Prostatic Diseases and Male
`Voiding Dysfunction
`
`Efficacy and Tolerability
`of Fesoterodine in Men With
`
`Overactive Bladder: A Pooled
`
`Analysis of 2 Phase III Studies
`
`Sender Herschorn, J. Stephen Jones, Matthias Oelke, Scott MacDiarmid,
`
`Joseph T. Wang, and Zhonghong Guan
`
`OBJECTIVES
`
`METHODS
`
`RESULTS
`
`CONCLUSIONS
`
`To assess the efficacy, safety, and tolerability of fesoterodine 4 and 8 mg in men with overactive
`bladder.
`
`This was a subanalysis of pooled data from 358 men enrolled in 2 double—blind, placebo-
`controlled phase 111 trials. Subjects with frequency and urgency or urgency urinary incontinence
`(UUI) were randomized to fesoterodine 4 mg, fesoterodine 8 mg, or placebo for 12 weeks. Efficacy
`endpoints included bladder diary variables and subject—reported treatment response.
`By week 12, men treated with fesoterodine 4 or 8 mg had significantly greater median percentage
`improvements in micturition frequency, urgency episodes, and UUI episodes versus placebo and
`significantly greater percentages reported a treatment response versus placebo. Significant in-
`creases in mean voided volume (MVV) per micturition versus placebo occurred with fcsotero—
`dine 8 mg only. At week 12, fesoterodine 8 mg was significantly more efficacious than fesotero-
`dine 4 mg in improving UUI episodes and MVV per micturition. The most commonly reported
`adverse events with fesoterodine 4 and 8 mg were dry mouth (12.5% and 37.7% vs 5.6% with
`placebo) and constipation (2.5% and 8.8% vs 0.8% with placebo). Symptoms suggestive of
`urinary retention were reported in 0.8%. 0.8%, and 5.3% of men in the placebo, fesoterodine 4
`mg, and fesoterodine 8 mg groups, respectively; only 1 subject, in the fesoterodine 8 mg group,
`was catheterized.
`
`Fesoterodine 4 and 8 mg are generally safe, efficacious, and well tolerated for the treatment of
`overactive bladder symptoms in men. The 8 mg dose provides additional benefit and allows for
`treatment individualization. UROLOGY 75: 1149-1155, 2010. © 2010 Elsevier lnc.
`
`I
`
`veractive bladder (OAB), defined as urgency
`with or without urgency incontinence and usu-
`ally with increased daytime frequency and noc-
`is widely believed to be associated with detrusor
`turia,
`overactivity.2 Approximately 11%»l6% of men have
`OAB, as reported in population—based studies conducted
`in North America and Europe, and the prevalence in-
`creases with age.3’4 Historically, lower urinary tract symp-
`toms in older men, including OAB symptoms, have been
`
`This stud); was funded by Scholar: EiuSricncL-s GmbH and Pfizer bu‘.
`Fmm the Sunnybmoic Health Sciences Centre. Division of Umlogy, Toronto,
`(}uia1'iu, Crinutla,‘ Uliclcrnun Uri:l(:i_Iicul E1” Kidricy Institute, Clewlcind (:ii1liC, Beach»
`wand, Ohio; Hanna:-er Medical School. Deparnnenr of Umlugjr, Hannuver. Gemmny:
`Alliunre lJi'(JlzlJg)' Sperizilists, Greensboro, North Czimlinzi; and i’fize'r inc, New Ymnic,
`New York
`Reprint requests: Sender llé'TSL'l’li)T‘i1, M.D.. Sunnybroolt lleulth Si.'ienx.'e:' Centre.
`2075 Buyuivw Aw, Toronto, ON M4N3M5, Cunrrrlu. E—rmu'l:
`s.l1i.'rschrrrn@
`umr0'nm.ca
`Sul91'nim:d:Jum: K}, 2009. LIL‘L‘Ej)£L’i'.l (with rcuisiimsi: September 1, 2009
`
`© 2010 Elsevier Inc.
`
`All Rights Reserved
`
`presumed to result from benign prostatic enlargement or
`bladder outlet obstruction (B00) and have been treated
`with agents that target the prostate or bladder outlet}
`However, evidence suggests that
`lower urinary tract
`symptoms in men, including OAB symptoms, often occur
`independently from benign prostatic enlargement or
`BOO. For example, many men report OAB symptoms in
`the absence of voiding symptoms associated with benign
`prostatic enlargement} and urodynamic studies have
`found that many men with storage symptoms or detrusor
`overactivity do not have BOO.” Further, men treated
`with drugs or surgery for prostatic enlargement may still
`experience persistent detrusor overactivity or OAB symp-
`toms.7'8
`
`Antimuscarinic agents are the mainstay of drug ther-
`apy for OAB. Antimuscarinics, either alone or in com—
`bination with an a—blocl<er, can significantly improve
`measures of OAB symptoms and health—related quality of
`
`00904295/10/$34.00
`doi:10.1016/j.urology/.2009.09.007
`
`1149
`
`Patent Owner, UCB Pharma GmbH — Exhibit 2080 - 0001
`
`

`
`life in rnen.7'9'19 The use of antimuscarinics for OAB in
`
`men has been limited by concern over the possibility of
`precipitating acute urinary retention and increasing
`postvoid residual (PVR) urinary volume?‘ However, a
`number of 12-week placebo-controlled studies suggest
`that antimuscarinics are safe and well tolerated in men
`with OAB.9‘l2‘l7‘m
`Fesoterodine is a new nonselective antimuscarinic
`
`agent for the treatment of OAB.“ After oral administra-
`tion, fesoterodine is rapidly converted by ubiquitous es-
`terases to the active metabolite, 5-hydroxymethyl tolterod-
`me; the parent compound is not detectable in plasma, and
`all pharmacologic activity is attributable to 5-hydroxy-
`methyl tolterodine.21 In phase I studies, fesoterodine was
`shown to have a dose-dependent pharrnacokinetic profile
`and low pharrnacokinetic variability. In pivotal phase III
`trials, fesoterodine improved bladder diary variables and
`health—related quality of life measures in subjects with
`OAB,22"7‘4 with an apparent dose response on several
`diary and health-related quality of life outcomes.24'25 The
`current subanalysis of pooled data from 2 phase III studies
`was conducted to assess the efficacy, safety, and tolera-
`bility of fesoterodine 4 and 8 mg vs placebo in men. The
`efficacy of the 8 mg dose vs 4 mg dose of fesoterodine was
`also compared, although the studies were not designed a
`priori to make this comparison. With a potential increase
`in the use of antimuscarinics in men, we believe that it is
`necessary to provide detailed information on the efficacy
`and safety of fesoterodine in men.
`
`MATERIAL AND METHODS
`
`This was a subanalysis of pooled data from 2 double-blind,
`placebo-controlled. fixed-dose, phase III trials, which had iden-
`tical inclusion and exclusion criteria.22’2'3 In both trials, eligible
`subjects were randomly assigned to treatment with fesoterodine
`4 mg. fesoterodine 8 mg, or placebo, with doses taken each
`morning for 12 weeks. One of the trials” had a parallel active-
`control arm with tolterodine extended-release 4 mg; subjects in
`this arm were not included in the current analysis.
`
`Subjects
`Inclusion criteria for both studies were men or women aged
`218 years with self-reported OAB symptoms for 26 months
`and urinary frequency (28 micturitions per 24 hours) and
`either urinary urgency (26 episodes) or urgency urinary incon-
`tinence (UUI; 23 episodes) documented in 3-day bladder di-
`aries at baseline. Subjects had to report at
`least moderate
`bladder—related problems on a 6-point Likert scale. Key exclu-
`sion criteria were lower urinary tract pathology that could, in
`the opinion of the investigator, be responsible for urgency or
`incontinence;
`this included stress incontinence, urolithiasis,
`interstitial cystitis, urothelial tumors, and clinically relevant
`BOO as judged by the investigator (including PVR > 100 ml.).
`Subjects who had symptomatic urinary tract infections; treat-
`ment within the past 2 weeks with antimuscarinic agents for
`OAB or any other medication indicated for treatment of OAB;
`treatment within the past 4 weeks with electrostimulation or
`bladder training; neurologic disease that could cause OAB; and
`those with clinically relevant arrhythmia, unstable angina, or a
`
`(Bazett’s formula) >500 millisecond
`corrected QT interval
`were not included.2Z’23 Only men were included in this pooled
`subanalysis.
`
`Efficacy Assessments
`Men recorded the time of each void, urgency episode, and UUI
`episode in a 3-day bladder diary completed before randomiza-
`tion and at 2 and 12 weeks after starting treatment. Subjects
`were instructed to consider urgency as “a sudden compelling
`desire to pass urine that is difficult to defer“ and to rate the
`degree of urgency for each episode, whether or not accompanied
`n in
`by voiding or incontinence, on a subjective 4-point scale: "no
`urgency," "mild urgency, moderate urgency," or “severe ur-
`gency." Subjects were also given a urine cup and asked to record
`their voided volume in milliliters for each micturition on 1 of
`
`the 3 days in the bladder diary. In the primary analyses of the
`2 phase III trials, the primary endpoint was the mean change
`from baseline to week 12 in number of micturitions per 24
`hours. Coprimary endpoints were the mean change from base-
`line to week 12 in UUI episodes and the percentage of subjects
`reporting a treatment response at week 12 (treatment response
`was a yesfno variable derived from the validated 4-point Treat-
`ment Benefit scalezfi). Other efficacy variables assessed were
`median percentage change from baseline in number of 1nicturi-
`tions, UUI episodes, and urgency episodes; mean change from
`baseline in urgency episodes; and mean voided volume (MVV)
`per micturition.
`
`Safety and Tolerability Assessments
`Safety and tolerability were evaluated on the basis of observa-
`tion and assessment of adverse events. The seriousness, severity,
`and relatedness to treatment of adverse events were determined
`
`by the investigator at each visit. Postvoid residual volume was
`measured using ultrasound at screening; baseline; and weeks 2,
`8, and 12; men who developed a PVR > 200 1nL while receiv-
`ing treatment were withdrawn from the trials. Urinary retention
`was defined as a PVR > 200 mL or based on the investigator's
`opinion that the subject had symptoms of retention. including
`urinary hesitation and decreased urine flow. Cardiovascular
`safety was monitored using electrocardiograms.
`
`Statistical Analysis
`Parametric analysis for continuous variables was performed for
`all randomized subjects for whom baseline and double-blind
`treatment data were obtained (full analysis set) using an anal-
`ysis of covariance model with treatment and region as factors
`and baseline value as a covariate. Nonparametric sensitivity
`analysis was conducted using the \)(/ilcoxon rank sum test.
`Treatment response was analyzed using the asymptotic normal
`approximation method. In exploratory analyses, median per-
`centage change from baseline to weeks 2 and 12 was calculated
`for bladder diary endpoints. and statistical hypothesis testing
`was conducted. Safety analyses were conducted using data from
`all men who took 21 dose of study medication after random-
`ization (safety population).
`
`RESULTS
`
`The safety population included 358 men (fesoterodine 4
`mg, n = 120; fesoterodine 8 mg, n = 114; placebo, n =
`124). Baseline demographic and clinical characteristics
`were statistically similar between treatment groups.
`
`1150
`
`UROLOGY 75 (5), 2010
`
`Patent Owner, UCB Pharma GmbH — Exhibit 2080 - 0002
`
`

`
`Most men were white (85.5%), with a mean age of 61
`years, and 65.9% were incontinent at baseline. The
`mean time since first diagnosis or onset of OAB was
`approximately 8 years, with 23.2% of men having been
`dia nosed at least 10
`ears earlier. Overactive bladder
`V
`g
`symptoms also were statistically similar among the groups at
`baseline (Table 1).
`
`Efflcacv
`At week 2 (first clinical evaluation after dosing), men
`treated with fesoterodine 4 mg had significantly greater
`median percentage improvement
`in UU1 episodes vs
`placebo (P = .0023) (Fig. 1). In the fesoterodine 8-mg
`h-
`-‘-llffi-
`d
`'-
`--
`‘fi-1
`group, c anges in a e cacy en points were signi cant y
`greater vs placebo at week 2, including median percent—
`age and least squares (LS) mean improvements in num—
`ber of micturitions (P = .0017, P = .0001, for median
`percentage and LS mean changes, respectively), urgency
`-
`1
`,
`-
`episodes
`(P — .0156, P — .0004). UU1 episodes
`(P <.000l, P = .0034), and MVV per micturition
`(P = .0015, P = .0036); and percentage of subjects
`reporting a treatment response (P = .005) (Fig. 1, Table
`1). Least squares mean improvements in micturition fre—
`quency and urgency episodes were significantly greater at
`week 2 with fesoterodine 8 mg compared with fesotero—
`.
`dine 4 mg (P = .0099, P = .0367 for frequency and
`urgency, respectively) (Table 1).
`By week 12 (end of treatment), men treated with
`fesoterodine 4 mg had significantly greater median per—
`centage and LS mean improvements from baseline in
`number of micturitions (P = .017, P = .022) and urgency
`episodes (P = .004, P = .008), as well as median per-
`centage improvements in UU1 episodes (P = .023) (Fig.
`1, Table 1). Least squares mean improvements in UU1
`.
`.
`.
`episodes and MVV were not significantly greater in men
`who received fesoterodine 4 mg compared with placebo
`(Table 1). Self-reported treatment response rates were
`significantly higher among men treated with fesoterodine
`,
`4 mg vs placebo at week 12 (P = .009) (Fig. 1). Men
`_
`_
`treated with fesoterodine 8 mg had statistically significant
`greater median percentage and LS mean improvements
`from baseline in number of micturitions, urgency epi—
`sodes, and UU1 episodes, as well as LS mean impi-ove—
`.
`.
`merits in MVV, compared with placebo at week 12
`(P <.00l for all) (Fig. 1, Table 1). Self-reported treat—
`merit response rates were significantly higher among men
`treated with fesoterodine 8 mg vs placebo at week 12
`.
`(P <.001) (Fig. 1).
`Improvements by week 12 were significantly greater
`with fesoterodine 8 mg vs fesoterodine 4 mg for MVV
`(P <.001) (Table 1) and median percentage change in
`UU1 episodes per 24 hours (P = .035) (Fig. 1).
`
`Safety and Tolerability
`The most common treatment—emergent adverse events
`(22% in any group) included dry mouth, constipation,
`and headache (Table 2). Most adverse events were of
`
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`
`UROLOGY 75 (5), 2010
`
`1151
`
`Patent Owner, UCB Pharma GmbH — Exhibit 2080 - 0003
`
`

`
`Week 1 2
`
`Week 12
`
`>
`
`
`
`UrgencyEpisodesper24hppeMicturitionFrequency
`0Median%Change0UL|le;hai:a:e:han:J2e4hmMedian"/oChange
`
`Treatment
`
`Iii Placebo
`Iii Fesoterodine 4 mg
`j Fesoterodine 8 mg
`
`I: Placebo
`(:1 Fesoterodine 4 mg
`Z Fesoterodine 6 mg
`
`l:| Placebo
`|:I Fasoterodine 4 mg
`1 Fesoterociine 8 mg
`
`I Placebo
`
`Z Fesoterodine 4 mg
`- Fesoterodine 8 mg
`
`
`
`Figure 1. Median percentage change from baseline in (A) micturition frequency, (B) urgency urinary incontinence (UUI)
`episodes, and (c) urgency episodes; and (D) percentage of subjects reporting treatment response at weeks 2 and 12 with
`fesoterodine 4 mg, fesoterodine 8 mg, or placebo. * P <.O5 vs placebo; "' P <.O5 vs fesoterodine 4 mg.
`
`mild or moderate severity. Only 1 subject (0.9%) in the
`Fesoterodine 8-mg group and none in the fesoterodine 4—mg
`or placebo groups discontinued treatment because of dry
`mouth. Fifteen men experienced treatmenpemergent uri-
`nary disorders other than urinary retention, including 4
`with dysuria (Fesoterodine 8 mg, n = 3; placebo, n = 1), 2
`with micturition urgency (fesoterodine 4 mg, n 2 1;
`fesoterodine 8 mg, n = 1), and 2 with hematuria (both in
`the fesoterodinc 4—1ng group). There was 1 case of enure-
`
`sis and 1 case of nocturia in the placebo group that were
`not present at baseline and that were reported as treat—
`menvemergent adverse events.
`The LS mean (standard error) changes in PVR were
`significantly greater, but well below the 50—ml. cut—off
`that is considered clinically relevant,” in the fesoterod-
`inc 4 and 8 mg groups compared with the placebo group:
`9.62 (3.57) and 20.19 (3.61) for fesoterodine 4« and
`8—rng, respectively, vs -0.58 (3.44) for placebo. The LS
`
`1152
`
`UROLOGY 75 (5), 2010
`
`Patent Owner, UCB Pharma GmbH — Exhibit 2080 - 0004
`
`

`
`Table 2. Treatmentemergent adverse events at study
`end (22% in any treatment group)
`
`No. (%) Subjects
`Fesoterodine Fesoterodine
`4 mg
`8 mg
`(n = 120)
`(n = 114)
`
`Placebo
`(n = 124)
`
`7 (5.6)
`1 (0.8)
`1 (0.8)
`
`15 (12.5)
`3 (2.5)
`1 (0.8)
`
`43 (37.7)
`10 (8.8)
`6 (5.3)
`
`O
`2 (1.6)
`2 (1.6)
`1 (0.8)
`3 (2.4)
`
`5 (4.0)
`2 (1.6)
`2 (1.6)
`2 (1.6)
`3 (2.4)
`
`5 (4.4)
`2 (1.8)
`1 (0.8)
`0
`2 (1.7)
`
`3 (2.5)
`4 (3.3)
`4 (3.3)
`3 (2.5)
`0
`
`1 (0.8)
`4 (3.3)
`3 (2.6)
`3 (2.6)
`2 (1.8)
`
`2 (1.8)
`1 (0.9)
`1 (0.9)
`1 (0.9)
`O
`
`Dry mouth
`Constipation
`Symptoms
`suggestive of
`urinary
`retention*
`
`Dyspepsia
`Hypertension
`Dry throat
`Dysuria
`Upper respiratory
`tract infection
`Headache
`Nasopharyngitis
`Diarrhea
`Dizziness
`Sinusitis
`
`* Symptoms suggestive Of urinary retention included, but were
`not restricted I0, decreased urine ‘HOW and hesitation.
`
`Table 3.
`
`incidence of urinary retention
`
`No. (%) Subjects
`Fesoterodine Fesoterodine
`4 mg
`8 mg
`(n : 120)
`(n = 114)
`
`Placebo
`(n : 124)
`
`1 (0.8)*
`0
`
`1 (0.8)"'
`1 (0.8)
`
`6 (5.3)*
`2 (1.8)
`
`0
`
`O
`
`2 (1.8)
`
`Urinary retention
`Decreased
`urine flow
`Urinary
`hesitation
`
`PVR > 200 mL 1 (0.8)
`
`1 (0.8)
`
`2 (1.8)
`
`PVR = postvoid residual volume.
`* This subject had PVR > 200 mL at last visit (end of treatment),
`and therefore did not discontinue prematurely.
`* This subject had both decreased urine flow and PVR > 200 mL.
`' Of the 6 subjects in the fesoterodine 8—mg group with urinary
`retention, only 1 subject was catheterized.
`
`mean change in PVR was significantly greater in the
`fesoterodine 8—mg group than in the fesoterodine 4-mg
`group (P = .035). A total of 8 subjects had symptoms
`suggestive of urinary retention (placebo, n = 1; fesotero—
`dine 4 mg, n = 1; fesoterodine 8 mg, n = 6), including
`4 subjects with PVR > 200 ml_, 3 subjects with decreased
`urine How, and 2 subjects with urinary hesitation (Table
`3). Only 1 subject, in the fesoterodine 8—mg group, was
`catheterized.
`
`Overall, 25 men (7.0%) discontinued treatment pre-
`maturely because of an adverse event during the treat-
`ment phase, including 6 (4.8%) in the placebo group, 8
`(6.7%) in the fesoterodine 4«mg group, and 11 (9.6%) in
`the fesoterodine 8-mg group. Four men, 1 in the fesotero—
`dine 4—mg group (0.8%) and 3 in the fesoterodine 8—mg
`group (2.6%), were withdrawn from the trials because of
`urinary retention, defined as PVR > 200 mL or symptoms
`suggestive of urinary retention.
`
`COMMENT
`
`In this post hoc subanalysis, fesoterodine 8 mg produced
`significantly greater improvements in all bladder diary
`measures and a significantly higher treatment response
`rate vs placebo in men with OAB after 12 weeks of
`treatment. Fesoterodine 4 mg produced significantly
`greater improvements vs placebo in most diary endpoints,
`including median percentage change in the number of
`micturitions, urgency episodes, and UUI episodes and LS
`mean change in micturitions and urgency episodes, as
`well as a significantly higher treatment response rate at
`week 12. Fesoterodine 8 mg yielded significantly greater
`improvement in UUI episodes and MVV per micturition
`compared with fesoterodine 4 mg at week 12. Improve»
`ments in diary variables and a higher treatment response
`rate vs placebo were observed as early as week 2 (first
`clinical evaluation) in subjects receiving fesoterodine 8 mg
`and were maintained to the end of the study; UUI episodes
`were improved at week 2 with fesoterodine 4 mg.
`Overall, fesoterodine was well tolerated by men in this
`study. As expected, adverse events reported with fe—
`soterodine were typical of those associated with antimus-
`carinics. including dry mouth, constipation, and dyspep-
`sia, and increased in an apparent dose-dependent fashion.
`The incidence of dry mouth was considerably higher in
`the fesoterodine groups, particularly the 8-mg group, than
`in the placebo group, but most occurrences were of mild
`to moderate severity and only 1 (0.9%) subject in the
`fesoterodine 8—mg group discontinued because of dry
`mouth. Constipation was reported in 2.5% and 8.8% of
`men taking fesoterodine 4 and 8 mg, respectively, com-
`pared with 0.8% of men in the placebo group. The low
`incidence of constipation observed with fesoterodine
`might reflect a lack of specificity for the muscarinic M3
`subtype, which mediates gastrointestinal motility and
`predominates over the M2 subtype in the gastrointestinal
`tract.”
`Postvoid residual volume > 200 mL was documented
`
`in 4 men, 1 of whom was given placebo. Most episodes of
`urinary retention, defined as PVR > 200 ml. or symptoms
`suggestive of urinary retention, with fesoterodine oc-
`curred in the fesoterodine 8-mg group, in men aged 266
`years, and within 1-14 days of beginning treatment. Only
`1 man (0.9%), who was in the fest)tert)dine 8—mg group,
`was catheterized. One and 3 subjects in the Fesoterodine
`4 and 8 mg groups, respectively, discontinued because of
`urinary retention, defined as PVR > 200 mL or symptoms
`suggestive of urinary retention.
`The results of this study are consistent with previous
`reports demonstrating that antimuscarinics effectively re-
`duce OAB symptoms and are generally well tolerated in
`men.9'”'m'Z0 The results from our post hoc analysis of
`male subjects are also similar to those obtained in the
`general population in these phase Ill trials.2z'23 In addi-
`tion, our results are consistent with those of a pooled
`analysis of data from the general population of these
`studies in which the 8-mg dose was significantly better
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`than the 4 mg dose in decreasing the number of UUI
`episodes and increasing MVV, although the studies were
`not powered for this comparison.” One exception is
`that, in one of the individual studies,” at the end of
`treatment, fesoterodine 4 mg was noted to be signifi-
`cantly more effective than placebo in increasing MVV,
`which was not observed in the present analysis.
`These findings are important because OAB symptoms
`are relatively prevalent in men (11%-16%),” have a
`negative effect on measures of health-related quality of
`life,3 and may be more bothersome than voiding symp-
`toms in men.” Moreover,
`the apparent dose response
`observed for several efficacy outcomes is uncommon in
`parallel-group studies of antimuscarinics that offer mul-
`tiple doses, and this is the first analysis demonstrating a
`dose response specifically in men with OAB. Addition-
`ally,
`the onset of efficacy appeared to be earlier with
`fesoterodine 8 mg compared with fesoterodine 4 mg for
`most endpoints. Collectively, these data suggest that the
`availability of 2 doses of fesoterodine will allow clinicians
`to tailor the dosing regimen to optimize the balance
`between efficacy and tolerability in men.
`This study should be interpreted within the context of
`its limitations. This was a post hoc analysis of data pooled
`from 2 clinical trials that were not designed or powered to
`assess the efficacy of fesoterodine 4 and 8 mg in men
`alone or to directly compare the 4 and 8 mg doses, so the
`results must be interpreted with caution. The duration of
`the trials that provided data for this analysis was 12
`weeks. Longer-term data on the efficacy and safety of
`fesoterodine in men are warranted, although recent data
`suggest that the risk of acute urinary retention in men
`treated with antimuscarinics is highest within 30 days of
`treatment initiatiomm the results from the present study
`are consistent with this finding. Additionally, prostate
`size and prostate-specific antigen levels were not mea-
`sured during this study, so we cannot assess whether
`treatment outcomes were different between men with
`
`larger vs smaller prostates or higher vs lower prostate-
`specific antigen levels. Finally, the trials that provided
`data for this analysis had an exclusion criterion of PVR >
`100 mL, but there was no formal assessment of flow rate
`to guide clinician assessment of the presence of BOO.
`Therefore, it is possible that some subjects with clinically
`relevant BOO may have been enrolled, although “clini-
`cally relevant BOO” was a specific exclusion criterion.
`The extent to which the subjects in this study are rep-
`resentative of patients seen in clinical practice is unclear.
`
`CONCLUSIONS
`
`Among men with OAB enrolled in 2 phase 111 studies,
`fesoterodine 4 and 8 mg significantly improved most
`bladder diary variables compared with placebo, and both
`doses were generally well tolerated and safe. Some of the
`improvements in OAB symptoms were dose dependent.
`The availability of 2 doses of fesoterodine allows for dose
`titration and treatment individualization in men.
`
`Acknowledgments. Editorial assistance was provided by Co-
`lin Mitchell and Nancy Sheridan of Complete Healthcare
`Communications, Inc., and was funded by Pfizer, Inc.
`
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`Patent Owner, UCB Pharma GmbH — Exhibit 2080 - 0007