Trial Outcomes & Findings for ADSTILADRIN (=INSTILADRIN) in Patients With High-Grade, Bacillus Calmette-Guerin (BCG) Unresponsive Non-Muscle Invasive Bladder Cancer (NMIBC) (NCT NCT02773849)

Last Updated: 2024-07-29

Results Overview

A patient in the CIS cohort was judged to have achieved CR where urine cytology was reported as normal, atypical, degenerative, reactive, inflammatory, or nonspecific AND cystoscopy was reported as normal or with findings that did not include evidence of low-grade or high-grade recurrence. Bladder biopsy, if performed (not mandatory), demonstrated an absence of low-grade or high-grade recurrence.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

157 participants

Primary outcome timeframe

12 Months

Results posted on

2024-07-29

Participant Flow

Patients enrolled in the study who had at entry, confirmed by a pathology report: CIS only or Ta/T1 high- grade disease with concomitant CIS, or Ta/T1 high-grade disease without concomitant CIS and were "BCG unresponsive" which referred to patients with high-grade NMIBC who were unlikely to benefit from and who did not receive further intravesical BCG.

Participant milestones

Participant milestones
Measure	ADSTILADRIN Intravesical administration of ADSTILADRIN into the bladder
Overall Study STARTED	157
Overall Study COMPLETED	95
Overall Study NOT COMPLETED	62

Reasons for withdrawal

Reasons for withdrawal
Measure	ADSTILADRIN Intravesical administration of ADSTILADRIN into the bladder
Overall Study Lost to Follow-up	11
Overall Study Death	26
Overall Study Withdrawal by Subject	5
Overall Study Withdrawal of Consent	9
Overall Study Other: not due to lack of tolerability	11

Baseline Characteristics

ADSTILADRIN (=INSTILADRIN) in Patients With High-Grade, Bacillus Calmette-Guerin (BCG) Unresponsive Non-Muscle Invasive Bladder Cancer (NMIBC)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Carcinoma in Situ n=107 Participants Patients with Carcinoma in situ (CIS) with or without concomitant high-grade Ta or T1 papillary disease	Papillary Disease n=50 Participants Patients with high-grade Ta or T1 papillary disease (without concomitant CIS)	Total n=157 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	25 Participants n=5 Participants	13 Participants n=7 Participants	38 Participants n=5 Participants
Age, Categorical >=65 years	82 Participants n=5 Participants	37 Participants n=7 Participants	119 Participants n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	16 Participants n=7 Participants	28 Participants n=5 Participants
Sex: Female, Male Male	95 Participants n=5 Participants	34 Participants n=7 Participants	129 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	99 Participants n=5 Participants	49 Participants n=7 Participants	148 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) White	99 Participants n=5 Participants	47 Participants n=7 Participants	146 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	107 participants n=5 Participants	50 participants n=7 Participants	157 participants n=5 Participants
Height	174.7 cm STANDARD_DEVIATION 9.8 • n=5 Participants	170.9 cm STANDARD_DEVIATION 10.3 • n=7 Participants	173.5 cm STANDARD_DEVIATION 10.1 • n=5 Participants
Weight	90.14 kg STANDARD_DEVIATION 20.9 • n=5 Participants	85.88 kg STANDARD_DEVIATION 18.6 • n=7 Participants	88.78 kg STANDARD_DEVIATION 20.2 • n=5 Participants
Body Mass Index	29.38 kg/m^2 STANDARD_DEVIATION 5.7 • n=5 Participants	29.28 kg/m^2 STANDARD_DEVIATION 5.1 • n=7 Participants	29.34 kg/m^2 STANDARD_DEVIATION 5.5 • n=5 Participants
ECOG Status Total ECOG of 0	97 Participants n=5 Participants	43 Participants n=7 Participants	140 Participants n=5 Participants
ECOG Status Total ECOG of 1	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
ECOG Status Total ECOG of 2	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 Months

Population: Subjects analyzed for this endpoint represent subjects who were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Carcinoma in Situ n=103 Participants CIS participants had at entry, confirmed by a pathology report: Carcinoma in situ (CIS) only or Ta/T1 highgrade disease with concomitant CIS AND were "BCG unresponsive" which referred to patients with highgrade NMIBC who were unlikely to benefit from and who did not receive further intravesical BCG. The term "BCG unresponsive" included patients who did not respond to BCG treatment and had a persistent high-grade recurrence within 12 months after BCG was initiated, and those who, despite an initial CR to BCG, relapsed with CIS within 12 months of their last intravesical treatment with BCG or relapsed with high-grade Ta/T1 NMIBC within 6 months of their last intravesical treatment with BCG.	Papillary Disease Patients with high-grade Ta or T1 papillary disease (without concomitant CIS)	Total All Patients
Number of Patients With a Complete Response Rate Based on Patients With Carcinoma in Situ (CIS), With or Without Concomitant High-grade Ta or T1 Papillary Disease.	55 participants Interval 43.3 to 63.3	—	—

SECONDARY outcome

Timeframe: Up to 57 months

Population: Patients who achieved CR

Durability of complete response (CR) was defined as the time from first observed CR to the documented treatment failure. Patients without treatment failure were censored at the last disease assessment not showing treatment failure, where treatment failure was defined as high-grade disease recurrence, disease progression, or death, whichever occurred earlier.

Outcome measures

Outcome measures
Measure	Carcinoma in Situ n=55 Participants CIS participants had at entry, confirmed by a pathology report: Carcinoma in situ (CIS) only or Ta/T1 highgrade disease with concomitant CIS AND were "BCG unresponsive" which referred to patients with highgrade NMIBC who were unlikely to benefit from and who did not receive further intravesical BCG. The term "BCG unresponsive" included patients who did not respond to BCG treatment and had a persistent high-grade recurrence within 12 months after BCG was initiated, and those who, despite an initial CR to BCG, relapsed with CIS within 12 months of their last intravesical treatment with BCG or relapsed with high-grade Ta/T1 NMIBC within 6 months of their last intravesical treatment with BCG.	Papillary Disease Patients with high-grade Ta or T1 papillary disease (without concomitant CIS)	Total All Patients
Durability of Complete Response in Patients With CIS (With or Without Concomitant Ta or T1 Papillary Disease) Who Achieve a Complete Response.	9.72 Months Interval 9.17 to 23.95	—	—

SECONDARY outcome

Timeframe: up to 57 months

Population: A patient was judged to have achieved HGRF survival at a time point (eg, Months 3, 6, 9, and 12) if the patient was alive and without documented recurrence of high-grade disease or muscle-invasive disease progression as assessed by the Investigator at that time point.

Complete response rate will be measured by determining the number of patients without recurrence of high-grade disease using results from urine cytology, cystoscopy, and biopsy of the bladder. Incidence of HGRF survival at Months 3, 6, 9, and 12, and every 3 months up to Month 24, and then at Months 36, 48, and 57.

Outcome measures

Outcome measures
Measure	Carcinoma in Situ n=48 Participants CIS participants had at entry, confirmed by a pathology report: Carcinoma in situ (CIS) only or Ta/T1 highgrade disease with concomitant CIS AND were "BCG unresponsive" which referred to patients with highgrade NMIBC who were unlikely to benefit from and who did not receive further intravesical BCG. The term "BCG unresponsive" included patients who did not respond to BCG treatment and had a persistent high-grade recurrence within 12 months after BCG was initiated, and those who, despite an initial CR to BCG, relapsed with CIS within 12 months of their last intravesical treatment with BCG or relapsed with high-grade Ta/T1 NMIBC within 6 months of their last intravesical treatment with BCG.	Papillary Disease Patients with high-grade Ta or T1 papillary disease (without concomitant CIS)	Total All Patients
Rate of Event-free Survival, Where Event-free Survival is Defined as High-grade Recurrence Free (HGRF) Survival in Patients With High-grade Ta or T1 Disease (Without Concomitant CIS) Month 3	35 Participants	—	—
Rate of Event-free Survival, Where Event-free Survival is Defined as High-grade Recurrence Free (HGRF) Survival in Patients With High-grade Ta or T1 Disease (Without Concomitant CIS) Month 6	30 Participants	—	—
Rate of Event-free Survival, Where Event-free Survival is Defined as High-grade Recurrence Free (HGRF) Survival in Patients With High-grade Ta or T1 Disease (Without Concomitant CIS) Month 9	28 Participants	—	—
Rate of Event-free Survival, Where Event-free Survival is Defined as High-grade Recurrence Free (HGRF) Survival in Patients With High-grade Ta or T1 Disease (Without Concomitant CIS) Month 12	21 Participants	—	—
Rate of Event-free Survival, Where Event-free Survival is Defined as High-grade Recurrence Free (HGRF) Survival in Patients With High-grade Ta or T1 Disease (Without Concomitant CIS) Month 24	16 Participants	—	—
Rate of Event-free Survival, Where Event-free Survival is Defined as High-grade Recurrence Free (HGRF) Survival in Patients With High-grade Ta or T1 Disease (Without Concomitant CIS) Month 36	11 Participants	—	—
Rate of Event-free Survival, Where Event-free Survival is Defined as High-grade Recurrence Free (HGRF) Survival in Patients With High-grade Ta or T1 Disease (Without Concomitant CIS) Month 48	7 Participants	—	—
Rate of Event-free Survival, Where Event-free Survival is Defined as High-grade Recurrence Free (HGRF) Survival in Patients With High-grade Ta or T1 Disease (Without Concomitant CIS) Month 57	7 Participants	—	—

SECONDARY outcome

Timeframe: Up to 57 months

Population: Patients with no recurrence of high-grade disease

HGRF survival was defined as the time from the first dose to the first recurrence of high-grade disease (including muscle-invasive disease progression and death due to any cause). Patients without high-grade disease recurrence were censored at the last disease assessment not showing high-grade disease recurrence.

Outcome measures

Outcome measures
Measure	Carcinoma in Situ n=103 Participants CIS participants had at entry, confirmed by a pathology report: Carcinoma in situ (CIS) only or Ta/T1 highgrade disease with concomitant CIS AND were "BCG unresponsive" which referred to patients with highgrade NMIBC who were unlikely to benefit from and who did not receive further intravesical BCG. The term "BCG unresponsive" included patients who did not respond to BCG treatment and had a persistent high-grade recurrence within 12 months after BCG was initiated, and those who, despite an initial CR to BCG, relapsed with CIS within 12 months of their last intravesical treatment with BCG or relapsed with high-grade Ta/T1 NMIBC within 6 months of their last intravesical treatment with BCG.	Papillary Disease n=48 Participants Patients with high-grade Ta or T1 papillary disease (without concomitant CIS)	Total n=151 Participants All Patients
Durability of High-grade-recurrence-free Survival in Patients With High-grade Ta or T1 Papillary Disease (With or Without Concomitant CIS) HGRF Survival	5.95 Months Interval 3.38 to 8.31	12.35 Months Interval 6.67 to 20.27	7.31 Months Interval 5.68 to 11.93
Durability of High-grade-recurrence-free Survival in Patients With High-grade Ta or T1 Papillary Disease (With or Without Concomitant CIS) Probability of duration of HGRF survival for 57 months	13.2 Months Interval 6.9 to 21.5	32.7 Months Interval 19.5 to 46.6	19.0 Months Interval 12.6 to 26.4
Durability of High-grade-recurrence-free Survival in Patients With High-grade Ta or T1 Papillary Disease (With or Without Concomitant CIS) Probability of duration of HGRF survival for 48 months	16.7 Months Interval 10.1 to 24.9	32.7 Months Interval 19.5 to 46.6	21.6 Months Interval 15.2 to 28.8
Durability of High-grade-recurrence-free Survival in Patients With High-grade Ta or T1 Papillary Disease (With or Without Concomitant CIS) Probability of duration of HGRF survival for 36 months	19.3 Months Interval 12.2 to 27.6	32.7 Months Interval 19.5 to 46.6	23.6 Months Interval 17.0 to 30.8

SECONDARY outcome

Timeframe: 60 Months

Population: Proportion of patients undergoing cystectomy within 5 years, 2 years and 12 months

The incidence of cystectomy is described as the proportion of patients undergoing radical cystectomy for any reason after the first dose, within 12 months, 2 years and 5 years.

Outcome measures

Outcome measures
Measure	Carcinoma in Situ n=103 Participants CIS participants had at entry, confirmed by a pathology report: Carcinoma in situ (CIS) only or Ta/T1 highgrade disease with concomitant CIS AND were "BCG unresponsive" which referred to patients with highgrade NMIBC who were unlikely to benefit from and who did not receive further intravesical BCG. The term "BCG unresponsive" included patients who did not respond to BCG treatment and had a persistent high-grade recurrence within 12 months after BCG was initiated, and those who, despite an initial CR to BCG, relapsed with CIS within 12 months of their last intravesical treatment with BCG or relapsed with high-grade Ta/T1 NMIBC within 6 months of their last intravesical treatment with BCG.	Papillary Disease n=48 Participants Patients with high-grade Ta or T1 papillary disease (without concomitant CIS)	Total n=151 Participants All Patients
Incidence of Cystectomy at 12 Months, 2 Years and 5 Years 12 months	27 Participants	7 Participants	34 Participants
Incidence of Cystectomy at 12 Months, 2 Years and 5 Years 2 years	35 Participants	10 Participants	45 Participants
Incidence of Cystectomy at 12 Months, 2 Years and 5 Years 5 years	42 Participants	14 Participants	56 Participants

SECONDARY outcome

Timeframe: 60 Months

Overall survival rate was defined as the time from the first dose to death due to any cause. Patients who were still alive were censored at the last date the patient was known to be alive. Overall survival rate is a Kaplan-Meier estimate of the survivor function at each specific time point. The 95% CI is calculated using the Greenwood's formula with a log-log transformation. Percentage is calculated using the number of patients in the column heading as the denominator.

Outcome measures

Outcome measures
Measure	Carcinoma in Situ n=103 Participants CIS participants had at entry, confirmed by a pathology report: Carcinoma in situ (CIS) only or Ta/T1 highgrade disease with concomitant CIS AND were "BCG unresponsive" which referred to patients with highgrade NMIBC who were unlikely to benefit from and who did not receive further intravesical BCG. The term "BCG unresponsive" included patients who did not respond to BCG treatment and had a persistent high-grade recurrence within 12 months after BCG was initiated, and those who, despite an initial CR to BCG, relapsed with CIS within 12 months of their last intravesical treatment with BCG or relapsed with high-grade Ta/T1 NMIBC within 6 months of their last intravesical treatment with BCG.	Papillary Disease n=48 Participants Patients with high-grade Ta or T1 papillary disease (without concomitant CIS)	Total n=151 Participants All Patients
Overall Survival Rate in All Patients 3 months	100 percentage of patients 95% confidence interval could not be calculated due to an insufficient number of participants with events	100 percentage of patients 95% confidence interval could not be calculated due to an insufficient number of participants with events	100 percentage of patients 95% confidence interval could not be calculated due to an insufficient number of participants with events
Overall Survival Rate in All Patients 6 months	99 percentage of patients Interval 93.0 to 99.9	100 percentage of patients 95% confidence interval could not be calculated due to an insufficient number of participants with events	99.3 percentage of patients Interval 95.3 to 99.9
Overall Survival Rate in All Patients 9 months	98 percentage of patients Interval 92.2 to 99.5	100 percentage of patients 95% confidence interval could not be calculated due to an insufficient number of participants with events	98.6 percentage of patients Interval 94.7 to 99.7
Overall Survival Rate in All Patients 12 months	98 percentage of patients Interval 92.2 to 99.5	97.9 percentage of patients Interval 85.8 to 99.7	98 percentage of patients Interval 93.8 to 99.3
Overall Survival Rate in All Patients 24 months	94.9 percentage of patients Interval 88.1 to 97.8	93.5 percentage of patients Interval 81.2 to 97.9	94.5 percentage of patients Interval 89.2 to 97.2
Overall Survival Rate in All Patients 48 months	83.6 percentage of patients Interval 74.3 to 89.8	88.9 percentage of patients Interval 75.4 to 95.3	85.4 percentage of patients Interval 78.3 to 90.3
Overall Survival Rate in All Patients 60 months	76.3 percentage of patients Interval 64.6 to 84.5	85.9 percentage of patients Interval 70.9 to 93.5	79.7 percentage of patients Interval 71.0 to 86.0

SECONDARY outcome

Timeframe: 12 Months

Population: Patients with Positive Immunogenic Response in Anti-Adenoviral Antibodies at Post-Baseline based on patients who had achieved High-Grade Recurrence Free Survival at 12 months

Measurement of anti-adenoviral antibody levels at each dosing period, withdrawal, and at 12 months were done. A patient was considered to have a positive immunogenic response in anti-adenoviral antibodies if a post-baseline titration demonstrated a greater than a 2-fold dilution increase from baseline. The table represent data at any time during the 12 months period, which means that the patients were included in the Yes group if they at any measurement during the trial had a 2-fold dilution increase from baseline.

Outcome measures

Outcome measures
Measure	Carcinoma in Situ n=89 Participants CIS participants had at entry, confirmed by a pathology report: Carcinoma in situ (CIS) only or Ta/T1 highgrade disease with concomitant CIS AND were "BCG unresponsive" which referred to patients with highgrade NMIBC who were unlikely to benefit from and who did not receive further intravesical BCG. The term "BCG unresponsive" included patients who did not respond to BCG treatment and had a persistent high-grade recurrence within 12 months after BCG was initiated, and those who, despite an initial CR to BCG, relapsed with CIS within 12 months of their last intravesical treatment with BCG or relapsed with high-grade Ta/T1 NMIBC within 6 months of their last intravesical treatment with BCG.	Papillary Disease n=45 Participants Patients with high-grade Ta or T1 papillary disease (without concomitant CIS)	Total n=134 Participants All Patients
Anti-adenoviral Antibody Levels for Correlation to Response Rate No	26 Participants	11 Participants	37 Participants
Anti-adenoviral Antibody Levels for Correlation to Response Rate Yes	63 Participants	34 Participants	97 Participants

SECONDARY outcome

Timeframe: 60 Months

Population: Safety Analysis Set

The type, incidence, relatedness and severity of treatment emergent adverse events of ADSTILADRIN as assessed by NCI-CTCAE V4.03 were monitored.

Outcome measures

Outcome measures
Measure	Carcinoma in Situ n=107 Participants CIS participants had at entry, confirmed by a pathology report: Carcinoma in situ (CIS) only or Ta/T1 highgrade disease with concomitant CIS AND were "BCG unresponsive" which referred to patients with highgrade NMIBC who were unlikely to benefit from and who did not receive further intravesical BCG. The term "BCG unresponsive" included patients who did not respond to BCG treatment and had a persistent high-grade recurrence within 12 months after BCG was initiated, and those who, despite an initial CR to BCG, relapsed with CIS within 12 months of their last intravesical treatment with BCG or relapsed with high-grade Ta/T1 NMIBC within 6 months of their last intravesical treatment with BCG.	Papillary Disease n=50 Participants Patients with high-grade Ta or T1 papillary disease (without concomitant CIS)	Total n=157 Participants All Patients
Safety of ADSTILADRIN TEAE	101 Participants	45 Participants	146 Participants
Safety of ADSTILADRIN Serious TEAE	10 Participants	9 Participants	19 Participants
Safety of ADSTILADRIN NCI-CTCAE Grade 3/4/5 TEAE	22 Participants	12 Participants	34 Participants

SECONDARY outcome

Timeframe: Up to 60 Months

Durability will be measured by determining the number of patients without recurrence of high-grade disease using results from urine cytology, cystoscopy, and biopsy of the bladder if clinically indicated.

Outcome measures

Outcome measures
Measure	Carcinoma in Situ n=107 Participants CIS participants had at entry, confirmed by a pathology report: Carcinoma in situ (CIS) only or Ta/T1 highgrade disease with concomitant CIS AND were "BCG unresponsive" which referred to patients with highgrade NMIBC who were unlikely to benefit from and who did not receive further intravesical BCG. The term "BCG unresponsive" included patients who did not respond to BCG treatment and had a persistent high-grade recurrence within 12 months after BCG was initiated, and those who, despite an initial CR to BCG, relapsed with CIS within 12 months of their last intravesical treatment with BCG or relapsed with high-grade Ta/T1 NMIBC within 6 months of their last intravesical treatment with BCG.	Papillary Disease n=50 Participants Patients with high-grade Ta or T1 papillary disease (without concomitant CIS)	Total n=157 Participants All Patients
Durability of Response During the Long-term Follow-up Period.	48.92 months Interval 37.88 to 59.47	59.01 months Interval 46.55 to 60.52	50.83 months Interval 39.1 to 60.02

Adverse Events

Carcinoma in Situ (CIS)

Serious events: 10 serious events

Other events: 101 other events

Deaths: 21 deaths

Papillary Disease (Without Concomitant CIS)

Serious events: 9 serious events

Other events: 45 other events

Deaths: 5 deaths

Total TEAE

Serious events: 19 serious events

Other events: 146 other events

Deaths: 26 deaths

Serious adverse events

Other adverse events

Additional Information

Global Clinical Compliance

Ferring Pharmaceuticals

Phone: +1 862-286-5200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Carcinoma in Situ (CIS) n=107 participants at risk Patients had at entry, confirmed by a pathology report: Carcinoma in situ (CIS) only or Ta/T1 high-grade disease with concomitant CIS and were "BCG unresponsive" which referred to patients with high-grade NMIBC who were unlikely to benefit from and who did not receive further intravesical BCG. The term "BCG unresponsive" included patients who did not respond to BCG treatment and had a persistent high-grade recurrence within 12 months after BCG was initiated, and those who, despite an initial CR to BCG, relapsed with CIS within 12 months of their last intravesical treatment with BCG or relapsed with high-grade Ta/T1 NMIBC within 6 months of their last intravesical treatment with BCG.	Papillary Disease (Without Concomitant CIS) n=50 participants at risk Patients had at entry, confirmed by a pathology report Ta/T1 high-grade disease without concomitant CIS and were "BCG unresponsive" which referred to patients with high-grade NMIBC who were unlikely to benefit from and who did not receive further intravesical BCG. The term "BCG unresponsive" included patients who did not respond to BCG treatment and had a persistent high-grade recurrence within 12 months after BCG was initiated, and those who, despite an initial CR to BCG, relapsed with high-grade Ta/T1 high-grade disease without concomitant CIS within 12 months of their last intravesical treatment with BCG or relapsed with high- grade Ta/T1 NMIBC within 6 months of their last intravesical treatment with BCG.	Total TEAE n=157 participants at risk Total Treatment-Emergent Adverse Events (TEAE) in the Study.
Cardiac disorders Acute coronary syndrome	0.93% 1/107 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	0.00% 0/50 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	0.64% 1/157 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Cardiac disorders Arrhythmia	0.93% 1/107 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	0.00% 0/50 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	0.64% 1/157 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Cardiac disorders Atrial fibrillation	0.93% 1/107 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	0.00% 0/50 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	0.64% 1/157 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Cardiac disorders Cardiac failure	0.00% 0/107 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	2.0% 1/50 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	0.64% 1/157 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Cardiac disorders Coronary Artery Disease	0.93% 1/107 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	2.0% 1/50 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	1.3% 2/157 • Number of events 2 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Cardiac disorders Myocardial infarction	0.00% 0/107 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	2.0% 1/50 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	0.64% 1/157 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Cardiac disorders Pericarditis	0.00% 0/107 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	2.0% 1/50 • Number of events 2 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	0.64% 1/157 • Number of events 2 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Hepatobiliary disorders Bile duct stone	0.00% 0/107 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	2.0% 1/50 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	0.64% 1/157 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Immune system disorders Anaphylactic reaction	0.00% 0/107 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	2.0% 1/50 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	0.64% 1/157 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Infections and infestations Pneumonia	0.00% 0/107 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	2.0% 1/50 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	0.64% 1/157 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Infections and infestations Sepsis	0.93% 1/107 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	2.0% 1/50 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	1.3% 2/157 • Number of events 2 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Injury, poisoning and procedural complications Corneal abrasion	0.00% 0/107 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	2.0% 1/50 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	0.64% 1/157 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Metabolism and nutrition disorders Dehydration	0.93% 1/107 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	0.00% 0/50 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	0.64% 1/157 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/107 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	2.0% 1/50 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	0.64% 1/157 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung cancer metastatic	0.00% 0/107 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	2.0% 1/50 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	0.64% 1/157 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.00% 0/107 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	2.0% 1/50 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	0.64% 1/157 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma	0.00% 0/107 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	2.0% 1/50 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	0.64% 1/157 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell cancer of the renal pelvis and ureter	0.00% 0/107 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	2.0% 1/50 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	0.64% 1/157 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Nervous system disorders Brain oedema	0.93% 1/107 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	0.00% 0/50 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	0.64% 1/157 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Nervous system disorders Syncope	0.93% 1/107 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	2.0% 1/50 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	1.3% 2/157 • Number of events 2 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Nervous system disorders Transient global amnesia	0.00% 0/107 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	2.0% 1/50 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	0.64% 1/157 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Renal and urinary disorders Haematuria	0.93% 1/107 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	0.00% 0/50 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	0.64% 1/157 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Skin and subcutaneous tissue disorders Subcutaneous emphysema	0.00% 0/107 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	2.0% 1/50 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	0.64% 1/157 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Cardiac disorders Atrial Flutter	0.93% 1/107 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	0.00% 0/50 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	0.64% 1/157 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Translational cell carcinoma	0.93% 1/107 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	0.00% 0/50 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	0.64% 1/157 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
General disorders Pyrexia	0.00% 0/107 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	2.0% 1/50 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	0.64% 1/157 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.

Measure	Carcinoma in Situ (CIS) n=107 participants at risk Patients had at entry, confirmed by a pathology report: Carcinoma in situ (CIS) only or Ta/T1 high-grade disease with concomitant CIS and were "BCG unresponsive" which referred to patients with high-grade NMIBC who were unlikely to benefit from and who did not receive further intravesical BCG. The term "BCG unresponsive" included patients who did not respond to BCG treatment and had a persistent high-grade recurrence within 12 months after BCG was initiated, and those who, despite an initial CR to BCG, relapsed with CIS within 12 months of their last intravesical treatment with BCG or relapsed with high-grade Ta/T1 NMIBC within 6 months of their last intravesical treatment with BCG.	Papillary Disease (Without Concomitant CIS) n=50 participants at risk Patients had at entry, confirmed by a pathology report Ta/T1 high-grade disease without concomitant CIS and were "BCG unresponsive" which referred to patients with high-grade NMIBC who were unlikely to benefit from and who did not receive further intravesical BCG. The term "BCG unresponsive" included patients who did not respond to BCG treatment and had a persistent high-grade recurrence within 12 months after BCG was initiated, and those who, despite an initial CR to BCG, relapsed with high-grade Ta/T1 high-grade disease without concomitant CIS within 12 months of their last intravesical treatment with BCG or relapsed with high- grade Ta/T1 NMIBC within 6 months of their last intravesical treatment with BCG.	Total TEAE n=157 participants at risk Total Treatment-Emergent Adverse Events (TEAE) in the Study.
Gastrointestinal disorders Abdominal pain	1.9% 2/107 • Number of events 2 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	10.0% 5/50 • Number of events 5 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	4.5% 7/157 • Number of events 7 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Gastrointestinal disorders Constipation	0.00% 0/107 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	6.0% 3/50 • Number of events 3 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	1.9% 3/157 • Number of events 3 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Gastrointestinal disorders Diarrhoea	9.3% 10/107 • Number of events 10 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	14.0% 7/50 • Number of events 7 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	10.8% 17/157 • Number of events 17 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Gastrointestinal disorders Nausea	7.5% 8/107 • Number of events 8 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	8.0% 4/50 • Number of events 4 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	7.6% 12/157 • Number of events 12 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Gastrointestinal disorders Vomiting	2.8% 3/107 • Number of events 3 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	6.0% 3/50 • Number of events 3 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	3.8% 6/157 • Number of events 6 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
General disorders Chills	16.8% 18/107 • Number of events 18 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	12.0% 6/50 • Number of events 6 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	15.3% 24/157 • Number of events 24 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
General disorders Fatigue	27.1% 29/107 • Number of events 29 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	16.0% 8/50 • Number of events 8 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	23.6% 37/157 • Number of events 37 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
General disorders Influenza like illness	3.7% 4/107 • Number of events 4 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	8.0% 4/50 • Number of events 4 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	5.1% 8/157 • Number of events 8 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
General disorders Instillation site discharge	34.6% 37/107 • Number of events 37 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	30.0% 15/50 • Number of events 15 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	33.1% 52/157 • Number of events 52 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
General disorders Malaise	1.9% 2/107 • Number of events 2 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	8.0% 4/50 • Number of events 4 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	3.8% 6/157 • Number of events 6 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
General disorders Pain	8.4% 9/107 • Number of events 9 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	4.0% 2/50 • Number of events 2 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	7.0% 11/157 • Number of events 11 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
General disorders Pyrexia	16.8% 18/107 • Number of events 18 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	14.0% 7/50 • Number of events 7 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	15.9% 25/157 • Number of events 25 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Infections and infestations Bronchitis	0.93% 1/107 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	10.0% 5/50 • Number of events 5 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	3.8% 6/157 • Number of events 6 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Infections and infestations Nasopharyngitis	7.5% 8/107 • Number of events 8 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	4.0% 2/50 • Number of events 2 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	6.4% 10/157 • Number of events 10 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Infections and infestations Sinusitus	2.8% 3/107 • Number of events 3 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	6.0% 3/50 • Number of events 3 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	3.8% 6/157 • Number of events 6 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Infections and infestations Urinary tract infection	10.3% 11/107 • Number of events 11 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	24.0% 12/50 • Number of events 12 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	14.6% 23/157 • Number of events 23 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Metabolism and nutrition disorders Decreased appetite	1.9% 2/107 • Number of events 2 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	6.0% 3/50 • Number of events 3 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	3.2% 5/157 • Number of events 5 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Musculoskeletal and connective tissue disorders Arthralgia	5.6% 6/107 • Number of events 6 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	8.0% 4/50 • Number of events 4 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	6.4% 10/157 • Number of events 10 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Musculoskeletal and connective tissue disorders Back pain	3.7% 4/107 • Number of events 4 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	8.0% 4/50 • Number of events 4 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	5.1% 8/157 • Number of events 8 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Musculoskeletal and connective tissue disorders Myalgia	6.5% 7/107 • Number of events 7 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	10.0% 5/50 • Number of events 5 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	7.6% 12/157 • Number of events 12 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Nervous system disorders Dizziness	7.5% 8/107 • Number of events 8 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	12.0% 6/50 • Number of events 6 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	8.9% 14/157 • Number of events 14 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Nervous system disorders Headache	15.0% 16/107 • Number of events 16 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	16.0% 8/50 • Number of events 8 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	15.3% 24/157 • Number of events 24 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Nervous system disorders Hypoaesthesia	0.93% 1/107 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	6.0% 3/50 • Number of events 3 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	2.5% 4/157 • Number of events 4 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Renal and urinary disorders Bladder pain	8.4% 9/107 • Number of events 9 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	6.0% 3/50 • Number of events 3 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	7.6% 12/157 • Number of events 12 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Renal and urinary disorders Bladder spasm	20.6% 22/107 • Number of events 22 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	18.0% 9/50 • Number of events 9 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	19.7% 31/157 • Number of events 31 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Renal and urinary disorders Dysuria	15.9% 17/107 • Number of events 17 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	16.0% 8/50 • Number of events 8 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	15.9% 25/157 • Number of events 25 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Renal and urinary disorders Haematuria	17.8% 19/107 • Number of events 19 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	14.0% 7/50 • Number of events 7 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	16.6% 26/157 • Number of events 26 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Renal and urinary disorders Micturition urgency	18.7% 20/107 • Number of events 20 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	18.0% 9/50 • Number of events 9 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	18.5% 29/157 • Number of events 29 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Renal and urinary disorders Pollakiuria	8.4% 9/107 • Number of events 9 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	12.0% 6/50 • Number of events 6 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	9.6% 15/157 • Number of events 15 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Renal and urinary disorders Urinary incontinence	7.5% 8/107 • Number of events 8 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	2.0% 1/50 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	5.7% 9/157 • Number of events 9 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Vascular disorders Hypertension	7.5% 8/107 • Number of events 8 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	6.0% 3/50 • Number of events 3 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	7.0% 11/157 • Number of events 11 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Renal and urinary disorders Nocturia	3.7% 4/107 • Number of events 4 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	6.0% 3/50 • Number of events 3 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	4.5% 7/157 • Number of events 7 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Renal and urinary disorders Urinary retention	3.7% 4/107 • Number of events 4 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	6.0% 3/50 • Number of events 3 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	4.5% 7/157 • Number of events 7 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Injury, poisoning and procedural complications Procedural pain	5.6% 6/107 • Number of events 6 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	2.0% 1/50 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	4.5% 7/157 • Number of events 7 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Skin and subcutaneous tissue disorders Night sweats	0.00% 0/107 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	8.0% 4/50 • Number of events 4 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	2.5% 4/157 • Number of events 4 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.
Respiratory, thoracic and mediastinal disorders Cough	0.93% 1/107 • Number of events 1 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	8.0% 4/50 • Number of events 4 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.	3.2% 5/157 • Number of events 5 • 60 months The Month 60 final dataset was used for all Adverse Event Reporting data.