Duloxetine versus Placebo for the Treatment of Korean Women with Stress Predominant Urinary Incontinence

Sang Yol Mah; Kyu Sung Lee; Myung Soo Choo; Ju Tae Seo; Jeong Zoo Lee; Won Hee Park; Joon Chul Kim; Seung Yun Lee; Yan Daniel Zhao; Julie Beyrer; Meghan Wulster-Radclifie; Louise Levine; Lars Viktrup

doi:10.4111/kju.2006.47.5.527

Journal List > Korean J Urol > v.47(5) > 1069899

Go to TopGo to Top Go to BottomGo to Bottom

TOOLS

Mah, Lee, Choo, Seo, Lee, Park, Kim, Lee, Zhao, Beyrer, Wulster-Radclifie, Levine, and Viktrup: Duloxetine versus Placebo for the Treatment of Korean Women with Stress Predominant Urinary Incontinence

Original Article

Korean J Urol 2006;47(5):527-535.

Published online: 18 December 2006

DOI: https://doi.org/10.4111/kju.2006.47.5.527

Duloxetine versus Placebo for the Treatment of Korean Women with Stress Predominant Urinary Incontinence

Sang Yol Mah¹, Kyu Sung Lee², Myung Soo Choo³, Ju Tae Seo⁴, Jeong Zoo Lee⁵, Won Hee Park⁶, Joon Chul Kim⁷, Seung Yun Lee⁸, Yan Daniel Zhao⁹, Julie Beyrer⁹, Meghan Wulster-Radclifie⁹, Louise Levine⁹, Lars Viktrup^9,

¹From the Department of Urology Yongdong Severance Hospital, Seoul

²Samsung Medical Center, Seoul

³Asan Medical Center, Seoul

⁴Samsung Cheil Hospital & Woman's Healthcare Center, Seoul

⁵Pusan National University Hospital, Busan

⁶Incheon Inha University Hospital, Incheon

⁷Kangnam St Mary's Hospital, Seoul

⁸Lilly Korea, Ltd, Seoul, Korea

⁹Lilly Research Laboratories, Indianapolis, IN, USA

Lars Viktrup, M.D., Ph.D. Eli Lilly and Company Lilly Corporate Center Indianapolis, Indiana 46285 TEL: 317-651-6219 FAX: 317-276-4789 E-mail: viktrupla@lilly.com

Received 12 October 2005 Accepted 27 January 2006

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose:

To compare duloxetine with placebo for the treatment of Korean women with stress urinary incontinence (SUI).

Materials and Methods:

This was a phase 3, double-blind, stratified, randomized, parallel, placebo-controlled, multi-center study investigating efficacy and safety of a of duloxetine compared with placebo in the treatment of SUI. After a 2-week no-drug screening period, women ages 29-69 were randomly assigned to placebo (n=60) or duloxetine (n=61) as 40mg twice daily for 8 weeks followed by a 2 week no-drug period. Women were seen at 4-week intervals. The primary efficacy variable was percent change in incontinence episodes frequency (IEF)/week. Secondary variables included percent change in, changes in Incontinence Quality of Life (I-QoL) total and 3 subscale scores, and Patient Global Impression of Improvement (PGI-I) ratings. Safety was evaluated by treatment emergent adverse events (TEAE), discontinuations due to adverse events, vital signs measurements, and clinical laboratory tests.

Results:

There were statistically significant improvements with duloxetine compared with placebo in IEF (duloxetine baseline 16.4IEF/wk, endpoint 7.7IEF/wk, median percent reduction=50.0% vs placebo baseline 13.3IEF/ wk, endpoint 8.8IEF/wk, median percent reduction=37.1%, p=0.033), and avoidance and limiting behavior subscale (p=0.006) in I-QoL. TEAEs were reported significantly more often in the duloxetine group compared with the placebo group (82.0% vs 31.7%; p く 0.001); common AEs (>5% in duloxetine-treated subjects and p く 0.05) were nausea, dizziness, anorexia, fatigue, lethargy, abdominal discomfort, and constipation. Discontinuation rates because of AEs were 34.4% for duloxetine and 8.3% for placebo.

Conclusions:

These data provide evidence for the safety and efficacy of duloxetine for the treatment for Korean women with SUI. (Korean J Urol 2006;47:527-535)

Keywords: Urinary incontinence, stress; Duloxetine

REFERENCES

1.Abrams P., Cardozo L., Khoury S., Wein A. International Consultation on Incontinence. 3rd ed.Plymouth: Health Publication Ltd;2005.

2.Oh SJ., Park WH., Park CH., Paick JS., Seo JT., Lee YS, et al. Prevalence of urinary incontinence and incontinence-related quality of life in Korean women: a population-based study. J Korean Continence Soc. 2003. 7:73–80.

3.Chen GD., Lin TL., Hu SW., Chen YC., Lin LY. Prevalence and correlation of urinary incontinence and overactive bladder in Taiwanese women. Neurourol Urodyn. 2003. 22:109–17.

4.Ju CC., Swan LK., Merriman A., Choon TE., Viegas O. Urinary incontinence among the elderly people of Singapore. Age Ageing. 1991. 20:262–6.

5.Ma SS. The prevalence of adult female urinary incontinence in Hong Kong Chinese. Int Urogynecol J Pelvic Floor Dysfunct. 1997. 8:327–31.

6.Yu HJ., Chen J., Lai MK., Chan KA., Chie WC. High prevalence of voiding symptoms in Taiwanese women. Br J Urol. 1998. 82:520–3.

7.Minassian VA., Drutz HP., Al Badr A. Urinary incontinence as a worldwide problem. Int J Gynaecol Obstet. 2003. 82:327–38.

8.Ueda T., Tamaki M., Kageyama S., Yoshimura N., Yoshida O. Urinary incontinence among community-dwelling people aged 40 years or older in Japan: prevalence, risk factors, knowledge and self-perception. Int J Urol. 2000. 7:95–103.

9.Fultz NH., Burgio K., Diokno AC., Kinchen KS., Obenchain R., Bump RC. Burden of stress urinary incontinence for community-dwelling women. Am J Obstet Gynecol. 2003. 189:1275–82.

10.Kinchen KS., Burgio K., Diokno AC., Fultz NH., Bump R., Obenchain R. Factors associated with women' s decisions to seek treatment for urinary incontinence. J Womens Health. 2003. 12:687–98.

11.Thor KB., Katofiasc MA. Effects of duloxetine, a combined serotonin and norepinephrine reuptake inhibitor, on central neural control of lower urinary tract function in the chloralose-anesthetized female cat. J Pharmacol Exp Ther. 1995. 274:1014–24.

12.Norton PA., Zinner NR., Yalcin I., Bump RC. Duloxetine versus placebo in the treatment of stress urinary incontinence. Am J Obstet Gynecol. 2002. 187:40–8.

13.Dmochowski RR., Miklos JR., Norton PA., Zinner NR., Yalcin I., Bump RC. Duloxetine versus placebo for the treatment of North American women with stress urinary incontinence. J Urol. 2003. 170:1259–63.

14.van Kerrebroeck P., Abrams P., Lange R., Slack M., Wyndaele JJ., Yalcin I, et al. Duloxetine versus placebo in the treatment of European and Canadian women with stress urinary incontinence. BJOG. 2004. 111:249–57.

15.Millard RJ., Moore K., Rencken R., Yalcin I., Bump RC. Duloxetine vs placebo in the treatment of stress urinary incontinence: a four-continent randomized clinical trial. BJU Int. 2004. 93:311–8.

16.Wyman JF., Fantl JA., McClish DK., Bump RC. Comparative efficacy of behavioral interventions in the management of female urinary incontinence. Continence Program for Women Research Group. Am J Obstet Gynecol. 1998. 179:999–1007.

17.Kondo A., Yokoyama E., Koshiba K., Fukui J., Gotoh M., Yoshikawa Y, et al. Bladder neck support prosthesis: a nonoperative treatment for stress or mixed urinary incontinence. J Urol. 1997. 157:824–7.

18.Bodell DM., Leach GE. Needle suspension procedures for female incontinence. Urol Clin North Am. 2002. 29:575–84.

19.Rodriguez LV., Raz S. Prospective analysis of patients treated with a distal urethral polypropylene sling for symptoms of stress urinary incontinence: surgical outcome and satisfaction determined by patient driven questionnaires. J Urol. 2003. 170:857–63.

20.Patrick DL., Martin ML., Bushnell DM., Yalcin I., Wagner TH., Buesching DP. Quality of life of women with urinary incontinence: further development of the incontinence quality of life instrument (I-QoL). Urology. 1999. 53:71–6.

21.Yalcin I., Bump RC. Validation of two global impression questionnaires for incontinence. Am J Obstet Gynecol. 2003. 189:98–101.

22.Os SJ., Park HG., Lim SH., Hong SK., Martin ML., Ting BL, et al. Translation and linguistic validation of Korean version of the incontinence quality of life (I-QoL) instrument. J Korean Continence Soc. 2002. 6:10–23.

23.Cardozo L., Drutz HP., Baygani SK., Bump RC. Pharmacological treatment of women awaiting surgery for stress urinary incontinence. Obstet Gynecol. 2004. 104:511–9.

24.Komaroff AL., Fagioli LR., Doolittle TH., Gandek B., Gleit MA., Guerriero RT, et al. Health status in patients with chronic fatigue syndrome and in general population and disease comparison groups. Am J Med. 1996. 101:281–90.

25.Lenderking WR., Nackley JF., Anderson RB., Testa MA. A review of the quality-of-life aspects of urinary urge incontinence. Pharmacoeconomics. 1996. 9:11–23.

26.Bump R., Yalcin I., Voss S. The effect of duloxetine dose escalation and tapering on the incidence of adverse events (Ae) in women with stress urinary incontinence. Int Continence Soc. 2005.

27.Yalcin I., Bump RC. The effect of previous treatment experience and incontinence severity on the placebo response of stress urinary incontinence. Am J Obstet Gynecol. 2004. 191:194–7.

Fig. 1.

Study design and the timing of acquiring the urinary diaries and reports on the quality of life measurements. I-QoL: Incontinence Quality of Life questionnaire, PGI-I: Patient Global Inpression of Improvement.

Table 1.

Baseline∗ clinical characteristics for all the randomized women

	Duloxetine	Placebo
Randomized N^†	61	60
Age, years	50.67 (±9.01)	48.52 (±8.05)
BMI, kg/m^‡	23.77 (±2.46)	23.42 (±3.17)
IEF/week (SD)	15.74 (±11.35)	13.27 (±7.04)
[range]	[3.0-59.0]	[6.42-41.42]
Mean time between voids, min	215.86(±60.72)	241.90 (±56.40)
Total I-QoL score	49.37 (±21.57)	51.38 (±20.66)
Previou scontinence surgery	3	2

∗Baseline is the last visit score on or prior to randomization, ^† : Every randomized subject did not provide information for each variable; percentages are calculated using the number of responding women as the denominator, ^‡: 0.01. Data are means (SD) unless otherwise indicated, BMI: body mass index, PFMT: pelvic floor muscle training, IEF: incontinence episode frequency, I-QoL: Incontinence Quality of Life questionnaire.

Table 2.

Frequency of incontinence episodes

Treatment group (N)∗	Time point	n^†	Absolute mean IEF/week	Median percent change from baseline	95% CI for median percent change in IEF	P
Placebo (60)	Baseline	53	11.00
	Endpoint		6.72
	Change		-3.83	-37.14	- 45.45, - 27.27
Duloxetine (61)	Baseline	45	12.92
	Endpoint		6.13
	Change		-6.54	− 50.00	− 60.20, −40.91	0.033

∗N: number randomized, ^† n: number with diary data available for specified analysis, CI: confidence interval, IEF: incontinence episode frequency

Table 3A.

Incontinence Quality of Life questionnaire: subscale scores

Treatment group (N)∗	Time point	n^†	I-QoL total score
Treatment group (N)∗	Time point	n^†	Mean I-QoL	Mean change in I-QoL from baseline^‡	95% CI for treatment difference in I-QoL^§	^p
Placebo (60)	Baseline	57	51.52
	Endpoint		60.23	8.71
Duloxetine (61)	Baseline	56	48.64
	Endpoint		63.41	14.77	一 0.37,11.16	0.066

∗N: number randomized, ^† n: number with diary data available for specified analysis, ^‡: Baseline is the last nonmissing visit score on or before randomization, ^§: 95% CI for treatment difference. CI: confidence interval, I-QoL: Incontinence Quality of Life questionnaire

Table 3B.

B. Incontinence Quality of Life questionnaire: subscale scores

Treatment group (N)	Time ∗ point	n^†	I-QoL avoidance and limiting behavior subscale score				I-QoL psychological impact subscale score				I-QoL social embarrassment subscale score
Treatment group (N)	Time ∗ point	n^†	Mean I-QoL	Mean change in I-QoL from baseline^‡	95% CI for treatment difference in I-QoL^§	P	Mean I-QoL	Mean change in I-QoL from baseline^‡	95% CI for treatment difference in I-QoL^§	P	Mean I-QoL	Mean change in I-QoL from baseline^‡	95% CI ρ for treatment difference in I-QoL^§	P
Placebo	Baseline	57	54.17				55.70				39.74
(60)	Endpoint		60.42	6.25			64.47	8.77			52.28	12.54
Duloxxetine	Baseline	56	50.78		13.88		52.33				38.57		9.80
(61)	Endpoint		66.35	15.57		0.006	65.97	13.64	-2.14 10.49	0.193	54.11	15.54		0.399

Table 4.

Treatment-emergency adverse events occurred in >5% of the women randomized to the duloxetine group or they occurred significantly more often with duloxetine than with placebo

	Duloxetine (n=61)	Placebo (n=60)	p
Total number of women with ≥1 TEAE	50 (82)	19 (31.7)	< 0.001
Nausea	23 (37.7)	4(6.7)	<0.001
Dizziness	20 (32.8)	2 (3.3)	< 0.001
Anorexia	17 (27.9)	2 (3.3)	< 0.001
Fatigue	14 (23.0)	1 (1.7)	< 0.001
Lethargy	9 (14.8)	0 (0.0)	0.003
Abdominal discomfort	8 (13.1)	1 (1.7)	0.032
Somnolence	7 (11.5)	1 (1.7)	0.061
Constipation	6 (9.8)	0 (0.0)	0.027
Headache	6 (9.8)	5 (8.3)	0.999
Dry mouth	5 (8.2)	2 (3.3)	0.439

Values are expressed as n (%).

Table 5.

Discontinuations due to adverse events occurred in >1% of women randomized to the duloxetine group

	Duloxetine (n=61)	Placebo (n=60)	p
For any adverse event	21 (34.4)	5 (8.3)	0.001
Fatigue	5 (8.2)	0 (0.0)	0.057
Lethargy	5 (8.2)	0 (0.0)	0.057
Nausea	5 (8.2)	1 (1.7)	0.207
Abdominal discomfort	2 (3.3)	0 (0.0)	0.496
Disturbance in attention	1 (1.6)	0 (0.0)	>0.999
Dizziness	1 (1.6)	1 (1.6)	>0.999
Dyspepsia	1 (1.6)	0(1.6)	>0.999

Values are expressed as n (%).

TOOLS

Similar articles