Trial Outcomes & Findings for Long Term Study of Solifenacin Succinate and Tamsulosin Hydrochloride Oral Controlled Absorption System (OCAS) in Males With Lower Urinary Tract Symptoms (NCT NCT01021332)

NCT ID: NCT01021332

Last Updated: 2024-12-03

Results Overview

Safety is monitored by collecting AEs, which include abnormal lab parameters, vital signs or ECG data if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study drug or was clinically significant. A serious AE (SAE) was an AE resulting in death, persistent or significant disability/incapacity or congenital anomaly/birth defect, was life-threatening, required or prolonged hospitalization or was considered medically important. AEs were assessed by the Investigator for intensity (mild-no disruption of normal daily activities, moderate-affected normal daily activities or severe-inability to perform daily activities) and for causal relationship to study drug. A treatment-emergent adverse event (TEAE) was defined as an AE that occurred after the intake of first dose of double-blind study drug (if on FDC in 905-CL-055) or after first open-label dose until 30 days after the last dose of open-label study drug (in 905-CL-057).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1067 participants
• Primary outcome timeframe: From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
• Results posted on: 2024-12-03

Participant Flow

Participants were eligible for Study 905-CL-057 if they completed 12 weeks of double-blind treatment in Study 905-CL-055, complied with inclusion criteria and did not meet any exclusion criteria. Participants treated with the FDC 0.4 mg/6 mg or 0.4 mg/9 mg for maximally 40 weeks.

All eligible participants started with 4 weeks of open-label FDC 0.4 mg/6 mg and were given the opportunity to adjust their dose at 3 monthly intervals thereafter if desired.

Participant milestones

Measure	Total Group Participants who received at least one dose of open-label FDC treatment
Overall Study STARTED	1066
Overall Study Safety Analysis Set (SAF)	1066
Overall Study Full Analysis Set (FAS)	1009
Overall Study COMPLETED	960
Overall Study NOT COMPLETED	106

Reasons for withdrawal

Measure	Total Group Participants who received at least one dose of open-label FDC treatment
Overall Study Not fulfilling incl./excl.criteria	5
Overall Study Adverse Event	43
Overall Study Lack of Efficacy	19
Overall Study Withdrawal of Consent	23
Overall Study Lost to Follow-up	4
Overall Study Protocol Violation	9
Overall Study Miscellaneous	3

Baseline Characteristics

Long Term Study of Solifenacin Succinate and Tamsulosin Hydrochloride Oral Controlled Absorption System (OCAS) in Males With Lower Urinary Tract Symptoms

Baseline characteristics by cohort

Measure	Total Group n=1066 Participants Participants who received at least one dose of open-label FDC treatment
Age, Customized <65 years	540 participants n=5 Participants
Age, Customized >65 and < 75 years	417 participants n=5 Participants
Age, Customized > 75 years	109 participants n=5 Participants
Sex/Gender, Customized Male	1066 participants n=5 Participants
Sex/Gender, Customized Female	0 participants n=5 Participants
Race/Ethnicity, Customized White	1060 participants n=5 Participants
Race/Ethnicity, Customized Black	3 participants n=5 Participants
Race/Ethnicity, Customized Asian	2 participants n=5 Participants
Race/Ethnicity, Customized Other	1 participants n=5 Participants
Total International Prostate Symptom Score (IPSS)	18.7 units on a scale STANDARD_DEVIATION 4.41 • n=5 Participants
Total International Prostate Symptom Score (IPSS) voiding score	9.8 units on a scale STANDARD_DEVIATION 3.58 • n=5 Participants
Total International Prostate Symptom Score (IPSS) storage score	8.9 units on a scale STANDARD_DEVIATION 2.37 • n=5 Participants
IPSS Quality of Life Score(Qol) score	4.1 units on a scale STANDARD_DEVIATION 1.09 • n=5 Participants
Total Urgency Frequency Score (TUFS) (previous known as Total Urgency Score (TUS)	27.18 units on a scale STANDARD_DEVIATION 8.59 • n=5 Participants
Micturitions/24 hour	11.44 micturitions STANDARD_DEVIATION 2.61 • n=5 Participants
Volume voided/micturition	162.81 ml STANDARD_DEVIATION 47.57 • n=5 Participants
Incontinence episodes/24 hour	1.77 incontinence episodes STANDARD_DEVIATION 2.04 • n=5 Participants
Urgency incontinence episodes /24 hour	1.74 urgency incontinence episodes STANDARD_DEVIATION 1.97 • n=5 Participants
Nocturia episodes/ 24 hour	2.40 nocturia episodes STANDARD_DEVIATION 1.26 • n=5 Participants

PRIMARY outcome

Timeframe: From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)

Population: Safety analysis set-participants who received at least 1 dose of the FDC tamsulosin/solifenacin 0.4 mg/6 mg or 0.4 mg/9 mg during the open-label treatment period and had any data reported after the first dose of the FDC during the open-label treatment period

Safety is monitored by collecting AEs, which include abnormal lab parameters, vital signs or ECG data if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study drug or was clinically significant. A serious AE (SAE) was an AE resulting in death, persistent or significant disability/incapacity or congenital anomaly/birth defect, was life-threatening, required or prolonged hospitalization or was considered medically important. AEs were assessed by the Investigator for intensity (mild-no disruption of normal daily activities, moderate-affected normal daily activities or severe-inability to perform daily activities) and for causal relationship to study drug. A treatment-emergent adverse event (TEAE) was defined as an AE that occurred after the intake of first dose of double-blind study drug (if on FDC in 905-CL-055) or after first open-label dose until 30 days after the last dose of open-label study drug (in 905-CL-057).

Outcome measures

Measure	Total Group n=1066 Participants Participants who received at least one dose of open-label FDC treatment
Number of Participants With Adverse Events (AEs) Participants With Treatment-Emergent Adverse Event	499 participants
Number of Participants With Adverse Events (AEs) Drug-related AEs	255 participants
Number of Participants With Adverse Events (AEs) Drug-related SAEs	12 participants
Number of Participants With Adverse Events (AEs) Any TEAE causing discontinuation of study drug.	69 participants

PRIMARY outcome

Timeframe: Baseline and up to 52 weeks of FDC treatment

Population: SAF population with at least one baseline and one post-baseline PVR volume measured.

PVR volume is the volume of urine retained after voiding. PVR volume was assessed by ultrasonography or bladder scan.

Outcome measures

Measure	Total Group n=1056 Participants Participants who received at least one dose of open-label FDC treatment
Change From Baseline to End of Treatment in Post Void Residual (PVR) Volume	10.7 ml Standard Deviation 49.28

PRIMARY outcome

Timeframe: Baseline and up to 52 weeks of FDC treatment

Population: SAF population with at least one baseine and one post-baseline micturition episode.

Qmax during a micturition (urination) was recorded using uroflowmetry.

Outcome measures

Measure	Total Group n=1047 Participants Participants who received at least one dose of open-label FDC treatment
Change From Baseline to End of Treatment in Maximum Flow Rate (Qmax)	4.54 ml/s Standard Deviation 5.927

PRIMARY outcome

Timeframe: Baseline and up to 52 weeks of FDC treatment

Population: SAF population with at least one baseline and one post-baseline micturition episode.

Qmean during a micturition (urination) was recorded using uroflowmetry.

Outcome measures

Measure	Total Group n=1047 Participants Participants who received at least one dose of open-label FDC treatment
Change From Baseline to End of Treatment in Average Flow Rate (Qmean)	2.05 ml/s Standard Deviation 2.884

PRIMARY outcome

Timeframe: Baseline and up to 52 weeks of FDC treatment

Population: Full Analysis Set (FAS)-participants who took at least 1 dose of the FDC during the open-label study, had a total IPSS or TUS at baseline and had at least one total IPSS or TUS after first dose of the FDC in Study 905-CL-057. Excluded 5 participants with invalid questionnaires. Last Observation Carried Forward (LOCF) imputation was used.

The International Prostate Symptom Score (IPSS) is a validated global questionnaire to assess the degree of urinary symptoms, based on answers to 7 questions concerning urinary symptoms: • Incomplete emptying of the bladder • Intermittency • Weak stream • Hesitancy • Frequency • Urgency • Nocturia Each question is assigned points from 0 to 5 indicating increasing severity of the symptom. Total score can range from 0 to 35 (mildly symptomatic to severely symptomatic).

Outcome measures

Measure	Total Group n=1004 Participants Participants who received at least one dose of open-label FDC treatment
Change From Baseline to End of Treatment in Total International Prostate Symptom Score (IPSS)	-9.0 units on a scale Standard Deviation 5.69

PRIMARY outcome

Timeframe: Baseline and up to 52 weeks of FDC treatment

Population: FAS population with data available at both baseline and end of treatment. LOCF imputation was used.

The Patient Perception of the Intensity of Urgency Scale (PPIUS) is a validated scale completed as part of the micturition diary. For each micturition and/or incontinence episode, the participant rated the degree of associated urgency according to the following 5-point categorical scale: • 0. No urgency; • 1. Mild urgency; • 2. Moderate urgency; • 3. Severe urgency; • 4. Urgency incontinence TUS/TUFS was calculated as the sum of the PPIUS gradings from the 3-day diary divided by the number of days on which urgency grading was recorded. Higher scores indicate more severe urgency.

Outcome measures

Measure	Total Group n=1005 Participants Participants who received at least one dose of open-label FDC treatment
Change From Baseline to End of Treatment in Total Urgency Frequency Score (TUFS) (Previously Known as Total Urgency Score [TUS])	-10.1 units on a scale Standard Deviation 9.23

SECONDARY outcome

Timeframe: Baseline and up to 52 weeks of FDC treatment

Population: FAS population with data available at both baseline and end of treatment. LOCF imputation was used.

A micturition is any voluntary urination, excluding episodes of incontinence only.The mean number of micturitions per 24 hours was calculated from data recorded by the participant in the micturition diary for the 3 days preceding each clinic visit.

Outcome measures

Measure	Total Group n=1008 Participants Participants who received at least one dose of open-label FDC treatment
Change From Baseline to End of Treatment in Mean Number of Micturitions Per 24 Hours	-2.5 micturitions Standard Deviation 2.37

SECONDARY outcome

Timeframe: Baseline and up to 52 weeks of FDC treatment

Population: FAS population with data available at both baseline and end of treatment. LOCF imputation was used.

A micturition is any voluntary urination, excluding episodes of incontinence only. The mean volume voided per micturition was calculated from data recorded by the participant in the micturition diary for the 3 days preceding each clinic visit.

Outcome measures

Measure	Total Group n=1008 Participants Participants who received at least one dose of open-label FDC treatment
Change From Baseline to End of Treatment in Mean Voided Volume Per Micturition	39.0 ml Standard Deviation 47.32

SECONDARY outcome

Timeframe: Baseline and up to 52 weeks of FDC treatment

Population: FAS population with data available at both baseline and end of treatment. LOCF imputation was used.

A micturition is any voluntary urination, excluding episodes of incontinence only. The maximum volume voided per micturition was calculated from data recorded by the participant in the micturition diary for the 3 days preceding each clinic visit.

Outcome measures

Measure	Total Group n=1008 Participants Participants who received at least one dose of open-label FDC treatment
Change From Baseline to End of Treatment in Maximum Volume Voided Per Micturition	16.6 ml Standard Deviation 101.24

SECONDARY outcome

Timeframe: Baseline and up to 52 weeks of FDC treatment

Population: FAS population with at least 1 urgency episode at baseline. LOCF imputation was used.

An urgency episode is defined as an episode of strong desire to void accompanied by fear of leakage or pain. The mean number of urgency episodes with PPIUS grade 3 (Severe urgency) or 4 (Urgency incontinence) per 24 hours was calculated from data recorded by the participant in the micturition diary for the 3 days preceding each clinic visit.

Outcome measures

Measure	Total Group n=1006 Participants Participants who received at least one dose of open-label FDC treatment
Change From Baseline to End of Treatment in Mean Number of Urgency Episodes (PPIUS Grade 3 or 4) Per 24 Hours	-3.1 urgency episodes Standard Deviation 3.45

SECONDARY outcome

Timeframe: Baseline and up to 52 weeks of FDC treatment

Population: FAS population and at least 1 urgency incontinence episode at baseline. LOCF imputation was used.

An urgency incontinence episode is defined as an episode with any involuntary leakage of urine accompanied by or immediately preceded by urgency. The mean number of urgency incontinence episodes with PPIUS grade 3 (Severe incontinence) or 4 (Urgency incontinence) per 24 hours was calculated from data recorded by the participant in the micturition diary for the 3 days preceding each clinic visit.

Outcome measures

Measure	Total Group n=234 Participants Participants who received at least one dose of open-label FDC treatment
Change From Baseline to End of Treatment in Mean Number of Urgency Incontinence Episodes Per 24 Hours	-1.5 urgency incontinence episodes Standard Deviation 2.02

SECONDARY outcome

Timeframe: Baseline and up to 52 weeks of FDC treatment

Population: FAS population and at least 1 incontinence episode at baseline. LOCF imputation was used.

An incontinence episode is defined as an episode with any involuntary loss of urine. The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in the micturition diary for the 3 days preceding each clinic visit.

Outcome measures

Measure	Total Group n=250 Participants Participants who received at least one dose of open-label FDC treatment
Change From Baseline to End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours	-1.4 incontinence episodes Standard Deviation 2.09

SECONDARY outcome

Timeframe: Baseline and up to 52 weeks of FDC treatment

Population: FAS population and at least 1 nocturia episode at baseline. LOCF imputation was used.

A nocturia episode is defined as waking up at night to void (i.e., any voiding associated with sleep disturbance between the time the participant goes to bed with the intention to sleep until the time the patient gets up in the morning with the intention to stay awake). The mean number of nocturia episodes per 24 hours was calculated from data recorded by the participant in the micturition diary for the 3 days preceding each clinic visit.

Outcome measures

Measure	Total Group n=968 Participants Participants who received at least one dose of open-label FDC treatment
Change From Baseline to End of Treatment in Mean Number of Nocturia Episodes Per 24 Hours	-0.7 nocturia episodes Standard Deviation 1.05

SECONDARY outcome

Timeframe: Baseline and up to 52 weeks of FDC treatment

Population: FAS population and at least 1 use of a pad at baseline. LOCF imputation was used.

The mean number of pads per 24 hours was calculated from data recorded by the participant in the micturition diary for the 3 days preceding each clinic visit.

Outcome measures

Measure	Total Group n=95 Participants Participants who received at least one dose of open-label FDC treatment
Change From Baseline to End of Treatment in Mean Number of Pads Used Per 24 Hours	-0.9 pads Standard Deviation 1.48

SECONDARY outcome

Timeframe: Baseline and up to 52 weeks of FDC treatment

Population: A total of 5 subjects has been excluded from the FAS analysis due to invalid questionnaires. LOCF imputation was used.

The IPSS is a validated global questionnaire to assess the degree of urinary symptoms based on answers to 7 questions. Each question is assigned points from 0 to 5 indicating increasing severity of the particular symptom. The voiding score is the sum of the responses to 4 voiding questions (incomplete emptying of the bladder, intermittency, weak stream, hesitancy) and ranges from 0 to 20 (mildly symptomatic to severely symptomatic).

Outcome measures

Measure	Total Group n=1004 Participants Participants who received at least one dose of open-label FDC treatment
Change From Baseline to End of Treatment in IPSS Voiding Score	-4.7 units on a scale Standard Deviation 4.09

SECONDARY outcome

Timeframe: Baseline and up to 52 weeks of FDC treatment

Population: A total of 5 subjects has been excluded from the FAS analysis due to invalid questionnaires. LOCF imputation was used.

The IPSS is a validated global questionnaire to assess the degree of urinary symptoms based on answers to 7 questions concerning urinary symptoms. Each question is assigned points from 0 to 5 indicating increasing severity of the particular symptom. The storage symptom score is the sum of the responses to 3 storage questions (frequency,urgency and nocturia) and ranges from 0 to 15 (mildly symptomatic to severely symptomatic).

Outcome measures

Measure	Total Group n=1004 Participants Participants who received at least one dose of open-label FDC treatment
Change From Baseline to End of Treatment in IPSS Storage Score	-4.3 units on a scale Standard Deviation 2.88

SECONDARY outcome

Timeframe: Baseline and up to 52 weeks of FDC treatment

Population: FAS population with data available at both baseline and end of treatment and the exclusion of 5 participants with invalid questionnaires. LOCF imputation was used

The QoL assessment was a single question asking the participant how he would feel about tolerating his current level of symptoms for the rest of his life. The answers ranged from 0 to 6 (delighted to terrible).

Outcome measures

Measure	Total Group n=1003 Participants Participants who received at least one dose of open-label FDC treatment
Change From Baseline to End of Treatment in IPSS Quality of Life (QoL) Score	-1.9 units on a scale Standard Deviation 1.53

SECONDARY outcome

Timeframe: Baseline and up to 52 weeks of FDC treatment

Population: A total of 5 subjects has been excluded from the FAS analysis due to invalid questionnaires. LOCF imputation was used.

The IPSS is a validated global questionnaire to assess the degree of urinary symptoms, based on answers to 7 questions concerning urinary symptoms: • Incomplete emptying of the bladder • Intermittency • Weak stream • Hesitancy • Frequency • Urgency • Nocturia Each question is assigned points from 0 to 5 indicating increasing severity of the symptom.

Outcome measures

Measure	Total Group n=1004 Participants Participants who received at least one dose of open-label FDC treatment
Change From Baseline to End of Treatment in Individual IPSS Scores Incomplete emptying of the bladder	-1.3 units on a scale Standard Deviation 1.49
Change From Baseline to End of Treatment in Individual IPSS Scores Frequency	-1.7 units on a scale Standard Deviation 1.41
Change From Baseline to End of Treatment in Individual IPSS Scores Intermittency	-1.0 units on a scale Standard Deviation 1.48
Change From Baseline to End of Treatment in Individual IPSS Scores Urgency	-1.8 units on a scale Standard Deviation 1.54
Change From Baseline to End of Treatment in Individual IPSS Scores Weak stream	-1.6 units on a scale Standard Deviation 1.62
Change From Baseline to End of Treatment in Individual IPSS Scores Hesitancy	-0.8 units on a scale Standard Deviation 1.42
Change From Baseline to End of Treatment in Individual IPSS Scores Nocturia	-0.9 units on a scale Standard Deviation 1.17

SECONDARY outcome

Timeframe: Baseline and up to 52 weeks of FDC treatment

Population: FAS population with data available at both baseline and end of treatment and the exclusion of 5 participants with invalid questionnaires. LOCF imputation was used

The Overactive Bladder Questionnaire (OAB-q) is a self-reported questionnaire with items relating to Symptom Bother and health-related quality of life (HRQoL). The Symptom Bother portion consists of an 8-item scale scored from 1 to 6.The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 to 100, with 100 indicating worst severity. A negative change from baseline indicates an improvement.

Outcome measures

Measure	Total Group n=1003 Participants Participants who received at least one dose of open-label FDC treatment
Change From Baseline to End of Treatment in Symptom Bother Score	-20.6 units on a scale Standard Deviation 17.45

SECONDARY outcome

Timeframe: Baseline and up to 52 weeks of FDC treatment

Population: FAS population with data available at both baseline and end of treatment and the exclusion of 5 participants with invalid questionnaires. LOCF imputation was used

The Overactive Bladder Questionnaire (OAB-q) is a self-reported questionnaire with items relating to Symptom Bother and health-related quality of life (HRQoL). The HRQoL portion consists of an 25-item HRQoL subscale containing the following domains scored from 1 to 6: • coping • concern • sleep • social interaction Coping score can range from 8 to 48 (none of the time to all of the time) and transformed to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicates an improvement.

Outcome measures

Measure	Total Group n=1000 Participants Participants who received at least one dose of open-label FDC treatment
Change From Baseline to End of Treatment in Health-related Quality of Life (HRQoL) Subscale: Coping Score	17.3 units on a scale Standard Deviation 18.98

SECONDARY outcome

Timeframe: Baseline and up to 52 weeks of FDC treatment

Population: FAS population with data available at both baseline and end of treatment and the exclusion of 5 participants with invalid questionnaires. LOCF imputation was used

The Overactive Bladder Questionnaire (OAB-q) is a self-reported questionnaire with items relating to Symptom Bother and health-related quality of life (HRQoL). The HRQoL portion consists of an 25-item HRQoL subscale containing the following domains scored from 1 to 6: • coping • concern • sleep • social interaction Concern score can range from 8 to 48 (none of the time to all of the time) and transformed to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicates an improvement.

Outcome measures

Measure	Total Group n=1000 Participants Participants who received at least one dose of open-label FDC treatment
Change From Baseline to End of Treatment in Health-related Quality of Life (HRQoL) Subscale: Concern Score	15.0 units on a scale Standard Deviation 18.15

SECONDARY outcome

Timeframe: Baseline and up to 52 weeks of FDC treatment

Population: FAS population with data available at both baseline and end of treatment and the exclusion of 5 participants with invalid questionnaires. LOCF imputation was used

The Overactive Bladder Questionnaire (OAB-q) is a self-reported questionnaire with items relating to Symptom Bother and health-related quality of life (HRQoL). The HRQoL portion consists of an 25-item HRQoL subscale containing the following domains scored from 1 to 6: • coping • concern • sleep • social interaction Sleep score can range from 8 to 48 (none of the time to all of the time) and transformed to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicates an improvement.

Outcome measures

Measure	Total Group n=1001 Participants Participants who received at least one dose of open-label FDC treatment
Change From Baseline to End of Treatment in Health-related Quality of Life (HRQoL) Subscale: Sleep Score	15.3 units on a scale Standard Deviation 19.61

SECONDARY outcome

Timeframe: Baseline and up to 52 weeks of FDC treatment

Population: FAS population with data available at both baseline and end of treatment and the exclusion of 5 participants with invalid questionnaires. LOCF imputation was used

The Overactive Bladder Questionnaire (OAB-q) is a self-reported questionnaire with items relating to Symptom Bother and health-related quality of life (HRQoL). The HRQoL portion consists of an 25-item HRQoL subscale containing the following domains scored from 1 to 6: • coping • concern • sleep • social interaction Social score can range from 8 to 48 (none of the time to all of the time) and transformed to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicates an improvement.

Outcome measures

Measure	Total Group n=1002 Participants Participants who received at least one dose of open-label FDC treatment
Change From Baseline to End of Treatment in Health-related Quality of Life (HRQoL) Subscale: Social Score	7.6 units on a scale Standard Deviation 15.15

SECONDARY outcome

Timeframe: Baseline and up to 52 weeks of FDC treatment

Population: FAS population with data available at both baseline and end of treatment and the exclusion of 5 participants with invalid questionnaires. LOCF imputation was used

The Overactive Bladder Questionnaire (OAB-q) is a self-reported questionnaire with items relating to Symptom Bother and health-related quality of life (HRQoL). The HRQoL portion consists of an 25-item HRQoL subscale containing the following domains scored from 1 to 6: • coping • concern • sleep • social interaction Total score is calculated by adding the 4 HRQoL subscale scores and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicates an improvement.

Outcome measures

Measure	Total Group n=1000 Participants Participants who received at least one dose of open-label FDC treatment
Change From Baseline to End of Treatment in Health-related Quality of Life (HRQoL) Subscale: Total Score	14.3 units on a scale Standard Deviation 15.59

SECONDARY outcome

Timeframe: Baseline and up to 52 weeks of FDC treatment

Population: FAS population with data available at both baseline and end of treatment and the exclusion of 5 participants with invalid questionnaires. LOCF imputation was used

A OAB-q responder was defined as a participant with an improvement from baseline in HRQoL subscale total score ≥ 10.

Outcome measures

Measure	Total Group n=1000 Participants Participants who received at least one dose of open-label FDC treatment
Number of OAB-q Responders Based on Health-related Quality of Life: Total Score	55.7 percentage of participants

SECONDARY outcome

Timeframe: Baseline and up to 52 weeks of FDC treatment

Population: FAS population with data available at both baseline and end of treatment and the exclusion of 5 participants with invalid questionnaires. LOCF imputation was used

The European quality of life-5 dimensions (EQ-5D) is an international standardized non-disease specific instrument for describing and valuing health status. The EQ5D has 5 domains: • mobility • self-care • usual activity • pain/discomfort • anxiety/depression Each domain has 3 response levels (1= no problem, 2= some problems, 3 = confined to bed).

Outcome measures

Measure	Total Group n=1003 Participants Participants who received at least one dose of open-label FDC treatment
Change From Baseline to End of Treatment in EQ-5D Mobility Score No problem -> No problem	775 participants
Change From Baseline to End of Treatment in EQ-5D Mobility Score No problem -> Some problem	58 participants
Change From Baseline to End of Treatment in EQ-5D Mobility Score No problem -> confined to bed	1 participants
Change From Baseline to End of Treatment in EQ-5D Mobility Score No problem -> no data	0 participants
Change From Baseline to End of Treatment in EQ-5D Mobility Score Some problem -> No problem	67 participants
Change From Baseline to End of Treatment in EQ-5D Mobility Score Some problem -> Some problem	102 participants
Change From Baseline to End of Treatment in EQ-5D Mobility Score Some problem -> confined to bed	0 participants
Change From Baseline to End of Treatment in EQ-5D Mobility Score Some problem -> No data	0 participants
Change From Baseline to End of Treatment in EQ-5D Mobility Score Confined to bed -> no problem	0 participants
Change From Baseline to End of Treatment in EQ-5D Mobility Score Confined to bed -> some problem	0 participants
Change From Baseline to End of Treatment in EQ-5D Mobility Score Confined to bed -> confined to bed	0 participants
Change From Baseline to End of Treatment in EQ-5D Mobility Score Confined to bed -> no data	0 participants
Change From Baseline to End of Treatment in EQ-5D Mobility Score No data -> no problem	1 participants
Change From Baseline to End of Treatment in EQ-5D Mobility Score No data -> some problem	0 participants
Change From Baseline to End of Treatment in EQ-5D Mobility Score No data -> confined to bed	0 participants
Change From Baseline to End of Treatment in EQ-5D Mobility Score No data -> no data	0 participants

SECONDARY outcome

Timeframe: Baseline and up to 52 weeks of FDC treatment

Population: FAS population with data available at both baseline and end of treatment and the exclusion of 5 participants with invalid questionnaires. LOCF imputation was used

The European quality of life-5 dimensions (EQ-5D) is an international standardized non-disease specific instrument for describing and valuing health status. The EQ5D has 5 domains: • mobility • self-care • usual activity • pain/discomfort • anxiety/depression Each domain has 3 response levels (1= no problem, 2= some problems, 3 = unable to wash/dress).

Outcome measures

Measure	Total Group n=1001 Participants Participants who received at least one dose of open-label FDC treatment
Change From Baseline to End of Treatment in EQ-5D Self-care Score No problem -> No problem	934 participants
Change From Baseline to End of Treatment in EQ-5D Self-care Score No problem -> Some problem	27 participants
Change From Baseline to End of Treatment in EQ-5D Self-care Score No problem -> Unable to wash/dress	1 participants
Change From Baseline to End of Treatment in EQ-5D Self-care Score No problem -> No data	0 participants
Change From Baseline to End of Treatment in EQ-5D Self-care Score Some problem -> no problem	18 participants
Change From Baseline to End of Treatment in EQ-5D Self-care Score Some problem -> some problem	19 participants
Change From Baseline to End of Treatment in EQ-5D Self-care Score Some problem -> unable to wash/dress	0 participants
Change From Baseline to End of Treatment in EQ-5D Self-care Score Some problem -> no data	0 participants
Change From Baseline to End of Treatment in EQ-5D Self-care Score Unable to wash/dress -> no problem	2 participants
Change From Baseline to End of Treatment in EQ-5D Self-care Score Unable to wash/dress -> some problem	0 participants
Change From Baseline to End of Treatment in EQ-5D Self-care Score Unable to wash/dress -> unable to wash/dress	0 participants
Change From Baseline to End of Treatment in EQ-5D Self-care Score Unable to wash/dress -> no data	0 participants
Change From Baseline to End of Treatment in EQ-5D Self-care Score No data -> no problem	3 participants
Change From Baseline to End of Treatment in EQ-5D Self-care Score No data -> some problem	0 participants
Change From Baseline to End of Treatment in EQ-5D Self-care Score No data -> unable to wash/dress	0 participants
Change From Baseline to End of Treatment in EQ-5D Self-care Score No data -> no data	0 participants

SECONDARY outcome

Timeframe: Baseline and up to 52 weeks of FDC treatment

Population: FAS population with data available at both baseline and end of treatment and the exclusion of 5 participants with invalid questionnaires. LOCF imputation was used

The European quality of life-5 dimensions (EQ-5D) is an international standardized non-disease specific instrument for describing and valuing health status. The EQ5D has 5 domains: • mobility • self-care • usual activity • pain/discomfort • anxiety/depression Each domain has 3 response levels (1= no problem, 2= some problems, 3 = unable to perform usual activities).

Outcome measures

Measure	Total Group n=1003 Participants Participants who received at least one dose of open-label FDC treatment
Change From Baseline to End of Treatment in EQ-5D Usual Activities Score No problem -> No problem	805 participants
Change From Baseline to End of Treatment in EQ-5D Usual Activities Score No problem -> Some problem	54 participants
Change From Baseline to End of Treatment in EQ-5D Usual Activities Score No problem -> unable to perform usual activities	1 participants
Change From Baseline to End of Treatment in EQ-5D Usual Activities Score No problem -> no data	0 participants
Change From Baseline to End of Treatment in EQ-5D Usual Activities Score Some problem -> no problem	80 participants
Change From Baseline to End of Treatment in EQ-5D Usual Activities Score Some problem -> some problem	60 participants
Change From Baseline to End of Treatment in EQ-5D Usual Activities Score Some problem -> unable to perform usual activities	0 participants
Change From Baseline to End of Treatment in EQ-5D Usual Activities Score Some problem -> no data	0 participants
Change From Baseline to End of Treatment in EQ-5D Usual Activities Score Unable to perform usual activities -> no problem	1 participants
Change From Baseline to End of Treatment in EQ-5D Usual Activities Score Unable to perform usual activities -> some problem	2 participants
Change From Baseline to End of Treatment in EQ-5D Usual Activities Score Unable to perform usual activities -> same status	0 participants
Change From Baseline to End of Treatment in EQ-5D Usual Activities Score Unable to perform usual activities -> no data	0 participants
Change From Baseline to End of Treatment in EQ-5D Usual Activities Score No data -> no problem	1 participants
Change From Baseline to End of Treatment in EQ-5D Usual Activities Score No data -> some problem	0 participants
Change From Baseline to End of Treatment in EQ-5D Usual Activities Score No data -> unable to perform usual activities	0 participants
Change From Baseline to End of Treatment in EQ-5D Usual Activities Score No data -> no data	0 participants

SECONDARY outcome

Timeframe: Baseline and up to 52 weeks of FDC treatment

Population: FAS population with data available at both baseline and end of treatment and the exclusion of 5 participants with invalid questionnaires. LOCF imputation was used

The European quality of life-5 dimensions (EQ-5D) is an international standardized non-disease specific instrument for describing and valuing health status. The EQ5D has 5 domains: • mobility • self-care • usual activity • pain/discomfort • anxiety/depression Each domain has 3 response levels (1= no pain, 2= moderate pain, 3 = extreme pain).

Outcome measures

Measure	Total Group n=1002 Participants Participants who received at least one dose of open-label FDC treatment
Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score No pain -> no pain	499 participants
Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score No pain -> moderate pain	71 participants
Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score No pain -> extreme pain	2 participants
Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score No pain -> no data	0 participants
Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score Moderate pain -> no pain	202 participants
Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score Moderate pain -> moderate pain	200 participants
Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score Moderate pain -> extreme pain	5 participants
Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score Moderate pain -> no data	0 participants
Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score Extreme pain -> no pain	10 participants
Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score Extreme pain -> moderate pain	7 participants
Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score Extreme pain -> extreme pain	6 participants
Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score Extreme pain -> no data	0 participants
Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score No data -> no pain	2 participants
Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score No data -> moderate pain	0 participants
Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score No data -> extreme pain	0 participants
Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score No data -> no data	0 participants

SECONDARY outcome

Timeframe: Baseline and up to 52 weeks of FDC treatment

Population: FAS population with data available at both baseline and end of treatment and the exclusion of 5 participants with invalid questionnaires. LOCF imputation was used

The European quality of life-5 dimensions (EQ-5D) is an international standardized non-disease specific instrument for describing and valuing health status. The EQ5D has 5 domains: • mobility • self-care • usual activity • pain/discomfort • anxiety/depression Each domain has 3 response levels (1= not anxious, 2= moderately anxious, 3 = extremely anxious).

Outcome measures

Measure	Total Group n=1003 Participants Participants who received at least one dose of open-label FDC treatment
Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score No data -> no data	0 participants
Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score Not anxious -> Not anxious	737 participants
Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score Not anxious -> moderately anxious	37 participants
Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score Not anxious -> extremely anxious	1 participants
Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score Not anxious -> no data	0 participants
Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score Moderately anxious -> not anxious	103 participants
Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score Moderately anxious -> moderately anxious	109 participants
Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score Moderately anxious -> extremely anxious	3 participants
Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score Moderately anxious -> no data	0 participants
Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score Extremely anxious -> not anxious	4 participants
Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score Extremely anxious -> moderately anxious	4 participants
Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score Extremely anxious -> extremely anxious	5 participants
Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score Extremely anxious -> no data	0 participants
Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score No data -> not anxious	1 participants
Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score No data -> moderately anxious	0 participants
Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score No data -> extremely anxious	0 participants

SECONDARY outcome

Timeframe: Baseline and up to 52 weeks of FDC treatment

Population: FAS population with data available at both baseline and end of treatment and the exclusion of 5 participants with invalid questionnaires. LOCF imputation was used

Visual Analogue Scale (VAS) is part of the EQ-5D questionnaire. The VAS is self-rated by the participant ranging from 0 to 100 (worst imaginable health state to best imaginable health state).

Outcome measures

Measure	Total Group n=1000 Participants Participants who received at least one dose of open-label FDC treatment
Change From Baseline to End of Treatment in EQ-5D Visual Analogue Scale (VAS) Score	6.4 units on a scale Standard Deviation 17.15

Adverse Events

Total Group

Serious events: 64 serious events

Other events: 180 other events

Deaths: 0 deaths

Serious adverse events

Measure	Total Group n=1066 participants at risk Participants who received at least one dose of open-label FDC treatment
Infections and infestations Lobar pnemonia	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.19% 2/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.19% 2/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.19% 2/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder transitional cell carcinoma	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant peritoneal neoplasm	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm skin	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neuroendocrine tumor	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostatic adenoma	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal neoplasm	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Cardiac disorders Angina pectoris	0.19% 2/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Cardiac disorders Atrial fibillation	0.19% 2/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Cardiac disorders Myocardial infarction	0.19% 2/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Cardiac disorders Cardiac failure	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Cardiac disorders Coronary artery disease	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Cardiac disorders Coronary artery stenosis	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Cardiac disorders Sick sinus syndrome	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.28% 3/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Musculoskeletal and connective tissue disorders Back pain	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Musculoskeletal and connective tissue disorders Intervertebral disc disorder	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Musculoskeletal and connective tissue disorders Osteoarthritis	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Musculoskeletal and connective tissue disorders Osteonecrosis	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Musculoskeletal and connective tissue disorders Spondylolisthesis	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Nervous system disorders Transient ischaemic attack	0.19% 2/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Nervous system disorders Cerebral disorder	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Nervous system disorders Cerebrovascular accident	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Nervous system disorders Cerebrovascular disorder	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Nervous system disorders Lateral medullary syndrome	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Nervous system disorders Parkinsonism	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Nervous system disorders Spinal cord compression	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Renal and urinary disorders Urinary retention	0.56% 6/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Renal and urinary disorders Renal failure acute	0.19% 2/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Renal and urinary disorders Calculus ureteric	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Renal and urinary disorders Urinary tract obstruction	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Injury, poisoning and procedural complications Ankle fracture	0.19% 2/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Injury, poisoning and procedural complications Femur fracture	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Injury, poisoning and procedural complications Post procedural haematoma	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Injury, poisoning and procedural complications Post procedural haematuria	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Injury, poisoning and procedural complications Procedural pain	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Injury, poisoning and procedural complications Radius fracture	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Gastrointestinal disorders Gastric ulcer	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Gastrointestinal disorders Haemorrhoids	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Gastrointestinal disorders Inguinal hernia	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Gastrointestinal disorders Proctalgia	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Infections and infestations Anal abscess	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Infections and infestations Appendicitis	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Infections and infestations Bronchietasis	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Vascular disorders Aortic aneurysm	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Vascular disorders Deep vein thrombosis	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Vascular disorders Femoral arterial stenosis	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Vascular disorders Iliac artery occulsion	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Vascular disorders Orthostatic hypotension	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Eye disorders Cataract	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Eye disorders Macular degeneration	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Hepatobiliary disorders Cholangitis	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Hepatobiliary disorders Cholelithiasis	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Blood and lymphatic system disorders Anemia	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Immune system disorders Allergy to arthropod sting	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Investigations Hepatic enzyme increased	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Metabolism and nutrition disorders Hypokalaemia	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Psychiatric disorders Completed suicide	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Psychiatric disorders Depression	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Reproductive system and breast disorders Prostatomegaly	0.09% 1/1066 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)

Other adverse events

Measure	Total Group n=1066 participants at risk Participants who received at least one dose of open-label FDC treatment
Gastrointestinal disorders Constipation	5.2% 55/1066 • Number of events 61 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)
Gastrointestinal disorders Dry Mouth	12.4% 132/1066 • Number of events 138 • From first dose of double-blind study drug (if on FDC in 905-CL-055) or first open-label dose up to 30 days after last dose of open-label study drug (in 905-CL-057) (up to 56 weeks)

Additional Information

Medical Director, Global Medical Science

Astellas Pharma Europe B.V.

Email: astellas.resultsdisclosure@astellas.com

Results disclosure agreements

• Principal investigator is a sponsor employee Institute and/or Principle Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site's manuscript at least 90 days prior to publication for review and comment. Sponsor may delay the publication to seek patent approval.
• Publication restrictions are in place

Restriction type: OTHER