Efficacy of Sanctura XR (Trospium Chloride) for Reducing Overactive Bladder Symptoms in Female Subjects Refractory to Detrol LA (Tolterodine Tartrate Extended Release) Daily

• Sponsor: Allergan (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01089751
• Collaborator: (none)
• Enrollment: 322
• Location: 1
• Arms: 2
• Duration (Months): 27
• Patients Per Site Per Month: 11.9

Study Details

Study Description

Brief Summary

This study will investigate the safety and efficacy of Sanctura XR (trospium chloride) daily in reducing urgency, urinary frequency and urinary urge incontinence in female patients with incontinence refractory to Detrol LA (tolterodine tartrate extended release) 4 mg therapy.

Condition or Disease	Intervention/Treatment	Phase
Overactive Bladder	Drug: trospium chloride; Drug: placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 322 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Study Start Date: Mar 1, 2010
• Actual Primary Completion Date: Jun 1, 2012
• Actual Study Completion Date: Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sanctura XR® Sanctura XR® (trospium chloride) 60 mg once daily on an empty stomach for 14 weeks.	Drug: trospium chloride; Sanctura XR® (trospium chloride) 60 mg once daily on an empty stomach for 14 weeks; Other Names: Sanctura XR®
Placebo Comparator: Placebo Placebo once daily on an empty stomach for 14 weeks.	Drug: placebo; Placebo once daily on an empty stomach for 14 weeks.

Outcome Measures

Primary Outcome Measures

1. Percentage of Patients Continent (PPC) [Week 14]

   PPC is the percentage of patients with complete continence (without any urgency urinary incontinence episodes) during the 3-day bladder diary period associated with the Week 14 visit.

Secondary Outcome Measures

1. Change From Baseline in Continent Days Per Week (CDW) [Baseline, Week 14]

   Continent Days per Week is the average of the number of times an individual has no incontinence episodes in a day within the 3-day collection period calculated as 7 x (number of dry days within the 3-day diary period) divided by the number of valid diary days with at least one valid bladder diary entry during the 3-day period. A positive change from Baseline (more continent/fewer incontinent days per week ) indicated improvement.

2. Change From Baseline in Nocturic Toilet Voids [Baseline, Week 14]

   A nocturic (nighttime) toilet void is identified if the patient marks "Yes" for both Toilet Voiding and Sleep Interruption in the 3-day bladder diary. The daily average number of nocturic toilet voids is obtained as the sum of all nighttime toilet voids over the 3-day bladder diary period divided by number of valid diary days with at least one valid bladder diary entry during the 3-day period. A negative change from Baseline (fewer nocturic toilet voids) indicated improvement.

3. Change From Baseline in Urgency-Related Toilet Voids [Baseline, Week 14]

   Urgency-related toilet void (or urinary urgency) is identified if the patient marks "Yes" for both Urgency Association Void and Toilet Voiding in the 3-day bladder diary. The daily average number of urgency-related voids is calculated as the sum of all urgency episodes over the 3-day bladder diary period divided by the number of valid diary days with at least one valid bladder diary entry during the 3-day period. A negative change from Baseline (fewer urgency related toilet voids) indicated improvement.

4. Change From Baseline in Daily Average Overactive Bladder-Symptom Composite Score (OAB-SCS) [Baseline, Week 14]

   The OAB-SCS is derived from the 3-day bladder diary which includes: 1) 24-hour voiding frequency; 2) the Indevus Urgency Severity Scale (IUSS) Score (0=no urgency, 1=aware of urgency but is tolerable, 2=urgency discomfort interferes with activities/tasks, 3=extreme urgency discomfort that abruptly stops activities/tasks associated with each toilet void); and 3) the frequency of Urgency Urinary Incontinence episodes. Each toilet void is then assigned a point value from 1 (IUSS Score=0) to 5 (UUI episode not associated with a toilet void). The daily average OAB-SCS is then calculated based on the diary entries and assigned point values. The lowest possible daily average OAB-SCS is 0 (corresponding to no urgency in every void). There is no upper limit since the score is based on the number of voids per day. Scores <= 30 indicate mild OAB, scores > 30 to 39 indicate moderate OAB, and scores >= 40 indicate severe OAB. A negative change from Baseline indicated improvement.

5. Change From Baseline in Voided Volume [Baseline, Week 14]

   Average volume of urine voided per toilet void is calculated by total volume collected in a 24-hour diary period divided by the number of individual entries of volume voided in that period. A positive change from Baseline (greater volume voided) indicated improvement. A negative change from Baseline (less volume voided) indicated a worsening.

6. Change From Baseline in Urgency Severity [Baseline, Week 14]

   The urgency severity per toilet void is based on the Indevus Urgency Severity Scale (IUSS). The patient recorded urinary urgency severity in a 3-day bladder diary using a 4-point scale: 0=None-no urgency (best), 1=Slight-aware of urgency but is tolerable, 2=Moderate-urgency discomfort interferes with activities/tasks, 3=Severe-extreme urgency discomfort that abruptly stops activities/tasks (worst). Urgency Severity is calculated as the sum of all IUSS scores during the 3-day diary period divided by the number of toilet voids recorded during that period. A negative change from Baseline indicated improvement.

7. Change From Baseline in Urgency Urinary Incontinence (UUI) [Baseline, Week 14]

   Urgency urinary incontinence is identified if the patient marks "Yes" for both Accidental Leakage and Urgency Associated Void in the 3-day bladder diary, and the Urgency Severity score is ≥ 1. Average daily episodes of UUI is calculated as the sum of all UUI episodes over 3-day diary period divided by the number of valid diary days with at least one valid bladder diary entry during the 3-day period. A negative change from Baseline indicated improvement.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Taking Detrol® LA 4mg daily for a minimum of 1 month prior to Screening/Qualification

• Overactive Bladder syndrome with urgency, urinary frequency and urgency urinary incontinence

• Taking five or more concomitant medications (may be prescription, non-prescription, or supplement/vitamin) daily for indications other than Overactive Bladder (OAB).

Exclusion Criteria:

• Predominant stress or insensate incontinence

• History of neurogenic bladder

• Two urinary tract infections in the last six months

• Gastric by-pass (Roux-en-Y) surgery (adjustable gastric banding is allowed)

• Donated >500mL blood in the 30 days prior to the screening visit

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		La Mesa	California	United States

Sponsors and Collaborators

• Allergan

Investigators

• Study Director: Medical Director, Allergan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Allergan
• ClinicalTrials.gov Identifier: NCT01089751
• Other Study ID Numbers: GMA-SXR-09-004
• First Posted: Mar 19, 2010
• Last Update Posted: Sep 26, 2013
• Last Verified: Sep 1, 2013

• Additional relevant MeSH terms: Urinary Bladder, Overactive; Trospium chloride

Study Results

Participant Flow

Arm/Group Title	Sanctura XR®	Placebo
Arm/Group Description	Sanctura XR® (trospium chloride) 60 mg once daily on an empty stomach for 14 weeks.	Placebo once daily on an empty stomach for 14 weeks.
Period Title: Overall Study
STARTED	163	159
COMPLETED	129	132
NOT COMPLETED	34	27

Baseline Characteristics

Arm/Group Title	Sanctura XR®	Placebo	Total
Arm/Group Description	Sanctura XR® (trospium chloride) 60 mg once daily on an empty stomach for 14 weeks.	Placebo once daily on an empty stomach for 14 weeks.	Total of all reporting groups
Overall Participants	163	159	322
Age (Years) [Mean (Full Range) ]
Mean (Full Range) [Years]	56.3	56.0	56.1
Sex: Female, Male (Count of Participants)
Female	163 100%	159 100%	322 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients Continent (PPC)
Description	PPC is the percentage of patients with complete continence (without any urgency urinary incontinence episodes) during the 3-day bladder diary period associated with the Week 14 visit.
Time Frame	Week 14

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population included all randomized participants who were incontinent at Baseline with at least one urinary episode marked "Yes" for both Accidental leakage and Urgency associated void, and an Urgency severity rating ≥ 1 in the bladder diary.

Arm/Group Title	Sanctura XR®	Placebo
Arm/Group Description	Sanctura XR® (trospium chloride) 60 mg once daily on an empty stomach for 14 weeks.	Placebo once daily on an empty stomach for 14 weeks.
Measure Participants	156	152
Number [Percentage of participants]	34.6 21.2%	17.1 10.8%

2. Secondary Outcome

Title	Change From Baseline in Continent Days Per Week (CDW)
Description	Continent Days per Week is the average of the number of times an individual has no incontinence episodes in a day within the 3-day collection period calculated as 7 x (number of dry days within the 3-day diary period) divided by the number of valid diary days with at least one valid bladder diary entry during the 3-day period. A positive change from Baseline (more continent/fewer incontinent days per week ) indicated improvement.
Time Frame	Baseline, Week 14

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population included all randomized participants who were incontinent at Baseline with at least one urinary episode marked "Yes" for both Accidental leakage and Urgency associated void, and an Urgency severity rating ≥ 1 in the bladder diary.

Arm/Group Title	Sanctura XR®	Placebo
Arm/Group Description	Sanctura XR® (trospium chloride) 60 mg once daily on an empty stomach for 14 weeks.	Placebo once daily on an empty stomach for 14 weeks.
Measure Participants	156	152
Baseline	0.8 (1.46)	1.0 (1.52)
Change from Baseline at Week 14	2.6 (2.96)	1.3 (2.73)

3. Secondary Outcome

Title	Change From Baseline in Nocturic Toilet Voids
Description	A nocturic (nighttime) toilet void is identified if the patient marks "Yes" for both Toilet Voiding and Sleep Interruption in the 3-day bladder diary. The daily average number of nocturic toilet voids is obtained as the sum of all nighttime toilet voids over the 3-day bladder diary period divided by number of valid diary days with at least one valid bladder diary entry during the 3-day period. A negative change from Baseline (fewer nocturic toilet voids) indicated improvement.
Time Frame	Baseline, Week 14

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population included all randomized participants who were incontinent at Baseline with at least one urinary episode marked "Yes" for both Accidental leakage and Urgency associated void, and an Urgency severity rating ≥ 1 in the bladder diary.

Arm/Group Title	Sanctura XR®	Placebo
Arm/Group Description	Sanctura XR® (trospium chloride) 60 mg once daily on an empty stomach for 14 weeks.	Placebo once daily on an empty stomach for 14 weeks.
Measure Participants	156	152
Baseline	2.2 (1.40)	2.3 (1.41)
Change from Baseline at Week 14	-0.6 (1.51)	-0.3 (1.42)

4. Secondary Outcome

Title	Change From Baseline in Urgency-Related Toilet Voids
Description	Urgency-related toilet void (or urinary urgency) is identified if the patient marks "Yes" for both Urgency Association Void and Toilet Voiding in the 3-day bladder diary. The daily average number of urgency-related voids is calculated as the sum of all urgency episodes over the 3-day bladder diary period divided by the number of valid diary days with at least one valid bladder diary entry during the 3-day period. A negative change from Baseline (fewer urgency related toilet voids) indicated improvement.
Time Frame	Baseline, Week 14

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population included all randomized participants who were incontinent at Baseline with at least one urinary episode marked "Yes" for both Accidental leakage and Urgency associated void, and an Urgency severity rating ≥ 1 in the bladder diary.

Arm/Group Title	Sanctura XR®	Placebo
Arm/Group Description	Sanctura XR® (trospium chloride) 60 mg once daily on an empty stomach for 14 weeks.	Placebo once daily on an empty stomach for 14 weeks.
Measure Participants	156	152
Baseline	7.6 (3.36)	7.5 (3.62)
Change from Baseline at Week 14	-2.3 (3.78)	-1.6 (3.87)

5. Secondary Outcome

Title	Change From Baseline in Daily Average Overactive Bladder-Symptom Composite Score (OAB-SCS)
Description	The OAB-SCS is derived from the 3-day bladder diary which includes: 1) 24-hour voiding frequency; 2) the Indevus Urgency Severity Scale (IUSS) Score (0=no urgency, 1=aware of urgency but is tolerable, 2=urgency discomfort interferes with activities/tasks, 3=extreme urgency discomfort that abruptly stops activities/tasks associated with each toilet void); and 3) the frequency of Urgency Urinary Incontinence episodes. Each toilet void is then assigned a point value from 1 (IUSS Score=0) to 5 (UUI episode not associated with a toilet void). The daily average OAB-SCS is then calculated based on the diary entries and assigned point values. The lowest possible daily average OAB-SCS is 0 (corresponding to no urgency in every void). There is no upper limit since the score is based on the number of voids per day. Scores <= 30 indicate mild OAB, scores > 30 to 39 indicate moderate OAB, and scores >= 40 indicate severe OAB. A negative change from Baseline indicated improvement.
Time Frame	Baseline, Week 14

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population included all randomized participants who were incontinent at Baseline with at least one urinary episode marked "Yes" for both Accidental leakage and Urgency associated void, and an Urgency severity rating ≥ 1 in the bladder diary.

Arm/Group Title	Sanctura XR®	Placebo
Arm/Group Description	Sanctura XR® (trospium chloride) 60 mg once daily on an empty stomach for 14 weeks.	Placebo once daily on an empty stomach for 14 weeks.
Measure Participants	156	152
Baseline	24.6 (9.07)	23.7 (10.70)
Change from Baseline at Week 14	-6.5 (10.23)	-3.4 (11.44)

6. Secondary Outcome

Title	Change From Baseline in Voided Volume
Description	Average volume of urine voided per toilet void is calculated by total volume collected in a 24-hour diary period divided by the number of individual entries of volume voided in that period. A positive change from Baseline (greater volume voided) indicated improvement. A negative change from Baseline (less volume voided) indicated a worsening.
Time Frame	Baseline, Week 14

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population included all randomized participants who were incontinent at Baseline with at least one urinary episode marked "Yes" for both Accidental leakage and Urgency associated void, and an Urgency severity rating ≥ 1 in the bladder diary.

Arm/Group Title	Sanctura XR®	Placebo
Arm/Group Description	Sanctura XR® (trospium chloride) 60 mg once daily on an empty stomach for 14 weeks.	Placebo once daily on an empty stomach for 14 weeks.
Measure Participants	156	152
Baseline	183.5 (79.78)	187.4 (78.76)
Change from Baseline at Week 14	20.6 (89.62)	-8.0 (71.56)

7. Secondary Outcome

Title	Change From Baseline in Urgency Severity
Description	The urgency severity per toilet void is based on the Indevus Urgency Severity Scale (IUSS). The patient recorded urinary urgency severity in a 3-day bladder diary using a 4-point scale: 0=None-no urgency (best), 1=Slight-aware of urgency but is tolerable, 2=Moderate-urgency discomfort interferes with activities/tasks, 3=Severe-extreme urgency discomfort that abruptly stops activities/tasks (worst). Urgency Severity is calculated as the sum of all IUSS scores during the 3-day diary period divided by the number of toilet voids recorded during that period. A negative change from Baseline indicated improvement.
Time Frame	Baseline, Week 14

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population included all randomized participants who were incontinent at Baseline with at least one urinary episode marked "Yes" for both Accidental leakage and Urgency associated void, and an Urgency severity rating ≥ 1 in the bladder diary.

Arm/Group Title	Sanctura XR®	Placebo
Arm/Group Description	Sanctura XR® (trospium chloride) 60 mg once daily on an empty stomach for 14 weeks.	Placebo once daily on an empty stomach for 14 weeks.
Measure Participants	156	152
Baseline	1.4 (0.60)	1.3 (0.56)
Change from Baseline at Week 14	-0.4 (0.67)	-0.3 (0.60)

8. Secondary Outcome

Title	Change From Baseline in Urgency Urinary Incontinence (UUI)
Description	Urgency urinary incontinence is identified if the patient marks "Yes" for both Accidental Leakage and Urgency Associated Void in the 3-day bladder diary, and the Urgency Severity score is ≥ 1. Average daily episodes of UUI is calculated as the sum of all UUI episodes over 3-day diary period divided by the number of valid diary days with at least one valid bladder diary entry during the 3-day period. A negative change from Baseline indicated improvement.
Time Frame	Baseline, Week 14

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population included all randomized participants who were incontinent at Baseline with at least one urinary episode marked "Yes" for both Accidental leakage and Urgency associated void, and an Urgency severity rating ≥ 1 in the bladder diary.

Arm/Group Title	Sanctura XR®	Placebo
Arm/Group Description	Sanctura XR® (trospium chloride) 60 mg once daily on an empty stomach for 14 weeks.	Placebo once daily on an empty stomach for 14 weeks.
Measure Participants	156	152
Baseline	2.9 (2.99)	3.0 (2.72)
Change from Baseline at Week 14	-1.1 (2.24)	-0.6 (2.22)

Adverse Events

Adverse Event Reporting Description	The safety population (all participants who took at least 1 dose of study medication) was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events.
Arm/Group Title	Sanctura XR®		Placebo
Arm/Group Description	Sanctura XR® (trospium chloride) 60 mg once daily on an empty stomach for 14 weeks.		Placebo once daily on an empty stomach for 14 weeks.
All Cause Mortality
	Sanctura XR®		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Sanctura XR®		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/162 (1.2%)		3/158 (1.9%)
Blood and lymphatic system disorders
Anaemia	1/162 (0.6%)		0/158 (0%)
Cardiac disorders
Pericardial effusion	0/162 (0%)		1/158 (0.6%)
Gastrointestinal disorders
Gastrooesophageal reflux disease	1/162 (0.6%)		0/158 (0%)
Infections and infestations
Gastroenteritis	1/162 (0.6%)		0/158 (0%)
Pyelonephritis acute	0/162 (0%)		1/158 (0.6%)
Metabolism and nutrition disorders
Diabetes mellitus	0/162 (0%)		1/158 (0.6%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/162 (0%)		1/158 (0.6%)
Other (Not Including Serious) Adverse Events
	Sanctura XR®		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/162 (12.3%)		8/158 (5.1%)
Gastrointestinal disorders
Dry mouth	11/162 (6.8%)		6/158 (3.8%)
Constipation	9/162 (5.6%)		2/158 (1.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.