Trial Outcomes & Findings for Efficacy of Sanctura XR (Trospium Chloride) for Reducing Overactive Bladder Symptoms in Female Subjects Refractory to Detrol LA (Tolterodine Tartrate Extended Release) Daily (NCT NCT01089751)

NCT ID: NCT01089751

Last Updated: 2013-09-26

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 322 participants
• Primary outcome timeframe: Week 14
• Results posted on: 2013-09-26

Participant Flow

Participant milestones

Measure	Sanctura XR® Sanctura XR® (trospium chloride) 60 mg once daily on an empty stomach for 14 weeks.	Placebo Placebo once daily on an empty stomach for 14 weeks.
Overall Study STARTED	163	159
Overall Study COMPLETED	129	132
Overall Study NOT COMPLETED	34	27

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Sanctura XR® n=163 Participants Sanctura XR® (trospium chloride) 60 mg once daily on an empty stomach for 14 weeks.	Placebo n=159 Participants Placebo once daily on an empty stomach for 14 weeks.	Total n=322 Participants Total of all reporting groups
Age Continuous	56.3 Years n=5 Participants	56.0 Years n=7 Participants	56.1 Years n=5 Participants
Sex: Female, Male Female	163 Participants n=5 Participants	159 Participants n=7 Participants	322 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 14

Population: 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.

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.

Outcome measures

Measure	Sanctura XR® n=156 Participants Sanctura XR® (trospium chloride) 60 mg once daily on an empty stomach for 14 weeks.	Placebo n=152 Participants Placebo once daily on an empty stomach for 14 weeks.
Percentage of Patients Continent (PPC)	34.6 Percentage of participants	17.1 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 14

Population: 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.

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.

Outcome measures

Measure	Sanctura XR® n=156 Participants Sanctura XR® (trospium chloride) 60 mg once daily on an empty stomach for 14 weeks.	Placebo n=152 Participants Placebo once daily on an empty stomach for 14 weeks.
Change From Baseline in Continent Days Per Week (CDW) Baseline	0.8 Continent days per week Standard Deviation 1.46	1.0 Continent days per week Standard Deviation 1.52
Change From Baseline in Continent Days Per Week (CDW) Change from Baseline at Week 14	2.6 Continent days per week Standard Deviation 2.96	1.3 Continent days per week Standard Deviation 2.73

SECONDARY outcome

Timeframe: Baseline, Week 14

Population: 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.

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.

Outcome measures

Measure	Sanctura XR® n=156 Participants Sanctura XR® (trospium chloride) 60 mg once daily on an empty stomach for 14 weeks.	Placebo n=152 Participants Placebo once daily on an empty stomach for 14 weeks.
Change From Baseline in Nocturic Toilet Voids Baseline	2.2 Nocturic toilet void Standard Deviation 1.40	2.3 Nocturic toilet void Standard Deviation 1.41
Change From Baseline in Nocturic Toilet Voids Change from Baseline at Week 14	-0.6 Nocturic toilet void Standard Deviation 1.51	-0.3 Nocturic toilet void Standard Deviation 1.42

SECONDARY outcome

Timeframe: Baseline, Week 14

Population: 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.

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.

Outcome measures

Measure	Sanctura XR® n=156 Participants Sanctura XR® (trospium chloride) 60 mg once daily on an empty stomach for 14 weeks.	Placebo n=152 Participants Placebo once daily on an empty stomach for 14 weeks.
Change From Baseline in Urgency-Related Toilet Voids Baseline	7.6 Toilet void Standard Deviation 3.36	7.5 Toilet void Standard Deviation 3.62
Change From Baseline in Urgency-Related Toilet Voids Change from Baseline at Week 14	-2.3 Toilet void Standard Deviation 3.78	-1.6 Toilet void Standard Deviation 3.87

SECONDARY outcome

Timeframe: Baseline, Week 14

Population: 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.

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.

Outcome measures

Measure	Sanctura XR® n=156 Participants Sanctura XR® (trospium chloride) 60 mg once daily on an empty stomach for 14 weeks.	Placebo n=152 Participants Placebo once daily on an empty stomach for 14 weeks.
Change From Baseline in Daily Average Overactive Bladder-Symptom Composite Score (OAB-SCS) Baseline	24.6 Score on a scale Standard Deviation 9.07	23.7 Score on a scale Standard Deviation 10.70
Change From Baseline in Daily Average Overactive Bladder-Symptom Composite Score (OAB-SCS) Change from Baseline at Week 14	-6.5 Score on a scale Standard Deviation 10.23	-3.4 Score on a scale Standard Deviation 11.44

SECONDARY outcome

Timeframe: Baseline, Week 14

Population: 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.

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.

Outcome measures

Measure	Sanctura XR® n=156 Participants Sanctura XR® (trospium chloride) 60 mg once daily on an empty stomach for 14 weeks.	Placebo n=152 Participants Placebo once daily on an empty stomach for 14 weeks.
Change From Baseline in Voided Volume Baseline	183.5 cubic centimeters (cc) Standard Deviation 79.78	187.4 cubic centimeters (cc) Standard Deviation 78.76
Change From Baseline in Voided Volume Change from Baseline at Week 14	20.6 cubic centimeters (cc) Standard Deviation 89.62	-8.0 cubic centimeters (cc) Standard Deviation 71.56

SECONDARY outcome

Timeframe: Baseline, Week 14

Population: 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.

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.

Outcome measures

Measure	Sanctura XR® n=156 Participants Sanctura XR® (trospium chloride) 60 mg once daily on an empty stomach for 14 weeks.	Placebo n=152 Participants Placebo once daily on an empty stomach for 14 weeks.
Change From Baseline in Urgency Severity Baseline	1.4 Score on a scale Standard Deviation 0.60	1.3 Score on a scale Standard Deviation 0.56
Change From Baseline in Urgency Severity Change from Baseline at Week 14	-0.4 Score on a scale Standard Deviation 0.67	-0.3 Score on a scale Standard Deviation 0.60

SECONDARY outcome

Timeframe: Baseline, Week 14

Population: 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.

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.

Outcome measures

Measure	Sanctura XR® n=156 Participants Sanctura XR® (trospium chloride) 60 mg once daily on an empty stomach for 14 weeks.	Placebo n=152 Participants Placebo once daily on an empty stomach for 14 weeks.
Change From Baseline in Urgency Urinary Incontinence (UUI) Baseline	2.9 UUI episodes Standard Deviation 2.99	3.0 UUI episodes Standard Deviation 2.72
Change From Baseline in Urgency Urinary Incontinence (UUI) Change from Baseline at Week 14	-1.1 UUI episodes Standard Deviation 2.24	-0.6 UUI episodes Standard Deviation 2.22

Adverse Events

Sanctura XR®

Serious events: 2 serious events

Other events: 20 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Measure	Sanctura XR® n=162 participants at risk Sanctura XR® (trospium chloride) 60 mg once daily on an empty stomach for 14 weeks.	Placebo n=158 participants at risk Placebo once daily on an empty stomach for 14 weeks.
Blood and lymphatic system disorders Anaemia	0.62% 1/162 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.	0.00% 0/158 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.
Cardiac disorders Pericardial effusion	0.00% 0/162 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.	0.63% 1/158 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.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.62% 1/162 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.	0.00% 0/158 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.
Infections and infestations Gastroenteritis	0.62% 1/162 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.	0.00% 0/158 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.
Infections and infestations Pyelonephritis acute	0.00% 0/162 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.	0.63% 1/158 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.
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/162 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.	0.63% 1/158 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.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/162 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.	0.63% 1/158 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.

Other adverse events

Measure	Sanctura XR® n=162 participants at risk Sanctura XR® (trospium chloride) 60 mg once daily on an empty stomach for 14 weeks.	Placebo n=158 participants at risk Placebo once daily on an empty stomach for 14 weeks.
Gastrointestinal disorders Dry mouth	6.8% 11/162 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.	3.8% 6/158 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.
Gastrointestinal disorders Constipation	5.6% 9/162 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.	1.3% 2/158 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.

Additional Information

Vice President Medical Affairs,

Allergan, Inc

Phone: 714-246-4500

Email: clinicaltrials@allergan.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER