A Study To Assess If 10 mg Vardenafil (BAY38-9456) Taken Twice Daily For 6 Weeks Has An Effect On Bladder Function

• Sponsor: Bayer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00478881
• Collaborator: (none)
• Enrollment: 397
• Locations: 55
• Arms: 2
• Duration (Months): 15
• Patients Per Site: 7.2
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this study is to assess if the study drug, Vardenafil (approved by Health Authorities is available on the market for treatment of erectile dysfunction) has an effect on bladder function and micturition frequency. The study drug is to be taken in the form of tablets twice a day, one tablet in the morning and one tablet in the evening. A non-active treatment (placebo), a sugar pill, will be used as a comparator to see if the new study drug works better than no drug. The timing of visits for the study is as follows: the 1st visit (screening visit) at beginning of run-in-assessment with qualifying tests for patients: electrocardiogram (ECG), safety laboratory and residual urine (by ultrasonography: a non-invasive examination using ultrasound for the assessment of the bladder). 2nd visit (randomization visit). During visit this should be performed: urodynamic measurements (filling cystometry and pressure flow investigations), ECG and safety laboratory. 3rd visit (safety visit) takes place at two up to three weeks of randomized treatment. 4th visit (final visit)-following test should be done: urodynamic measurements (filling cystometry and pressure flow investigations), ECG, safety laboratory and residual urine (by ultrasonography); A phone call 24 hours after visit 4 to assess any SAEs.

Condition or Disease	Intervention/Treatment	Phase
Overactive Bladder; Detrusor Overactivity	Drug: Vardenafil HCl (Levitra, BAY38-9456); Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 397 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Randomized, Double-blind, Placebo-controlled, Parallel Group Study of Vardenafil 10 mg Twice Daily to Assess the Effect on Urodynamics in Patients With Overactive Bladder (Detrusor Overactivity)
• Study Start Date: Aug 1, 2007
• Actual Primary Completion Date: Nov 1, 2008
• Actual Study Completion Date: Nov 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vardenafil HCl (Levitra, BAY38-9456) vardenafil hydrochloride 10 mg film-coated tablets twice daily (BID) for oral (by mouth) intake for 6 weeks	Drug: Vardenafil HCl (Levitra, BAY38-9456); vardenafil hydrochloride 10 mg film-coated tablets twice daily (BID) for oral (by mouth) intake for 6 weeks
Placebo Comparator: Placebo vardenafil hydrochloride-matching film-coated tablets BID for oral intake for 6 weeks	Drug: Placebo; vardenafil hydrochloride-matching film-coated tablets BID for oral intake for 6 weeks

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Bladder Volume at First Detrusor Contraction at 6 Weeks [baseline and up to 6 weeks of treatment Last Observation Carried Forward (LOCF)]

   Bladder volume was measure by means of urodynamic assessments (cystometry) for up to 6 weeks. Missing data were imputed with last observation carried forward (LOCF).

2. Change From Baseline in Average Number of Daily Micturitions at 6 Weeks [baseline and up to 6 weeks of treatment LOCF]

   Change from baseline in the number of daily micturitions (bladder voidings), as reported in the participant diaries for up to 6 weeks. Missing data were imputed with last observation carried forward (LOCF).

Secondary Outcome Measures

1. Change From Baseline in H2O Detrusor Pressure at First Contraction at 6 Weeks [baseline and up to 6 weeks of treatment LOCF]

   Detrusor pressure was measured by means of urodynamic assessment (cystometry) for up to 6 weeks. Missing data were imputed by last observation carried forward (LOCF).

2. Change From Baseline in Volume at First Detectable Leakage at 6 Weeks [baseline and up to 6 weeks of treatment LOCF]

   First detectable leakage was determined by means of cystometry as an obligatory urodynamic measure. Missing data was imputed by last observation carried forward (LOCF).

3. Change From Baseline in Maximum Cystometric Bladder Capacity at 6 Weeks [baseline and up to 6 weeks of treatment LOCF]

   Maximum cystometric bladder capacity was defined as the volume at which either significant leakage or discomfort/pain occurred. Missing data were imputed by last observation carried forward (LOCF).

4. Change From Baseline in Volume at First Desire to Void at 6 Weeks [baseline and up to 6 weeks of treatment LOCF]

   Volume at first desire to void was recorded during urodynamic assessments. Missing data were imputed by last observation carried forward (LOCF).

5. Change From Baseline in Average Number of Urgencies Per Day at 6 Weeks [baseline and up to 6 weeks of treatment LOCF]

   The average number of urgencies was derived from the number of urgencies reported by the participants in a 7 day micturition diary. Missing data were imputed by last observation carried forward.

6. Change From Baseline in Average Number of Daily Involuntary Discharges of Urine at 6 Weeks [baseline and up to 6 weeks of treatment LOCF]

   The average number of daily involuntary discharges of urine was derived from the number of discharges reported by the participants in a 7 day micturition diary. Missing data were imputed by last observation carried forward.

7. Change From Baseline in Peak Urinary Flow at 6 Weeks in Men Aged 50 Years and Older [baseline and up to 6 weeks of treatment LOCF]

   Peak urinary flow (Qmax) was measured using urodynamic assessments (voiding / flow cystometry) for up to 6 weeks. Missing data were imputed by last observation carried forward (LOCF).

8. Change From Baseline in the Total Score of the Overactive Bladder Questionnaire (OAB-q) at 6 Weeks [baseline and up to 6 weeks of treatment LOCF]

   The OAB-q is a validated, self-administered questionnaire that quantifies bladder symptoms and quality of life. It comprises 33 items (6-point scale for each item). The total score ranges from 33 (minimum symptoms) to 198 (maximum symptoms). On each item, participants provide their rating over the past 4 weeks. Missing data were imputed by LOCF.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male and female patients aged > 18 years (females either postmenopausal or using adequate birth control)

• Urodynamic criteria:

• Entire bladder capacity (= maximum cystometric bladder capacity) < 300 mL OR

• In accordance with International Continence Society (ICS)-guidelines: Detrusor overactivity as defined as spontaneous involuntary detrusor contraction during filling phase OR

• Detrusor contraction during filling phase leading to involuntarily initiated micturition before a normal bladder capacity is reached

• Patient micturition diary criteria: at least 8 micturitions per day AND at least 1 urgency episode per day

• Signed and dated written Patient Informed Consent Form

Exclusion Criteria:

• Treatment with drugs known to affect urinary bladder function

• Known other reasons for micturition problems than detrusor overactivity

• Recent intervention in urogenital tract

• Abnormal liver or renal lab values

• Treatment with nitrates or nitric oxide donors, alpha-blockers, potent inhibitors of CYP-450 3A4, acenocoumarol, heparin, drugs known to prolong QT-interval

• NAION, hereditary regenerative retinal disorders, severe cardiovascular conditions, recent history of myocardial infarction/stroke/life-threatening arrhythmia

• congenital QT-prolongation, left ventricular outflow obstruction, severe hypo- or hypertension, symptomatic postural hypotension

• History of positive test for Hepatitis B surface antigen (HBsAg) or Hepatitis C

• Significant active peptic ulceration

• Severe chronic or acute liver disease, history of moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment

• In men: Clinically significant chronic haematological disease which may lead to priapism

• History of malignancy of any organ system within the past 5 years

• Bleeding disorder

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Bruxelles - Brussel		Belgium	1200
2		Victoria	British Columbia	Canada	V8V 3N1
3		Brantford	Ontario	Canada	N3R 4N3
4		Kitchener	Ontario	Canada	N2N 2B9
5		Montreal	Quebec	Canada	H3T 1E2
6		Olomouc		Czech Republic	775 20
7		Praha 4		Czech Republic	140 59
8		Praha 6		Czech Republic	160 00
9		Paris Cedex 20		France	75970
10		Paris		France	75571
11		Emmendingen	Baden-Württemberg	Germany	79312
12		Bad Griesbach-Therme	Bayern	Germany	94086
13		Weiden	Bayern	Germany	92637
14		Schwedt	Brandenburg	Germany	16303
15		Greifswald	Mecklenburg-Vorpommern	Germany	17475
16		Düsseldorf	Nordrhein-Westfalen	Germany	40235
17		Essen	Nordrhein-Westfalen	Germany	45147
18		Mönchengladbach	Nordrhein-Westfalen	Germany	41063
19		Wuppertal	Nordrhein-Westfalen	Germany	42103
20		Neunkirchen	Saarland	Germany	66538
21		Leipzig	Sachsen	Germany	04103
22		Berlin		Germany	10115
23		Berlin		Germany	13347
24		Budapest		Hungary	1082
25		Budapest		Hungary	1126
26		Haifa		Israel	31096
27		Jerusalem		Israel	91031
28		Petach Tikva		Israel
29		Eindhoven	Noord-Brabant	Netherlands	5623 EJ
30		Amsterdam		Netherlands	1081 HV
31		Amsterdam		Netherlands	1105 AZ
32		Maastricht		Netherlands	6229 HX
33		Rotterdam		Netherlands	3015 CE
34		Utrecht		Netherlands	3584 CX
35		Bydgoszcz		Poland	85-168
36		Chorzow		Poland	41-500
37		Siedlce		Poland	08-110
38		Warszawa		Poland	01-432
39		Warszawa		Poland	02-005
40		Warszawa		Poland	02-777
41		Amadora		Portugal	2720-276
42		Lisboa		Portugal	1069-166
43		Porto		Portugal	4050-013
44		Porto		Portugal	4099-001
45		S. Martinho do Bispo		Portugal	3046-853
46		Moscow		Russian Federation	105425
47		Moscow		Russian Federation	125206
48		St. Petersburg		Russian Federation	198013
49		Santiago de Compostela	A Coruña	Spain	15706
50		Barcelona		Spain	08035
51		Barcelona		Spain	08036
52		Granada		Spain	18014
53		Madrid		Spain	28046
54		Valencia		Spain	46010
55		Basel	Basel-Stadt	Switzerland	4031

Sponsors and Collaborators

• Bayer

Investigators

• Study Director: Bayer Study Director, Bayer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe

Publications

None provided.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT00478881
• Other Study ID Numbers: 12392; 2006-005145-11
• First Posted: May 25, 2007
• Last Update Posted: Dec 11, 2014
• Last Verified: Nov 1, 2014

• Additional relevant MeSH terms: Urinary Bladder, Overactive; Vardenafil Dihydrochloride

Study Results

Participant Flow

Recruitment Details	Enrollment started on 31 August 2007 and the last study visit occurred on 13 November 2008. The study was conducted at 56 centers in 13 countries: 45 centers in Europe, 4 centers in Canada, 4 centers in Russia, and 3 centers in Israel.
Pre-assignment Detail	Number of participants screened: 635. Number of participants enrolled and randomized (started Overall study): 397. Number of participants who had taken at least one dose (Safety population): 396.

Arm/Group Title	Vardenafil HCl (Levitra, BAY38-9456)	Placebo
Arm/Group Description	vardenafil hydrochloride 10 mg film-coated tablets twice daily (BID) for oral (by mouth) intake for 6 weeks	vardenafil hydrochloride-matching film-coated tablets BID for oral intake for 6 weeks
Period Title: Overall Study
STARTED	199	198
Received Medication	198	198
COMPLETED	160	176
NOT COMPLETED	39	22

Baseline Characteristics

Arm/Group Title	Vardenafil HCl (Levitra, BAY38-9456)	Placebo	Total
Arm/Group Description	vardenafil hydrochloride 10 mg film-coated tablets twice daily (BID) for oral (by mouth) intake for 6 weeks	vardenafil hydrochloride-matching film-coated tablets BID for oral intake for 6 weeks	Total of all reporting groups
Overall Participants	198	198	396
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.5 (14.2)	58.3 (12.8)	56.9 (13.5)
Sex: Female, Male (Count of Participants)
Female	116 58.6%	113 57.1%	229 57.8%
Male	82 41.4%	85 42.9%	167 42.2%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Bladder Volume at First Detrusor Contraction at 6 Weeks
Description	Bladder volume was measure by means of urodynamic assessments (cystometry) for up to 6 weeks. Missing data were imputed with last observation carried forward (LOCF).
Time Frame	baseline and up to 6 weeks of treatment Last Observation Carried Forward (LOCF)

Outcome Measure Data

Analysis Population Description

Modified intention-to-treat (mITT): participants included in the safety sample (received at least one dose), randomized correctly according to the Urodynamic Adjudication Board (UDAB), having one valid baseline and one valid (UDAB) on treatment urodynamic measurement. The number is not identical to participants who "completed" the study.

Arm/Group Title	Vardenafil HCl (Levitra, BAY38-9456)	Placebo
Arm/Group Description	vardenafil hydrochloride 10 mg film-coated tablets twice daily (BID) for oral (by mouth) intake for 6 weeks	vardenafil hydrochloride-matching film-coated tablets BID for oral intake for 6 weeks
Measure Participants	122	136
Least Squares Mean (Standard Error) [mL]	44.993 (9.2774)	36.948 (8.7786)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vardenafil HCl (Levitra, BAY38-9456), Placebo
	Comments	Countries were pooled into 2 clusters, which allowed for testing of Treatment by Center interaction. An ANCOVA including Baseline (Visit 2) as a covariate with main effects for treatment and country (see pooling above) was used to test treatment difference for the primary variable and co-primary variable.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5293
	Comments	Bladder volume (mL) at first detrusor contraction tested first. If significant, the change in the average number of daily micturitions was to be tested using a P<0.05.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-8.045
	Confidence Interval	() 95%; -33.194 to 17.104
	Parameter Dispersion	Type: Value:
	Estimation Comments	Placebo-Vardenafil

2. Primary Outcome

Title	Change From Baseline in Average Number of Daily Micturitions at 6 Weeks
Description	Change from baseline in the number of daily micturitions (bladder voidings), as reported in the participant diaries for up to 6 weeks. Missing data were imputed with last observation carried forward (LOCF).
Time Frame	baseline and up to 6 weeks of treatment LOCF

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population: all randomized participants with at least one study drug medication were to be included provided they had a baseline measurement (if scheduled) and a follow-up measurement in any clinical variable. The number is not identical to participants who "completed".

Arm/Group Title	Vardenafil HCl (Levitra, BAY38-9456)	Placebo
Arm/Group Description	vardenafil hydrochloride 10 mg film-coated tablets twice daily (BID) for oral (by mouth) intake for 6 weeks	vardenafil hydrochloride-matching film-coated tablets BID for oral intake for 6 weeks
Measure Participants	163	178
Least Squares Mean (Standard Error) [micturitions per day]	-2.247 (0.2530)	-1.579 (0.2431)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vardenafil HCl (Levitra, BAY38-9456), Placebo
	Comments	Countries were pooled into 2 clusters, which allowed for testing of Treatment by Center interaction. An ANCOVA including Baseline (Visit 2) as a covariate with main effects for treatment and country (see pooling above) was used to test treatment difference for the primary variable and co-primary variable.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0575
	Comments	Bladder volume (mL) at first detrusor contraction tested first. If significant, the change in the average number of daily micturitions was to be tested using a P <0.05.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.668
	Confidence Interval	() 95%; -0.021 to 1.358
	Parameter Dispersion	Type: Value:
	Estimation Comments	Placebo - Vardenafil

3. Secondary Outcome

Title	Change From Baseline in H2O Detrusor Pressure at First Contraction at 6 Weeks
Description	Detrusor pressure was measured by means of urodynamic assessment (cystometry) for up to 6 weeks. Missing data were imputed by last observation carried forward (LOCF).
Time Frame	baseline and up to 6 weeks of treatment LOCF

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (mITT) population: participants included in the safety sample (received at least one dose), randomized correctly according to the Urodynamic Adjudication Board (UDAB), having one valid baseline and one valid (UDAB) on treatment urodynamic measurement. The number is not identical to participants who "completed" the study.

Arm/Group Title	Vardenafil HCl (Levitra, BAY38-9456)	Placebo
Arm/Group Description	vardenafil hydrochloride 10 mg film-coated tablets twice daily (BID) for oral (by mouth) intake for 6 weeks	vardenafil hydrochloride-matching film-coated tablets BID for oral intake for 6 weeks
Measure Participants	119	135
Least Squares Mean (Standard Error) [millimeters of mercury (mmHg)]	0.085 (2.5821)	0.743 (2.4199)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vardenafil HCl (Levitra, BAY38-9456), Placebo
	Comments	ANCOVA models used for the secondary efficacy variables were the models determined for the primary efficacy variable or co-primary efficacy variable depending on the type of variable.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8533
	Comments	P-values were reported as nominal values and without any adjustments for multiplicity.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.657
	Confidence Interval	() 95%; -6.335 to 7.650
	Parameter Dispersion	Type: Value:
	Estimation Comments	Placebo- Vardenafil

4. Secondary Outcome

Title	Change From Baseline in Volume at First Detectable Leakage at 6 Weeks
Description	First detectable leakage was determined by means of cystometry as an obligatory urodynamic measure. Missing data was imputed by last observation carried forward (LOCF).
Time Frame	baseline and up to 6 weeks of treatment LOCF

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (mITT): participants included in the safety sample (received at least one dose), randomized correctly according to the Urodynamic Adjudication Board (UDAB), having one valid baseline and one valid (UDAB) on treatment urodynamic measurement. The number is not identical to participants who "completed" the study.

Arm/Group Title	Vardenafil HCl (Levitra, BAY38-9456)	Placebo
Arm/Group Description	vardenafil hydrochloride 10 mg film-coated tablets twice daily (BID) for oral (by mouth) intake for 6 weeks	vardenafil hydrochloride-matching film-coated tablets BID for oral intake for 6 weeks
Measure Participants	121	134
Least Squares Mean (Standard Error) [mL]	42.307 (7.9013)	26.717 (7.5039)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vardenafil HCl (Levitra, BAY38-9456), Placebo
	Comments	ANCOVA models used for the secondary efficacy variables were the models determined for the primary efficacy variable or co-primary efficacy variable depending on the type of variable.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1539
	Comments	P-values were reported as nominal values and without any adjustments for multiplicity.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-15.590
	Confidence Interval	() 95%; -37.057 to 5.876
	Parameter Dispersion	Type: Value:
	Estimation Comments	Placebo- Vardenafil

5. Secondary Outcome

Title	Change From Baseline in Maximum Cystometric Bladder Capacity at 6 Weeks
Description	Maximum cystometric bladder capacity was defined as the volume at which either significant leakage or discomfort/pain occurred. Missing data were imputed by last observation carried forward (LOCF).
Time Frame	baseline and up to 6 weeks of treatment LOCF

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (mITT): participants included in the safety sample (received at least one dose), randomized correctly according to the Urodynamic Adjudication Board (UDAB), having one valid baseline and one valid (UDAB) on treatment urodynamic measurement. The number is not identical to participants who "completed" the study.

Arm/Group Title	Vardenafil HCl (Levitra, BAY38-9456)	Placebo
Arm/Group Description	vardenafil hydrochloride 10 mg film-coated tablets twice daily (BID) for oral (by mouth) intake for 6 weeks	vardenafil hydrochloride-matching film-coated tablets BID for oral intake for 6 weeks
Measure Participants	125	136
Least Squares Mean (Standard Error) [mL]	40.274 (7.4986)	27.900 (7.1839)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vardenafil HCl (Levitra, BAY38-9456), Placebo
	Comments	ANCOVA models used for the secondary efficacy variables were the models determined for the primary efficacy variable or co-primary efficacy variable depending on the type of variable.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2348
	Comments	P-values were reported as nominal values and without any adjustments for multiplicity.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-12.374
	Confidence Interval	() 95%; -32.834 to 8.087
	Parameter Dispersion	Type: Value:
	Estimation Comments	placebo - vardenafil

6. Secondary Outcome

Title	Change From Baseline in Volume at First Desire to Void at 6 Weeks
Description	Volume at first desire to void was recorded during urodynamic assessments. Missing data were imputed by last observation carried forward (LOCF).
Time Frame	baseline and up to 6 weeks of treatment LOCF

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (mITT): participants included in the safety sample (received at least one dose), randomized correctly according to the Urodynamic Adjudication Board (UDAB), having one valid baseline and one valid (UDAB) on treatment urodynamic measurement. The number is not identical to participants who "completed" the study.

Arm/Group Title	Vardenafil HCl (Levitra, BAY38-9456)	Placebo
Arm/Group Description	vardenafil hydrochloride 10 mg film-coated tablets twice daily (BID) for oral (by mouth) intake for 6 weeks	vardenafil hydrochloride-matching film-coated tablets BID for oral intake for 6 weeks
Measure Participants	125	136
Least Squares Mean (Standard Error) [mL]	30.655 (6.0503)	22.460 (5.7959)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vardenafil HCl (Levitra, BAY38-9456), Placebo
	Comments	ANCOVA models used for the secondary efficacy variables were the models determined for the primary efficacy variable or co-primary efficacy variable depending on the type of variable.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3289
	Comments	P-values were reported as nominal values and without any adjustments for multiplicity.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-8.195
	Confidence Interval	() 95%; -24.692 to 8.303
	Parameter Dispersion	Type: Value:
	Estimation Comments	placebo - vardenafil

7. Secondary Outcome

Title	Change From Baseline in Average Number of Urgencies Per Day at 6 Weeks
Description	The average number of urgencies was derived from the number of urgencies reported by the participants in a 7 day micturition diary. Missing data were imputed by last observation carried forward.
Time Frame	baseline and up to 6 weeks of treatment LOCF

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population: all randomized participants with at least one study drug medication were to be included provided they had a baseline measurement (if scheduled) and a follow-up measurement in any clinical variable. The number is not identical to participants who "completed".

Arm/Group Title	Vardenafil HCl (Levitra, BAY38-9456)	Placebo
Arm/Group Description	vardenafil hydrochloride 10 mg film-coated tablets twice daily (BID) for oral (by mouth) intake for 6 weeks	vardenafil hydrochloride-matching film-coated tablets BID for oral intake for 6 weeks
Measure Participants	163	178
Least Squares Mean (Standard Error) [urgencies per day]	-1.861 (0.2768)	-1.139 (0.2658)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vardenafil HCl (Levitra, BAY38-9456), Placebo
	Comments	ANCOVA models used for the secondary efficacy variables were the models determined for the primary efficacy variable or co-primary efficacy variable depending on the type of variable.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0609
	Comments	P-values were reported as nominal values and without any adjustments for multiplicity.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.721
	Confidence Interval	() 95%; -0.033 to 1.476
	Parameter Dispersion	Type: Value:
	Estimation Comments	placebo - vardenafil

8. Secondary Outcome

Title	Change From Baseline in Average Number of Daily Involuntary Discharges of Urine at 6 Weeks
Description	The average number of daily involuntary discharges of urine was derived from the number of discharges reported by the participants in a 7 day micturition diary. Missing data were imputed by last observation carried forward.
Time Frame	baseline and up to 6 weeks of treatment LOCF

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population: all randomized participants with at least one study drug medication were to be included provided they had a baseline measurement (if scheduled) and a follow-up measurement in any clinical variable. The number is not identical to participants who "completed".

Arm/Group Title	Vardenafil HCl (Levitra, BAY38-9456)	Placebo
Arm/Group Description	vardenafil hydrochloride 10 mg film-coated tablets twice daily (BID) for oral (by mouth) intake for 6 weeks	vardenafil hydrochloride-matching film-coated tablets BID for oral intake for 6 weeks
Measure Participants	162	178
Least Squares Mean (Standard Error) [involuntary discharges per day]	-0.566 (0.1241)	0.447 (0.1188)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vardenafil HCl (Levitra, BAY38-9456), Placebo
	Comments	ANCOVA models used for the secondary efficacy variables were the models determined for the primary efficacy variable or co-primary efficacy variable depending on the type of variable.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4928
	Comments	P-values were reported as nominal values and without any adjustments for multiplicity.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.118
	Confidence Interval	() 95%; -0.220 to 0.456
	Parameter Dispersion	Type: Value:
	Estimation Comments	placebo - vardenafil

9. Secondary Outcome

Title	Change From Baseline in Peak Urinary Flow at 6 Weeks in Men Aged 50 Years and Older
Description	Peak urinary flow (Qmax) was measured using urodynamic assessments (voiding / flow cystometry) for up to 6 weeks. Missing data were imputed by last observation carried forward (LOCF).
Time Frame	baseline and up to 6 weeks of treatment LOCF

Outcome Measure Data

Analysis Population Description

mITT: Participants who received at least one dose, randomized correctly according to Urodynamic Adjudication Board (UDAB), having one valid baseline and one valid (UDAB) on treatment urodynamic measurement. Qmax is based on men predominantly aged 50 years and older but includes a few males who had Qmax collected even if younger than 50 years.

Arm/Group Title	Vardenafil HCl (Levitra, BAY38-9456)	Placebo
Arm/Group Description	vardenafil hydrochloride 10 mg film-coated tablets twice daily (BID) for oral (by mouth) intake for 6 weeks	vardenafil hydrochloride-matching film-coated tablets BID for oral intake for 6 weeks
Measure Participants	39	55
Least Squares Mean (Standard Error) [milliliter per second (mL/s)]	1.129 (0.6301)	0.306 (0.5351)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vardenafil HCl (Levitra, BAY38-9456), Placebo
	Comments	ANCOVA models used for the secondary efficacy variables were the models determined for the primary efficacy variable or co-primary efficacy variable depending on the type of variable.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3248
	Comments	P-values were reported as nominal values and without any adjustments for multiplicity.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.823
	Confidence Interval	() 95%; -2.476 to 0.829
	Parameter Dispersion	Type: Value:
	Estimation Comments	placebo - vardenafil

10. Secondary Outcome

Title	Change From Baseline in the Total Score of the Overactive Bladder Questionnaire (OAB-q) at 6 Weeks
Description	The OAB-q is a validated, self-administered questionnaire that quantifies bladder symptoms and quality of life. It comprises 33 items (6-point scale for each item). The total score ranges from 33 (minimum symptoms) to 198 (maximum symptoms). On each item, participants provide their rating over the past 4 weeks. Missing data were imputed by LOCF.
Time Frame	baseline and up to 6 weeks of treatment LOCF

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population: all randomized participants with at least one study drug medication were to be included provided they had a baseline measurement (if scheduled) and a follow-up measurement in any clinical variable. The number is not identical to participants who "completed".

Arm/Group Title	Vardenafil HCl (Levitra, BAY38-9456)	Placebo
Arm/Group Description	vardenafil hydrochloride 10 mg film-coated tablets twice daily (BID) for oral (by mouth) intake for 6 weeks	vardenafil hydrochloride-matching film-coated tablets BID for oral intake for 6 weeks
Measure Participants	156	169
Least Squares Mean (Standard Error) [scores on a scale]	8.929 (1.2627)	7.834 (1.2181)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vardenafil HCl (Levitra, BAY38-9456), Placebo
	Comments	ANCOVA models used for the secondary efficacy variables were the models determined for the primary efficacy variable or co-primary efficacy variable depending on the type of variable.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5312
	Comments	P-values were reported as nominal values and without any adjustments for multiplicity.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.095
	Confidence Interval	() 95%; -4.533 to 2.342
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Vardenafil HCl (Levitra, BAY38-9456)		Placebo
Arm/Group Description	vardenafil hydrochloride 10 mg film-coated tablets twice daily (BID) for oral (by mouth) intake for 6 weeks		vardenafil hydrochloride-matching film-coated tablets BID for oral intake for 6 weeks
All Cause Mortality
	Vardenafil HCl (Levitra, BAY38-9456)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Vardenafil HCl (Levitra, BAY38-9456)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/198 (2%)		4/198 (2%)
Cardiac disorders
Angina pectoris	0/198 (0%)		1/198 (0.5%)
Angina unstable	0/198 (0%)		1/198 (0.5%)
Coronary artery disease	0/198 (0%)		1/198 (0.5%)
Eye disorders
Vision blurred	1/198 (0.5%)		0/198 (0%)
Gastrointestinal disorders
Diarrhoea	1/198 (0.5%)		0/198 (0%)
Injury, poisoning and procedural complications
Wrist fracture	0/198 (0%)		1/198 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	1/198 (0.5%)		0/198 (0%)
Nervous system disorders
Headache	1/198 (0.5%)		0/198 (0%)
Multiple sclerosis	1/198 (0.5%)		0/198 (0%)
Reproductive system and breast disorders
Prostatitis	0/198 (0%)		1/198 (0.5%)
Vascular disorders
Hypertension	0/198 (0%)		1/198 (0.5%)
Other (Not Including Serious) Adverse Events
	Vardenafil HCl (Levitra, BAY38-9456)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	78/198 (39.4%)		39/198 (19.7%)
Gastrointestinal disorders
Abdominal pain upper	4/198 (2%)		0/198 (0%)
Constipation	4/198 (2%)		0/198 (0%)
Diarrhoea	6/198 (3%)		7/198 (3.5%)
Dyspepsia	10/198 (5.1%)		1/198 (0.5%)
Flatulence	4/198 (2%)		0/198 (0%)
Nausea	5/198 (2.5%)		4/198 (2%)
General disorders
Asthenia	4/198 (2%)		0/198 (0%)
Fatigue	7/198 (3.5%)		3/198 (1.5%)
Infections and infestations
Urinary tract infection	8/198 (4%)		5/198 (2.5%)
Musculoskeletal and connective tissue disorders
Back pain	8/198 (4%)		5/198 (2.5%)
Muscle spasms	4/198 (2%)		1/198 (0.5%)
Myalgia	9/198 (4.5%)		1/198 (0.5%)
Nervous system disorders
Dizziness	8/198 (4%)		4/198 (2%)
Headache	37/198 (18.7%)		18/198 (9.1%)
Vascular disorders
Flushing	5/198 (2.5%)		1/198 (0.5%)
Hot flush	2/198 (1%)		4/198 (2%)

Limitations/Caveats

635 participants were screened; 238 were not randomized because they did not fulfill the inclusion/exclusion criteria. Cystometric bladder compliance not presented since only relevant to characterization of detrusor overactivity, not to efficacy.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Publishing incl confidential information only after Bayer written approval. Manuscript to Bayer 60 days before submission. Confidential Information to be deleted. Other Bayer comments to be considered, if they do not alter the scientific character. If no Bayer comment within 45 days, consider approval given. If multisite study Principal Investigator (PI) not to independently publish results before publication of multisite paper, but PI not restricted from 24 months from study completion onwards.