BOTOX® Intravesical Instillation in Participants With Ove... | NCT03320850

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
100U cohort - BOTOX® plus Hydrogel admixture	Experimental	100U BOTOX® (onabotulinumtoxinA) and Hydrogel admixture administered as a single intravesical instillation on Day 1	Drug: OnabotulinumtoxinA and Hydrogel admixture
100U cohort - Placebo plus Hydrogel admixture	Placebo Comparator	Placebo and Hydrogel admixture administered as a single intravesical instillation on Day 1	Drug: Placebo and Hydrogel admixture
300U cohort - BOTOX® plus Hydrogel admixture	Experimental	300U BOTOX® (onabotulinumtoxinA) and Hydrogel admixture administered as a single intravesical instillation on Day 1	Drug: OnabotulinumtoxinA and Hydrogel admixture
300U cohort - Placebo plus Hydrogel admixture	Placebo Comparator	Placebo and Hydrogel admixture administered as a single intravesical instillation on Day 1	Drug: Placebo and Hydrogel admixture
400U cohort - BOTOX® plus Hydrogel admixture	Experimental	400U BOTOX® (onabotulinumtoxinA) and Hydrogel admixture administered as a single intravesical instillation on Day 1

Interventions

Name	Type	Description	Arm Group Labels	Other Names
OnabotulinumtoxinA and Hydrogel admixture	Drug	BOTOX® (onabotulinumtoxinA) and Hydrogel admixture administered as a single intravesical instillation	100U cohort - BOTOX® plus Hydrogel admixture

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Stage 2: Change From Baseline in the Average Number of Urinary Incontinence Episodes (UIEs) Per Day	The participant recorded urinary incontinence (lack of voluntary control over urination) in a 3-day bladder diary. The average number of UIEs per day is the average of the 3-day diary entries. A negative change from Baseline indicates improvement. Baseline is defined as the last non-missing assessment before the first dose of study treatment. An analysis of covariance (ANCOVA) model was used for analyses.	Baseline (3 consecutive days during Day -14 to Day -1) to 3 consecutive days in the Week prior to Week 12
Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAEs) in the Treatment Period	An adverse event (AE) is any untoward medical occurrence in a participants or clinical study investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. A TEAE is an AE that occurs or worsens after receiving study drug.	Up to End of Study (Stage 1: Up to 114 days and Stage 2: Up to 35.1 weeks)

Secondary Outcomes

Measure	Description	Time Frame
Stage 2: Change From Baseline in the Average Number of Micturition Episodes Per Day	The participant recorded the number of micturition (urination in toilet or catherization) episodes per day in a 3-day bladder diary. The average number of micturition episodes per day is the average of the 3-day diary entries. A negative change from Baseline indicates improvement. Baseline is defined as the last non-missing assessment before the first dose of study treatment. ANCOVA model was used for analyses.

Name	Affiliation	Role
Till Geib	Allergan	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of Alabama at Birmingham		Birmingham	Alabama	35249	United States
Coastal Clinical Research, Inc., an AMR company

Label	URL
Additional information on study locations near you may be found at AllerganClinicalTrials.com.	View source

ID	Title	Description
FG000	Stage 1: Placebo + Hydrogel Admixture	BOTOX® matching-placebo and hydrogel admixture administered as a single intravesical instillation on Day 1.
FG001	Stage 1: BOTOX® 100U + Hydrogel Admixture

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Dec 20, 2018	Jul 21, 2021

Arm/Group Information

ID	Title	Description
BG000	Stage 1: Placebo + Hydrogel Admixture	BOTOX® matching-placebo and hydrogel admixture administered as a single intravesical instillation on Day 1.
BG001	Stage 1: BOTOX® 100U + Hydrogel Admixture	BOTOX® 100 units (U) (onabotulinumtoxinA; botulinum toxin Type A) and hydrogel admixture administered as a single intravesical instillation on Day 1.
BG002	Stage 1: BOTOX® 300U + Hydrogel Admixture	BOTOX® 300U (onabotulinumtoxinA) and hydrogel admixture administered as a single intravesical instillation on Day 1.
BG003	Stage 1: BOTOX® 400U + Hydrogel Admixture	BOTOX® 400U (onabotulinumtoxinA) and hydrogel admixture administered as a single intravesical instillation on Day 1.
BG004	Stage 1: BOTOX® 500U + Hydrogel Admixture	BOTOX® 500U (onabotulinumtoxinA) and hydrogel admixture administered as a single intravesical instillation on Day 1.
BG005	Stage 2: Placebo + Hydrogel Admixture	BOTOX® matching-placebo and hydrogel admixture administered as a single intravesical instillation on Day 1.
BG006	Stage 2: BOTOX® 100U + Hydrogel Admixture	BOTOX® 100U (onabotulinumtoxinA) and hydrogel admixture administered as a single intravesical instillation on Day 1.
BG007	Stage 2: BOTOX® 300U + Hydrogel Admixture	BOTOX® 300U (onabotulinumtoxinA) and hydrogel admixture administered as a single intravesical instillation on Day 1.
BG008	Stage 2: BOTOX® 400U + Hydrogel Admixture	BOTOX® 400U (onabotulinumtoxinA) and hydrogel admixture administered as a single intravesical instillation on Day 1.
BG009	Stage 2: BOTOX® 500U + Hydrogel Admixture	BOTOX® 500U (onabotulinumtoxinA) and hydrogel admixture administered as a single intravesical instillation on Day 1.
BG010	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Stage 1: Safety Analysis Set included all participants who were randomized and treated.

Mean

Standard Deviation

years

Title	Denominators	Categories
	ParticipantsBG00018 ParticipantsBG00112 ParticipantsBG00218 ParticipantsBG003

Age, Continuous

Stage 2: Intent-to-treat (ITT) Analysis Set included all randomized participants.

Mean

Standard Deviation

years

Title	Denominators	Categories
	ParticipantsBG0000 ParticipantsBG0010 ParticipantsBG002

Sex: Female, Male

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00018 ParticipantsBG00112 ParticipantsBG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00018 ParticipantsBG00112 ParticipantsBG002

Race (NIH/OMB)

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00018 ParticipantsBG00112 ParticipantsBG002

Stage 1: Average Number of Urinary Incontinence Episodes (UIE)

The participant recorded urinary incontinence (lack of voluntary control over urination) in a 3-day bladder diary. The average number of urinary incontinence episodes per day is the average of the 3-day diary entries.

Safety Analysis Set included all participants who were randomized and treated in Stage 1.

Mean

Standard Deviation

episodes per day

Title	Denominators	Categories
	ParticipantsBG00018 ParticipantsBG00112

Stage 2: Average Number of Urinary Incontinence Episodes

ITT Analysis Set included all randomized participants in Stage 2. Overall number analyzed is the number of participants with data available for analyses at the Baseline.

Mean

Standard Deviation

episodes per day

Title	Denominators	Categories
	ParticipantsBG0000 ParticipantsBG001

Stage 1: Average Number of Micturition Episodes per Day

Safety Analysis Set included all participants who were randomized and treated in Stage 1.

Mean

Standard Deviation

episodes per day

Title	Denominators	Categories
	ParticipantsBG00018 ParticipantsBG00112

Stage 2: Average Number of Micturition Episodes per Day

ITT Analysis Set included all randomized participants in Stage 2. Overall number analyzed is the number of participants with data available for analyses at the Baseline.

Mean

Standard Deviation

episodes per day

Title	Denominators	Categories
	ParticipantsBG0000 ParticipantsBG001

Stage 1: Average Volume Voided per Micturition

Volume voided per micturition was recorded over one 24-hour period during the 3-day bladder diary.

Safety Analysis Set included all participants who were randomized and treated in Stage 1.

Mean

Standard Deviation

milliliter (mL)

Title	Denominators	Categories
	ParticipantsBG00018 ParticipantsBG00112 ParticipantsBG002

Stage 2: Average Volume Voided per Micturition

Volume voided per micturition was recorded over one 24-hour period during the 3-day bladder diary.

ITT Analysis Set included all randomized participants in Stage 2. Overall number analyzed is the number of participants with data available for analyses at the Baseline.

Mean

Standard Deviation

Title	Denominators	Categories
	ParticipantsBG0000 ParticipantsBG0010 ParticipantsBG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Stage 2: Change From Baseline in the Average Number of Urinary Incontinence Episodes (UIEs) Per Day

The participant recorded urinary incontinence (lack of voluntary control over urination) in a 3-day bladder diary. The average number of UIEs per day is the average of the 3-day diary entries. A negative change from Baseline indicates improvement. Baseline is defined as the last non-missing assessment before the first dose of study treatment. An analysis of covariance (ANCOVA) model was used for analyses.

Participants from the Intent-to-treat (ITT) Analysis Set, all randomized participants in Stage 2, with data available for analysis at Baseline and Week 12. As per protocol, this endpoint is only applicable to the Stage 2 arms.

Posted

Least Squares Mean

Standard Error

episodes per day

Baseline (3 consecutive days during Day -14 to Day -1) to 3 consecutive days in the Week prior to Week 12

ID	Title	Description
OG000	Stage 2: Placebo + Hydrogel Admixture	BOTOX® matching-placebo and hydrogel admixture administered as a single intravesical instillation on Day 1.
OG001	Stage 2: BOTOX® 100U + Hydrogel Admixture	BOTOX® 100U (onabotulinumtoxinA) and hydrogel admixture administered as a single intravesical instillation on Day 1.
OG002	Stage 2: BOTOX® 300U + Hydrogel Admixture	BOTOX® 300U (onabotulinumtoxinA) and hydrogel admixture administered as a single intravesical instillation on Day 1.
OG003	Stage 2: BOTOX® 400U + Hydrogel Admixture	BOTOX® 400U (onabotulinumtoxinA) and hydrogel admixture administered as a single intravesical instillation on Day 1.
OG004	Stage 2: BOTOX® 500U + Hydrogel Admixture	BOTOX® 500U (onabotulinumtoxinA) and hydrogel admixture administered as a single intravesical instillation on Day 1.

Units	Counts
Participants	OG00057 OG00157 OG00260 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-2.72± 0.534 OG001-1.62± 0.539 OG002-0.89± 0.521 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The null hypothesis is that there is no difference between each (BOTOX® and Hydrogel admixture group) and (placebo and Hydrogel admixture) in the mean change from Baseline in daily average number of UIEs at Week 12.	ANCOVA		0.0845		Least Squares Mean Difference	1.10	Standard Error of the Mean	0.635	2-Sided	95	-0.15	2.35			Least square estimates and contrast t-test were used to compare specified treatment groups and were based on ANCOVA model with Baseline value as covariate and treatment group, sex (male, female) as factors.		Superiority

Primary

Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAEs) in the Treatment Period

An adverse event (AE) is any untoward medical occurrence in a participants or clinical study investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. A TEAE is an AE that occurs or worsens after receiving study drug.

Safety Analysis Set included all randomized and treated participants in Stages 1 and 2.

Posted

Count of Participants

Participants

Up to End of Study (Stage 1: Up to 114 days and Stage 2: Up to 35.1 weeks)

ID	Title	Description
OG000	Stage 1: Placebo + Hydrogel Admixture	BOTOX® matching-placebo and hydrogel admixture administered as a single intravesical instillation on Day 1.
OG001	Stage 1: BOTOX® 100U + Hydrogel Admixture	BOTOX® 100 units (U) (onabotulinumtoxinA; botulinum toxin Type A) and hydrogel admixture administered as a single intravesical instillation on Day 1.
OG002	Stage 1: BOTOX® 300U + Hydrogel Admixture

Secondary

Stage 2: Change From Baseline in the Average Number of Micturition Episodes Per Day

The participant recorded the number of micturition (urination in toilet or catherization) episodes per day in a 3-day bladder diary. The average number of micturition episodes per day is the average of the 3-day diary entries. A negative change from Baseline indicates improvement. Baseline is defined as the last non-missing assessment before the first dose of study treatment. ANCOVA model was used for analyses.

Participants from the ITT Analysis Set, all randomized participants in Stage 2, with data available for analysis at Baseline and Week 12. As per protocol, this endpoint is only applicable to the Stage 2 arms.

Posted

Least Squares Mean

Standard Error

episodes per day

Baseline (3 consecutive days during Days -14 to Day -1) to 3 consecutive days in the Week prior to Week 12

ID	Title	Description
OG000	Stage 2: Placebo + Hydrogel Admixture	BOTOX® matching-placebo and hydrogel admixture administered as a single intravesical instillation on Day 1.
OG001	Stage 2: BOTOX® 100U + Hydrogel Admixture	BOTOX® 100U (onabotulinumtoxinA) and hydrogel admixture administered as a single intravesical instillation on Day 1.
OG002	Stage 2: BOTOX® 300U + Hydrogel Admixture

Secondary

Stage 2: Change From Baseline in the Average Volume Voided Per Micturition

Volume voided per micturition was recorded over one 24-hour period during the 3-day bladder diary. The volume voided during each 24-hour period was divided by the number of micturitions during the period. The average volume voided per micturition is the average of the 3-day diary entries. A negative change from Baseline indicates improvement. Baseline is defined as the last non-missing assessment before the first dose of study treatment. ANCOVA model was used for analyses.

Posted

Least Squares Mean

Standard Error

Baseline (3 consecutive days during Days -14 to Day -1) to 3 consecutive days in the Week prior to Week 12

ID	Title	Description
OG000	Stage 2: Placebo + Hydrogel Admixture	BOTOX® matching-placebo and hydrogel admixture administered as a single intravesical instillation on Day 1.
OG001	Stage 2: BOTOX® 100U + Hydrogel Admixture	BOTOX® 100U (onabotulinumtoxinA) and hydrogel admixture administered as a single intravesical instillation on Day 1.
OG002	Stage 2: BOTOX® 300U + Hydrogel Admixture

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Stage 1: Placebo + Hydrogel Admixture	BOTOX® matching-placebo and hydrogel admixture administered as a single intravesical instillation on Day 1.	18	0	18	6	18
EG001	Stage 1: BOTOX® 100U + Hydrogel Admixture	BOTOX® 100 units (U) (onabotulinumtoxinA; botulinum toxin Type A) and hydrogel admixture administered as a single intravesical instillation on Day 1.	12	0	12	4	12
EG002	Stage 1: BOTOX® 300U + Hydrogel Admixture	BOTOX® 300U (onabotulinumtoxinA) and hydrogel admixture administered as a single intravesical instillation on Day 1.	18	0	18	4	18
EG003	Stage 1: BOTOX® 400U + Hydrogel Admixture	BOTOX® 400U (onabotulinumtoxinA) and hydrogel admixture administered as a single intravesical instillation on Day 1.	22	0	22	4	22
EG004	Stage 1: BOTOX® 500U + Hydrogel Admixture	BOTOX® 500U (onabotulinumtoxinA) and hydrogel admixture administered as a single intravesical instillation on Day 1.	19	0	19	6	19
EG005	Stage 2: Placebo + Hydrogel Admixture	BOTOX® matching-placebo and hydrogel admixture administered as a single intravesical instillation on Day 1.	58	1	57	10	57
EG006	Stage 2: BOTOX® 100U + Hydrogel Admixture	BOTOX® 100U (onabotulinumtoxinA) and hydrogel admixture administered as a single intravesical instillation on Day 1.	57	3	57	17	57
EG007	Stage 2: BOTOX® 300U + Hydrogel Admixture	BOTOX® 300U (onabotulinumtoxinA) and hydrogel admixture administered as a single intravesical instillation on Day 1.	60	1	60	17	60
EG008	Stage 2: BOTOX® 400U + Hydrogel Admixture	BOTOX® 400U (onabotulinumtoxinA) and hydrogel admixture administered as a single intravesical instillation on Day 1.	60	2	60	16	60
EG009	Stage 2: BOTOX® 500U + Hydrogel Admixture	BOTOX® 500U (onabotulinumtoxinA) and hydrogel admixture administered as a single intravesical instillation on Day 1.	59	0	58	19	58

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Supraventricular tachycardia	Cardiac disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected18 at risk EG0010 affected12 at risk EG0020 affected18 at risk EG0030 affected22 at risk EG0040 affected19 at risk EG0050 affected57 at risk EG0061 affected57 at risk EG0070 affected60 at risk EG0080 affected60 at risk EG0090 affected58 at risk
Cellulitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected18 at risk EG0010 affected12 at risk EG0020 affected18 at risk EG003
Influenza	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected18 at risk EG0010 affected12 at risk EG0020 affected18 at risk EG003
Road traffic accident	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0000 affected18 at risk EG0010 affected12 at risk EG0020 affected18 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0000 affected18 at risk EG0010 affected12 at risk EG0020 affected18 at risk EG003
Hip fracture	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0000 affected18 at risk EG0010 affected12 at risk EG0020 affected18 at risk EG003
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.1	Systematic Assessment	EG0000 affected18 at risk EG0010 affected12 at risk EG0020 affected18 at risk EG003
Cerebrovascular accident	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected18 at risk EG0010 affected12 at risk EG0020 affected18 at risk EG003
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected18 at risk EG0010 affected12 at risk EG0020 affected18 at risk EG003
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected18 at risk EG0010 affected12 at risk EG0020 affected18 at risk EG003
Peripheral artery thrombosis	Vascular disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected18 at risk EG0010 affected12 at risk EG0020 affected18 at risk EG003
Peripheral vascular disorder	Vascular disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected18 at risk EG0010 affected12 at risk EG0020 affected18 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Abdominal pain	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment		EG0000 affected18 at risk EG0011 affected12 at risk EG0020 affected18 at risk EG0030 affected22 at risk EG0040 affected19 at risk EG0050 affected57 at risk EG0060 affected57 at risk EG0070 affected60 at risk EG0080 affected60 at risk EG0090 affected58 at risk
Vomiting	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment		EG0000 affected18 at risk EG0011 affected12 at risk EG0020 affected18 at risk EG003
Gastric ulcer	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment		EG0000 affected18 at risk EG0010 affected12 at risk EG0020 affected18 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment		EG0000 affected18 at risk EG0010 affected12 at risk EG0020 affected18 at risk EG003
Asthenia	General disorders	MedDRA 21.1	Systematic Assessment		EG0000 affected18 at risk EG0011 affected12 at risk EG0020 affected18 at risk EG003
Instillation site discomfort	General disorders	MedDRA 21.1	Systematic Assessment		EG0000 affected18 at risk EG0010 affected12 at risk EG0020 affected18 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 21.1	Systematic Assessment		EG0001 affected18 at risk EG0010 affected12 at risk EG0020 affected18 at risk EG003
Asymptomatic bacteriuria	Infections and infestations	MedDRA 21.1	Systematic Assessment		EG0001 affected18 at risk EG0010 affected12 at risk EG0020 affected18 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 21.1	Systematic Assessment		EG0000 affected18 at risk EG0010 affected12 at risk EG0021 affected18 at risk EG003
Vulvovaginal mycotic infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	Number of participants at risk are Female participants as this adverse event is specific to Females.	EG0000 affected17 at risk EG0010 affected12 at risk EG0020 affected15 at risk EG003
Bronchitis	Infections and infestations	MedDRA 21.1	Systematic Assessment		EG0000 affected18 at risk EG0010 affected12 at risk EG0020 affected18 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 21.1	Systematic Assessment		EG0000 affected18 at risk EG0010 affected12 at risk EG0020 affected18 at risk EG003
Pneumonia	Infections and infestations	MedDRA 21.1	Systematic Assessment		EG0000 affected18 at risk EG0010 affected12 at risk EG0020 affected18 at risk EG003
Bacteriuria	Infections and infestations	MedDRA 21.1	Systematic Assessment		EG0000 affected18 at risk EG0010 affected12 at risk EG0020 affected18 at risk EG003
Acetonaemia	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment		EG0000 affected18 at risk EG0010 affected12 at risk EG0020 affected18 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment		EG0000 affected18 at risk EG0010 affected12 at risk EG0020 affected18 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment		EG0001 affected18 at risk EG0010 affected12 at risk EG0020 affected18 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment		EG0000 affected18 at risk EG0010 affected12 at risk EG0020 affected18 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA 21.1	Systematic Assessment		EG0000 affected18 at risk EG0011 affected12 at risk EG0020 affected18 at risk EG003
Headache	Nervous system disorders	MedDRA 21.1	Systematic Assessment		EG0000 affected18 at risk EG0011 affected12 at risk EG0020 affected18 at risk EG003
Leukocyturia	Renal and urinary disorders	MedDRA 21.1	Systematic Assessment		EG0001 affected18 at risk EG0010 affected12 at risk EG0021 affected18 at risk EG003
Proteinuria	Renal and urinary disorders	MedDRA 21.1	Systematic Assessment		EG0001 affected18 at risk EG0010 affected12 at risk EG0020 affected18 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA 21.1	Systematic Assessment		EG0000 affected18 at risk EG0011 affected12 at risk EG0020 affected18 at risk EG003
Urethral pain	Renal and urinary disorders	MedDRA 21.1	Systematic Assessment		EG0000 affected18 at risk EG0010 affected12 at risk EG0021 affected18 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA 21.1	Systematic Assessment		EG0000 affected18 at risk EG0010 affected12 at risk EG0020 affected18 at risk EG003
Pelvic pain	Reproductive system and breast disorders	MedDRA 21.1	Systematic Assessment		EG0001 affected18 at risk EG0010 affected12 at risk EG0020 affected18 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment		EG0000 affected18 at risk EG0010 affected12 at risk EG0020 affected18 at risk EG003
Dermatitis allergic	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment		EG0000 affected18 at risk EG0010 affected12 at risk EG0021 affected18 at risk EG003
Night sweats	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment		EG0000 affected18 at risk EG0010 affected12 at risk EG0021 affected18 at risk EG003
Hypertension	Vascular disorders	MedDRA 21.1	Systematic Assessment		EG0001 affected18 at risk EG0011 affected12 at risk EG0020 affected18 at risk EG003

ID	Term
D014555	Urination Disorders
D014570	Urologic Diseases
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D052801	Male Urogenital Diseases
D059411	Lower Urinary Tract Symptoms
D020924	Urological Manifestations
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D001905	Botulinum Toxins
D008666	Metalloendopeptidases
D010450	Endopeptidases
D010447	Peptide Hydrolases
D006867	Hydrolases
D004798	Enzymes
D045762	Enzymes and Coenzymes
D045726	Metalloproteases
D001426	Bacterial Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D001427	Bacterial Toxins
D014118	Toxins, Biological
D001685	Biological Factors