Trial Outcomes & Findings for Safety and Efficacy Study of OnabotulinumtoxinA for the Treatment of Urinary Incontinence Due to Neurogenic Detrusor Overactivity (NDO) in Non-Catheterizing Patients With Multiple Sclerosis (MS) (NCT NCT01600716)

Last Updated: 2019-04-30

Results Overview

Incontinence is defined as involuntary loss of urine as recorded in a patient bladder diary. The number of episodes of urinary incontinence is recorded over a 3-day period the week of the study visit. A negative number change from baseline indicates a reduction in incontinence episodes (improvement) and a positive number change indicates an increase in incontinence episodes (worsening).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

144 participants

Primary outcome timeframe

Baseline, Week 6

Results posted on

2019-04-30

Participant Flow

Participant milestones

Participant milestones
Measure	OnabotulinumtoxinA OnabotulinumtoxinA 100 U is administered into the detrusor at Day 1. After a minimum of 12 weeks, patients could request/qualify for a second onabotulinumtoxinA injection.	Placebo (Normal Saline) Placebo (normal saline) is administered into the detrusor at Day 1. After a minimum of 12 weeks, patients could request/qualify for an onabotulinumtoxinA injection.
Overall Study STARTED	66	78
Overall Study COMPLETED	59	71
Overall Study NOT COMPLETED	7	7

Reasons for withdrawal

Reasons for withdrawal
Measure	OnabotulinumtoxinA OnabotulinumtoxinA 100 U is administered into the detrusor at Day 1. After a minimum of 12 weeks, patients could request/qualify for a second onabotulinumtoxinA injection.	Placebo (Normal Saline) Placebo (normal saline) is administered into the detrusor at Day 1. After a minimum of 12 weeks, patients could request/qualify for an onabotulinumtoxinA injection.
Overall Study Other Reasons	3	1
Overall Study Personal Reasons	0	2
Overall Study Lost to Follow-up	0	2
Overall Study Pregnancy	1	0
Overall Study Lack of Efficacy	2	1
Overall Study Adverse Event	1	1

Baseline Characteristics

Safety and Efficacy Study of OnabotulinumtoxinA for the Treatment of Urinary Incontinence Due to Neurogenic Detrusor Overactivity (NDO) in Non-Catheterizing Patients With Multiple Sclerosis (MS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	OnabotulinumtoxinA n=66 Participants OnabotulinumtoxinA 100 U is administered into the detrusor at Day 1. After a minimum of 12 weeks, patients could request/qualify for a second onabotulinumtoxinA injection.	Placebo (Normal Saline) n=78 Participants Placebo (normal saline) is administered into the detrusor at Day 1. After a minimum of 12 weeks, patients could request/qualify for an onabotulinumtoxinA injection.	Total n=144 Participants Total of all reporting groups
Age, Customized <65 years	62 Participants n=5 Participants	71 Participants n=7 Participants	133 Participants n=5 Participants
Age, Customized ≥65 years	4 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants
Sex: Female, Male Female	57 Participants n=5 Participants	70 Participants n=7 Participants	127 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 6

Population: Intent-to-Treat Population: all randomized patients

Outcome measures

Outcome measures
Measure	OnabotulinumtoxinA n=66 Participants OnabotulinumtoxinA 100 U is administered into the detrusor at Day 1. After a minimum of 12 weeks, patients could request/qualify for a second onabotulinumtoxinA injection.	Placebo (Normal Saline) n=78 Participants Placebo (normal saline) is administered into the detrusor at Day 1. After a minimum of 12 weeks, patients could request/qualify for an onabotulinumtoxinA injection.
Change From Baseline in Daily Average Frequency of Urinary Incontinence Episodes Baseline	4.18 Episodes Standard Deviation 3.167	4.32 Episodes Standard Deviation 2.422
Change From Baseline in Daily Average Frequency of Urinary Incontinence Episodes Change from Baseline at Week 6	-3.34 Episodes Standard Deviation 2.881	-1.10 Episodes Standard Deviation 2.083

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: Intent-to-Treat Population: all randomized patients with data at the time points

MCC represents the maximum volume of urine the bladder holds. A positive number change from baseline represents an improvement (increase) in the maximum volume of urine the bladder holds and a negative number change from baseline represents a worsening (decrease) in the maximum volume of urine the bladder holds.

Outcome measures

Outcome measures
Measure	OnabotulinumtoxinA n=65 Participants OnabotulinumtoxinA 100 U is administered into the detrusor at Day 1. After a minimum of 12 weeks, patients could request/qualify for a second onabotulinumtoxinA injection.	Placebo (Normal Saline) n=78 Participants Placebo (normal saline) is administered into the detrusor at Day 1. After a minimum of 12 weeks, patients could request/qualify for an onabotulinumtoxinA injection.
Change From Baseline in Maximum Cystometric Capacity (MCC) Baseline	246.4 Milliliters (mL) Standard Deviation 138.49	245.7 Milliliters (mL) Standard Deviation 133.90
Change From Baseline in Maximum Cystometric Capacity (MCC) Change from Baseline at Week 6 (N=62,72)	127.2 Milliliters (mL) Standard Deviation 139.25	-1.8 Milliliters (mL) Standard Deviation 93.23

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: Intent-to-Treat Population: all randomized patients with data at the time points

Maximum detrusor pressure represents the maximum pressure (peak amplitude) in the bladder during the first involuntary contraction of the bladder muscle. A negative number change from baseline indicates an improvement in pressure and a positive number change from baseline indicates a worsening in pressure.

Outcome measures

Outcome measures
Measure	OnabotulinumtoxinA n=57 Participants OnabotulinumtoxinA 100 U is administered into the detrusor at Day 1. After a minimum of 12 weeks, patients could request/qualify for a second onabotulinumtoxinA injection.	Placebo (Normal Saline) n=69 Participants Placebo (normal saline) is administered into the detrusor at Day 1. After a minimum of 12 weeks, patients could request/qualify for an onabotulinumtoxinA injection.
Change From Baseline in Maximum Detrusor Pressure During the First Involuntary Detrusor Contraction (IDC) Change from Baseline at Week 6 (N=25,51)	-19.6 Centimeters of Water (cm H2O) Standard Deviation 37.61	3.7 Centimeters of Water (cm H2O) Standard Deviation 33.24
Change From Baseline in Maximum Detrusor Pressure During the First Involuntary Detrusor Contraction (IDC) Baseline	35.9 Centimeters of Water (cm H2O) Standard Deviation 34.90	36.1 Centimeters of Water (cm H2O) Standard Deviation 37.21

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: Intent-to-Treat Population: all randomized patients with data at the time points

The I-QOL is a validated, disease-specific quality of life (QOL) questionnaire containing 22 questions designed to measure impact of urinary incontinence on patients' lives. Each question is answered on a 5-point scale (1 = worst QOL, and 5 = best QOL). The scores are totaled over the 22 questions and normalized to a score of 0-100 (0=worst QOL and 100=best QOL). A positive change from baseline represents an improvement and a negative change from baseline represents a worsening.

Outcome measures

Outcome measures
Measure	OnabotulinumtoxinA n=58 Participants OnabotulinumtoxinA 100 U is administered into the detrusor at Day 1. After a minimum of 12 weeks, patients could request/qualify for a second onabotulinumtoxinA injection.	Placebo (Normal Saline) n=74 Participants Placebo (normal saline) is administered into the detrusor at Day 1. After a minimum of 12 weeks, patients could request/qualify for an onabotulinumtoxinA injection.
Change From Baseline in Incontinence Quality of Life Instrument (I-QOL) Total Summary Score Baseline	32.43 Scores on a Scale Standard Deviation 16.337	34.24 Scores on a Scale Standard Deviation 21.163
Change From Baseline in Incontinence Quality of Life Instrument (I-QOL) Total Summary Score Change from Baseline at Week 6 (N=55,68)	40.39 Scores on a Scale Standard Deviation 26.499	9.92 Scores on a Scale Standard Deviation 15.863

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 52 Weeks

Population: Intent-to-Treat Population: all randomized patients

The duration of treatment effect is the time to patient request for retreatment.

Outcome measures

Outcome measures
Measure	OnabotulinumtoxinA n=66 Participants OnabotulinumtoxinA 100 U is administered into the detrusor at Day 1. After a minimum of 12 weeks, patients could request/qualify for a second onabotulinumtoxinA injection.	Placebo (Normal Saline) n=78 Participants Placebo (normal saline) is administered into the detrusor at Day 1. After a minimum of 12 weeks, patients could request/qualify for an onabotulinumtoxinA injection.
Duration of Treatment Effect Through Week 52	51.7 Weeks Interval 36.9 to The upper confidence limit was not estimable since too few patients had requested retreatment prior to the end of the study.	12.6 Weeks Interval 12.3 to 13.0

Adverse Events

OnabotulinumtoxinA Treatment Cycle 1

Serious events: 7 serious events

Other events: 50 other events

Deaths: 0 deaths

Placebo (Normal Saline)

Serious events: 3 serious events

Other events: 44 other events

Deaths: 0 deaths

OnabotulinumtoxinA/OnabotulinumtoxinA Treatment Cycle 2

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

Placebo (Normal Saline)/OnabotulinumtoxinA

Serious events: 2 serious events

Other events: 38 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	OnabotulinumtoxinA Treatment Cycle 1 n=66 participants at risk OnabotulinumtoxinA 100 U is administered into the detrusor at Day 1. Median duration of exposure is 50.7 weeks.	Placebo (Normal Saline) n=78 participants at risk Placebo (normal saline) is administered into the detrusor at Day 1. Median duration of exposure is 15.2 weeks.	OnabotulinumtoxinA/OnabotulinumtoxinA Treatment Cycle 2 n=30 participants at risk OnabotulinumtoxinA 100 U is administered into the detrusor at Day 1. After a minimum of 12 weeks, a second onabotulinumtoxinA injection is given. Median duration of exposure is 12.5 weeks.	Placebo (Normal Saline)/OnabotulinumtoxinA n=67 participants at risk Placebo (normal saline) is administered into the detrusor at Day 1. After a minimum of 12 weeks, an onabotulinumtoxinA injection is given. Median duration of exposure is 12.2 weeks.
Cardiac disorders Acute Coronary Syndrome	1.5% 1/66 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/78 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/30 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/67 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).
Infections and infestations Urinary Tract Infection	4.5% 3/66 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/78 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/30 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/67 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).
Infections and infestations Infectious Colitis	0.00% 0/66 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	1.3% 1/78 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/30 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/67 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).
Injury, poisoning and procedural complications Spinal Compression Fracture	1.5% 1/66 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	1.3% 1/78 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/30 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/67 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).
Injury, poisoning and procedural complications Fall	1.5% 1/66 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/78 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/30 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	1.5% 1/67 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).
Musculoskeletal and connective tissue disorders Muscular Weakness	1.5% 1/66 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/78 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/30 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/67 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).
Nervous system disorders Multiple Sclerosis Relapse	0.00% 0/66 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	1.3% 1/78 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/30 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/67 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).
General disorders Pyrexia	1.5% 1/66 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/78 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/30 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/67 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).
Renal and urinary disorders Dysuria	1.5% 1/66 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/78 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/30 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/67 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).
Nervous system disorders Multiple sclerosis	0.00% 0/66 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/78 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/30 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	1.5% 1/67 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).

Other adverse events

Additional Information

Therapeutic Area Head,

Allergan, Inc

Phone: 714-246-4500

Email: [email protected]

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

Measure	OnabotulinumtoxinA Treatment Cycle 1 n=66 participants at risk OnabotulinumtoxinA 100 U is administered into the detrusor at Day 1. Median duration of exposure is 50.7 weeks.	Placebo (Normal Saline) n=78 participants at risk Placebo (normal saline) is administered into the detrusor at Day 1. Median duration of exposure is 15.2 weeks.	OnabotulinumtoxinA/OnabotulinumtoxinA Treatment Cycle 2 n=30 participants at risk OnabotulinumtoxinA 100 U is administered into the detrusor at Day 1. After a minimum of 12 weeks, a second onabotulinumtoxinA injection is given. Median duration of exposure is 12.5 weeks.	Placebo (Normal Saline)/OnabotulinumtoxinA n=67 participants at risk Placebo (normal saline) is administered into the detrusor at Day 1. After a minimum of 12 weeks, an onabotulinumtoxinA injection is given. Median duration of exposure is 12.2 weeks.
Infections and infestations Urinary tract infection	39.4% 26/66 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	11.5% 9/78 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	30.0% 9/30 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	25.4% 17/67 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).
Renal and urinary disorders Urinary Retention	16.7% 11/66 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	3.8% 3/78 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	20.0% 6/30 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	13.4% 9/67 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).
Investigations Residual Urine Volume	16.7% 11/66 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	2.6% 2/78 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	3.3% 1/30 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	7.5% 5/67 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).
Infections and infestations Bacteriuria	18.2% 12/66 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	7.7% 6/78 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	10.0% 3/30 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	9.0% 6/67 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).
Renal and urinary disorders Leukocyturia	6.1% 4/66 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	7.7% 6/78 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	3.3% 1/30 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	3.0% 2/67 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).
Renal and urinary disorders Dysuria	9.1% 6/66 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	1.3% 1/78 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	10.0% 3/30 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	1.5% 1/67 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).
Renal and urinary disorders Haematuria	4.5% 3/66 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	7.7% 6/78 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/30 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	3.0% 2/67 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).
Gastrointestinal disorders Diarrhoea	1.5% 1/66 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	5.1% 4/78 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	3.3% 1/30 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/67 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).
Infections and infestations Nasopharyngitis	6.1% 4/66 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	1.3% 1/78 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/30 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/67 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).
Renal and urinary disorders Renal Cyst	4.5% 3/66 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	3.8% 3/78 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	10.0% 3/30 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	1.5% 1/67 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).
Psychiatric disorders Insomnia	0.00% 0/66 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	1.3% 1/78 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	6.7% 2/30 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/67 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).
Renal and urinary disorders Micturition Urgency	3.0% 2/66 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/78 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	6.7% 2/30 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/67 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).
Nervous system disorders Multiple Sclerosis Relapse	0.00% 0/66 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	2.6% 2/78 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	6.7% 2/30 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/67 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).
Renal and urinary disorders Pollakiuria	3.0% 2/66 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/78 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	6.7% 2/30 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/67 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).
Renal and urinary disorders Urine Abnormality	1.5% 1/66 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/78 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	6.7% 2/30 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/67 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).
Renal and urinary disorders Urine Odour Abnormal	1.5% 1/66 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/78 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	6.7% 2/30 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).	0.00% 0/67 Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).