efficacy and safety of vardenafil for the treatment of erectile dysfunction in men with metabolic...

Efficacy and Safety of Vardenafil for the Treatment of ErectileDysfunction in Men with Metabolic Syndrome: Results of aRandomized, Placebo-Controlled Trialjsm_2383 2904..2911

Tim Schneider, MD,* Jochen Gleißner, MD,† Frank Merfort, MD,‡ Monika Hermanns, MD,§

Manfred Beneke, PhD, Dipl. Psych,¶ and Ernst Ulbrich, MD§

*PUR/R Praxisklinik Urologie Rhein-Ruhr, Mülheim an der Ruhr, Germany; †DGU, Die Gesundheitsunion, Wuppertal,Germany; ‡Diabetologic Office, Grevenbroich, Germany; §Bayer Vital GmbH, Leverkusen, Germany; ¶Bayer HealthCareAG, Bayer Schering Pharma, Wuppertal, Germany

DOI: 10.1111/j.1743-6109.2011.02383.x

A B S T R A C T

Introduction. The prevalence of erectile dysfunction (ED) is increased in men with metabolic syndrome comparedwith the general population.Aim. The aim of this study was to evaluate the efficacy and safety of vardenafil vs. placebo in men who had ED andmetabolic syndrome.Methods. This was a 12-week, double-blind, randomized, multicenter, parallel-group, placebo-controlled prospec-tive study in men with ED and metabolic syndrome (assessed by the International Diabetes Federation criteria).Vardenafil was administered at a starting dose of 10 mg, which could be titrated to 5 mg or 20 mg after 4 weeks,depending on efficacy and tolerability.Main Outcome Measures. Primary efficacy measures were the erectile function domain of the International Indexof Erectile Function (IIEF-EF) and Sexual Encounter Profile (SEP) diary questions 2/3. Secondary efficacy measuresincluded SEP1, a diary question assessing ejaculation, the percentage of men achieving “return-to-normal” erectilefunction, and the percentage of men who titrated to a different dose. Adverse events (AEs) were recorded throughoutthe study.Results. The intent-to-treat population included 145 men (vardenafil, N = 75; placebo, N = 70). Baseline leastsquares IIEF-EF domain scores were low (vardenafil: 12.0; placebo: 12.7), indicative of moderate-to-severe ED.Vardenafil was statistically significantly superior to placebo for all primary efficacy measures (P < 0.0001) and showednominally statistically significant superiority compared with placebo for SEP1/ejaculation success rates (P = 0.0003and P < 0.0001, respectively) and the percentage of subjects reporting “return-to-normal” erectile function(P = 0.0004). Treatment-emergent AEs were mild-to-moderate in severity and consistent with the known AE profileof phosphodiesterase type 5 inhibitors.Conclusions. This is the first study to assess the efficacy and safety of vardenafil, taken alone, for ED therapy in apopulation of men who all had metabolic syndrome. Although baseline erectile function in these patients was low,vardenafil treatment was associated with significant improvements in erectile function and rates of successfulintercourse, and was well tolerated. Schneider T, Gleißner J, Merfort F, Hermanns M, Beneke M, and UlbrichE. Efficacy and safety of vardenafil for the treatment of erectile dysfunction in men with metabolicsyndrome: results of a randomized, placebo-controlled trial. J Sex Med 2011;8:2904–2911.

Key Words. Vardenafil; Erectile Dysfunction; Metabolic Syndrome; PDE-5 Inhibitors for Men with MetabolicSyndrome

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Introduction

M etabolic syndrome is an umbrella term usedto describe a cluster of metabolic risk

factors, including abdominal obesity, atherogenicdyslipidemia (elevated triglycerides [TG] andreduced high-density lipoprotein [HDL] choles-terol), elevated blood pressure (BP), glucose intol-erance and insulin resistance, and the presence of aprothrombotic state (elevated levels of coagulationfactors and decreased fibrinolysis) and/or a proin-flammatory state (elevated levels of C-reactiveprotein and inflammatory cytokines) [1].

The exact etiology of metabolic syndrome canvary between individuals. The International Dia-betes Federation (IDF) defines metabolic syn-drome as central (abdominal) obesity plus any twoof the following four factors: elevated TG,reduced HDL cholesterol, raised BP or previouslydiagnosed hypertension, and raised fasting plasmaglucose or previously diagnosed type 2 diabetesmellitus [2]. Whatever the combination of factors,men with metabolic syndrome are at greater risk ofdeveloping cardiovascular disease and diabetes[1,3], and the prevalence of erectile dysfunction(ED) is increased in men with metabolic syndromecompared with the general population [4]. Thereported prevalence of ED in men with metabolicsyndrome ranges from 27% to 96.5% [4–6], andthe relative risk and severity of ED increase inproportion to the number of metabolic syndromecomponents that are present [4,5,7–9]. Defectivenitric oxide activity leading to endothelial dysfunc-tion has been proposed as a possible link betweenmetabolic syndrome and ED. It has been shownthat as the number of metabolic syndrome com-ponents increase, endothelial function test scoresdecrease and the prevalence of ED increases, cor-respondingly [4].

Many risk factors for organic ED are the sameas those for cardiovascular disease, including dia-betes mellitus, hypertension, dyslipidemia, andmetabolic syndrome [3,10]. As such, many menwith ED have one or more underlying conditions,and the increased severity of ED in this populationof men can make it more difficult to treat [6,11].The efficacy and safety of the phosphodiesterasetype-5 (PDE-5) inhibitor, vardenafil, for the treat-ment of ED has been widely demonstrated inseveral clinical studies [12–17], including in menwith underlying conditions [18–21].

This is the first prospective study to evaluatethe efficacy and safety of vardenafil film-coatedtablet, given alone in men with ED, where 100%

of the study population had metabolic syndrome(as defined by IDF criteria) [2].

Methods

Study DesignThis was a double-blind, randomized, multicenter,parallel-group, placebo-controlled prospectivestudy at 15 centers in Germany. In total, 165 menaged 18–64 years were enrolled, of which 150 wererandomized to receive vardenafil or placebo.Blinding was maintained for the duration of thestudy. All patients provided written informedconsent, and the study was conducted according tothe Good Clinical Practice guidelines and theprinciples detailed in the Declaration of Helsinki,and in keeping with applicable local laws andregulations.

All electrocardiogram and laboratory param-eters relevant for assessment of the inclusionand exclusion criteria (including whether or notthe criteria of metabolic syndrome were met)were obtained no longer than 3 months beforescreening.

The main inclusion criteria were men with ahistory of ED (as defined by the National Insti-tutes of Health Consensus Development Panel onImpotence [22]) for at least 6 months; aged 18–64years; in a stable, heterosexual relationship for atleast 6 months; having an erectile function domainof the International Index of Erectile Function(IIEF-EF) score (at visit 2) of �21 to ensure thatall subjects had ED of mild-to-moderate or greaterseverity; and motivated to obtain treatment forED. As a further inclusion criterion, all subjectsmust have been previously diagnosed by theirdoctor (i.e., as documented in their patienthistory), within the prior 3 months, as havingmetabolic syndrome defined by the IDF criteria ofcentral obesity (body mass index >30 kg/m2 orwaist circumference >94 cm) and at least two ofthe following four conditions: history of hyperlipi-demia based upon TG levels �150 mg/dL(1.7 mmol/L), or treatment with lipid-loweringdrugs; history of HDL cholesterol, <40 mg/dL(1.03 mmol/L), or specific treatment for this lipidabnormality; history of hypertension (systolic BP>130 mm Hg and/or diastolic BP �85 mm Hg),or treatment of previously diagnosed hyperten-sion; and fasting plasma glucose levels�100 mg/dL (5.6 mmol/L) and <125 mg/dL(6.9 mmol/L), or history of type 2 diabetes melli-tus [2].

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The main exclusion criteria were the presenceof any underlying cardiovascular condition thatprecludes sexual activity; history of severe cardio-vascular disorder within 6 months prior to firstvisit; atrial fibrillation at screening; resting systolicBP <90 mm Hg or >170 mm Hg, or resting dias-tolic BP >110 mm Hg; history of prostatectomybecause of prostate cancer; spinal cord injury;hepatic or renal insufficiency; and clinical signs ofhypogonadism and/or documented total testoster-one <12 nmol/L. Patients were also excluded ifthey were taking certain concomitant medications,including nitrates/nitric oxide donors, androgens,antiandrogens, alpha-blockers, cytochrome P4503A4 inhibitors, medications that prolong the QTinterval, any investigational drug (includingplacebo) within 30 days of visit 1, and any EDtreatment during the study period (including oralmedication, vacuum devices, constrictive devices,injections, suppositories, and gels).

The duration of the study was 12 weeks, con-sisting of a 4-week nonmedicated run-in period,followed by an 8-week randomized treatmentperiod. The presence of ED was reassessed(IIEF-EF score �21) following the run-in period.Patients were randomized (1:1) at visit 2 to receiveeither 10 mg vardenafil (supplied as film-coatedtablets) or placebo (no more than one dose ofstudy medication taken per day). Following 4weeks of treatment, the dose could be lowered to5 mg, or up-titrated to 20 mg if required. Patientswere not permitted to up-titrate if their IIEF-EFscore increased by �6 points between visit 2 andvisit 3 (week 4) and if they were satisfied withtheir erectile function, or if normal erectile func-tion (IIEF-EF score �26) was achieved followingtreatment.

Efficacy and Safety VariablesPrimary efficacy variables were the IIEF-EF scoreat week 8 or last observation carried forward(LOCF) compared with baseline, and baseline-adjusted cumulative success rates for SexualEncounter Profile (SEP) questions 2 (SEP2:“Were you able to insert your penis into yourpartner’s vagina?”), and 3 (SEP3: “Did your erec-tion last long enough for you to have successfulintercourse?”).

Secondary efficacy variables included the per-centage of subjects achieving “return-to-normal”erectile function (IIEF-EF score �26) at week 8 orLOCF; SEP question 1 (SEP1: “Were you able toachieve at least some erection [some enlargementof the penis?”]) and an additional diary question

assessing ejaculation (“Did you ejaculate?”),assessed over the entire treatment period; and per-centage of subjects who remained on the 10 mgvardenafil dose and did not require uptitration.

Safety variables included adverse events (AEs)recorded at all visits following visit 1 and vitalsigns, supine and standing heart rate, and BP mea-sured at all visits. Further parameters assessedincluded body weight measured at first and finalvisit and physical examinations performed at allvisits.

Statistical AnalysesEfficacy was analyzed in both the intent-to-treat(ITT) population (patients who had taken at leastone dose of study medication and who had baselineand postbaseline efficacy data using LOCF) andthe per-protocol (PP) population (patients whosatisfied the ITT criteria and who completed 8weeks of randomized treatment without any majorprotocol violations). The safety populationincluded all randomized subjects taking at leastone dose of study medication and having at leastone postbaseline safety assessment.

Primary end-point analyses were performed forthe ITT and PP populations, while secondary effi-cacy analyses were performed for the ITT popu-lation only. IIEF-EF scores and SEP2/3 successrates were evaluated using analysis of covariance(ancova) with baseline as covariate, and treatmentand study center as factors. All primary efficacyvariables were required to be significant at the 5%level (P < 0.05). Secondary efficacy variables wereevaluated using the same ancova model and Pvalues of <0.05 were considered to be nominallysignificant.

Results

Study PopulationIn total, 165 subjects were enrolled in 15 investi-gational centers in Germany. Of these subjects,150 were randomized to treatment with eithervardenafil (N = 76) or placebo (N = 74). The ITTpopulation included 145 subjects (vardenafil,N = 75; placebo, N = 70), the PP populationincluded 98 subjects (vardenafil, N = 47; placebo,N = 51), and the safety population included 147subjects (vardenafil, N = 75; placebo, N = 72;Figure 1). The main reasons for exclusion fromthe PP population included insufficient or pro-longed treatment duration and less than 30%failure rate of sexual intercourse attempts duringthe unmedicated run-in period.

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The demographics and baseline characteristicsof the safety population were similar betweentreatment groups (Table 1). Mean age (standarddeviation [SD]) at enrollment was 56.3 (5.9) yearsand 55.6 (6.7) years in the vardenafil and placebogroups, respectively. The majority of subjects(65.3% for both vardenafil and placebo groups)were suffering from ED of organic etiology. Theprevalence of underlying conditions, includingelevated cholesterol, hyperlipidemia, diabetes mel-litus, and hypertension, was similar betweenpatients in both treatment groups.

In total, 11 subjects prematurely discontinuedthe study (vardenafil, N = 4 [5%]; placebo, N = 7[9%]). The most common reasons for discontinu-ation were AEs (vardenafil, N = 3 [4%]; placebo,N = 1 [1%]) and patient lost at follow-up (vard-enafil, N = 0 [0%]; placebo, N = 3 [4%]) (Table 2).

Primary Efficacy VariablesAll efficacy analyses reported here were performedusing the ITT population. At baseline, the leastsquares (LS) mean IIEF-EF scores in this popula-

tion of men with metabolic syndrome were low:12.0 and 12.7 for vardenafil and placebo, respec-tively. At week 8 (LOCF), the LS mean IIEF-EFscore was statistically significantly greater follow-ing vardenafil treatment compared with placebo(21.0 vs. 14.2, respectively; P < 0.0001). The LSmean overall SEP2 success rate (successful pen-etration) was statistically significantly greater fol-lowing vardenafil treatment compared withplacebo (vardenafil, 73.5% vs. placebo, 52.8%;P < 0.0001). Corresponding values at baselinewere 42.8% (vardenafil) and 44.6% (placebo).Similarly, statistically significant improvements inLS mean overall SEP3 success rate (successfulintercourse) were observed following vardenafiltreatment compared with placebo (vardenafil,53.2% vs. placebo, 27.0%; P < 0.0001), with cor-responding values at baseline being 15.9% (vard-enafil) and 16.6% (placebo; Figure 2).

Secondary Efficacy VariablesVardenafil showed nominally statistically signifi-cant superiority compared with placebo for the

Subjects enrolled(N=165)

Subjects randomized(n=150)

Safety(n=72)

Safety(n=75)

ITT(n=70)

ITT(n=75)

PP(n=51)

PP(n=47)

Placebo(n=74)

Excluded from analysis (n=2)Never took medication 2

Excluded from analysis (n=1)Never took medication 1

Excluded from analysis (n=2)No post-baseline efficacy data 2

Excluded from analysis (n=28)Non-compliance with study medication 1

Insufficient duration of treatment 7At least one required post-baseline efficacy measurement missing 2

<3 attempts at sexual intercourse at baseline 1530% of attempts during baseline period were not unsuccessful 3

Excluded from analysis (n=19)Non-compliance with study medication 3

Insufficient duration of treatment 6At least one required post-baseline efficacy measurement missing 3

<3 attempts at sexual intercourse at baseline 630% of attempts during baseline period were not unsuccessful 1

Vardenafil(n=76)

Figure 1 Disposition of subjects during the study. ITT = intent-to-treat, PP = per-protocol.


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following secondary efficacy variables: LS meanoverall success rates for SEP1 (some erection/enlargement of the penis) (baseline: 76.8% vs.75.0%, overall: 91.4% vs. 75.8%, for vardenafil

and placebo, respectively; P = 0.0003) and theadditional diary question (successful ejaculation)(baseline: 39.9% vs. 37.7%, overall: 71.3% vs.44.0%, for vardenafil and placebo, respectively;P < 0.0001) (Figure 3), and the percentage of sub-jects reporting “return-to-normal” erectile func-tion (vardenafil, 35.0% vs. placebo, 10.0%;P = 0.0004). The percentage of subjects who, inconsultation with their physician, chose to titrateup to 20 mg vardenafil after 4 weeks of treatmentwas lower in the vardenafil group than the placebogroup (vardenafil, 58.7% vs. placebo, 80.0%), and37.3% and 18.6% of all subjects taking vardenafilor placebo, respectively, did not titrate from theinitial 10 mg dose. Overall, only one subject(0.7%) down-titrated to the 5 mg dose. No dosetitration information was available for 2.1% ofsubjects (vardenafil, 2.7%; placebo, 1.4%).

SafetyTreatment-emergent AEs were transient andmostly mild-to-moderate in severity. There was ahigher incidence of treatment-emergent AEs inthe vardenafil group compared with placebo(21.3% vs. 11.1%, respectively), and a higher inci-dence of treatment-emergent, drug-related AEswith vardenafil compared with placebo (8.0% vs.0%, respectively). One subject taking vardenafilprematurely discontinued the study because ofheadache. The event occurred during the study, 2days after visit 2 (January 1, 2009). Study medica-tion was continued for the duration of the event,which resolved 12 days after the last dose of studymedication. The patient was prematurely with-drawn from the study on January 27, 2009. ThisAE was judged by the investigator as not beingrelated to the study drug. The most frequentlyreported drug-related, treatment-emergent AE inthe vardenafil group was headache (4.0%), whichis consistent with the known AE profile of PDE-5inhibitors (Table 3). There was one case ofarrhythmia that occurred in the vardenafil treat-ment group, which was considered at the time tobe drug-related. However, after extensive discus-sion of the case, the event was considered to be sicksinus syndrome due to underlying coronary arterydisease, and not related to the study drug. At thispoint, the database had been frozen and was notreopened to reflect this change.

Discussion

This double-blind, randomized, multicenter,parallel-group, placebo-controlled prospective

Table 1 Demographics and baseline characteristics ofthe safety population (N = 147), stratified by treatmentgroup

Placebo(N = 72)

Vardenafil(N = 75)

Race, N (%)White 72 (100) 75 (100)

Age at enrollment (years)Mean (SD) 55.6 (6.7) 56.3 (5.9)Min–max 38.0–65.0 36.0–63.0

Weight (kg)Mean (SD) 96.7 (12.7) 96.2 (12.9)Min–max 70.0–144.0 75.0–135.0

Height (cm)Mean (SD) 178.3 (6.8) 177.8 (6.2)Min–max 164.0–197.0 162.0–192.0

Underlying conditions, N (%)Vascular hypertensive disorders 53 (73.6) 56 (74.7)Diabetes mellitus 26 (36.1) 27 (36.0)Elevated cholesterol 16 (22.2) 29 (38.7)Hyperlipidemia 9 (12.5) 11 (14.7)Elevated triglycerides 9 (12.5) 8 (10.7)

Current alcohol consumption, N (%)Abstinent 15 (20.8) 16 (21.3)Light 50 (69.4) 49 (65.3)Moderate 7 (9.7) 10 (13.3)

Smoking status, N (%)Nonsmoker 43 (59.7) 38 (50.7)Past or present smoker 29 (40.3) 37 (49.3)

ED etiology, N (%)Organic 47 (65.3) 49 (65.3)Psychogenic 1 (1.4) 1 (1.3)Mixed 24 (33.3) 25 (33.3)

Time since ED diagnosis (years)Mean (SD) 5.0 (4.9) 4.5 (3.7)Min–max 0–25.7 0–16.1

Time since ED onset (years)Mean (SD) 6.1 (5.2) 5.5 (4.2)Min–max 0.5–25.8 0.7–24.3

Previous use of oral PDE-5 inhibitors for ED, N (%)Yes 49 (68.1) 51 (68.0)No 23 (31.9) 24 (32.0)

ED = erectile dysfunction; PDE-5 = phosphodiesterase type-5; SD = standarddeviation.

Table 2 Primary reasons for premature discontinuation,stratified by treatment for all randomized subjects (N = 150)

ReasonPlacebo,N (%)

Vardenafil,N (%)

Randomized subjects 74 (100) 76 (100)Premature discontinuation 7 (9) 4 (5)

Adverse event 1 (1) 3 (4)Consent withdrawn 1 (1) 0 (0)Insufficient therapeutic effect 1 (1) 0 (0)Patient lost at follow-up 3 (4) 0 (0)Noncompliant with study medication 1 (1) 0 (0)Protocol violation 0 (0) 1 (1)


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study is the first study to evaluate the efficacy andsafety of a PDE-5 inhibitor alone for the treatmentof ED, in a population exclusively comprised ofmen with metabolic syndrome. Treatment withvardenafil was statistically significantly superior toplacebo (P < 0.0001) with respect to change frombaseline at week 8/LOCF for IIEF-EF scores andoverall SEP2 and SEP3 success rates. All second-ary efficacy measures demonstrated nominally sta-tistically significant differences in favor ofvardenafil. Overall success rates for SEP1 and theadditional diary question on ejaculation were sig-nificantly greater in the vardenafil group than theplacebo group (P = 0.0003 and P < 0.0001, respec-tively). Compared with those receiving placebo(80%), fewer subjects in the vardenafil group(58.7%) up-titrated from the initial 10 mg dose ofvardenafil to 20 mg. This indicates that 10 mgvardenafil was deemed efficacious for the treat-ment of ED for many men in this population ofpatients with metabolic syndrome.

The optimal outcome of ED treatment is toallow a man to return his sex life to how it wasbefore the onset of ED [23]. Significantly higher

percentages of subjects taking vardenafil reported“return-to-normal” erectile function than thosetaking placebo (35.0% vs. 10.0%, respectively;P = 0.0004). This rate was comparable with that ofa previous study in a broad population of men withED, in which 42.8% of patients taking 10 mgvardenafil experienced a “return-to-normal” erec-tile function after a period of 12 weeks of treat-ment [24].

In this study, all subjects were required to havemoderate-to-severe ED at baseline. LS meanIIEF-EF scores were 12.0 in the vardenafil groupand 12.7 in the placebo group, comparable withbaseline values seen in previous studies of menwith ED and diabetes mellitus, dyslipidemia, orhypertension. These men typically have moresevere ED, which is more difficult to treat, com-pared with men without these underlying condi-tions [18–21]. Similarly, baseline SEP2/3 successrates (successful penetration/successful inter-course) in this study (SEP2: 42.8% and 44.6%,SEP3: 15.9% and 16.6% for vardenafil andplacebo, respectively) were also similar to thoseseen in previous studies in men with ED and

Figure 2 Improvement in LS mean IIEF-EF scores at week 8/LOCF, and overall SEP2 and SEP3 success rates, followingtreatment with vardenafil or placebo in the ITT population. *P < 0.0001 for vardenafil vs. placebo. IIEF-EF = erectile functiondomain of the International Index of Erectile Function, ITT = intent-to-treat, LOCF = last observation carried forward,LS = least squares, SEP = Sexual Encounter Profile question.

Figure 3 Improvement in LS meanoverall SEP1 and ejaculation successrates, following treatment with vard-enafil or placebo in the ITT population.*P = 0.0003, **P < 0.0001 for vardena-fil vs. placebo (nominal statistical sig-nificance). ITT = intent-to-treat, LS =least squares, SEP = Sexual Encoun-ter Profile question.


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underlying conditions [19–21]. Despite the poorbaseline erectile function of this population of menwith metabolic syndrome, 10 mg vardenafil washighly efficacious. A total of 58.7% of men choseto titrate up to 20 mg, which is comparable withother studies of 10 mg vardenafil in broad popula-tions of men with ED [13,25].

Vardenafil was well tolerated in this populationof men with ED and metabolic syndrome. Theincidence and type of AEs were consistent withthose seen previously for vardenafil [13–15] andwere in keeping with the known AE profile ofPDE-5 inhibitors established in a broad popula-tion of men with ED.

There are some potential limitations to thisstudy. Efficacy variables were assessed in the ITTpopulation; however, there was a notable differ-ence between the number of subjects included inthe ITT population (N = 145) and the PP popu-lation (N = 98), with reasons for exclusion fromthe PP population including insufficient durationof treatment, noncompliance with study drug, andinsufficient failure rate of sexual intercourse atbaseline.

This study, the first to assess the efficacy andsafety of vardenafil given alone in a population ofmen who all had ED and metabolic syndrome,builds on previous data showing that vardenafil isefficacious in men with underlying conditions[18–21] and supports its use as first-line therapy inmen with ED and metabolic syndrome.

Conclusions

In this first-ever study to evaluate the efficacy andsafety of vardenafil for the treatment of ED in a

population of men who all had metabolic syn-drome, participants’ baseline erectile function wascomparable with that of men with diabetes melli-tus, dyslipidemia, and hypertension, who typicallyhave more severe ED, which is more difficult totreat, compared with men without these underly-ing conditions. Vardenafil showed favorable effi-cacy and tolerability for the treatment of ED inthese men with metabolic syndrome, with themajority of subjects experiencing significantimprovements in erectile function and rates of suc-cessful intercourse.

Acknowledgments

This study was funded by Bayer Schering Pharma. Edi-torial support in developing the manuscript was providedby Fishawack Communications. Study investigators:Tim Schneider, Mülheim, Germany; Frank Merfort,Grevenbroich, Germany; Jochen Gleißner, Wuppertal,Germany; Michael Netzer, Homburg, Germany;Michael Stephan-Odenthal, Leverkusen, Germany;Dieter Popp, Regensburg, Germany; Andre Rollen-hagen, Berlin, Germany; Mark Indig, Trier, Germany;Alexander Von Keitz, Marburg, Germany; Heinz-PeterFischer, Koblenz, Germany; Hartmut Porst, Hamburg,Germany; Jorg Willgerodt, Leipzig, Germany; ManuelFichtlscherer, Cham, Germany; Torsten Drescher,Stuhr, Germany.

Corresponding Author: Tim Schneider, PUR/R, Prax-isklinik Urologie Rhein-Ruhr, Schulstraße 11, D-45468Mülheim, Germany. Tel: (49) 208 94067 900/-919; Fax:(49) 208 94067 915; E-mail: [email protected]

Conflicts of Interest: T. Schneider has acted as a speaker,investigator, and advisory board member for BayerSchering Pharma, Pfizer, and Astellas. J. Gleißner hasno conflicts of interest to declare. F. Merfort has acted asa speaker, investigator, and advisory board member forBayer Schering Pharma, Novo Nordisk, and Eli Lilly.M. Hermanns and E. Ulbrich are employees of BayerVital GmbH. M. Beneke is an employee of, and ownsstocks in, Bayer HealthCare AG.

Statement of Authorship

Category 1(a) Conception and Design

Tim Schneider; Jochen Gleißner; Frank Merfort;Monika Hermanns; Manfred Beneke; Ernst Ulbrich

(b) Acquisition of DataTim Schneider; Jochen Gleißner; Frank Merfort;Monika Hermanns

(c) Analysis and Interpretation of DataTim Schneider; Jochen Gleißner; Frank Merfort;Monika Hermanns; Manfred Beneke; Ernst Ulbrich

Table 3 Incidence rates of adverse events occurring inthe safety population (N = 147)

Adverse event*

Placebo,N (%)N = 72

Vardenafil,N (%)N = 75

Treatment-emergent AEsAny event 8 (11.1) 16 (21.3)

Drug-related, treatment-emergent AEsAny event 0 (0) 6 (8.0)

Headache 0 (0) 3 (4.0)Arrhythmia 0 (0) 1 (1.3)Flushing 0 (0) 1 (1.3)Pain in extremity 0 (0) 1 (1.3)Reflux esophagitis 0 (0) 1 (1.3)

Treatment-emergent AEs leading to discontinuationAny event 0 (0) 1 (1.3)

Headache 0 (0) 1 (1.3)

*MedDRA (Medical Dictionary for Regulatory Activities) preferred term.AE = adverse event.


J Sex Med 2011;8:2904–2911

Category 2(a) Drafting the Article


(b) Revising It for Intellectual ContentTim Schneider; Jochen Gleißner; Frank Merfort;Monika Hermanns; Manfred Beneke; Ernst Ulbrich

Category 3(a) Final Approval of the Completed Article


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J Sex Med 2011;8:2904–2911

efficacy and safety of vardenafil for the treatment of erectile dysfunction in men with metabolic...

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