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511 Effects of tolterodine extended release in patients with overactive bladder: Perceived treatment benefits improve with efficacy
509 CLINICAL VALUE CONTRACTION
OF PERCEPTION
OF INVOLUNTARY
DETRUSOR
De Wachter S., Van Meel T.D., Wyndaele J.J. University
Addla
of Antwerp, Department of Urology, Antwerp, Belgium
INTRODUCTION & OBJECTIVES: The efficacy of anticholinergic agents to reduce symptoms of an overactive bladder is variable and difficult to predict. This may be due to the presence of different pathophysiologic entities in overactive bladder syndrome. If present and demonstrable on cystometry, detrusor overactivity (DOA) can be qualified according to cause in neurogenic and idiopathic DOA, or according to pattern of occurrence in phasic and terminal DOA. TIus study evaluates whether the perception of involuntary detmsor contraction (IDC) may provide a parameter to classify patients with DOA. MATERIAL & METHODS: Forty-five patxnts (23 wmen 22 men, age 60 1-15 years) with overactive bladder symptoms and cystomehically verified DOA were studied. Durmg cystometry, patients were asked to describe all sensations related to bladder filling. If an IDC was perceived as a sensation of bladder filling, DOA was classified as “DOA with sensation”. Excluded were patients with overt signs of neurologic impairment, bladder sensory threshold > 15 mA and positive ice water test. Parameters studied were: number of IDC, volume and amplitude of Is’ IDC, amplitude of highest IDC and maximal cystometric capacity (MCC). Furthermore electrical sensory thresholds were determined in the bladder, proximal and distal urethra. In 24 patients the efficacy of anticholinergic treatment was evaluated. Treatment was defined as successful if frequency and episodes of urinary incontinence subjectively decreased. RESULTS: Twenty-three patients did not perceive any of the IDC (“DOA without sensation’), whereas 22 perceived at least one IDC as a sensahon of filling (“DOA with sensation”). Age and sex were not different between both groups (P > 0.1). Urodynamic parameters and sensory thresholds are compared in the table. 1DOA without
Number IDC Vol 1” IDC (mL) Amplt 1” IDC (cmH20) Amplt highest IDC (cmHZ0) MCC (mL) Involuntary start mictirition (%) Bladder (mA) Proximal urethra (mA) Distal urethra (mA)
510 ASSESSMENT FREQUENCY
1DOA with
j-Egg-15*7 20+9 233+131 61 11.3-tz.o 6.411.4 3.210.9
8.8zt2.4 5.011.6 2.4+0.6
P (MWU test)
T 0.0002 0.0000005 0.5 0.6 0.016 0.023 0.0006 0.0006 0.0005
Treatnxnt success with anticholinergxs was higher in the group “DOA compared to the group “DOA without sensation” (50%) (p=O.OZS).
with sensation”
OF RELIABILITY VOLUME CHARTS
S.‘, Adeyoju
‘Stepping ZBlaclbum
A.‘, Neilson
OF
l-DAY,
3-DAY
D.’
Hill Hospital, Department of Urology, Royal Infirmary, Department of Urology,
Stockport, Blackbum,
Van Kerrebroeck
MATERIAL & METHODS: We studied 80 patients who were being investigated for nocturia and other lower urinary tract symptoms. Patients were requested to complete a FVC for 7 consecutive days. These FVC were then analyzed into three different groups - lday (dayl), 3 day (day2 to 4) and 7 day. The lday FVC analysis included the first morning void on day 2. The analysis of 3 day FVC included the first morning void on day 5, similarly the 7-day FVC analysis included the first morning void on day 8. The 9 parameters included were daytime frequency, night time frequency, 24-hour frequency, daytime urine output, night time urine out-put, 24 hour urine out-put, maximum voided volume, nocturia index and Night time to Daytime diuresis ratio (N/D diuresis ratio).
(92%)
IN PATIENTS TREATMENT
CONCLUSIONS: A properly performed l-day FVC, which includes the first morning void the following day, is a reasonable tool to gain insight into the voiding habits during normal daily routine. 3 day FVC is adequate for accurate assessment of lower urinary tract symptoms and recommended for confinning a consistent clinical pattern and day-to-day practice. A 7-day FVC should be used in atypical clinical scenarios and for clinical research.
Department of Urology,
Maastricht,
The Netherlands, *Pfizer Inc,
INTRODUCTION & OBJECTIVES: To evaluate the effect of tolterodme extended release (ER) 4 mg mxe daily on patients’ perceptions of overall treatment benefit in patients with overactive bladder (OAB). MATERIAL & METHODS: This was a 12-week, multicentre, double-blind, placebo-controlled study of tolterodine ER 4 mg qd in patients with symptoms of OAB (? 8 micturitionsi24 hrs, t 5 incontinence episodes per week, mean void 5 200 ml per micturition). Assessments were made at baseline and at week 12. A subanalysis of patients’ perceived treatment benefit (none, little, much) versus objective (incontinence, pad use, volume voided, frequency) and subjective end points (urgency and bladder perception) was completed. Adverse events were recorded throughout the study. RESULTS: After a I-week washout, 508 and 507 patients, respectively, were randomized to placebo or tolterodine ER. Approximately 80% of patients were women with a mean age of 60 years. Other baseline demographic variables were comparable between treatment groups. After 12 weeks of treahnent, significantly more patients on tolterodine ER perceived having much treatment benefit (43%) compared with those on placebo (24%, P
much treatment
benefit, %
Incontinence (>50% decrease in episodes per day) Pad Use (>30% reduction per day) Volume voided (>45mL increase per micturition) Urinary frequency (Decrease of >1 episode per day) Improved perception of urgency Improved perception of bladder condition
Urology
Supplements
IN IMPROVING BLADDER: A POOLED
THE MAJOR ANALYSIS OF
3 (2004)
Royal Hallamshire Hospital, Department of Urology, Sheffield, United Kingdom INTRODUCTION & OBJECTIVES: To evaluate the efficacy, tolerability and safety of danfenaan, an M, selective receptor antagonist (M3 SRA), in a pooled analysis of 3 multicentre, double-blind, placebocontrolled studies with identical inclusion criteria in patients with overactive bladder (OAB). MATERIAL & METHODS: The pooled population comprised 1,049 adults (female 85%; 19-88 years) with OAB symptoms for >6 months. After a Z-week washout and Z-week placebo mn-m, patients were random&d to 12 weeks’ once-daily treatment with oral darifenacin controlled-release tablets 7.5 mg (n=335) aud matching placebo (n=271) or darifenacin 15 mg (n=330) and matching placebo (n=384). Efficacy was evaluated usmg electronic diaries to record incontinence episodes and a range of secondary efficacy parameters (Table I). Tolerability and safety were also determmed. RESULTS: Both doses of darifenacin were significantly superior to placebo in reducing incontinence episodes (Table 1). There was also a dose-response effect for patumts achievmg ?50% reduction in incontinence episodes/week: 7.5 mg 66% and 15 mg 70% (p
Incontinence episodes/week Mxturition frequency/day Bladder capaaty (mean volume voided; mL) Frequency of urgency/day Severity of urgency Incontinence episodes resulting in a change of clothing or pads/week
Darifenacin 7.5 mg -8.8 (-68.4%)*
Placebo
-1.6 (-16.6%)** 15.4 (9.6%)*
-7.0 (-53.8%) -0.9 (-9.1%) 7.6 (4.9%)
-2.0 (-29%)** -7.8 (-14.2%)** -4.0 (-77.1.%)**
-1.0 (-14.3%) -4.2 (-7.8%) -2.0 (-47.7%)
Placebo
Tolterodine ER
P value
16.2
34.4
<0.0001
12.6
30.8
<0.0001
Results are expressed as mahan (and %) change from baselme to week 12 *p
5.7
20.3
<0.0001
16.3 13.7 18.0
32.2 25.1 35.1
<0.0001 <0.0001 c0.0001
The most common treatment-related AEs were dose-related dry mouth (7.5 mg 20%; 15 mg 35%; placebo 8%) and constipation (7.5 mg 15%; 15 mg 21%; placebo 6%) and together these resulted in low discontmuation rates (darifenacin 7.5 mg 0.6%; darifenacin 15 mg 2 1%; placebo 0.3%). CNS and cardiovascular (CV) safety were comparable to placebo at both doses.
CONCLUSIONS: These data suggest that patient-perceived associated with improved symptoms of OAB.
European
512 DARIFENACIN IS EFFECTIVE SYMPTOMS OF OVERACTIVE PHASE III STUDIES Chatmle C.
P.E.l, Wang J2, Guan Z.2
lUniversity Hospital Maastricht, New York, United States
United Kingdom, United Kingdom
INTRODUCTION & OBJECTIVES: Frequency Volume Chart (FVC) is one of the basic investigative tools in urological practice. This provides a good objective evidence of subjective symptoms. FVC’s have evolved over the past 25 years, from simple voiding charts to complex urinary diaries. Now, we not only record frequency and volume but also episodes of stress and urge incontinence, fluid intake and the patients’ activities in relation to their urinary symptoms. The ideal time period for a FVC remains unclear despite previous published studies. The objective of this study was to compare the relative reliability of FVC’s maintained for 1, 3 and 7 days using 9 parameters.
511 OF TOLTERODINE EXTENDED RELEASE OVERACTIVE BLADDER: PERCEIVED IMPROVE WITH EFFICACY
7- DAY
RESULTS: The mean percentage difference between l-day and 7-day FVC, 3 day and 7 day FVC for all parameters was 2 1.9 and 11.3 percent respectively. Among the clinically significant parameters, maximum mean difference between 7 day and 1 day was noted for N/D diuresis ratio (26.1%). However considering N/D diuresis ratio of 1.5 as a cut-off for diagnosing nocturnal polyuria only 9180 in the l-day group and 5/80 in the 3 day group had inconsistency in their diagnosis compared to 7 day analysis.
CONCLUSIONS: Differences in cvstometric uarameters and sensorv thresholds were shown between patients who did or did noi perceive bOA as sensation of filling. Whether both types reuresent different entities or different erades of the same entitv needs to be further studied. However. o&preliminary data suggest that such rlassification might be &nically relevant as treatment outcome was significantly different in both groups.
EFFECTS WITH BENEFITS
AND
benefits of tolterodine ER treatment are
No. 2, pp.
130
CONCLUSIONS: Darifenacin, the first M, SRA, is weli tolerated and provides slgmficant improvement in the debilitatmg symptoms of OAB. Doses of 7.5 mg and 15 mg once daily are effectwe and well tolerated. Consistent with the M, selectivity protile of darifenacin, there were no CV safety concerns. Supported by Novartis Pharma AG, Basel, Swtzerland.
OF PERCEPTION
OF INVOLUNTARY
DETRUSOR
De Wachter S., Van Meel T.D., Wyndaele J.J. University
Addla
of Antwerp, Department of Urology, Antwerp, Belgium
INTRODUCTION & OBJECTIVES: The efficacy of anticholinergic agents to reduce symptoms of an overactive bladder is variable and difficult to predict. This may be due to the presence of different pathophysiologic entities in overactive bladder syndrome. If present and demonstrable on cystometry, detrusor overactivity (DOA) can be qualified according to cause in neurogenic and idiopathic DOA, or according to pattern of occurrence in phasic and terminal DOA. TIus study evaluates whether the perception of involuntary detmsor contraction (IDC) may provide a parameter to classify patients with DOA. MATERIAL & METHODS: Forty-five patxnts (23 wmen 22 men, age 60 1-15 years) with overactive bladder symptoms and cystomehically verified DOA were studied. Durmg cystometry, patients were asked to describe all sensations related to bladder filling. If an IDC was perceived as a sensation of bladder filling, DOA was classified as “DOA with sensation”. Excluded were patients with overt signs of neurologic impairment, bladder sensory threshold > 15 mA and positive ice water test. Parameters studied were: number of IDC, volume and amplitude of Is’ IDC, amplitude of highest IDC and maximal cystometric capacity (MCC). Furthermore electrical sensory thresholds were determined in the bladder, proximal and distal urethra. In 24 patients the efficacy of anticholinergic treatment was evaluated. Treatment was defined as successful if frequency and episodes of urinary incontinence subjectively decreased. RESULTS: Twenty-three patients did not perceive any of the IDC (“DOA without sensation’), whereas 22 perceived at least one IDC as a sensahon of filling (“DOA with sensation”). Age and sex were not different between both groups (P > 0.1). Urodynamic parameters and sensory thresholds are compared in the table. 1DOA without
Number IDC Vol 1” IDC (mL) Amplt 1” IDC (cmH20) Amplt highest IDC (cmHZ0) MCC (mL) Involuntary start mictirition (%) Bladder (mA) Proximal urethra (mA) Distal urethra (mA)
510 ASSESSMENT FREQUENCY
1DOA with
j-Egg-15*7 20+9 233+131 61 11.3-tz.o 6.411.4 3.210.9
8.8zt2.4 5.011.6 2.4+0.6
P (MWU test)
T 0.0002 0.0000005 0.5 0.6 0.016 0.023 0.0006 0.0006 0.0005
Treatnxnt success with anticholinergxs was higher in the group “DOA compared to the group “DOA without sensation” (50%) (p=O.OZS).
with sensation”
OF RELIABILITY VOLUME CHARTS
S.‘, Adeyoju
‘Stepping ZBlaclbum
A.‘, Neilson
OF
l-DAY,
3-DAY
D.’
Hill Hospital, Department of Urology, Royal Infirmary, Department of Urology,
Stockport, Blackbum,
Van Kerrebroeck
MATERIAL & METHODS: We studied 80 patients who were being investigated for nocturia and other lower urinary tract symptoms. Patients were requested to complete a FVC for 7 consecutive days. These FVC were then analyzed into three different groups - lday (dayl), 3 day (day2 to 4) and 7 day. The lday FVC analysis included the first morning void on day 2. The analysis of 3 day FVC included the first morning void on day 5, similarly the 7-day FVC analysis included the first morning void on day 8. The 9 parameters included were daytime frequency, night time frequency, 24-hour frequency, daytime urine output, night time urine out-put, 24 hour urine out-put, maximum voided volume, nocturia index and Night time to Daytime diuresis ratio (N/D diuresis ratio).
(92%)
IN PATIENTS TREATMENT
CONCLUSIONS: A properly performed l-day FVC, which includes the first morning void the following day, is a reasonable tool to gain insight into the voiding habits during normal daily routine. 3 day FVC is adequate for accurate assessment of lower urinary tract symptoms and recommended for confinning a consistent clinical pattern and day-to-day practice. A 7-day FVC should be used in atypical clinical scenarios and for clinical research.
Department of Urology,
Maastricht,
The Netherlands, *Pfizer Inc,
INTRODUCTION & OBJECTIVES: To evaluate the effect of tolterodme extended release (ER) 4 mg mxe daily on patients’ perceptions of overall treatment benefit in patients with overactive bladder (OAB). MATERIAL & METHODS: This was a 12-week, multicentre, double-blind, placebo-controlled study of tolterodine ER 4 mg qd in patients with symptoms of OAB (? 8 micturitionsi24 hrs, t 5 incontinence episodes per week, mean void 5 200 ml per micturition). Assessments were made at baseline and at week 12. A subanalysis of patients’ perceived treatment benefit (none, little, much) versus objective (incontinence, pad use, volume voided, frequency) and subjective end points (urgency and bladder perception) was completed. Adverse events were recorded throughout the study. RESULTS: After a I-week washout, 508 and 507 patients, respectively, were randomized to placebo or tolterodine ER. Approximately 80% of patients were women with a mean age of 60 years. Other baseline demographic variables were comparable between treatment groups. After 12 weeks of treahnent, significantly more patients on tolterodine ER perceived having much treatment benefit (43%) compared with those on placebo (24%, P
much treatment
benefit, %
Incontinence (>50% decrease in episodes per day) Pad Use (>30% reduction per day) Volume voided (>45mL increase per micturition) Urinary frequency (Decrease of >1 episode per day) Improved perception of urgency Improved perception of bladder condition
Urology
Supplements
IN IMPROVING BLADDER: A POOLED
THE MAJOR ANALYSIS OF
3 (2004)
Royal Hallamshire Hospital, Department of Urology, Sheffield, United Kingdom INTRODUCTION & OBJECTIVES: To evaluate the efficacy, tolerability and safety of danfenaan, an M, selective receptor antagonist (M3 SRA), in a pooled analysis of 3 multicentre, double-blind, placebocontrolled studies with identical inclusion criteria in patients with overactive bladder (OAB). MATERIAL & METHODS: The pooled population comprised 1,049 adults (female 85%; 19-88 years) with OAB symptoms for >6 months. After a Z-week washout and Z-week placebo mn-m, patients were random&d to 12 weeks’ once-daily treatment with oral darifenacin controlled-release tablets 7.5 mg (n=335) aud matching placebo (n=271) or darifenacin 15 mg (n=330) and matching placebo (n=384). Efficacy was evaluated usmg electronic diaries to record incontinence episodes and a range of secondary efficacy parameters (Table I). Tolerability and safety were also determmed. RESULTS: Both doses of darifenacin were significantly superior to placebo in reducing incontinence episodes (Table 1). There was also a dose-response effect for patumts achievmg ?50% reduction in incontinence episodes/week: 7.5 mg 66% and 15 mg 70% (p
Incontinence episodes/week Mxturition frequency/day Bladder capaaty (mean volume voided; mL) Frequency of urgency/day Severity of urgency Incontinence episodes resulting in a change of clothing or pads/week
Darifenacin 7.5 mg -8.8 (-68.4%)*
Placebo
-1.6 (-16.6%)** 15.4 (9.6%)*
-7.0 (-53.8%) -0.9 (-9.1%) 7.6 (4.9%)
-2.0 (-29%)** -7.8 (-14.2%)** -4.0 (-77.1.%)**
-1.0 (-14.3%) -4.2 (-7.8%) -2.0 (-47.7%)
Placebo
Tolterodine ER
P value
16.2
34.4
<0.0001
12.6
30.8
<0.0001
Results are expressed as mahan (and %) change from baselme to week 12 *p
5.7
20.3
<0.0001
16.3 13.7 18.0
32.2 25.1 35.1
<0.0001 <0.0001 c0.0001
The most common treatment-related AEs were dose-related dry mouth (7.5 mg 20%; 15 mg 35%; placebo 8%) and constipation (7.5 mg 15%; 15 mg 21%; placebo 6%) and together these resulted in low discontmuation rates (darifenacin 7.5 mg 0.6%; darifenacin 15 mg 2 1%; placebo 0.3%). CNS and cardiovascular (CV) safety were comparable to placebo at both doses.
CONCLUSIONS: These data suggest that patient-perceived associated with improved symptoms of OAB.
European
512 DARIFENACIN IS EFFECTIVE SYMPTOMS OF OVERACTIVE PHASE III STUDIES Chatmle C.
P.E.l, Wang J2, Guan Z.2
lUniversity Hospital Maastricht, New York, United States
United Kingdom, United Kingdom
INTRODUCTION & OBJECTIVES: Frequency Volume Chart (FVC) is one of the basic investigative tools in urological practice. This provides a good objective evidence of subjective symptoms. FVC’s have evolved over the past 25 years, from simple voiding charts to complex urinary diaries. Now, we not only record frequency and volume but also episodes of stress and urge incontinence, fluid intake and the patients’ activities in relation to their urinary symptoms. The ideal time period for a FVC remains unclear despite previous published studies. The objective of this study was to compare the relative reliability of FVC’s maintained for 1, 3 and 7 days using 9 parameters.
511 OF TOLTERODINE EXTENDED RELEASE OVERACTIVE BLADDER: PERCEIVED IMPROVE WITH EFFICACY
7- DAY
RESULTS: The mean percentage difference between l-day and 7-day FVC, 3 day and 7 day FVC for all parameters was 2 1.9 and 11.3 percent respectively. Among the clinically significant parameters, maximum mean difference between 7 day and 1 day was noted for N/D diuresis ratio (26.1%). However considering N/D diuresis ratio of 1.5 as a cut-off for diagnosing nocturnal polyuria only 9180 in the l-day group and 5/80 in the 3 day group had inconsistency in their diagnosis compared to 7 day analysis.
CONCLUSIONS: Differences in cvstometric uarameters and sensorv thresholds were shown between patients who did or did noi perceive bOA as sensation of filling. Whether both types reuresent different entities or different erades of the same entitv needs to be further studied. However. o&preliminary data suggest that such rlassification might be &nically relevant as treatment outcome was significantly different in both groups.
EFFECTS WITH BENEFITS
AND
benefits of tolterodine ER treatment are
No. 2, pp.
130
CONCLUSIONS: Darifenacin, the first M, SRA, is weli tolerated and provides slgmficant improvement in the debilitatmg symptoms of OAB. Doses of 7.5 mg and 15 mg once daily are effectwe and well tolerated. Consistent with the M, selectivity protile of darifenacin, there were no CV safety concerns. Supported by Novartis Pharma AG, Basel, Swtzerland.