Study to Compare the Safety and Efficacy of Solifenacin With Oxybutynin for the Treatment of Overactive Bladder (VECTOR)

• Sponsor: Astellas Pharma Inc (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00431041
• Collaborator: Astellas Pharma Canada, Inc. (Industry)
• Enrollment: 132
• Locations: 12
• Arms: 2
• Duration (Months): 14
• Patients Per Site: 11
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the safety and efficacy of solifenacin with oxybutynin immediate-release (IR) for the treatment of overactive bladder (OAB).

Condition or Disease	Intervention/Treatment	Phase
Overactive Bladder	Drug: solifenacin; Drug: oxybutynin immediate release	Phase 4

Detailed Description

This study is a prospective randomized, double-blind, double-dummy, multicentre, 2-arm (1 Active, Active Control) comparative parallel group study to compare the safety and efficacy of solifenacin with oxybutynin immediate-release (IR) for the treatment of overactive bladder (OAB).

Study Design

• Study Type: Interventional
• Actual Enrollment: 132 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: VECTOR: A Randomized Double-blind Study to Assess the Safety and Efficacy of Solifenacin (Vesicare®) in Comparison to Oxybutynin for Overactive Bladder Patients
• Study Start Date: Dec 1, 2006
• Actual Primary Completion Date: Feb 1, 2008
• Actual Study Completion Date: Feb 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Solifenacin Solifenacin succinate: 5 mg tablets, taken orally, once daily	Drug: solifenacin; Oral; Other Names: VESIcare® YM905
Active Comparator: Oxybutynin IR Oxybutynin Immediate Release: 5 mg capsules, taken orally, 3 times a day	Drug: oxybutynin immediate release; Oral

Outcome Measures

Primary Outcome Measures

1. The Number of Subjects Reporting Incidence of Dry Mouth as an Adverse Event [8 weeks]

   The number of subjects reporting incidence of dry mouth as an adverse event (AE) following direct questioning at each patient follow-up visit

2. The Severity of Dry Mouth Reported as an Adverse Event [8 weeks]

   The number of subjects reporting dry mouth at each severity level when dry mouth was reported as an Adverse Event (AE). Dry mouth severity was categorized as "mild" (relieved with fluid/hard candy), "moderate" (dry mouth and throat with no difficulty swallowing solid food/water) & "severe" (very dry mouth & throat, difficulty swallowing solid food without water)

Secondary Outcome Measures

1. Change From Baseline in Micturition Frequency as Reported in Subject 3-day Diary [Baseline and 8 Weeks]

   Subjects were instructed to complete the diary in the 3 day period immediately proceding the visit. Subjects recorded each micturition or instance of passing urine in the toliet. The mean was calculated for each time point as the average of the day 1-3 measurements from the associated 3 day diary. Change from baseline was calculated as Week 8- Baseline.

2. Change From Baseline in Urgency Episodes as Reported in Subject 3-day Diary [Baseline and 8 weeks]

   Subjects were instructed to complete the diary in the 3 day period immediately preceding the visit. Subjects recorded each urgency episode or instance of strong desire to pass urine. The mean was calculated for each time point as the average of the day 1-3 measurements from the associated 3 day diary. Change from Baseline was calculated as Week 8- Baseline.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Adults 18 years and older.

• Overactive bladder symptoms for greater than or equal to 3 months and as documented in a 3-day patient diary following screening and preceding baseline visit: > 1 urge episodes/24 hours (average); greater than or equal to 8 micturitions/24 hours (average)

Exclusion Criteria:

• Urinary tract infection, chronic inflammation such as interstitial cystitis and bladder stones

• Clinically significant outflow obstruction

• Uncontrolled narrow angle glaucoma, urinary, or gastric retention

• Severe renal or hepatic impairment

• Chronic severe constipation or history of diagnosed GI obstructive disease

• Significant stress incontinence or mixed stress/urge incontinence where stress is the predominant factor

• Diagnosis or history of neurogenic bladder

• History of bladder or pelvic cancer

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Calgary	Alberta	Canada	T2V 4R6
2		Edmonton	Alberta	Canada	T5H 3V9
3		Vancouver	British Columbia	Canada	V6T 2B5
4		Victoria	British Columbia	Canada	V8T 5G1
5		Halifax	Nova Scotia	Canada	B3H 3A7
6		Guelph	Ontario	Canada	N1H 5J1
7		Kitchener	Ontario	Canada	N2N 2B9
8		Toronto	Ontario	Canada	M4N 3M5
9		Toronto	Ontario	Canada	M5G 1Z5
10		Toronto	Ontario	Canada	M5T 2S8
11		Toronto	Ontario	Canada	M6A 3B5
12		Montreal	Quebec	Canada	H3T 1E2

Sponsors and Collaborators

• Astellas Pharma Inc
• Astellas Pharma Canada, Inc.

Investigators

• Study Director: Use Central Contact, Astellas Pharma Canada, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

• Herschorn S, Stothers L, Carlson K, Egerdie B, Gajewski JB, Pommerville P, Schulz J, Radomski S, Drutz H, Barkin J, Paradiso-Hardy F. Tolerability of 5 mg solifenacin once daily versus 5 mg oxybutynin immediate release 3 times daily: results of the VECTOR trial. J Urol. 2010 May;183(5):1892-8. doi: 10.1016/j.juro.2010.01.012. Epub 2010 Mar 29.

• ClinicalTrials.gov Identifier: NCT00431041
• Other Study ID Numbers: VES-001
• First Posted: Feb 2, 2007
• Last Update Posted: Jun 8, 2010
• Last Verified: Jun 1, 2010

• Keywords provided by , ,: Solifenacin succinate; Oxybutynin immediate release; Xerostomia; Overactive bladder
• Additional relevant MeSH terms: Urinary Bladder, Overactive; Solifenacin Succinate; Oxybutynin

Study Results

Participant Flow

Arm/Group Title	Solifenacin	Oxybutynin IR
Arm/Group Description	Solifenacin succinate: 5 mg tablets, taken orally, once daily	Oxybutynin Immediate Release: 5 mg capsules, taken orally, 3 times a day
Period Title: Overall Study
STARTED	68	64
COMPLETED	52	40
NOT COMPLETED	16	24

Baseline Characteristics

Arm/Group Title	Solifenacin	Oxybutynin IR	Total
Arm/Group Description	Solifenacin succinate: 5 mg tablets, taken orally, once daily	Oxybutynin Immediate Release: 5 mg capsules, taken orally, 3 times a day	Total of all reporting groups
Overall Participants	68	64	132
Age, Customized (participants) [Number]
<=65 years	41 60.3%	34 53.1%	75 56.8%
>65 years	27 39.7%	30 46.9%	57 43.2%
Sex: Female, Male (Count of Participants)
Female	51 75%	52 81.3%	103 78%
Male	17 25%	12 18.8%	29 22%
Race/Ethnicity, Customized (participants) [Number]
Caucasian	62 91.2%	57 89.1%	119 90.2%
Black	2 2.9%	5 7.8%	7 5.3%
Asian	3 4.4%	0 0%	3 2.3%
Aboriginal	0 0%	1 1.6%	1 0.8%
Hispanic	0 0%	0 0%	0 0%
Other	1 1.5%	1 1.6%	2 1.5%

Outcome Measures

1. Primary Outcome

Title	The Number of Subjects Reporting Incidence of Dry Mouth as an Adverse Event
Description	The number of subjects reporting incidence of dry mouth as an adverse event (AE) following direct questioning at each patient follow-up visit
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

Data represents ITT Population: all randomized subjects

Arm/Group Title	Solifenacin	Oxybutynin IR
Arm/Group Description	Solifenacin succinate: 5 mg tablets, taken orally, once daily	Oxybutynin Immediate Release: 5 mg capsules, taken orally, 3 times a day
Measure Participants	68	64
Number [participants]	24 35.3%	53 82.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Solifenacin, Oxybutynin IR
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Chi-squared
	Comments

2. Primary Outcome

Title	The Severity of Dry Mouth Reported as an Adverse Event
Description	The number of subjects reporting dry mouth at each severity level when dry mouth was reported as an Adverse Event (AE). Dry mouth severity was categorized as "mild" (relieved with fluid/hard candy), "moderate" (dry mouth and throat with no difficulty swallowing solid food/water) & "severe" (very dry mouth & throat, difficulty swallowing solid food without water)
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

Data represents ITT Population: all randomized subjects

Arm/Group Title	Solifenacin	Oxybutynin IR
Arm/Group Description	Solifenacin succinate: 5 mg tablets, taken orally, once daily	Oxybutynin Immediate Release: 5 mg capsules, taken orally, 3 times a day
Measure Participants	68	64
Mild	18 26.5%	16 25%
Moderate	3 4.4%	22 34.4%
Severe	3 4.4%	15 23.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Solifenacin, Oxybutynin IR
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0010
	Comments	P-value represents overall comparison of severity of dry mouth.
	Method	Chi-squared
	Comments

3. Secondary Outcome

Title	Change From Baseline in Micturition Frequency as Reported in Subject 3-day Diary
Description	Subjects were instructed to complete the diary in the 3 day period immediately proceding the visit. Subjects recorded each micturition or instance of passing urine in the toliet. The mean was calculated for each time point as the average of the day 1-3 measurements from the associated 3 day diary. Change from baseline was calculated as Week 8- Baseline.
Time Frame	Baseline and 8 Weeks

Outcome Measure Data

Analysis Population Description

Data represents ITT Population: all randomized subjects. The numbers of subjects for each time point are noted in the category titles. Data for week 8 and Change from Baseline to week 8 includes all subjects who completed the study

Arm/Group Title	Solifenacin	Oxybutynin IR
Arm/Group Description	Solifenacin succinate: 5 mg tablets, taken orally, once daily	Oxybutynin Immediate Release: 5 mg capsules, taken orally, 3 times a day
Measure Participants	68	64
Change in micturition frequency at 8 wks(N=52; 40)	-2.3 (3.3)	-3.1 (2.7)
Micturition frequency at Baseline (N=68; 64)	12.4 (3.2)	12.5 (3.1)
Micturition frequency at 8 weeks (N=52; 40)	9.9 (3.7)	9.0 (2.9)

4. Secondary Outcome

Title	Change From Baseline in Urgency Episodes as Reported in Subject 3-day Diary
Description	Subjects were instructed to complete the diary in the 3 day period immediately preceding the visit. Subjects recorded each urgency episode or instance of strong desire to pass urine. The mean was calculated for each time point as the average of the day 1-3 measurements from the associated 3 day diary. Change from Baseline was calculated as Week 8- Baseline.
Time Frame	Baseline and 8 weeks

Outcome Measure Data

Analysis Population Description

Data represents ITT Population: all randomized subjects. The numbers of subjects for each time point are noted in the category titles. Data for week 8 and Change from Baseline to week 8 includes all subjects who completed the study

Arm/Group Title	Solifenacin	Oxybutynin IR
Arm/Group Description	Solifenacin succinate: 5 mg tablets, taken orally, once daily	Oxybutynin Immediate Release: 5 mg capsules, taken orally, 3 times a day
Measure Participants	68	64
Change in urgency episodes at 8 weeks (N=52; 40)	-2.65 (4.54)	-3.70 (3.26)
Urgency episodes at Baseline (N= 68; 64)	6.3 (3.98)	6.6 (4.43)
Urgency episodes at 8 weeks (N=52; 40)	3.8 (5.04)	2.1 (2.88)

Adverse Events

Arm/Group Title	Solifenacin		Oxybutynin IR
Arm/Group Description	Solifenacin succinate: 5 mg tablets, taken orally, once daily		Oxybutynin Immediate Release: 5 mg capsules, taken orally, 3 times a day
All Cause Mortality
	Solifenacin		Oxybutynin IR
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Solifenacin		Oxybutynin IR
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/68 (4.4%)		0/64 (0%)
Injury, poisoning and procedural complications
fracture, right foot	1/68 (1.5%)	1	0/64 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cervical adenocarcinoma in situ	1/68 (1.5%)	1	0/64 (0%)	0
Psychiatric disorders
Worsening depression	1/68 (1.5%)	1	0/64 (0%)	0
Other (Not Including Serious) Adverse Events
	Solifenacin		Oxybutynin IR
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/68 (52.9%)		56/64 (87.5%)
Eye disorders
Dry Eye	0/68 (0%)	0	3/64 (4.7%)	3
Gastrointestinal disorders
Constipation	9/68 (13.2%)	10	4/64 (6.3%)	4
Dry Mouth	24/68 (35.3%)	25	53/64 (82.8%)	56
Dysphagia	1/68 (1.5%)	1	5/64 (7.8%)	5
General disorders
Fatigue	4/68 (5.9%)	4	6/64 (9.4%)	6
Infections and infestations
Nasopharyngitis	0/68 (0%)	0	3/64 (4.7%)	3
Urinary tract infection	3/68 (4.4%)	5	3/64 (4.7%)	3
Nervous system disorders
Dizziness	2/68 (2.9%)	2	6/64 (9.4%)	6
Headache	2/68 (2.9%)	2	4/64 (6.3%)	4
Somnolence	1/68 (1.5%)	1	3/64 (4.7%)	3
Respiratory, thoracic and mediastinal disorders
Cough	1/68 (1.5%)	1	3/64 (4.7%)	3
Dry throat	0/68 (0%)	0	3/64 (4.7%)	3
Dysphonia	0/68 (0%)	0	5/64 (7.8%)	6
Nasal dryness	0/68 (0%)	0	9/64 (14.1%)	9
Skin and subcutaneous tissue disorders
Dry skin	0/68 (0%)	0	3/64 (4.7%)	3

Limitations/Caveats

The relatively high incidence of AEs, specifically dry mouth, in both groups may be a result of the direct questioning methodology used. Subjects were also informed the primary objectives were the relative frequency and severity of dry mouth.

More Information

Certain Agreements

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

PIs may not present or publish data prior to publication of the multicenter data or 12 months have elapsed following database lock. Sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period of up to 90 days from the time submitted to the sponsor for review. PIs may not engage in contacts with the media related to the study, study interventions or data without prior written consent.