Ilker Yalcin

Indiana University-Purdue University Indianapolis, Indianapolis, Indiana, United States

Are you Ilker Yalcin?

Claim your profile

Publications (33)97.96 Total impact

  • Ilker Yalcin · Guangbin Peng · Lars Viktrup · Richard C Bump
    [Show abstract] [Hide abstract]
    ABSTRACT: To expand our understanding of the clinical importance to patients with stress urinary incontinence (SUI) of reductions in incontinence episode frequency (IEF) that fall short of a complete cure. We used an integrated database that included data from 1,913 women with SUI who were enrolled in four randomized, placebo-controlled pharmaceutical clinical trials and examined the relationship between various levels of reduction in IEF and minimally clinical important difference (MCID) levels established for the validated Incontinence Quality of Life (I-QOL) questionnaire. The first decile of IEF reduction to exceed the within-group MCID was considered to be the point at which the reduction in IEF first became clinically important. The between-group MCID was then used to determine when further reductions in incontinence represented clinically relevant incremental improvements for patients. Improvements in condition-specific quality of life were not clinically important until the fifth decile of IEF reduction, representing a reduction in IEF >40% to <or=50%. Patients appreciated incremental clinically important benefits when IEF reductions exceeded 70%, with progressive improvements in condition-specific quality of life with higher levels of IEF reduction. The difference between a >70% to <or=80% reduction and a >90% to <or=100% reduction was clinically important. Reductions in IEF <or=40% do not appear to be clinically important for women with SUI. Patients appear to recognize important clinical value at reductions of approximately 50% and important incremental clinical value at reductions of approximately 75% and 90-100%. These thresholds may not apply to women seeking non-pharmaceutical treatments for SUI.
    Neurourology and Urodynamics 01/2009; 29(3):344-7. DOI:10.1002/nau.20744 · 2.87 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Evaluate duloxetine in the treatment of women with mixed urinary incontinence (MUI). 588 women, 19-85 years old with >or=4 incontinence episodes/week were randomly assigned to duloxetine 80 mg/day (N = 300) or placebo (N = 288). Patients were classified into three symptom subgroups: stress or urge predominant MUI (SPMUI or UPMUI) or balanced MUI (BMUI) based on their responses to the validated Stress/Urge Incontinence Questionnaire. Half the population was randomly assigned to have urodynamics; SPMUI, UPMUI, and BMUI condition diagnoses were based on signs, symptoms, and urodynamic observations. The primary outcome measure was the change in incontinence episode frequency (IEF). Secondary outcome measures included the Incontinence Quality of Life (I-QOL) scores, the ICI Quality of Life (ICIQ-SF) score, and the Patient Global Impression of Improvement (PGI-I) rating. At baseline, women with SPMUI averaged 15.9 IEF/week (61% stress), those with UPMUI averaged 13.2 (70% urge), and those with BMUI averaged 16.5 (52% urge). Overall IEF decreases were significantly greater with duloxetine than placebo (median percent reduction 60% vs. 47%, P < 0.001); both UUI and SUI episodes were significantly decreased with duloxetine (median SUI IEF reduction 59% vs. 43%, P = 0.001; UUI IEF reduction 58% vs. 40%, P < 0.001). Duloxetine IEF decreases were significantly greater for patients with SPMUI conditions and symptoms and for those with UPMUI conditions but not symptoms. Significant benefits were also demonstrated with duloxetine for improvements in I-QOL total score (11.5 points vs. 8.1 points, P = 0.002), all three I-QOL subscale scores, and for the ICIQ-SF score (-2.6 vs. -1.7, P = 0.002) as well as for PGI-I ratings (much/very much better 44.2% vs. 27.3%, P = 0.001). Duloxetine demonstrated significant efficacy in this population of women with MUI.
    Neurourology and Urodynamics 03/2008; 27(3):212-21. DOI:10.1002/nau.20471 · 2.87 Impact Factor
  • Ilker Yalcin · Lars Viktrup
    [Show abstract] [Hide abstract]
    ABSTRACT: Compare the subjective and objective assessment of stress urinary incontinence (SUI) severity and improvement with treatment using patient- and clinician-rated global impression of severity (PGI-S, CGI-S) and improvement (PGI-I, CGI-I) scales. Five hundred fifty-three women with mild SUI were recruited via media advertising into a placebo-controlled duloxetine trial. PGI-S and CGI-S (normal, mild, moderate, severe) were administered at baseline and PGI-I and CGI-I (seven responses from "very much worse" to "very much better") during treatment. Incontinence episode frequency (IEF) was determined from diaries. Agreements between clinician and patient ratings were assessed using Kappa and degree of association with Spearman's correlation. There was only a slight agreement regarding severity, with 53% of ratings being different (Kappa = 0.14; 95%CI = 0.08, 0.20). When ratings differed, clinicians rated severity worse in 72% of cases than did patients. Agreement regarding improvement was moderate, with 42% of ratings being different (Kappa = 0.45; 95%CI = 0.39, 0.50). When ratings differed, clinicians rated improvement greater than did patients in 54% of cases. Patients' assessments of severity correlated better with IEF (0.33) than did the clinicians' (0.15). The correlations of PGI-I and CGI-I with IEF changes were similar (0.46 and 0.44). In this study, the subjective (patient) and objective (clinician) assessments of SUI improvement with treatment appear to be more closely aligned than are the assessments of initial SUI severity.
    International Urogynecology Journal 12/2007; 18(11):1291-5. DOI:10.1007/s00192-007-0326-8 · 1.96 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate duloxetine (a serotonin-noradrenaline reuptake inhibitor) in women with symptoms of overactive bladder (OAB), as it has been shown to increase the bladder capacity in an animal model. In all, 306 women (aged 21-84 years) were recruited and randomly assigned to placebo (153) or duloxetine (80-mg/day for 4 weeks increased to 120-mg/day for 8 weeks; 153). Symptoms of OAB were defined as bothersome urinary urgency and/or urge urinary incontinence (UI) for > or =3 months. Participants were also required to have a mean daytime voiding interval (VI) of < or=2 h and urodynamic observations of either detrusor overactivity (DOA) or urgency which limited bladder capacity to <400 mL, both with no stress UI (SUI). The primary efficacy analysis compared the treatment effects on mean change from baseline to endpoint in the mean number of voiding episodes (VE)/24 h. The secondary efficacy analyses compared the treatment effects on the number of UI episodes (IE)/24 h, in the Incontinence Quality of Life questionnaire (I-QOL) score, and on the mean daytime VI. Safety was assessed with vital signs, adverse event reporting, routine laboratory testing, electrocardiogram, and the measurement of postvoid residual urine volumes (PVR). Patients randomized to duloxetine had significant improvements over those randomized to placebo for decreases in VE and IE, for increases in the daytime VI, and for improvements in I-QOL scores at both doses of duloxetine. Urodynamic studies showed no significant increases in maximum cystometric capacity or in the volume threshold for DOA. The most common treatment-emergent adverse events with duloxetine (nausea, 31%; dry mouth, 16%; dizziness, 14%; constipation, 14%; insomnia, 13%; and fatigue, 11%) were the same as those reported by women with SUI and were significantly more common with duloxetine than placebo. Laboratory assessments, vital signs and electrocardiograms were stable relative to baseline, with no relevant differences detected between groups. There was a significant difference in the change in PVR with duloxetine (<5 mL mean increase) but no patient reported hesitancy or retention. In this trial, duloxetine was better than placebo for treating women with 'wet' and 'dry' symptoms of OAB associated with DOA or a bladder capacity of <400 mL.
    BJU International 09/2007; 100(2):337-45. DOI:10.1111/j.1464-410X.2007.06980.x · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To assess the impact of duloxetine dose escalation on tolerability and efficacy, 516 women with stress urinary incontinence were randomized to receive placebo or duloxetine in one of three regimens: 40 mg BID for 8 weeks, 40 mg QD for 2 weeks escalating to 40 mg BID for 6 weeks or 20 mg BID for 2 weeks escalating to 40 mg BID for 6 weeks. A non-inferiority analysis confirmed that the 20 mg BID starting dose was significantly better than the other two duloxetine regimens for nausea reduction (16.5% vs 25.2% and 29.4%). There were also significant differences in the discontinuation rates (7.5% vs 11.8% and 16.2%). The efficacy after 4 weeks was significantly better with duloxetine than with placebo. Starting duloxetine at 20 mg BID for 2 weeks before increasing to 40 mg BID significantly improved tolerability but did not impact duloxetine efficacy after all the subjects had been on 40 mg BID for at least 2 weeks.
    International Urogynecology Journal 09/2007; 18(8):919-29. DOI:10.1007/s00192-006-0256-x · 1.96 Impact Factor
  • Lars Viktrup · Ilker Yalcin
    [Show abstract] [Hide abstract]
    ABSTRACT: To identify poor responders, we evaluated the impact of demographic characteristics and comorbidities on efficacy using an integrated database including data from four large randomized controlled trials. Duloxetine has been shown to be effective in women with stress urinary incontinence (SUI). A total of 1913 women 22-83 years of age with predominant SUI (diagnosed using a validated clinical algorithm) were randomly assigned to receive placebo (n = 955) or duloxetine (n = 958) for 12 weeks. Efficacy outcome variables included a weekly incontinence episodes frequency (IEF) from patient-completed diaries, the Incontinence Quality-of-Life (I-QOL) questionnaire score, and a Patient Global Impression of Improvement rating. Subgroups selected a priori included: ethnicity, age, body mass index (BMI), chronic lung disease, hypoestrogenism, diabetes mellitus, and depression. For safety comparisons, adverse events were compared across age and ethnicity subgroups. Reduction in IEF was minimal and not significantly different between duloxetine and placebo in women with chronic lung disease. The decrease in IEF for women > or =65 years of age was slightly diminished for duloxetine and placebo groups, but the treatment differences were maintained. There was a significantly different I-QOL improvement by BMI subgroup, with greater increases in scores associated with a higher BMI (>28 kg/m2). There were no other notable subgroup impacts on efficacy. With the possible exception of chronic lung disease, no characteristic was identified that predicted a lack of treatment response with duloxetine in the treatment of women with SUI. Elderly patients may experience lower response rates to duloxetine presumably due to age related changes in the lower urinary tract.
    European Journal of Obstetrics & Gynecology and Reproductive Biology 07/2007; 133(1):105-13. DOI:10.1016/j.ejogrb.2006.05.003 · 1.70 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The safety and tolerability of duloxetine for major depressive disorder (MDD), generalized anxiety disorder (GAD), diabetic peripheral neuropathic pain (DPNP), fibromyalgia, and lower urinary tract disorders (LUTD) (including female stress urinary incontinence [SUI] and other LUTDs) has been established in individual clinical studies. The objective of this manuscript is to characterize the overall safety profile of duloxetine, regardless of indication, based on data from the duloxetine exposures integrated safety database. The duloxetine exposures integrated safety database was examined using pooled data from 23,983 patients randomized to receive duloxetine in 64 studies for MDD, GAD, DPNP, fibromyalgia, or LUTDs. Evaluated aspects of drug safety included treatment-emergent adverse events (TEAEs), adverse events leading to discontinuation, serious adverse events (SAEs), clinical laboratory tests, vital signs, and electrocardiograms. Common TEAEs included nausea, headache, dry mouth, insomnia, constipation, dizziness, fatigue, somnolence, diarrhea, and hyperhidrosis. Most TEAEs emerged early; the majority were mild to moderate in severity, and did not worsen. Overall, discontinuation rates due to AEs were 20.0%. SAEs occurred at a rate of 3.5% and no single event was predominant. Mean pulse increased by < 2 beats per minute. Mean increases in systolic and diastolic blood pressure were < 1 mmHg. Mean alanine transaminase and aspartate transaminase values increased by < 2 U/L. The safety profile for the molecule from the overall duloxetine exposures integrated safety database suggests that benign and common pharmacologic side effects occur with duloxetine treatment. Because these pooled analyses do not allow for statistical comparison to placebo or active comparator, and include data from five different studied indications, these data do not suggest causality for AEs, nor are they necessarily generalizable to each disease stated studied.
    Current Medical Research and Opinion 01/2007; 23(1):175-84. DOI:10.1185/030079906X162719 · 2.65 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To determine the clinically relevant reference points for the Incontinence Quality of Life (I-QOL) questionnaire scores in women with stress urinary incontinence and compare them with the treatment effects observed with duloxetine and placebo. Using data from 1133 women with predominant stress urinary incontinence in two randomized, placebo-controlled duloxetine studies, the within-treatment and between-treatment minimal clinically important differences (MCIDs) were obtained by anchoring the I-QOL scores to the validated Patient Global Impression of Improvement scale (PGI-I). The within-treatment MCID (mean I-QOL for women rating their condition "a little better" with treatment) and between-treatment MCID (difference in scores between the group ratings of "no change" and "a little better") were derived. The treatment effects were compared with these MCIDs. Real-time urinary diaries were completed, along with the I-QOL and PGI-I. The within-treatment and between-treatment MCID for the I-QOL total score was 6.3 and 2.5, respectively. The total and subscale scores had almost identical MCIDs. Duloxetine 80 mg significantly improved the I-QOL total and subscale scores. Treatment differences in the I-QOL scores exceeded the between-treatment MCID and the duloxetine I-QOL treatment effect exceeded the within-treatment MCID. The number of patients needed to treat to gain an additional I-QOL responder was 6.8. Improvements in I-QOL scores should be greater than the within-treatment MCID, and differences between two treatments should be greater than the between-treatment MCIDs, for statistically significant differences to be considered clinically meaningful. We propose 2.5 points as a reasonable guide for the I-QOL between-treatment MCID and 6.3 points for the within-treatment MCID.
    Urology 07/2006; 67(6):1304-8. DOI:10.1016/j.urology.2005.12.006 · 2.19 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The objective was to characterize the safety of duloxetine for treatment of stress urinary incontinence (SUI) in women, using an integrated database generated from four published placebo-controlled clinical trials. The database included 1913 women randomized to duloxetine (N=958) or placebo (N=955), examining adverse events (AEs), serious adverse events (SAEs), vital signs, electrocardiograms, and laboratory analytes. AEs occurring initially or worsening during the double-blind treatment period were considered treatment-emergent (TEAE). Differences between duloxetine-treated and placebo-treated groups were compared statistically. Common TEAEs included: nausea (23.2%), dry mouth (13.4%), fatigue (12.7%), insomnia (12.6%), constipation (11.0%), headache (9.7%), dizziness (9.5%), somnolence (6.8%), and diarrhea (5.1%). Most TEAEs that emerged early were mild to moderate, rarely worsened, and resolved quickly. Overall AE discontinuation rates were 20.5% for duloxetine and 3.9% for placebo (P<.001). Most discontinuations (83%) occurred within the first month of treatment. SAEs were uncommon and did not differ between treatments. Statistically significant, but clinically unimportant mean increases in heart rate (2.4 bpm) and systolic and diastolic blood pressure (<or=2 mmHg) occurred. No arrhythmogenic potential was observed and any rare, transient, asymptomatic increases in hepatocellular enzymes normalized. Duloxetine was safe and tolerable, although transient AEs were not uncommon.
    European Journal of Obstetrics & Gynecology and Reproductive Biology 03/2006; 125(1):120-8. DOI:10.1016/j.ejogrb.2005.08.006 · 1.70 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Duloxetine is the first relatively balanced serotonin and noradrenaline re-uptake inhibitor to be widely available for three indications including: major depressive disorder, peripheral diabetic neuropathic pain and female stress urinary incontinence, although it is not currently approved for all indications in all countries. Generally, duloxetine is safe and well-tolerated across indications, with few reported serious side effects. Common adverse events are consistent with the pharmacology of the molecule and are mainly referable to the gastrointestinal and the nervous systems. The studied dose range is up to 400 mg/day (administered 200 mg b.i.d) but the maximum dose approved for marketing is 120 mg/day (administered 60 mg b.i.d). Duloxetine is eliminated (half-life = 12.1 hours) primarily in the urine after extensive hepatic metabolism by multiple oxidative pathways, methylation and conjugation. Duloxetine would not be expected to cause clinically significant inhibition of the metabolic clearance of drugs metabolised by P450 (CYP)3A, (CYP)1A2, (CYP)2C9, or (CYP)2C19, but would be expected to cause some inhibition of CYP 2D6. Duloxetine should not be used in combination CYP 1A2 inhibitors or nonselective, irreversible monoamine oxidase inhibitors. The purpose of this review is to provide an overview of some of the most important information related to safety and tolerability of duloxetine.
    Expert Opinion on Drug Safety 12/2005; 4(6):987-93. DOI:10.1517/14740338.4.6.987 · 2.91 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate the reproducibility, construct validity, and preferences for the 2-item Stress/Urge Incontinence Questionnaire. The questionnaire asks a patient to recall the number of stress urinary incontinence and urge urinary incontinence episodes she experienced during the preceding week. The 4-week prospective study included 3 office visits and enrolled women with stress, urge, or mixed urinary incontinence symptoms. The test-retest reproducibility was assessed after 3 days, and the construct validity of the questionnaire was evaluated against a diary and other measures of incontinence severity and effect. The bother associated with completing (patients) or analyzing (physicians) the diary was assessed. Both groups also reported their time requirements and preferences for the questionnaire or diary. Reproducibility for the classification of symptoms was moderately strong (kappa = .536). Test-retest agreement was good (64-80%) for all but balanced mixed incontinence (38%). Intraclass correlations revealed good reproducibility for the number of stress (.694), urge (.703), and total (.726) incontinence episodes. Significant (P < .01) correlations with other measures of incontinence established construct validity. Patients and physicians reported it took less time to complete the questionnaire than the diary, but the majority said the completion or analysis of the diary was of little or no bother and preferred the diary. The Stress/Urge Incontinence Questionnaire is a valid tool that can be used in clinical practice to differentiate between symptoms of stress and urge urinary incontinence to make an initial diagnosis, especially in primary care where incontinence is not a focus of the practice.
    Obstetrics and Gynecology 10/2005; 106(4):767-73. DOI:10.1097/01.AOG.0000178168.33249.49 · 5.18 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We primarily compared the effectiveness of combined pelvic floor muscle training (PFMT) and duloxetine with imitation PFMT and placebo for 12 weeks in women with stress urinary incontinence (SUI). In addition, we compared the effectiveness of combined treatment with single treatments, single treatments with each other and single treatments with no treatment. This blinded, doubly controlled, randomized trial enrolled 201 women 18 to 75 years old with SUI at 17 incontinence centers in the Netherlands, United Kingdom and United States. Women averaged 2 or more incontinence episodes daily and were randomized to 1 of 4 combinations of 80 mg duloxetine daily, placebo, PFMT and imitation PFMT, including combined treatment (in 52), no active treatment (in 47), PFMT only (in 50) and duloxetine only (in 52). The primary efficacy measure was incontinence episode frequency. Other efficacy variables included the number of continence pads used and the Incontinence Quality of Life questionnaire score. The intent to treat population incontinence episode frequency analysis demonstrated the superiority of duloxetine with or without PFMT compared with no treatment or with PFMT alone. However, pad and Incontinence Quality of Life analyses suggested greater improvement with combined treatment than single treatment. A completer population analysis demonstrated the efficacy of duloxetine with or without PFMT and suggested combined treatment was more effective than either treatment alone. The data support significant efficacy of combined PFMT and duloxetine in the treatment of women with SUI. We hypothesize that complementary modes of action of duloxetine and PFMT may result in an additive effect of combined treatment.
    The Journal of Urology 06/2005; 173(5):1647-53. DOI:10.1097/01.ju.0000154167.90600.c6 · 4.47 Impact Factor
  • A. Monga · A. Gousse · C. Klutke · A. Bent · S. Hendrix · C. Yuen · I. Yalcin · R. Bump
    European Urology Supplements 03/2005; 4(3):90-90. DOI:10.1016/S1569-9056(05)80357-4 · 3.37 Impact Factor
  • A. Monga · A. Gousse · C. Klutke · A. Bent · S. Hendrix · C. Yuen · I. Yalcin · R. Bump
    European Urology Supplements 03/2005; 4(3):90-90. DOI:10.1016/S1569-9056(05)80358-6 · 3.37 Impact Factor
  • Journal of Pelvic Medicine and Surgery 01/2005; 11(Supplement 1). DOI:10.1097/01.spv.0000178924.99311.70
  • Ilker Yalcin · Richard C Bump
    [Show abstract] [Hide abstract]
    ABSTRACT: The placebo response associated with stress urinary incontinence (SUI) is sizeable but poorly understood. The aim of this study was to examine the relationship between previous treatment experience and baseline urinary incontinence severity with placebo response. Nine hundred twenty-one women ages 24 to 83 years received placebo in 4 12-week randomized trials evaluating duloxetine for SUI in 16 countries in Africa, Australia, Europe, and North and South America. Incontinence episode frequency (IEF) was calculated before and after randomization with entries from subject-completed real-time diaries. At baseline, subjects reported on their experience with previous continence surgery and with current pelvic floor muscle training (PFMT) with standardized questions. Analyses included Pearson correlations and the Wilcoxon two-sample test, and were based on intent-to-treat principles. The placebo group averaged 17 IEF per week at baseline. Fifty-five percent of placebo-treated subjects averaged >or=14 IEF/wk, 11.8% had previous continence surgery, and 16.5% currently performed PFMT. The overall median decrease in IEF with placebo was 33%, but ranged from 11% to 57% for individual countries. The placebo response was lower in women with more severe SUI (29.6% vs 36.4%, P=.07), in those who had previous continence surgery (25.0% vs 33.3%, P=.26), and for those using PFMT (23.6% vs 33.3%, P=.02). There was a significant positive correlation (rho=.44; P <.0001) between the placebo response within a country and that country's use rate for PFMT. Treatment naivete and less severe incontinence are associated with an increased placebo response in clinical trials for stress urinary incontinence, although this difference was statistically significant only for PFMT.
    American Journal of Obstetrics and Gynecology 08/2004; 191(1):194-7. DOI:10.1016/j.ajog.2004.03.089 · 4.70 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We assessed the accuracy with which a clinical diagnostic algorithm for stress urinary incontinence (SUI) based on symptoms and signs without including urodynamics predicted the observation of urodynamic SUI and the condition of SUI. Such an algorithm would have applicability to ensure that the majority of women entering large SUI clinical trials would have urodynamic SUI and/or the condition of SUI without performing urodynamic testing in all subjects. A total of 1455 women with urinary incontinence at least 3 months in duration were enrolled in 3 randomized clinical trials (1 phase 2 and 2 phase 3 trials) of duloxetine vs placebo for the treatment of SUI in Europe and North America. Subjects were identified as having SUI based on a clinical algorithm that required a predominant symptom of SUI with a weekly incontinence episode frequency of 4 or greater (phase 2 study), or 7 or greater (phase 3 studies), absent predominant urge symptoms, normal diurnal and nocturnal frequency, a bladder capacity of 400 ml or greater, and a positive cough stress (sign of SUI) and stress pad test. Multichannel urodynamic studies were performed in a subset of 184 women at 23 study sites. Of these urodynamic tracings 173 (94%) were of adequate quality to make an assessment of the filling phase and assign a diagnosis of urodynamic SUI, detrusor overactivity or a normal filling phase. Two-sided 95% exact CIs for the proportions were calculated. The clinical algorithm had a positive predictive value of 90.2% for urodynamic SUI with or without detrusor overactivity and 76.9% for urodynamic SUI only (pure urodynamic SUI). The positive predictive value for the condition of pure SUI was 85.0%, while for the condition of SUI in pure and mixed forms the positive predictive value was 98.3%. Patient age, previous continence surgery or the severity of incontinence did not influence algorithm accuracy. The algorithm is suitably feasible and sufficiently predictive to be used in large clinical trials designed to evaluate conservative treatment for women with SUI. It ensures that the overwhelming majority of the study population would have urodynamic SUI and the condition of SUI.
    The Journal of Urology 07/2004; 171(6 Pt 1):2321-5. DOI:10.1097/01.ju.0000124909.31527.a9 · 4.47 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To assess the efficacy and safety of duloxetine in women with stress urinary incontinence. Randomised double-blind, placebo-controlled clinical trial. Fort-six centres in seven European countries and Canada. Four hundred and ninety-four women aged 24-83 years identified as having predominant symptoms of stress urinary incontinence using a clinical algorithm that was 100% predictive of urodynamic stress urinary incontinence in a subgroup of 34 women. The case definition included a predominant symptom of stress urinary incontinence with a weekly incontinence episode frequency > or =7, the absence of predominant symptoms of urge incontinence, normal diurnal and nocturnal frequencies, a bladder capacity > or =400 mL and both a positive cough stress test and positive stress pad test. Subjects completed two urinary diaries prior to randomisation and three diaries during the active treatment phase of the study, each completed during the week prior to monthly visits. Subjects also completed quality of life questionnaires at each visit. Safety was assessed by the evaluation of treatment-emergent adverse events, discontinuation of treatment because of adverse events, serious adverse events, vital sign measurements, electrocardiograms (ECG) and clinical laboratory tests. After a two-week placebo lead-in, women received placebo or duloxetine 40 mg BD for 12 weeks. The percentage decrease in incontinence episode frequency and the change in the Incontinence Quality of Life (I-QOL) questionnaire total score were prespecified as co-primary outcome variables in the protocol. Incontinence episode frequency decreased significantly with duloxetine compared with placebo (median decrease of 50%vs 29%; P= 0.002) with comparable improvements in the more severely incontinent subgroup (those experiencing at least 14 incontinence episodes per week at baseline; 56%vs 27% decreases; P < 0.001). The primary analysis of I-QOL scores did not reveal a significant difference between treatment groups, due primarily to the carrying forward of low scores from patients who discontinued treatment very early due to duloxetine-associated adverse events. The increase in I-QOL scores was significantly greater for duloxetine than for placebo at each of the three postrandomisation visits after 4, 8, and 12 weeks of treatment. Discontinuation rates for adverse events were higher for duloxetine (22%vs 5%; P < 0.001) with nausea being the most common reason for discontinuation (5.3%). Nausea tended to be mild to moderate, not progressive, and transient. The findings support duloxetine as a potential treatment for women with stress urinary incontinence.
    BJOG An International Journal of Obstetrics & Gynaecology 04/2004; 111(3):249-57. DOI:10.1111/j.1471-0528.2004.00067.x · 3.45 Impact Factor
  • R.J. Millard · K Moore · R Rencken · I Yalcin · R.C. Bump
    [Show abstract] [Hide abstract]
    ABSTRACT: To further assess, in a phase 3 study, treatment with duloxetine for women with stress urinary incontinence (SUI) in other geographical regions, including Argentina, Australia, Brazil, Finland, Poland, South Africa and Spain, as previous trials in North America and Europe provided evidence for the safety and efficacy of duloxetine as a pharmacological treatment for SUI in women. The study included 458 women aged 27-79 years enrolled in a double-blind, placebo-controlled trial. The patients with predominantly SUI were identified using a validated clinical algorithm. They were randomly assigned to receive placebo (231) or duloxetine 40 mg twice daily (227) for 12 weeks. The primary outcome variables included the incontinence episode frequency (IEF) and the Incontinence Quality of Life (I-QOL) questionnaire. Van Elteren's test was used to analyse the percentage changes in IEF where the stratification variable was weekly baseline IEF (IEF < 14 and > or = 14). Analysis of covariance was used to analyse I-QOL scores. The mean baseline IEF was 18.4/week; 55% of patients had a baseline IEF of > or = 14. There was a significantly greater median decrease in IEF with duloxetine with placebo (54% vs 40%, P = 0.05), with comparable significant improvements in quality of life (I-QOL score increases of 10.3 vs 6.4, P = 0.007). The improvements with duloxetine were associated with significantly greater increases in voiding intervals than with placebo (20.4 vs 8.5 min, P < 0.001). The placebo response was 10.7% and 12.5% higher than those reported in two European and North American phase 3 trials. This may have been related to more patients being naïve for incontinence management in the current trial. Discontinuation rates for adverse events were 1.7% for placebo and 17.2% for duloxetine (P < 0.001), with nausea being the most common reason for discontinuation (3.1%); it was the most common adverse event with duloxetine, but was mild or moderate in most (81%), did not worsen in any patient and resolved within 7 days in 60% and within 1 month in 86% of continuing patients; 88% of women who experienced nausea while taking duloxetine completed the trial. These results show improvements in incontinence and quality of life with duloxetine 40 mg twice daily for 12 weeks that are in keeping with those reported in two other recently completed phase 3 trials in Europe and North America.
    BJU International 03/2004; 93(3):311-8. DOI:10.1111/j.1464-410X.2004.04607.x · 3.53 Impact Factor
  • I. Yalcin · R. bump
    European Urology Supplements 02/2004; 3(2):200-200. DOI:10.1016/S1569-9056(04)90780-4 · 3.37 Impact Factor

Publication Stats

2k Citations
97.96 Total Impact Points


  • 2004
    • Indiana University-Purdue University Indianapolis
      Indianapolis, Indiana, United States
  • 2002–2004
    • Eli Lilly
      • Lilly Research Laboratories
      Indianapolis, Indiana, United States