safe and well tolerated.
`Both travoprost BAC-free and travoprost 0.004%
`produced IOP reductions from baseline that were significant
`and clinically relevant. The peak effect for travoprost is
`achieved by 12 hours postdosing.18 In this study, the
`greatest reductions in IOP were observed at the 8 AM time
`point (12 h postdosing). At 8 AM, IOP reductions ranged
`from 8.3 to 8.5 mm Hg for travoprost BAC-free, and were
`8.4 mm Hg at all the 3 visits for travoprost 0.004%.
`Published data from previous studies of travoprost 0.004%
`show similar reductions at 8 AM; 7.1 to 8.0 mm Hg from 2
`large multicenter (US) studies with approximately 400
`patients treated for up to 12 months.17,18 Travoprost
`0.004% has been shown to provide clinically relevant
`IOP-lowering throughout the day following dosing the
`previous evening.17–20 Data from the present study show
`that the IOP-lowering effect at 4 PM for both treatment
`groups was substantial; 7.4 to 7.5 mm Hg for travoprost
`BAC-free and 7.4 to 7.7 mm Hg for travoprost 0.004%.
`Both treatment groups had favorable overall safety
`profiles. The most frequent adverse event reported in this
`study was ocular hyperemia. Adverse events for ocular
`hyperemia were reported for 6.4% of patients in the
`travoprost BAC-free group and for 9.0% of patients in
`the travoprost group. In this study, adverse events were
`collected for ocular hyperemia if there was a patient
`
`complaint, or if a patient was discontinued from the study
`due to ocular hyperemia. Although the frequency of
`ocular hyperemia adverse events is lower for the BAC-
`free
`formulation,
`the difference
`is not
`statistically
`significant. The frequency of all other ocular adverse
`events is low and similar overall for the 2 treatment
`groups. Patient comfort was not assessed and further
`study directed at the relative comfort of the 2 formula-
`tions may reveal differences.
`effects on the
`The possibility of detrimental
`conjunctival tissue and cornea in patients chronically
`treated with BAC-preserved ocular hypotensive drops has
`been reported by others.3–12 Although we did not evaluate
`differences in such parameters as corneal permeability or
`ocular comfort, in the present study, no clinically relevant
`differences were found between the 2 formulations with
`regard to the ocular adverse events reported. The patient
`population for this study was selected to represent the
`general population of patients with OHT or glaucoma
`likely to be treated with travoprost for IOP-lowering. In
`this population, BAC-preserved travoprost is known,
`through large clinical
`trials and extensive marketing
`experience, to be safe and well tolerated. If the inclusion
`criteria instead had selected for individuals with con-
`comitant ocular surface disease and/or a sensitivity to
`BAC (eg, patients with severe dry eye), a different
`tolerability profile may have emerged. Further study
`may help to better define this subpopulation.
`This study showed that travoprost BAC-free, dosed
`once-daily, was equivalent at all study visits and times
`in IOP-lowering efficacy to travoprost 0.004%, with a
`similar safety profile. Both formulations were found to
`have a low incidence of ocular hyperemia (6.4% for
`travoprost BAC-free; 9.0% for travoprost 0.004%).
`Travoprost BAC-free ophthalmic solution, 0.004% was
`found to be safe and well tolerated in patients with OAG
`or OHT. The development of an alternative formulation
`without BAC might prove to be beneficial for patients
`
`102
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`r 2007 Lippincott Williams & Wilkins
`
`

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`J Glaucoma  Volume 16, Number 1, January 2007
`
`Travoprost BAC-free
`
`having concomitant ocular surface disease and for those
`with a sensitivity to this preservative, and may provide a
`treatment option for practitioners who prefer to prescribe
`a BAC-free product for chronic therapy.
`
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`
`APPENDIX
`
`The Travoprost BAC-free Study Group
`
`Jason Bacharach, MD; Petaluma, CA
`Stanley Jay Berke, MD; Lynbrook, NY
`Michael Berlin, MD; Los Angeles, CA
`E. Randy Craven, MD; Littleton, CO
`William F. Davitt, III, MD; El Paso, TX
`Douglas G. Day, MD; Atlanta, GA
`Efraim Duzman, MD; Irvine, CA
`Richard M. Evans, MD; San Antonio, TX
`Catherine T. Fitzmorris, MD; Metairie, LA
`Ronald E. P. Frenkel, MD; Stuart, FL
`Mark S. Gorovoy, MD; Fort Myers, FL
`Thomas T. Henderson, MD; Austin, TX
`Bret A. Hughes, MD; Detroit, MI
`Jane L. Hughes, MD; San Antonio, TX
`Martin B. Kaback, MD; Slingerlands, NY
`Michael Kottler, MD; Salt Lake City, UT
`Bradley R. Kwapiszeski, MD; Shawnee Mission, KS
`Jeffrey R. Lozier, MD; San Diego, CA
`Eugene B. McLaurin, MD; Memphis, TN
`Katherine I. Ochsner, MD; Wilmington, NC
`James H. Peace, MD; Inglewood, CA
`Bernard R. Perez, MD; Tampa, FL
`
`Ravi K. Reddy, MD; Henderson, NV
`Tushina A. Reddy, MD; Las Vegas, NV
`Ned Reinstein, MD; Tulsa, OK
`Michael Rotberg, MD; Charlotte, NC
`Kenneth Sall, MD; Artesia, CA
`Paul Schacknow, MD; Lake Worth, FL
`Howard Schenker, MD; Rochester, NY
`Stephen V. Scoper, MD; Norfolk, VA
`Elizabeth D. Sharpe, MD; Mount Pleasant, SC
`Robert L. Shields, MD; Denver, CO
`Shannon L. Smith, MD; Nacodoches, TX
`Emil A. Stein, MD; Las Vegas, NV
`Robert H. Stewart, MD; Houston, TX
`Michael E. Tepedino, MD; High Point, NC
`Stuart Terry, MD; San Antonio, TX
`Robert A. Thomas, MD; Phoenix, AZ
`George C. Thorne, MD; Austin, TX
`Jonathan Stanwood Till, MD; Salem, VA
`Nikhil S. Wagle, MD; Davenport, IA
`Thomas Walters, MD; Austin, TX
`Robert Williams, MD; Louisville, KY
`David L. Wirta, MD; Newport Beach, CA
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