Benign Prostatic Hyperplasia, Lower Urinary Tract Symptoms
Conditions
Keywords
EC905, Solifenacin succinate, Tamsulosin hydrochloride OCAS, Treatment, Benign Prostatic Hyperplasia, Vesomni, Lower Urinary Tract Symptoms
Brief summary
Clinical study to examine the efficacy, safety and tolerability of combination therapy of tamsulosin hydrochloride and solifenacin succinate compared to monotherapy of tamsulosin hydrochloride in the treatment of males with LUTS associated with BPH with a substantial storage component.
Interventions
DRUGPlacebo tamsulosin hydrochloride OCAS 0.4 mg
tablet
DRUGPlacebo FDC tamsulosin hydrochloride/solifenacin succinate 0.4 mg/6 mg
tablet
DRUGPlacebo FDC tamsulosin hydrochloride/solifenacin succinate 0.4 mg/9 mg
tablet
tablet
Sponsors
Astellas Pharma Europe B.V.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
45 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Voiding and storage symptoms diagnosed as LUTS associated with BPH for ≥ 3 months * A total International Prostate Symptom Score (IPSS) of ≥13 * A maximum urinary flow rate of ≥4.0 mL/s and ≤12.0 mL/s, with voided volume of ≥120 mL during free flow * A micturition frequency of ≥8 and at least 2 episodes of urgency with Patient Perception of the Intensity of Urgency Scale grade 3 or 4 per day on average on the 3 day micturition diary (at randomization)
Exclusion criteria
* Any significant Post Void Residual volume (\>150 mL) * A prostate with estimated weight ≥75 ml as assessed by transvesical or transrectal ultrasound * Evidence of a symptomatic urinary tract infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to End of Treatment in Total International Prostate Symptom Score | Baseline and Week 12 | 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). |
| Change From Baseline to End of Treatment in Total Urgency Frequency Score (TUFS, Previously Known as Total Urgency Score [TUS]) | Baseline and Week 12 | 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 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to End of Treatment in Maximum Volume Voided Per Micturition | Baseline and Week 12 | 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. |
| Change From Baseline to End of Treatment in Mean Number of Urgency Episodes (PPIUS Grade 3 or 4) Per 24 Hours | Baseline and Week 12 | 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. |
| Change From Baseline to End of Treatment in Mean Number of Urgency Incontinence Episodes Per 24 Hours | Baseline and Week 12 | 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. |
| Change From Baseline to End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours | Baseline and Week 12 | 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. |
| Change From Baseline to End of Treatment in Mean Number of Nocturia Episodes Per 24 Hours | Baseline and Week 12 | 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. |
| Change From Baseline to End of Treatment in Mean Number of Pads Used Per 24 Hours | Baseline and Week 12 | 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. |
| Change From Baseline to End of Treatment in IPSS Voiding Score | Baseline and Week 12 | 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). |
| Change From Baseline to End of Treatment in IPSS Storage Score | Baseline and Week 12 | 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). |
| Change From Baseline to End of Treatment in IPSS QoL Score | Baseline and Week 12 | 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). |
| Change From Baseline to End of Treatment in Individual IPSS Scores | Baseline and Week 12 | 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. |
| Change From Baseline to End of Treatment in Symptom Bother Score | Baseline and Week 12 | 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. |
| Change From Baseline to End of Treatment in Health Related QoL (HRQoL) Subscale: Coping Score | Baseline and Week 12 | 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. |
| Change From Baseline to End of Treatment in HRQoL Subscale: Concern Score | Baseline and Week 12 | 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. |
| Change From Baseline to End of Treatment in HRQoL Subscale: Sleep Score | Baseline and Week 12 | 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. |
| Change From Baseline to End of Treatment in HRQoL Subscale: Social Score | Baseline and Week 12 | 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. |
| Change From Baseline to End of Treatment in HRQoL Subscale: Total Score | Baseline and Week 12 | 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. |
| Percentage of Participants Who Were OAB-q Responders at End of Treatment | Week 12 (end of treatment) | A OAB-q responder was defined as a participant with an improvement from baseline in HRQoL subscale total score ≥ 10. |
| Change From Baseline to End of Treatment in EQ-5D Mobility Score | Baseline and Week 12 | 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). |
| Change From Baseline to End of Treatment in EQ-5D Self-care Score | Baseline and Week 12 | 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). |
| Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | Baseline and Week 12 | 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). |
| Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | Baseline and Week 12 | 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). |
| Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Baseline and Week 12 | 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). |
| Change From Baseline to End of Treatment in EQ-5D Visual Analogue Scale (VAS) Score | Baseline and Week 12 | 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). |
| Patient Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Baseline and Week 12 | The Patient Global Impression (PGI) is a global questionnaire completed by the participant to assess both the change in the participants overall condition and the change in bladder symptoms since the start of the study. The questionnaire consists of 2 questions with 7 response levels ranging from 1 to 7 (very much improved to very much worse). |
| Patient Global Impression Scale at End of Treatment: General Health | Baseline and Week 12 | The Patient Global Impression (PGI) is a global questionnaire completed by the participant to assess both the change in the participants overall condition and the change in bladder symptoms since the start of the study. The questionnaire consists of 2 questions with 7 response levels ranging from 1 to 7 (very much improved to very much worse). |
| Clinician Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Baseline and Week 12 | The Clinician Global Impression (CGI) is a questionnaire completed by the physician to assess change in the participants bladder symptoms since the start of the study. The questionnaire consists of 1 question with 7 response levels ranging from 1 to 7 (very much improved to very much worse). |
| Number of Participants With Adverse Events (AEs) | From first dose of double-blind study drug up to 14 days of last dose of double-blind study drug (up to 14 weeks) | Safety is monitored by collecting AEs, which include abnormal laboratory parameters, vital signs or ECG data if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study medication or was clinically significant. A serious AE (SAE) was an event resulting in death, persistent or significant disability/incapacity or congenital anomaly or birth defect, was life-threatening, required or prolonged hospitalization or was considered medically important. AEs were assessed by the Investigator for intensity as 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 administration of the first dose of double-blind study drug until 14 days after the last dose of double-blind study drug. |
| Change From Baseline to End of Treatment in Post Void Residual (PVR) Volume | Baseline and Week 12 | PVR volume is the volume of urine retained after voiding. PVR volume was assessed by ultrasonography or bladder scan. |
| Change From Baseline to End of Treatment in Maximum Flow Rate (Qmax) | Baseline and Week 12 | Qmax during a micturition (urination) was recorded using uroflowmetry. |
| Change From Baseline to End of Treatment in Average Flow Rate (Qmean) | Baseline and Week 12 | Qmean during a micturition (urination) was recorded using uroflowmetry. |
| Apparent Clearance (CL/F) of Tamsulosin | Week 4, Week 8 and Week 12 | — |
| Maximum Concentration at Steady State (Cmaxss) of Tamsulosin | Week 4, Week 8 and Week 12 | — |
| Minimum Concentration at Steady State (Cminss) of Tamsulosin | Week 4, Week 8 and Week 12 | — |
| Time of Maximum Concentration at Steady State (Tmaxss) of Tamsulosin | Week 4, Week 8 and Week 12 | — |
| Area Under the Curve at Steady State (AUCss) of Tamsulosin | Week 4, Week 8 and Week 12 (collection time points: trough, 1-3 hours post dose, 4-5 hours post-dose and 7-10 hours post-dose) | — |
| CL/F of Solifenacin | Week 4, Week 8 and Week 12 | — |
| Change From Baseline to End of Treatment in Mean Number of Micturitions Per 24 Hours | Baseline and Week 12 | 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. |
| Cminss of Solifenacin | Week 4, Week 8 and Week 12 | — |
| Tmaxss of Solifenacin | Week 4, Week 8 and Week 12 | — |
| AUCss of Solifenacin | Week 4, Week 8 and Week 12 (collection time points: trough, 1-3 hours post dose, 4-5 hours post-dose and 7-10 hours post-dose) | — |
| Cmaxss of Solifenacin | Week 4, Week 8 and Week 12 | — |
| Change From Baseline to End of Treatment in Mean Voided Volume Per Micturition | Baseline and Week 12 | 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. |
Countries
Austria, Belarus, Belgium, Czechia, France, Germany, Hungary, Italy, Netherlands, Poland, Russia, Slovakia, United Kingdom
Participant flow
Pre-assignment details
Prior to randomization, participants entered a single-blind placebo run-in period for 2 weeks and completed a 3-day micturition diary. After the placebo run-in period, participants' eligibility criteria were re-confirmed and the participants were then randomized into the double-blind treatment period of the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received 3 tablets once a day for 12 weeks. Placebo tamsulosin hydrochloride oral controlled absorption system (OCAS) 0.4 mg tablet; Placebo fixed dose combination (FDC) tamsulosin hydrochloride/solifenacin succinate 0.4 mg/6 mg tablet; Placebo FDC tamsulosin hydrochloride/solifenacin succinate 0.4 mg/9 mg tablet | 341 |
| TOCAS 0.4 mg Participants received 3 tablets once a day for 12 weeks. Tamsulosin hydrochloride OCAS (TOCAS) 0.4 mg tablet; Placebo FDC tamsulosin hydrochloride/solifenacin succinate 0.4 mg/6 mg tablet; Placebo FDC tamsulosin hydrochloride/solifenacin succinate 0.4 mg/9 mg tablet | 326 |
| FDC 0.4 mg/6 mg Participants received 3 tablets once a day for 12 weeks. Placebo TOCAS 0.4 mg tablet; FDC tamsulosin hydrochloride/solifenacin succinate 0.4 mg/6 mg tablet; Placebo FDC tamsulosin hydrochloride/solifenacin succinate 0.4 mg/9 mg tablet | 337 |
| FDC 0.4 mg/9 mg Participants received 3 tablets once a day for 12 weeks. Placebo TOCAS 0.4 mg tablet; Placebo FDC tamsulosin hydrochloride/solifenacin succinate 0.4 mg/6 mg tablet; FDC tamsulosin hydrochloride/solifenacin succinate 0.4 mg/9 mg tablet | 324 |
| Total | 1,328 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 9 | 13 | 10 |
| Overall Study | Lack of Efficacy | 4 | 1 | 1 | 2 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 |
| Overall Study | Miscellaneous | 0 | 2 | 0 | 0 |
| Overall Study | Not fulfilling eligibility criteria | 6 | 7 | 7 | 3 |
| Overall Study | Protocol Violation | 5 | 8 | 7 | 9 |
| Overall Study | Withdrawal by Subject | 6 | 5 | 11 | 9 |
Baseline characteristics
| Characteristic | TOCAS 0.4 mg | Total | FDC 0.4 mg/9 mg | Placebo | FDC 0.4 mg/6 mg |
|---|---|---|---|---|---|
| Age, Continuous | 65.1 years STANDARD_DEVIATION 7.98 | 65.4 years STANDARD_DEVIATION 8.13 | 65.5 years STANDARD_DEVIATION 7.71 | 65.6 years STANDARD_DEVIATION 8.41 | 65.3 years STANDARD_DEVIATION 8.39 |
| Incontinence episodes/24 hours | 1.82 incontinence episodes STANDARD_DEVIATION 1.73 | 1.73 incontinence episodes STANDARD_DEVIATION 2.03 | 1.60 incontinence episodes STANDARD_DEVIATION 2.23 | 1.79 incontinence episodes STANDARD_DEVIATION 2.27 | 1.70 incontinence episodes STANDARD_DEVIATION 1.74 |
| IPSS Quality of Life (QoL) score | 4.1 units on a scale STANDARD_DEVIATION 1.07 | 4.1 units on a scale STANDARD_DEVIATION 1.11 | 4.1 units on a scale STANDARD_DEVIATION 1.08 | 4.1 units on a scale STANDARD_DEVIATION 1.12 | 4.0 units on a scale STANDARD_DEVIATION 1.15 |
| IPSS storage score | 8.9 units on a scale STANDARD_DEVIATION 2.33 | 8.8 units on a scale STANDARD_DEVIATION 2.38 | 8.8 units on a scale STANDARD_DEVIATION 2.36 | 9.0 units on a scale STANDARD_DEVIATION 2.42 | 8.6 units on a scale STANDARD_DEVIATION 2.39 |
| IPSS voiding score | 9.8 units on a scale STANDARD_DEVIATION 3.63 | 9.8 units on a scale STANDARD_DEVIATION 3.6 | 9.7 units on a scale STANDARD_DEVIATION 3.63 | 10.0 units on a scale STANDARD_DEVIATION 3.53 | 9.7 units on a scale STANDARD_DEVIATION 3.61 |
| Micturitions/24 hours | 11.68 micturitions STANDARD_DEVIATION 2.86 | 11.44 micturitions STANDARD_DEVIATION 2.64 | 11.23 micturitions STANDARD_DEVIATION 2.56 | 11.37 micturitions STANDARD_DEVIATION 2.52 | 11.48 micturitions STANDARD_DEVIATION 2.61 |
| Nocturia episodes/24 hours | 2.50 nocturia episodes STANDARD_DEVIATION 1.31 | 2.42 nocturia episodes STANDARD_DEVIATION 1.27 | 2.41 nocturia episodes STANDARD_DEVIATION 1.26 | 2.41 nocturia episodes STANDARD_DEVIATION 1.31 | 2.37 nocturia episodes STANDARD_DEVIATION 1.19 |
| Race/Ethnicity, Customized Asian | 0 participants | 4 participants | 0 participants | 3 participants | 1 participants |
| Race/Ethnicity, Customized Black | 1 participants | 4 participants | 2 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Other | 0 participants | 3 participants | 1 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized White | 325 participants | 1317 participants | 321 participants | 337 participants | 334 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 326 Participants | 1328 Participants | 324 Participants | 341 Participants | 337 Participants |
| Total International Prostate Symptom Score (IPSS) | 18.7 units on a scale STANDARD_DEVIATION 4.63 | 18.6 units on a scale STANDARD_DEVIATION 4.44 | 18.6 units on a scale STANDARD_DEVIATION 4.31 | 19.0 units on a scale STANDARD_DEVIATION 4.48 | 18.3 units on a scale STANDARD_DEVIATION 4.31 |
| Total Urgency Frequency Score (TUFS) (previously known as Total Urgency Score ([TUS]) | 27.85 units on a scale STANDARD_DEVIATION 9.02 | 27.09 units on a scale STANDARD_DEVIATION 8.71 | 26.39 units on a scale STANDARD_DEVIATION 8.34 | 27.15 units on a scale STANDARD_DEVIATION 8.8 | 26.97 units on a scale STANDARD_DEVIATION 8.66 |
| Urgency episodes/24 hours | 5.51 urgency episodes STANDARD_DEVIATION 3.27 | 5.36 urgency episodes STANDARD_DEVIATION 3.21 | 5.18 urgency episodes STANDARD_DEVIATION 3.09 | 5.47 urgency episodes STANDARD_DEVIATION 3.26 | 5.28 urgency episodes STANDARD_DEVIATION 3.22 |
| Urgency incontinence episodes/24 hours | 1.90 urgency incontinence episodes STANDARD_DEVIATION 1.75 | 1.70 urgency incontinence episodes STANDARD_DEVIATION 1.89 | 1.60 urgency incontinence episodes STANDARD_DEVIATION 2.24 | 1.62 urgency incontinence episodes STANDARD_DEVIATION 1.86 | 1.71 urgency incontinence episodes STANDARD_DEVIATION 1.59 |
| Volume voided/micturition | 158.80 mL STANDARD_DEVIATION 47.21 | 161.82 mL STANDARD_DEVIATION 48.14 | 167.35 mL STANDARD_DEVIATION 50.32 | 160.49 mL STANDARD_DEVIATION 47.24 | 160.74 mL STANDARD_DEVIATION 47.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 341 | 3 / 326 | 36 / 337 | 43 / 324 |
| serious Total, serious adverse events | 3 / 341 | 10 / 326 | 5 / 337 | 9 / 324 |
Outcome results
Primary
Change From Baseline to End of Treatment in Total International Prostate Symptom Score
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).
Time frame: Baseline and Week 12
Population: Full Analysis Set (FAS)-participants who received at least 1 dose of double-blind study drug and had either a total IPSS or TUS at baseline and at least 1 postbaseline total IPSS or TUS. Excluded 5 participants with invalid questionnaires. Last Observation Carried Forward (LOCF) imputation was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to End of Treatment in Total International Prostate Symptom Score | -5.4 units on a scale | Standard Error 0.41 |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in Total International Prostate Symptom Score | -6.2 units on a scale | Standard Error 0.42 |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in Total International Prostate Symptom Score | -7.0 units on a scale | Standard Error 0.41 |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in Total International Prostate Symptom Score | -6.5 units on a scale | Standard Error 0.42 |
Comparison: The non-inferiority of FDC vs TOCAS on the change from baseline to end of treatment in total IPSS. A FDC was regarded successful if it showed superiority vs. placebo for total IPSS, noninferiority vs. TOCAS alone for total IPSS along with superiority vs. TOCAS alone for TUS.p-value: 0.00197.5% CI: [-1.73, 0.11]Mixed Models Analysis
Comparison: The non-inferiority of FDC vs. TOCAS on the change from baseline to end of treatment in total IPSS. A FDC was regarded successful if it showed superiority vs. placebo for total IPSS, noninferiority vs. TOCAS alone for total IPSS along with superiority vs. TOCAS alone for TUS.p-value: 0.02897.5% CI: [-1.22, 0.64]Mixed Models Analysis
Comparison: The superiority of FDC vs. TOCAS on the change from baseline to end of treatment in total IPSS.p-value: 0.048Mixed Models Analysis
Comparison: The superiority of FDC vs. TOCAS on the change from baseline to end of treatment in total IPSS.p-value: 0.483Mixed Models Analysis
Comparison: The superiority of the FDC vs placebo on the change from baseline to end of treatment in total IPSS. A FDC was regarded successful if it showed superiority vs. placebo for total IPSS, noninferiority vs. TOCAS alone for total IPSS along with superiority vs. TOCAS alone for TUS.p-value: <0.00195% CI: [-2.4, -0.9]Mixed Models Analysis
Comparison: The superiority of the FDC vs. placebo on the change from baseline to end of treatment in total IPSS. A FDC was regarded successful if it showed superiority vs. placebo for total IPSS, noninferiority vs. TOCAS alone for total IPSS along with superiority vs. TOCAS alone for TUS.p-value: 0.00695% CI: [-1.9, -0.3]Mixed Models Analysis
Comparison: The superiority of TOCAS vs. placebo on the change from baseline to end of treatment in total IPSS. With a sample size of 274 participants per arm, the overall power to meet this outcome measure was 97% power for superiority vs placebo for total IPSS.p-value: 0.03995% CI: [-1.6, 0]Mixed Models Analysis
Primary
Change From Baseline to End of Treatment in Total Urgency Frequency Score (TUFS, Previously Known as Total Urgency Score [TUS])
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 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.
Time frame: Baseline and Week 12
Population: FAS population. LOCF imputation was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to End of Treatment in Total Urgency Frequency Score (TUFS, Previously Known as Total Urgency Score [TUS]) | -4.4 units on a scale | Standard Error 0.68 |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in Total Urgency Frequency Score (TUFS, Previously Known as Total Urgency Score [TUS]) | -6.7 units on a scale | Standard Error 0.69 |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in Total Urgency Frequency Score (TUFS, Previously Known as Total Urgency Score [TUS]) | -8.1 units on a scale | Standard Error 0.67 |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in Total Urgency Frequency Score (TUFS, Previously Known as Total Urgency Score [TUS]) | -7.6 units on a scale | Standard Error 0.69 |
Comparison: The superiority of FDC 0.4 mg/6 mg vs. TOCAS in the change from baseline to end of treatment in TUS. A FDC was regarded successful if it showed superiority vs. placebo for total IPSS, noninferiority vs. TOCAS alone for total IPSS along with superiority vs. TOCAS alone for TUS.p-value: 0.02597.5% CI: [-2.9, 0]Mixed Models Analysis
Comparison: The superiority of FDC 0.4 mg/6 mg vs. TOCAS in the change from baseline to end of treatment in TUS. A FDC was regarded successful if it showed superiority vs. placebo for total IPSS, noninferiority vs. TOCAS alone for total IPSS along with superiority vs. TOCAS alone for TUS.p-value: 0.16297.5% CI: [-2.3, 0.5]Mixed Models Analysis
Comparison: The superiority of FDC 0.4 mg/6 mg vs. placebo on the change from baseline to end of treatment in TUS.p-value: <0.00195% CI: [-4.9, -2.5]Mixed Models Analysis
Comparison: The superiority of FDC 0.4 mg/9 mg vs. placebo on the change from baseline to end of treatment in TUS.p-value: <0.00195% CI: [-4.4, -1.9]Mixed Models Analysis
Comparison: The superiority of TOCAS vs. placebo on the change from baseline to end of treatment in TUS.p-value: <0.00195% CI: [-3.5, -1]Mixed Models Analysis
Secondary
Apparent Clearance (CL/F) of Tamsulosin
Time frame: Week 4, Week 8 and Week 12
Population: Pharmacokinetics Analysis Set (PKAS)- randomized participants who received at least 1 dose of double-blind study drug and had at least 1 quantifiable plasma concentration of tamsulosin OCAS and/or solifenacin. N indicates the number of participants with available data at each timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Apparent Clearance (CL/F) of Tamsulosin | Week 12 [N=163; 167; 166] | 2.52 L/h | Geometric Coefficient of Variation 85.3 |
| Placebo | Apparent Clearance (CL/F) of Tamsulosin | Week 8 [N=255; 259; 248] | 2.62 L/h | Geometric Coefficient of Variation 79 |
| Placebo | Apparent Clearance (CL/F) of Tamsulosin | Week 4 [N=263; 281; 274] | 2.78 L/h | Geometric Coefficient of Variation 84.8 |
| TOCAS 0.4 mg | Apparent Clearance (CL/F) of Tamsulosin | Week 12 [N=163; 167; 166] | 2.40 L/h | Geometric Coefficient of Variation 74.1 |
| TOCAS 0.4 mg | Apparent Clearance (CL/F) of Tamsulosin | Week 8 [N=255; 259; 248] | 2.41 L/h | Geometric Coefficient of Variation 79.5 |
| TOCAS 0.4 mg | Apparent Clearance (CL/F) of Tamsulosin | Week 4 [N=263; 281; 274] | 2.61 L/h | Geometric Coefficient of Variation 85.8 |
| FDC 0.4 mg/6 mg | Apparent Clearance (CL/F) of Tamsulosin | Week 12 [N=163; 167; 166] | 2.46 L/h | Geometric Coefficient of Variation 85.9 |
| FDC 0.4 mg/6 mg | Apparent Clearance (CL/F) of Tamsulosin | Week 4 [N=263; 281; 274] | 2.53 L/h | Geometric Coefficient of Variation 79.3 |
| FDC 0.4 mg/6 mg | Apparent Clearance (CL/F) of Tamsulosin | Week 8 [N=255; 259; 248] | 2.36 L/h | Geometric Coefficient of Variation 93.3 |
Secondary
Area Under the Curve at Steady State (AUCss) of Tamsulosin
Time frame: Week 4, Week 8 and Week 12 (collection time points: trough, 1-3 hours post dose, 4-5 hours post-dose and 7-10 hours post-dose)
Population: PKAS population. N indicates the number of participants with available data at each timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Area Under the Curve at Steady State (AUCss) of Tamsulosin | Week 12 [N= 163; 167; 166] | 159 ng.h/mL | Geometric Coefficient of Variation 78.1 |
| Placebo | Area Under the Curve at Steady State (AUCss) of Tamsulosin | Week 8 [N= 255; 259; 248] | 153 ng.h/mL | Geometric Coefficient of Variation 81.6 |
| Placebo | Area Under the Curve at Steady State (AUCss) of Tamsulosin | Week 4 [N= 263; 281; 274] | 144 ng.h/mL | Geometric Coefficient of Variation 96.7 |
| TOCAS 0.4 mg | Area Under the Curve at Steady State (AUCss) of Tamsulosin | Week 12 [N= 163; 167; 166] | 167 ng.h/mL | Geometric Coefficient of Variation 77.4 |
| TOCAS 0.4 mg | Area Under the Curve at Steady State (AUCss) of Tamsulosin | Week 8 [N= 255; 259; 248] | 166 ng.h/mL | Geometric Coefficient of Variation 84 |
| TOCAS 0.4 mg | Area Under the Curve at Steady State (AUCss) of Tamsulosin | Week 4 [N= 263; 281; 274] | 153 ng.h/mL | Geometric Coefficient of Variation 111 |
| FDC 0.4 mg/6 mg | Area Under the Curve at Steady State (AUCss) of Tamsulosin | Week 12 [N= 163; 167; 166] | 162 ng.h/mL | Geometric Coefficient of Variation 94.8 |
| FDC 0.4 mg/6 mg | Area Under the Curve at Steady State (AUCss) of Tamsulosin | Week 8 [N= 255; 259; 248] | 169 ng.h/mL | Geometric Coefficient of Variation 96.9 |
| FDC 0.4 mg/6 mg | Area Under the Curve at Steady State (AUCss) of Tamsulosin | Week 4 [N= 263; 281; 274] | 158 ng.h/mL | Geometric Coefficient of Variation 96.5 |
Secondary
AUCss of Solifenacin
Time frame: Week 4, Week 8 and Week 12 (collection time points: trough, 1-3 hours post dose, 4-5 hours post-dose and 7-10 hours post-dose)
Population: PKAS population. N indicates the number of participants with available data at each timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | AUCss of Solifenacin | Week 4 [N= 281; 273] | 657 ng.h/mL | Geometric Coefficient of Variation 46.8 |
| Placebo | AUCss of Solifenacin | Week 8 [N= 258; 248] | 673 ng.h/mL | Geometric Coefficient of Variation 50.3 |
| Placebo | AUCss of Solifenacin | Week 12 [N= 166; 167] | 652 ng.h/mL | Geometric Coefficient of Variation 51.8 |
| TOCAS 0.4 mg | AUCss of Solifenacin | Week 4 [N= 281; 273] | 970 ng.h/mL | Geometric Coefficient of Variation 53.7 |
| TOCAS 0.4 mg | AUCss of Solifenacin | Week 8 [N= 258; 248] | 1020 ng.h/mL | Geometric Coefficient of Variation 50.7 |
| TOCAS 0.4 mg | AUCss of Solifenacin | Week 12 [N= 166; 167] | 988 ng.h/mL | Geometric Coefficient of Variation 53 |
Secondary
Change From Baseline to End of Treatment in Average Flow Rate (Qmean)
Qmean during a micturition (urination) was recorded using uroflowmetry.
Time frame: Baseline and Week 12
Population: SAF population with at least one baseline and one post-baseline micturition episode.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to End of Treatment in Average Flow Rate (Qmean) | 1.5 mL/s | Standard Deviation 2.61 |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in Average Flow Rate (Qmean) | 1.3 mL/s | Standard Deviation 2.16 |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in Average Flow Rate (Qmean) | 1.9 mL/s | Standard Deviation 2.75 |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in Average Flow Rate (Qmean) | 1.7 mL/s | Standard Deviation 2.98 |
Secondary
Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score
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).
Time frame: Baseline and Week 12
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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Not anxious -> Moderately anxious | 16 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | No data -> Not anxious | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Moderately anxious -> No data | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Moderately anxious -> Not anxious | 34 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Moderately anxious -> Moderately anxious | 42 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Extremely anxious -> No data | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Extremely anxious -> Moderately anxious | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Extremely anxious -> Extremely anxious | 1 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Moderately anxious -> Extremely anxious | 1 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Not anxious -> Extremely anxious | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | No data -> Extremely anxious | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Not anxious -> No data | 3 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Extremely anxious -> Not anxious | 2 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | No data -> Moderately anxious | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | No data -> No data | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Not anxious -> Not anxious | 219 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Extremely anxious -> Not anxious | 0 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | No data -> Not anxious | 1 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | No data -> Moderately anxious | 0 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Not anxious -> No data | 0 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | No data -> Extremely anxious | 0 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | No data -> No data | 0 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Moderately anxious -> Not anxious | 25 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Moderately anxious -> Moderately anxious | 43 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Not anxious -> Moderately anxious | 11 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Moderately anxious -> Extremely anxious | 2 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Moderately anxious -> No data | 1 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Not anxious -> Not anxious | 213 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Extremely anxious -> Moderately anxious | 0 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Not anxious -> Extremely anxious | 0 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Extremely anxious -> Extremely anxious | 2 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Extremely anxious -> No data | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | No data -> No data | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Not anxious -> Not anxious | 233 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | No data -> Extremely anxious | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Extremely anxious -> Extremely anxious | 3 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Extremely anxious -> Not anxious | 1 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Not anxious -> No data | 1 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Not anxious -> Extremely anxious | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Extremely anxious -> Moderately anxious | 1 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | No data -> Not anxious | 1 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | No data -> Moderately anxious | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Moderately anxious -> Extremely anxious | 1 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Not anxious -> Moderately anxious | 16 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Moderately anxious -> Moderately anxious | 39 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Moderately anxious -> Not anxious | 27 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Extremely anxious -> No data | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Moderately anxious -> No data | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | No data -> No data | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Not anxious -> Not anxious | 214 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Not anxious -> Moderately anxious | 18 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Not anxious -> Extremely anxious | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Not anxious -> No data | 3 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Moderately anxious -> Not anxious | 25 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Moderately anxious -> Moderately anxious | 34 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Moderately anxious -> Extremely anxious | 1 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Moderately anxious -> No data | 1 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Extremely anxious -> Not anxious | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Extremely anxious -> Moderately anxious | 3 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Extremely anxious -> Extremely anxious | 2 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | Extremely anxious -> No data | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | No data -> Not anxious | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | No data -> Extremely anxious | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Anxiety/Depression Score | No data -> Moderately anxious | 0 participants |
Secondary
Change From Baseline to End of Treatment in EQ-5D Mobility Score
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).
Time frame: Baseline and Week 12
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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Change From Baseline to End of Treatment in EQ-5D Mobility Score | No data -> Some problem | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Mobility Score | Some problem -> No problem | 19 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Mobility Score | No problem -> No problem | 240 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Mobility Score | Some problem -> No data | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Mobility Score | No problem -> Some problem | 16 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Mobility Score | Some problem -> Some problem | 40 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Mobility Score | Confined to bed -> Confined to bed | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Mobility Score | Some problem -> Confined to bed | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Mobility Score | No data -> No problem | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Mobility Score | No data -> Confined to bed | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Mobility Score | Confined to bed -> No data | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Mobility Score | Confined to bed -> Some problem | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Mobility Score | No problem -> Confined to bed | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Mobility Score | No data -> No data | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Mobility Score | No problem -> No data | 3 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Mobility Score | Confined to bed -> No problem | 0 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | No data -> Some problem | 0 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | No data -> No problem | 1 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | No problem -> No data | 1 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | No data -> Confined to bed | 0 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | No data -> No data | 0 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | No problem -> No problem | 230 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | Some problem -> No problem | 21 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | Some problem -> Some problem | 31 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | No problem -> Some problem | 13 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | Some problem -> Confined to bed | 0 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | Some problem -> No data | 0 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | Confined to bed -> No problem | 0 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | Confined to bed -> Some problem | 0 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | No problem -> Confined to bed | 1 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | Confined to bed -> Confined to bed | 0 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | Confined to bed -> No data | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | No problem -> No problem | 255 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | No data -> No data | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | Confined to bed -> Confined to bed | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | Confined to bed -> No problem | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | No problem -> No data | 1 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | No data -> Confined to bed | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | No problem -> Confined to bed | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | Confined to bed -> Some problem | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | No data -> No problem | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | Some problem -> Some problem | 35 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | No data -> Some problem | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | Some problem -> Confined to bed | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | No problem -> Some problem | 10 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | Some problem -> No problem | 12 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | Confined to bed -> No data | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | Some problem -> No data | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | Confined to bed -> Some problem | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | No problem -> No problem | 233 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | No problem -> Some problem | 13 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | No problem -> Confined to bed | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | No problem -> No data | 3 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | Some problem -> No problem | 19 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | Some problem -> Some problem | 31 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | Some problem -> Confined to bed | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | Some problem -> No data | 1 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | Confined to bed -> No problem | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | No data -> No data | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | Confined to bed -> Confined to bed | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | Confined to bed -> No data | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | No data -> No problem | 1 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | No data -> Some problem | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Mobility Score | No data -> Confined to bed | 0 participants |
Secondary
Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score
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).
Time frame: Baseline and Week 12
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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | No pain -> Moderate pain | 14 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | Moderate pain-> No pain | 55 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | No data -> No pain | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | Moderate pain-> No data | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | Extreme pain -> Extreme pain | 1 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | Moderate pain-> Moderate pain | 73 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | No pain -> No data | 3 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | Moderate pain-> Extreme pain | 2 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | No data -> Extreme pain | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | No data -> Moderate pain | 2 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | Extreme pain -> Moderate pain | 4 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | Extreme pain -> No pain | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | No data -> No data | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | Extreme pain -> No data | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | No pain -> Extreme pain | 2 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | No pain -> No pain | 162 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | Moderate pain-> No pain | 41 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | No data -> No pain | 2 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | No data -> Moderate pain | 0 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | No pain -> No data | 0 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | No data -> Extreme pain | 0 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | No data -> No data | 0 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | No pain -> Moderate pain | 14 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | Moderate pain-> Moderate pain | 72 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | Moderate pain-> Extreme pain | 2 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | Moderate pain-> No data | 2 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | Extreme pain -> No pain | 1 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | No pain -> Extreme pain | 1 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | Extreme pain -> Moderate pain | 2 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | Extreme pain -> Extreme pain | 2 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | No pain -> No pain | 159 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | Extreme pain -> No data | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | No data -> No data | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | No pain -> No data | 1 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | No data -> No pain | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | Extreme pain -> No pain | 1 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | Extreme pain -> Extreme pain | 2 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | No data -> Extreme pain | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | Extreme pain -> No data | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | Extreme pain -> Moderate pain | 2 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | No pain -> Moderate pain | 19 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | Moderate pain-> Moderate pain | 72 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | No pain -> Extreme pain | 1 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | Moderate pain-> Extreme pain | 1 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | No pain -> No pain | 153 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | Moderate pain-> No pain | 61 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | No data -> Moderate pain | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | Moderate pain-> No data | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | No data -> No data | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | No pain -> No pain | 152 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | No pain -> Moderate pain | 24 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | No pain -> Extreme pain | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | No pain -> No data | 2 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | Moderate pain-> No pain | 41 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | Moderate pain-> Moderate pain | 70 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | Moderate pain-> Extreme pain | 1 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | Moderate pain-> No data | 2 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | Extreme pain -> No pain | 3 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | Extreme pain -> Moderate pain | 4 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | Extreme pain -> Extreme pain | 2 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | Extreme pain -> No data | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | No data -> No pain | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | No data -> Moderate pain | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Pain/Discomfort Score | No data -> Extreme pain | 0 participants |
Secondary
Change From Baseline to End of Treatment in EQ-5D Self-care Score
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).
Time frame: Baseline and Week 12
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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Change From Baseline to End of Treatment in EQ-5D Self-care Score | Some problem -> No problem | 8 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Self-care Score | No problem -> Some problem | 8 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Self-care Score | No problem -> Unable to wash/ dress | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Self-care Score | No problem -> No Data | 3 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Self-care Score | No problem -> No problem | 295 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Self-care Score | Some problem -> Some problem | 3 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Self-care Score | Some problem -> Unable to wash/ dress | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Self-care Score | Some problem -> No data | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Self-care Score | Unable to wash/ dress -> No problem | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Self-care Score | Unable to wash/ dress -> Some problem | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Self-care Score | Unable to wash/ dress -> Unable to wash/ dress | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Self-care Score | Unable to wash/ dress -> No data | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Self-care Score | No data -> No problem | 1 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Self-care Score | No data -> Some problem | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Self-care Score | No data -> Unable to wash/ dress | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Self-care Score | No data -> No data | 0 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | Some problem -> Some problem | 8 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | Unable to wash/ dress -> No problem | 0 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | No data -> No data | 0 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | Unable to wash/ dress -> No data | 0 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | No data -> Unable to wash/ dress | 0 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | Unable to wash/ dress -> Some problem | 0 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | No problem -> Unable to wash/ dress | 0 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | Unable to wash/ dress -> Unable to wash/ dress | 1 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | Some problem -> No problem | 6 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | Some problem -> Unable to wash/ dress | 0 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | No problem -> No Data | 1 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | No problem -> Some problem | 8 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | No data -> No problem | 1 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | Some problem -> No data | 0 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | No data -> Some problem | 0 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | No problem -> No problem | 273 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | Some problem -> Some problem | 6 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | Some problem -> No problem | 8 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | No data -> Some problem | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | Some problem -> Unable to wash/ dress | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | Some problem -> No data | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | No data -> No data | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | Unable to wash/ dress -> No problem | 1 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | Unable to wash/ dress -> Some problem | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | No data -> Unable to wash/ dress | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | Unable to wash/ dress -> Unable to wash/ dress | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | Unable to wash/ dress -> No data | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | No problem -> No problem | 293 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | No problem -> Some problem | 3 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | No data -> No problem | 1 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | No problem -> Unable to wash/ dress | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | No problem -> No Data | 1 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | No data -> No data | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | Some problem -> No data | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | No problem -> Unable to wash/ dress | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | No problem -> No problem | 286 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | No data -> Some problem | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | Some problem -> Unable to wash/ dress | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | No data -> No problem | 1 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | No problem -> Some problem | 4 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | Some problem -> No problem | 3 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | Unable to wash/ dress -> Some problem | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | Some problem -> Some problem | 3 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | Unable to wash/ dress -> Unable to wash/ dress | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | No data -> Unable to wash/ dress | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | Unable to wash/ dress -> No problem | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | No problem -> No Data | 4 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Self-care Score | Unable to wash/ dress -> No data | 0 participants |
Secondary
Change From Baseline to End of Treatment in EQ-5D Usual Activities Score
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).
Time frame: Baseline and Week 12
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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | No problem -> No problem | 254 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | Some problem -> No problem | 21 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | No problem -> No data | 3 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | Unable to perform usual activities -> No problem | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | No problem -> Some problem | 18 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | Some problem -> Some problem | 22 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | Some problem -> No data | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | No data -> Unable to perform usual activities | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | Some problem -> Unable to perform usual activities | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | No data -> Some problem | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | Unable to perform usual activities -> same status | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | Unable to perform usual activities -> Some problem | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | No data -> No data | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | Unable to perform usual activities -> No data | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | No problem -> Unable to perform usual activities | 0 participants |
| Placebo | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | No data -> No problem | 0 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | Unable to perform usual activities -> same status | 1 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | No data -> No problem | 2 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | No data -> Some problem | 0 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | No problem -> No data | 1 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | No data -> Unable to perform usual activities | 0 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | No data -> No data | 0 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | Some problem -> Some problem | 28 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | Some problem -> No problem | 22 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | No problem -> Some problem | 13 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | Some problem -> Unable to perform usual activities | 0 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | Some problem -> No data | 0 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | No problem -> No problem | 228 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | Unable to perform usual activities -> No problem | 1 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | Unable to perform usual activities -> Some problem | 1 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | No problem -> Unable to perform usual activities | 1 participants |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | Unable to perform usual activities -> No data | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | Some problem -> No problem | 26 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | No data -> No problem | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | Unable to perform usual activities -> No problem | 2 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | No data -> No data | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | No problem -> No data | 1 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | No problem -> No problem | 248 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | Unable to perform usual activities -> Some problem | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | Unable to perform usual activities -> No data | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | No data -> Unable to perform usual activities | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | No data -> Some problem | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | Some problem -> Unable to perform usual activities | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | No problem -> Some problem | 14 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | Some problem -> Some problem | 22 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | Unable to perform usual activities -> same status | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | Some problem -> No data | 0 participants |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | No problem -> Unable to perform usual activities | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | No data -> No data | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | No problem -> No problem | 235 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | No problem -> Some problem | 18 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | No problem -> Unable to perform usual activities | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | No problem -> No data | 3 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | Some problem -> No problem | 27 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | Some problem -> Some problem | 17 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | Some problem -> Unable to perform usual activities | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | Some problem -> No data | 1 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | Unable to perform usual activities -> No problem | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | Unable to perform usual activities -> Some problem | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | Unable to perform usual activities -> same status | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | Unable to perform usual activities -> No data | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | No data -> No problem | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | No data -> Some problem | 0 participants |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Usual Activities Score | No data -> Unable to perform usual activities | 0 participants |
Secondary
Change From Baseline to End of Treatment in EQ-5D Visual Analogue Scale (VAS) Score
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).
Time frame: Baseline and Week 12
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to End of Treatment in EQ-5D Visual Analogue Scale (VAS) Score | 4.0 units on a scale | Standard Deviation 14.48 |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in EQ-5D Visual Analogue Scale (VAS) Score | 3.7 units on a scale | Standard Deviation 12.69 |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in EQ-5D Visual Analogue Scale (VAS) Score | 5.5 units on a scale | Standard Deviation 13.58 |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in EQ-5D Visual Analogue Scale (VAS) Score | 6.2 units on a scale | Standard Deviation 15.52 |
Secondary
Change From Baseline to End of Treatment in Health Related QoL (HRQoL) Subscale: Coping Score
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.
Time frame: Baseline and Week 12
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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to End of Treatment in Health Related QoL (HRQoL) Subscale: Coping Score | 8.8 units on a scale | Standard Error 1.24 |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in Health Related QoL (HRQoL) Subscale: Coping Score | 11.0 units on a scale | Standard Error 1.26 |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in Health Related QoL (HRQoL) Subscale: Coping Score | 13.9 units on a scale | Standard Error 1.24 |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in Health Related QoL (HRQoL) Subscale: Coping Score | 13.4 units on a scale | Standard Error 1.26 |
Comparison: Mean change vs TOCAS.p-value: 0.01195% CI: [0.7, 5.2]Mixed Models Analysis
Comparison: Mean change vs TOCAS.p-value: 0.03595% CI: [0.2, 4.8]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: <0.00195% CI: [2.8, 7.3]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: <0.00195% CI: [2.3, 6.8]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: 0.06895% CI: [-0.2, 4.4]Mixed Models Analysis
Secondary
Change From Baseline to End of Treatment in HRQoL Subscale: Concern Score
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.
Time frame: Baseline and Week 12
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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to End of Treatment in HRQoL Subscale: Concern Score | 7.5 units on a scale | Standard Error 1.19 |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in HRQoL Subscale: Concern Score | 9.3 units on a scale | Standard Error 1.21 |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in HRQoL Subscale: Concern Score | 12.0 units on a scale | Standard Error 1.19 |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in HRQoL Subscale: Concern Score | 11.5 units on a scale | Standard Error 1.21 |
Comparison: Mean change vs TOCAS.p-value: 0.01395% CI: [0.5, 4.7]Mixed Models Analysis
Comparison: Mean change vs TOCAS.p-value: 0.04395% CI: [0.1, 4.3]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: <0.00195% CI: [2.4, 6.5]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: <0.00195% CI: [1.9, 6.1]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: 0.09295% CI: [-0.3, 3.9]Mixed Models Analysis
Secondary
Change From Baseline to End of Treatment in HRQoL Subscale: Sleep Score
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.
Time frame: Baseline and Week 12
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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to End of Treatment in HRQoL Subscale: Sleep Score | 8.3 units on a scale | Standard Error 1.31 |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in HRQoL Subscale: Sleep Score | 8.8 units on a scale | Standard Error 1.33 |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in HRQoL Subscale: Sleep Score | 11.9 units on a scale | Standard Error 1.31 |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in HRQoL Subscale: Sleep Score | 10.0 units on a scale | Standard Error 1.33 |
Comparison: Mean change vs TOCAS.p-value: 0.01195% CI: [0.7, 5.5]Mixed Models Analysis
Comparison: Mean change vs TOCAS.p-value: 0.31495% CI: [-1.2, 3.6]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: 0.00395% CI: [1.2, 5.9]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: 0.16195% CI: [-0.7, 4.1]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: 0.70895% CI: [-1.9, 2.8]Mixed Models Analysis
Secondary
Change From Baseline to End of Treatment in HRQoL Subscale: Social Score
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.
Time frame: Baseline and Week 12
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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to End of Treatment in HRQoL Subscale: Social Score | 3.8 units on a scale | Standard Error 0.96 |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in HRQoL Subscale: Social Score | 4.5 units on a scale | Standard Error 0.97 |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in HRQoL Subscale: Social Score | 6.2 units on a scale | Standard Error 0.95 |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in HRQoL Subscale: Social Score | 5.8 units on a scale | Standard Error 0.97 |
Comparison: Mean change vs TOCAS.p-value: 0.04395% CI: [0.1, 3.3]Mixed Models Analysis
Comparison: Mean change vs TOCAS.p-value: 0.1295% CI: [-0.3, 3]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: 0.00395% CI: [0.8, 4]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: 0.01495% CI: [0.4, 3.7]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: 0.38495% CI: [-0.9, 2.4]Mixed Models Analysis
Secondary
Change From Baseline to End of Treatment in HRQoL Subscale: Total Score
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.
Time frame: Baseline and Week 12
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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to End of Treatment in HRQoL Subscale: Total Score | 7.4 units on a scale | Standard Error 1.06 |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in HRQoL Subscale: Total Score | 8.8 units on a scale | Standard Error 1.08 |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in HRQoL Subscale: Total Score | 11.4 units on a scale | Standard Error 1.06 |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in HRQoL Subscale: Total Score | 10.7 units on a scale | Standard Error 1.08 |
Comparison: Mean change vs TOCAS.p-value: 0.00495% CI: [0.8, 4.4]Mixed Models Analysis
Comparison: Mean change vs TOCAS.p-value: 0.03595% CI: [0.1, 3.8]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: <0.00195% CI: [2.2, 5.8]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: <0.00195% CI: [1.5, 5.1]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: 0.14295% CI: [-0.5, 3.2]Mixed Models Analysis
Secondary
Change From Baseline to End of Treatment in Individual IPSS Scores
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.
Time frame: Baseline and Week 12
Population: FAS population with the exclusion of 5 participants with invalid questionnaires. LOCF imputation was used.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to End of Treatment in Individual IPSS Scores | Incomplete emptying of the bladder | -0.9 units on a scale | Standard Error 1.54 |
| Placebo | Change From Baseline to End of Treatment in Individual IPSS Scores | Hesitancy | -0.5 units on a scale | Standard Error 1.37 |
| Placebo | Change From Baseline to End of Treatment in Individual IPSS Scores | Weak stream | -1.1 units on a scale | Standard Error 1.54 |
| Placebo | Change From Baseline to End of Treatment in Individual IPSS Scores | Frequency | -1.0 units on a scale | Standard Error 1.36 |
| Placebo | Change From Baseline to End of Treatment in Individual IPSS Scores | Nocturia | -0.5 units on a scale | Standard Error 1.23 |
| Placebo | Change From Baseline to End of Treatment in Individual IPSS Scores | Intermittency | -0.9 units on a scale | Standard Error 1.41 |
| Placebo | Change From Baseline to End of Treatment in Individual IPSS Scores | Urgency | -1.2 units on a scale | Standard Error 1.55 |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in Individual IPSS Scores | Hesitancy | -0.7 units on a scale | Standard Error 1.26 |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in Individual IPSS Scores | Urgency | -1.3 units on a scale | Standard Error 1.61 |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in Individual IPSS Scores | Intermittency | -0.8 units on a scale | Standard Error 1.35 |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in Individual IPSS Scores | Weak stream | -1.3 units on a scale | Standard Error 1.57 |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in Individual IPSS Scores | Nocturia | -0.7 units on a scale | Standard Error 1.08 |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in Individual IPSS Scores | Frequency | -1.2 units on a scale | Standard Error 1.42 |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in Individual IPSS Scores | Incomplete emptying of the bladder | -0.9 units on a scale | Standard Error 1.52 |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in Individual IPSS Scores | Urgency | -1.4 units on a scale | Standard Error 1.51 |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in Individual IPSS Scores | Incomplete emptying of the bladder | -1.0 units on a scale | Standard Error 1.63 |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in Individual IPSS Scores | Frequency | -1.3 units on a scale | Standard Error 1.49 |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in Individual IPSS Scores | Intermittency | -1.0 units on a scale | Standard Error 1.47 |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in Individual IPSS Scores | Weak stream | -1.3 units on a scale | Standard Error 1.51 |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in Individual IPSS Scores | Hesitancy | -0.8 units on a scale | Standard Error 1.34 |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in Individual IPSS Scores | Nocturia | -0.8 units on a scale | Standard Error 1.08 |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in Individual IPSS Scores | Intermittency | -0.7 units on a scale | Standard Error 1.34 |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in Individual IPSS Scores | Nocturia | -0.6 units on a scale | Standard Error 1.15 |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in Individual IPSS Scores | Hesitancy | -0.7 units on a scale | Standard Error 1.29 |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in Individual IPSS Scores | Frequency | -1.4 units on a scale | Standard Error 1.41 |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in Individual IPSS Scores | Incomplete emptying of the bladder | -1.0 units on a scale | Standard Error 1.48 |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in Individual IPSS Scores | Weak stream | -1.3 units on a scale | Standard Error 1.56 |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in Individual IPSS Scores | Urgency | -1.6 units on a scale | Standard Error 1.5 |
Secondary
Change From Baseline to End of Treatment in IPSS QoL Score
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).
Time frame: Baseline and Week 12
Population: FAS population with the exclusion of 5 participants with invalid questionnaires. LOCF imputation was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to End of Treatment in IPSS QoL Score | -0.9 units on a scale | Standard Error 0.11 |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in IPSS QoL Score | -1.0 units on a scale | Standard Error 0.11 |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in IPSS QoL Score | -1.3 units on a scale | Standard Error 0.11 |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in IPSS QoL Score | -1.3 units on a scale | Standard Error 0.11 |
Comparison: Mean change vs TOCAS.p-value: 0.00895% CI: [-0.5, -0.1]Mixed Models Analysis
Comparison: Mean change vs TOCAS.p-value: 0.02195% CI: [-0.4, 0]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: <0.00195% CI: [-0.6, -0.2]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: <0.00195% CI: [-0.6, -0.2]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: 0.13995% CI: [-0.3, 0]Mixed Models Analysis
Secondary
Change From Baseline to End of Treatment in IPSS Storage Score
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).
Time frame: Baseline and Week 12
Population: FAS population with the exclusion of 5 participants with invalid questionnaires. LOCF imputation was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to End of Treatment in IPSS Storage Score | -2.4 units on a scale | Standard Error 0.2 |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in IPSS Storage Score | -2.9 units on a scale | Standard Error 0.2 |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in IPSS Storage Score | -3.5 units on a scale | Standard Error 0.2 |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in IPSS Storage Score | -3.3 units on a scale | Standard Error 0.21 |
Comparison: Mean change vs TOCAS.p-value: 0.00995% CI: [-0.9, -0.1]Mixed Models Analysis
Comparison: Mean change vs TOCAS.p-value: 0.04595% CI: [-0.8, 0]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: <0.00195% CI: [-1.4, -0.7]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: 0.01195% CI: [-0.9, -0.1]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: <0.00195% CI: [-1.3, -0.5]Mixed Models Analysis
Secondary
Change From Baseline to End of Treatment in IPSS Voiding Score
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).
Time frame: Baseline and Week 12
Population: FAS population with the exclusion of 5 participants with invalid questionnaires. LOCF imputation was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to End of Treatment in IPSS Voiding Score | -3.0 units on a scale | Standard Error 0.27 |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in IPSS Voiding Score | -3.3 units on a scale | Standard Error 0.28 |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in IPSS Voiding Score | -3.7 units on a scale | Standard Error 0.27 |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in IPSS Voiding Score | -3.2 units on a scale | Standard Error 0.28 |
Comparison: Mean change vs TOCAS.p-value: 0.2195% CI: [-0.9, 0.2]Mixed Models Analysis
Comparison: Mean change vs TOCAS.p-value: 0.77595% CI: [-0.5, 0.6]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: 0.0195% CI: [-1.2, -0.2]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: 0.31795% CI: [-0.8, 0.3]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: 0.19695% CI: [-0.9, 0.2]Mixed Models Analysis
Secondary
Change From Baseline to End of Treatment in Maximum Flow Rate (Qmax)
Qmax during a micturition (urination) was recorded using uroflowmetry.
Time frame: Baseline and Week 12
Population: SAF population with at least one baseline and one post-baseline micturition episode.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to End of Treatment in Maximum Flow Rate (Qmax) | 3.3 mL/s | Standard Deviation 4.69 |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in Maximum Flow Rate (Qmax) | 3.2 mL/s | Standard Deviation 4.62 |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in Maximum Flow Rate (Qmax) | 3.8 mL/s | Standard Deviation 5.3 |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in Maximum Flow Rate (Qmax) | 3.5 mL/s | Standard Deviation 5.35 |
Secondary
Change From Baseline to End of Treatment in Maximum Volume Voided Per Micturition
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.
Time frame: Baseline and Week 12
Population: FAS population with data available at both baseline and end of treatment. LOCF imputation was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to End of Treatment in Maximum Volume Voided Per Micturition | -5.9 mL | Standard Error 6.43 |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in Maximum Volume Voided Per Micturition | -1.8 mL | Standard Error 6.62 |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in Maximum Volume Voided Per Micturition | 12.7 mL | Standard Error 6.45 |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in Maximum Volume Voided Per Micturition | 12.9 mL | Standard Error 6.63 |
Comparison: Mean change vs TOCAS.p-value: 0.05395% CI: [-0.2, 29.3]Mixed Models Analysis
Comparison: Mean change vs TOCAS.p-value: 0.05395% CI: [-0.2, 29.6]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: 0.01295% CI: [4.1, 33]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: 0.01295% CI: [4.1, 33.4]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: 0.59195% CI: [-10.7, 18.7]Mixed Models Analysis
Secondary
Change From Baseline to End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours
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.
Time frame: Baseline and Week 12
Population: FAS population and at least 1 incontinence episode at baseline. LOCF imputation was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours | 0.1 incontinence episodes | Standard Error 0.19 |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours | -0.2 incontinence episodes | Standard Error 0.22 |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours | 0.0 incontinence episodes | Standard Error 0.2 |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours | 0.1 incontinence episodes | Standard Error 0.19 |
Comparison: Mean change vs TOCAS.p-value: 0.51195% CI: [-0.3, 0.6]Mixed Models Analysis
Comparison: Mean change vs TOCAS.p-value: 0.18295% CI: [-0.2, 0.8]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: 0.55295% CI: [-0.6, 0.3]Mixed Models Analysis
Comparison: Mean change vs placebop-value: 0.89195% CI: [-0.4, 0.5]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: 0.21595% CI: [-0.8, 0.2]Mixed Models Analysis
Secondary
Change From Baseline to End of Treatment in Mean Number of Micturitions Per 24 Hours
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.
Time frame: Baseline and Week 12
Population: FAS population with data available at both baseline and end of treatment. LOCF imputation was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to End of Treatment in Mean Number of Micturitions Per 24 Hours | -1.1 micturitions | Standard Error 0.16 |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in Mean Number of Micturitions Per 24 Hours | -1.7 micturitions | Standard Error 0.16 |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in Mean Number of Micturitions Per 24 Hours | -2.3 micturitions | Standard Error 0.16 |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in Mean Number of Micturitions Per 24 Hours | -1.9 micturitions | Standard Error 0.16 |
Comparison: Mean change vs TOCAS.p-value: <0.00195% CI: [-1, -0.3]Mixed Models Analysis
Comparison: Mean change vs TOCAS.p-value: 0.22395% CI: [-0.6, 0.1]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: <0.00195% CI: [-1.5, -0.8]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: <0.00195% CI: [-1.1, -0.4]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: 0.00295% CI: [-0.9, -0.2]Mixed Models Analysis
Secondary
Change From Baseline to End of Treatment in Mean Number of Nocturia Episodes Per 24 Hours
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.
Time frame: Baseline and Week 12
Population: FAS population and at least 1 nocturia episode at baseline. LOCF imputation was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to End of Treatment in Mean Number of Nocturia Episodes Per 24 Hours | -0.3 nocturia episodes | Standard Error 0.07 |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in Mean Number of Nocturia Episodes Per 24 Hours | -0.4 nocturia episodes | Standard Error 0.08 |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in Mean Number of Nocturia Episodes Per 24 Hours | -0.5 nocturia episodes | Standard Error 0.07 |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in Mean Number of Nocturia Episodes Per 24 Hours | -0.4 nocturia episodes | Standard Error 0.07 |
Comparison: Mean change vs TOCAS.p-value: 0.38395% CI: [-0.2, 0.1]Mixed Models Analysis
Comparison: Mean change vs TOCAS.p-value: 0.40295% CI: [-0.1, 0.2]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: 0.02195% CI: [-0.3, 0]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: 0.58495% CI: [-0.2, 0.1]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: 0.16695% CI: [-0.3, 0]Mixed Models Analysis
Secondary
Change From Baseline to End of Treatment in Mean Number of Pads Used Per 24 Hours
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.
Time frame: Baseline and Week 12
Population: FAS population and at least 1 use of a pad at baseline. LOCF imputation was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to End of Treatment in Mean Number of Pads Used Per 24 Hours | -0.7 pads | Standard Error 0.23 |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in Mean Number of Pads Used Per 24 Hours | -0.8 pads | Standard Error 0.27 |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in Mean Number of Pads Used Per 24 Hours | -1.2 pads | Standard Error 0.24 |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in Mean Number of Pads Used Per 24 Hours | -1.2 pads | Standard Error 0.24 |
Comparison: Mean change vs TOCAS.p-value: 0.18795% CI: [-1, 0.2]Mixed Models Analysis
Comparison: Mean change vs TOCAS.p-value: 0.20395% CI: [-1, 0.2]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: 0.0995% CI: [-1.1, 0.1]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: 0.09895% CI: [-1.1, 0.1]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: 0.77295% CI: [-0.7, 0.5]Mixed Models Analysis
Secondary
Change From Baseline to End of Treatment in Mean Number of Urgency Episodes (PPIUS Grade 3 or 4) Per 24 Hours
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.
Time frame: Baseline and Week 12
Population: FAS population and at least 1 urgency episode at baseline. LOCF imputation was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to End of Treatment in Mean Number of Urgency Episodes (PPIUS Grade 3 or 4) Per 24 Hours | -1.6 urgency episodes | Standard Error 0.24 |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in Mean Number of Urgency Episodes (PPIUS Grade 3 or 4) Per 24 Hours | -2.5 urgency episodes | Standard Error 0.25 |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in Mean Number of Urgency Episodes (PPIUS Grade 3 or 4) Per 24 Hours | -2.6 urgency episodes | Standard Error 0.24 |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in Mean Number of Urgency Episodes (PPIUS Grade 3 or 4) Per 24 Hours | -2.8 urgency episodes | Standard Error 0.25 |
Comparison: Mean change vs TOCAS.p-value: 0.61695% CI: [-0.6, 0.4]Mixed Models Analysis
Comparison: Mean change vs TOCAS.p-value: 0.31995% CI: [-0.7, 0.2]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: <0.00195% CI: [-1.5, -0.6]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: <0.00195% CI: [-1.7, -0.7]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: <0.00195% CI: [-1.4, -0.4]Mixed Models Analysis
Secondary
Change From Baseline to End of Treatment in Mean Number of Urgency Incontinence Episodes Per 24 Hours
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.
Time frame: Baseline and Week 12
Population: FAS population and at least 1 urgency incontinence episode at baseline. LOCF imputation was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to End of Treatment in Mean Number of Urgency Incontinence Episodes Per 24 Hours | -1.0 urgency incontinence episodes | Standard Error 0.15 |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in Mean Number of Urgency Incontinence Episodes Per 24 Hours | -1.4 urgency incontinence episodes | Standard Error 0.18 |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in Mean Number of Urgency Incontinence Episodes Per 24 Hours | -1.3 urgency incontinence episodes | Standard Error 0.16 |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in Mean Number of Urgency Incontinence Episodes Per 24 Hours | -1.1 urgency incontinence episodes | Standard Error 0.16 |
Comparison: Mean change vs TOCAS.p-value: 0.59195% CI: [-0.3, 0.5]Mixed Models Analysis
Comparison: Mean change vs TOCAS.p-value: 0.10295% CI: [-0.1, 0.8]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: 0.20495% CI: [-0.6, 0.1]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: 0.93695% CI: [-0.4, 0.4]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: 0.08195% CI: [-0.8, 0]Mixed Models Analysis
Secondary
Change From Baseline to End of Treatment in Mean Voided Volume Per Micturition
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.
Time frame: Baseline and Week 12
Population: FAS population with data available at both baseline and end of treatment. LOCF imputation was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to End of Treatment in Mean Voided Volume Per Micturition | 11.1 mL | Standard Error 2.94 |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in Mean Voided Volume Per Micturition | 15.5 mL | Standard Error 3.02 |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in Mean Voided Volume Per Micturition | 38.6 mL | Standard Error 2.94 |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in Mean Voided Volume Per Micturition | 38.7 mL | Standard Error 3.01 |
Comparison: Mean change vs TOCAS.p-value: <0.00195% CI: [16.6, 29.6]Mixed Models Analysis
Comparison: Mean change vs TOCAS.p-value: <0.00195% CI: [16.6, 29.8]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: <0.00195% CI: [21, 33.9]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: <0.00195% CI: [21.1, 34.1]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: 0.18995% CI: [-2.2, 10.9]Mixed Models Analysis
Secondary
Change From Baseline to End of Treatment in Post Void Residual (PVR) Volume
PVR volume is the volume of urine retained after voiding. PVR volume was assessed by ultrasonography or bladder scan.
Time frame: Baseline and Week 12
Population: SAF population with at least one baseline and one post-baseline PVR volume measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to End of Treatment in Post Void Residual (PVR) Volume | -6.1 mL | Standard Deviation 36.39 |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in Post Void Residual (PVR) Volume | -5.0 mL | Standard Deviation 38.22 |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in Post Void Residual (PVR) Volume | 3.8 mL | Standard Deviation 45.39 |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in Post Void Residual (PVR) Volume | 12.3 mL | Standard Deviation 46.61 |
Secondary
Change From Baseline to End of Treatment in Symptom Bother Score
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.
Time frame: Baseline and Week 12
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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to End of Treatment in Symptom Bother Score | -11.8 units on a scale | Standard Error 1.26 |
| TOCAS 0.4 mg | Change From Baseline to End of Treatment in Symptom Bother Score | -14.4 units on a scale | Standard Error 1.28 |
| FDC 0.4 mg/6 mg | Change From Baseline to End of Treatment in Symptom Bother Score | -16.5 units on a scale | Standard Error 1.26 |
| FDC 0.4 mg/9 mg | Change From Baseline to End of Treatment in Symptom Bother Score | -17.1 units on a scale | Standard Error 1.28 |
Comparison: Mean change vs TOCAS.p-value: 0.06895% CI: [-4.3, 0.2]Mixed Models Analysis
Comparison: Mean change vs TOCAS.p-value: 0.0295% CI: [-4.9, -0.4]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: <0.00195% CI: [-6.9, -2.5]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: <0.00195% CI: [-7.5, -3.1]Mixed Models Analysis
Comparison: Mean change vs placebo.p-value: 0.02295% CI: [-4.8, 0.4]Mixed Models Analysis
Secondary
CL/F of Solifenacin
Time frame: Week 4, Week 8 and Week 12
Population: PKAS population. N indicates the number of participants with available data at each timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | CL/F of Solifenacin | Week 4 [N= 281;273] | 6.88 L/h | Geometric Coefficient of Variation 53.6 |
| Placebo | CL/F of Solifenacin | Week 8 [N= 258; 248] | 6.72 L/h | Geometric Coefficient of Variation 51.7 |
| Placebo | CL/F of Solifenacin | Week 12 [N= 166; 167] | 6.94 L/h | Geometric Coefficient of Variation 59.3 |
| TOCAS 0.4 mg | CL/F of Solifenacin | Week 4 [N= 281;273] | 7.00 L/h | Geometric Coefficient of Variation 70.7 |
| TOCAS 0.4 mg | CL/F of Solifenacin | Week 8 [N= 258; 248] | 6.67 L/h | Geometric Coefficient of Variation 61.3 |
| TOCAS 0.4 mg | CL/F of Solifenacin | Week 12 [N= 166; 167] | 6.87 L/h | Geometric Coefficient of Variation 74.1 |
Secondary
Clinician Global Impression Scale at End of Treatment: Overall Bladder Symptoms
The Clinician Global Impression (CGI) is a questionnaire completed by the physician to assess change in the participants bladder symptoms since the start of the study. The questionnaire consists of 1 question with 7 response levels ranging from 1 to 7 (very much improved to very much worse).
Time frame: Baseline and Week 12
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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Clinician Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Very Much Improved | 9 participants |
| Placebo | Clinician Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Much Worse | 1 participants |
| Placebo | Clinician Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Minimally Worse | 9 participants |
| Placebo | Clinician Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Much Improved | 95 participants |
| Placebo | Clinician Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Very Much Worse | 0 participants |
| Placebo | Clinician Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Minimally Improved | 111 participants |
| Placebo | Clinician Global Impression Scale at End of Treatment: Overall Bladder Symptoms | No Change | 72 participants |
| TOCAS 0.4 mg | Clinician Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Much Worse | 1 participants |
| TOCAS 0.4 mg | Clinician Global Impression Scale at End of Treatment: Overall Bladder Symptoms | No Change | 54 participants |
| TOCAS 0.4 mg | Clinician Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Minimally Improved | 98 participants |
| TOCAS 0.4 mg | Clinician Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Minimally Worse | 5 participants |
| TOCAS 0.4 mg | Clinician Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Very Much Worse | 0 participants |
| TOCAS 0.4 mg | Clinician Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Much Improved | 106 participants |
| TOCAS 0.4 mg | Clinician Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Very Much Improved | 15 participants |
| FDC 0.4 mg/6 mg | Clinician Global Impression Scale at End of Treatment: Overall Bladder Symptoms | No Change | 48 participants |
| FDC 0.4 mg/6 mg | Clinician Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Very Much Improved | 22 participants |
| FDC 0.4 mg/6 mg | Clinician Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Much Improved | 117 participants |
| FDC 0.4 mg/6 mg | Clinician Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Minimally Improved | 97 participants |
| FDC 0.4 mg/6 mg | Clinician Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Minimally Worse | 2 participants |
| FDC 0.4 mg/6 mg | Clinician Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Much Worse | 1 participants |
| FDC 0.4 mg/6 mg | Clinician Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Very Much Worse | 0 participants |
| FDC 0.4 mg/9 mg | Clinician Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Minimally Improved | 92 participants |
| FDC 0.4 mg/9 mg | Clinician Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Very Much Worse | 0 participants |
| FDC 0.4 mg/9 mg | Clinician Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Much Worse | 4 participants |
| FDC 0.4 mg/9 mg | Clinician Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Much Improved | 124 participants |
| FDC 0.4 mg/9 mg | Clinician Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Very Much Improved | 20 participants |
| FDC 0.4 mg/9 mg | Clinician Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Minimally Worse | 3 participants |
| FDC 0.4 mg/9 mg | Clinician Global Impression Scale at End of Treatment: Overall Bladder Symptoms | No Change | 37 participants |
Comparison: Difference vs TOCAS.p-value: 0.11Chi-squared
Comparison: Difference vs TOCAS.p-value: 0.071Chi-squared
Comparison: Difference vs placebo.p-value: <0.001Chi-squared
Comparison: Difference vs placebo.p-value: <0.001Chi-squared
Comparison: Difference vs placebo.p-value: 0.019Chi-squared
Secondary
Cmaxss of Solifenacin
Time frame: Week 4, Week 8 and Week 12
Population: PKAS population. N indicates the number of participants with available data at each timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Cmaxss of Solifenacin | Week 4 [N= 281; 273] | 29.4 ng/mL | Geometric Coefficient of Variation 44.8 |
| Placebo | Cmaxss of Solifenacin | Week 8 [N= 258; 248] | 30.0 ng/mL | Geometric Coefficient of Variation 48 |
| Placebo | Cmaxss of Solifenacin | Week 12 [N= 166; 167] | 29.1 ng/mL | Geometric Coefficient of Variation 49.6 |
| TOCAS 0.4 mg | Cmaxss of Solifenacin | Week 4 [N= 281; 273] | 43.4 ng/mL | Geometric Coefficient of Variation 51.4 |
| TOCAS 0.4 mg | Cmaxss of Solifenacin | Week 8 [N= 258; 248] | 45.3 ng/mL | Geometric Coefficient of Variation 48.5 |
| TOCAS 0.4 mg | Cmaxss of Solifenacin | Week 12 [N= 166; 167] | 44.1 ng/mL | Geometric Coefficient of Variation 50.7 |
Secondary
Cminss of Solifenacin
Time frame: Week 4, Week 8 and Week 12
Population: PKAS population. N indicates the number of participants with available data at each timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Cminss of Solifenacin | Week 12 [N= 166; 167] | 24.4 ng/mL | Geometric Coefficient of Variation 55.6 |
| Placebo | Cminss of Solifenacin | Week 4 [N= 281; 273] | 24.5 ng/mL | Geometric Coefficient of Variation 50.5 |
| Placebo | Cminss of Solifenacin | Week 8 [N= 258; 248] | 25.2 ng/mL | Geometric Coefficient of Variation 54.1 |
| TOCAS 0.4 mg | Cminss of Solifenacin | Week 12 [N= 166; 167] | 37.0 ng/mL | Geometric Coefficient of Variation 56.8 |
| TOCAS 0.4 mg | Cminss of Solifenacin | Week 4 [N= 281; 273] | 36.1 ng/mL | Geometric Coefficient of Variation 57.8 |
| TOCAS 0.4 mg | Cminss of Solifenacin | Week 8 [N= 258; 248] | 38.2 ng/mL | Geometric Coefficient of Variation 54.3 |
Secondary
Maximum Concentration at Steady State (Cmaxss) of Tamsulosin
Time frame: Week 4, Week 8 and Week 12
Population: PKAS population. N indicates the number of participants with available data at each timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Maximum Concentration at Steady State (Cmaxss) of Tamsulosin | Week 12 [N= 163; 167; 166] | 7.97 ng/mL | Geometric Coefficient of Variation 68.6 |
| Placebo | Maximum Concentration at Steady State (Cmaxss) of Tamsulosin | Week 8 [N= 255; 259; 248] | 7.69 ng/mL | Geometric Coefficient of Variation 71.2 |
| Placebo | Maximum Concentration at Steady State (Cmaxss) of Tamsulosin | Week 4 [N= 263; 281; 274] | 7.38 ng/mL | Geometric Coefficient of Variation 82.8 |
| TOCAS 0.4 mg | Maximum Concentration at Steady State (Cmaxss) of Tamsulosin | Week 12 [N= 163; 167; 166] | 8.38 ng/mL | Geometric Coefficient of Variation 69 |
| TOCAS 0.4 mg | Maximum Concentration at Steady State (Cmaxss) of Tamsulosin | Week 4 [N= 263; 281; 274] | 7.80 ng/mL | Geometric Coefficient of Variation 94.3 |
| TOCAS 0.4 mg | Maximum Concentration at Steady State (Cmaxss) of Tamsulosin | Week 8 [N= 255; 259; 248] | 8.32 ng/mL | Geometric Coefficient of Variation 73.4 |
| FDC 0.4 mg/6 mg | Maximum Concentration at Steady State (Cmaxss) of Tamsulosin | Week 12 [N= 163; 167; 166] | 8.16 ng/mL | Geometric Coefficient of Variation 82.7 |
| FDC 0.4 mg/6 mg | Maximum Concentration at Steady State (Cmaxss) of Tamsulosin | Week 8 [N= 255; 259; 248] | 8.46 ng/mL | Geometric Coefficient of Variation 84.9 |
| FDC 0.4 mg/6 mg | Maximum Concentration at Steady State (Cmaxss) of Tamsulosin | Week 4 [N= 263; 281; 274] | 8.00 ng/mL | Geometric Coefficient of Variation 83.3 |
Secondary
Minimum Concentration at Steady State (Cminss) of Tamsulosin
Time frame: Week 4, Week 8 and Week 12
Population: PKAS population. N indicates the number of participants with available data at each timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Minimum Concentration at Steady State (Cminss) of Tamsulosin | Week 8 [N= 255; 259; 248] | 4.63 ng/mL | Geometric Coefficient of Variation 103 |
| Placebo | Minimum Concentration at Steady State (Cminss) of Tamsulosin | Week 4 [N= 263; 281; 274] | 4.19 ng/mL | Geometric Coefficient of Variation 127 |
| Placebo | Minimum Concentration at Steady State (Cminss) of Tamsulosin | Week 12 [N= 163; 167; 166] | 4.84 ng/mL | Geometric Coefficient of Variation 97.7 |
| TOCAS 0.4 mg | Minimum Concentration at Steady State (Cminss) of Tamsulosin | Week 8 [N= 255; 259; 248] | 5.08 ng/mL | Geometric Coefficient of Variation 106 |
| TOCAS 0.4 mg | Minimum Concentration at Steady State (Cminss) of Tamsulosin | Week 4 [N= 263; 281; 274] | 4.55 ng/mL | Geometric Coefficient of Variation 146 |
| TOCAS 0.4 mg | Minimum Concentration at Steady State (Cminss) of Tamsulosin | Week 12 [N= 163; 167; 166] | 5.05 ng/mL | Geometric Coefficient of Variation 96.2 |
| FDC 0.4 mg/6 mg | Minimum Concentration at Steady State (Cminss) of Tamsulosin | Week 4 [N= 263; 281; 274] | 4.75 ng/mL | Geometric Coefficient of Variation 124 |
| FDC 0.4 mg/6 mg | Minimum Concentration at Steady State (Cminss) of Tamsulosin | Week 12 [N= 163; 167; 166] | 4.94 ng/mL | Geometric Coefficient of Variation 119 |
| FDC 0.4 mg/6 mg | Minimum Concentration at Steady State (Cminss) of Tamsulosin | Week 8 [N= 255; 259; 248] | 5.19 ng/mL | Geometric Coefficient of Variation 122 |
Secondary
Number of Participants With Adverse Events (AEs)
Safety is monitored by collecting AEs, which include abnormal laboratory parameters, vital signs or ECG data if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study medication or was clinically significant. A serious AE (SAE) was an event resulting in death, persistent or significant disability/incapacity or congenital anomaly or birth defect, was life-threatening, required or prolonged hospitalization or was considered medically important. AEs were assessed by the Investigator for intensity as 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 administration of the first dose of double-blind study drug until 14 days after the last dose of double-blind study drug.
Time frame: From first dose of double-blind study drug up to 14 days of last dose of double-blind study drug (up to 14 weeks)
Population: Safety Analysis Set (SAF) - consisted of participants who received at least one dose of double blind study drug and for whom any data was reported after intake of the first dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Adverse Events (AEs) | Deaths | 0 participants |
| Placebo | Number of Participants With Adverse Events (AEs) | SAEs | 3 participants |
| Placebo | Number of Participants With Adverse Events (AEs) | Drug-related TEAEs | 30 participants |
| Placebo | Number of Participants With Adverse Events (AEs) | Total TEAEs | 87 participants |
| Placebo | Number of Participants With Adverse Events (AEs) | Drug-related AEs Leading to Discontin | 3 participants |
| Placebo | Number of Participants With Adverse Events (AEs) | Moderate TEAEs | 25 participants |
| Placebo | Number of Participants With Adverse Events (AEs) | AEs Leading to Discontin | 5 participants |
| Placebo | Number of Participants With Adverse Events (AEs) | Severe TEAEs | 3 participants |
| Placebo | Number of Participants With Adverse Events (AEs) | Mild TEAEs | 59 participants |
| TOCAS 0.4 mg | Number of Participants With Adverse Events (AEs) | Moderate TEAEs | 29 participants |
| TOCAS 0.4 mg | Number of Participants With Adverse Events (AEs) | Mild TEAEs | 42 participants |
| TOCAS 0.4 mg | Number of Participants With Adverse Events (AEs) | Severe TEAEs | 3 participants |
| TOCAS 0.4 mg | Number of Participants With Adverse Events (AEs) | Drug-related TEAEs | 27 participants |
| TOCAS 0.4 mg | Number of Participants With Adverse Events (AEs) | SAEs | 10 participants |
| TOCAS 0.4 mg | Number of Participants With Adverse Events (AEs) | Deaths | 1 participants |
| TOCAS 0.4 mg | Number of Participants With Adverse Events (AEs) | AEs Leading to Discontin | 9 participants |
| TOCAS 0.4 mg | Number of Participants With Adverse Events (AEs) | Drug-related AEs Leading to Discontin | 5 participants |
| TOCAS 0.4 mg | Number of Participants With Adverse Events (AEs) | Total TEAEs | 74 participants |
| FDC 0.4 mg/6 mg | Number of Participants With Adverse Events (AEs) | Severe TEAEs | 4 participants |
| FDC 0.4 mg/6 mg | Number of Participants With Adverse Events (AEs) | Moderate TEAEs | 27 participants |
| FDC 0.4 mg/6 mg | Number of Participants With Adverse Events (AEs) | Drug-related AEs Leading to Discontin | 9 participants |
| FDC 0.4 mg/6 mg | Number of Participants With Adverse Events (AEs) | Total TEAEs | 99 participants |
| FDC 0.4 mg/6 mg | Number of Participants With Adverse Events (AEs) | Drug-related TEAEs | 57 participants |
| FDC 0.4 mg/6 mg | Number of Participants With Adverse Events (AEs) | AEs Leading to Discontin | 13 participants |
| FDC 0.4 mg/6 mg | Number of Participants With Adverse Events (AEs) | Deaths | 1 participants |
| FDC 0.4 mg/6 mg | Number of Participants With Adverse Events (AEs) | Mild TEAEs | 68 participants |
| FDC 0.4 mg/6 mg | Number of Participants With Adverse Events (AEs) | SAEs | 5 participants |
| FDC 0.4 mg/9 mg | Number of Participants With Adverse Events (AEs) | Mild TEAEs | 68 participants |
| FDC 0.4 mg/9 mg | Number of Participants With Adverse Events (AEs) | Moderate TEAEs | 27 participants |
| FDC 0.4 mg/9 mg | Number of Participants With Adverse Events (AEs) | Deaths | 0 participants |
| FDC 0.4 mg/9 mg | Number of Participants With Adverse Events (AEs) | AEs Leading to Discontin | 10 participants |
| FDC 0.4 mg/9 mg | Number of Participants With Adverse Events (AEs) | SAEs | 9 participants |
| FDC 0.4 mg/9 mg | Number of Participants With Adverse Events (AEs) | Total TEAEs | 100 participants |
| FDC 0.4 mg/9 mg | Number of Participants With Adverse Events (AEs) | Drug-related AEs Leading to Discontin | 8 participants |
| FDC 0.4 mg/9 mg | Number of Participants With Adverse Events (AEs) | Drug-related TEAEs | 65 participants |
| FDC 0.4 mg/9 mg | Number of Participants With Adverse Events (AEs) | Severe TEAEs | 5 participants |
Secondary
Patient Global Impression Scale at End of Treatment: General Health
The Patient Global Impression (PGI) is a global questionnaire completed by the participant to assess both the change in the participants overall condition and the change in bladder symptoms since the start of the study. The questionnaire consists of 2 questions with 7 response levels ranging from 1 to 7 (very much improved to very much worse).
Time frame: Baseline and Week 12
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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Patient Global Impression Scale at End of Treatment: General Health | Minimally Worse | 15 participants |
| Placebo | Patient Global Impression Scale at End of Treatment: General Health | • Very Much Worse | 0 participants |
| Placebo | Patient Global Impression Scale at End of Treatment: General Health | Minimally Improved | 79 participants |
| Placebo | Patient Global Impression Scale at End of Treatment: General Health | Much Improved | 43 participants |
| Placebo | Patient Global Impression Scale at End of Treatment: General Health | Very Much Improved | 5 participants |
| Placebo | Patient Global Impression Scale at End of Treatment: General Health | Much Worse | 2 participants |
| Placebo | Patient Global Impression Scale at End of Treatment: General Health | No Change | 152 participants |
| TOCAS 0.4 mg | Patient Global Impression Scale at End of Treatment: General Health | Very Much Improved | 9 participants |
| TOCAS 0.4 mg | Patient Global Impression Scale at End of Treatment: General Health | Minimally Worse | 9 participants |
| TOCAS 0.4 mg | Patient Global Impression Scale at End of Treatment: General Health | • Very Much Worse | 0 participants |
| TOCAS 0.4 mg | Patient Global Impression Scale at End of Treatment: General Health | Much Improved | 58 participants |
| TOCAS 0.4 mg | Patient Global Impression Scale at End of Treatment: General Health | No Change | 126 participants |
| TOCAS 0.4 mg | Patient Global Impression Scale at End of Treatment: General Health | Minimally Improved | 77 participants |
| TOCAS 0.4 mg | Patient Global Impression Scale at End of Treatment: General Health | Much Worse | 3 participants |
| FDC 0.4 mg/6 mg | Patient Global Impression Scale at End of Treatment: General Health | No Change | 110 participants |
| FDC 0.4 mg/6 mg | Patient Global Impression Scale at End of Treatment: General Health | Very Much Improved | 10 participants |
| FDC 0.4 mg/6 mg | Patient Global Impression Scale at End of Treatment: General Health | Much Improved | 72 participants |
| FDC 0.4 mg/6 mg | Patient Global Impression Scale at End of Treatment: General Health | Minimally Improved | 87 participants |
| FDC 0.4 mg/6 mg | Patient Global Impression Scale at End of Treatment: General Health | Minimally Worse | 8 participants |
| FDC 0.4 mg/6 mg | Patient Global Impression Scale at End of Treatment: General Health | Much Worse | 0 participants |
| FDC 0.4 mg/6 mg | Patient Global Impression Scale at End of Treatment: General Health | • Very Much Worse | 0 participants |
| FDC 0.4 mg/9 mg | Patient Global Impression Scale at End of Treatment: General Health | Minimally Improved | 94 participants |
| FDC 0.4 mg/9 mg | Patient Global Impression Scale at End of Treatment: General Health | • Very Much Worse | 0 participants |
| FDC 0.4 mg/9 mg | Patient Global Impression Scale at End of Treatment: General Health | Much Worse | 1 participants |
| FDC 0.4 mg/9 mg | Patient Global Impression Scale at End of Treatment: General Health | Much Improved | 75 participants |
| FDC 0.4 mg/9 mg | Patient Global Impression Scale at End of Treatment: General Health | Very Much Improved | 7 participants |
| FDC 0.4 mg/9 mg | Patient Global Impression Scale at End of Treatment: General Health | Minimally Worse | 10 participants |
| FDC 0.4 mg/9 mg | Patient Global Impression Scale at End of Treatment: General Health | No Change | 94 participants |
Comparison: Difference vs TOCAS.p-value: 0.053Chi-squared
Comparison: Difference vs TOCAS.p-value: 0.031Chi-squared
Comparison: Difference vs placebo.p-value: <0.001Chi-squared
Comparison: Difference vs placebo.p-value: <0.001Chi-squared
Comparison: Difference vs placebo.p-value: 0.018Chi-squared
Secondary
Patient Global Impression Scale at End of Treatment: Overall Bladder Symptoms
The Patient Global Impression (PGI) is a global questionnaire completed by the participant to assess both the change in the participants overall condition and the change in bladder symptoms since the start of the study. The questionnaire consists of 2 questions with 7 response levels ranging from 1 to 7 (very much improved to very much worse).
Time frame: Baseline and Week 12
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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Patient Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Very Much Improved | 7 participants |
| Placebo | Patient Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Much Worse | 5 participants |
| Placebo | Patient Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Minimally Worse | 12 participants |
| Placebo | Patient Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Much Improved | 75 participants |
| Placebo | Patient Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Very Much Worse | 0 participants |
| Placebo | Patient Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Minimally Improved | 113 participants |
| Placebo | Patient Global Impression Scale at End of Treatment: Overall Bladder Symptoms | No Change | 86 participants |
| TOCAS 0.4 mg | Patient Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Much Worse | 3 participants |
| TOCAS 0.4 mg | Patient Global Impression Scale at End of Treatment: Overall Bladder Symptoms | No Change | 68 participants |
| TOCAS 0.4 mg | Patient Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Minimally Improved | 99 participants |
| TOCAS 0.4 mg | Patient Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Minimally Worse | 13 participants |
| TOCAS 0.4 mg | Patient Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Very Much Worse | 0 participants |
| TOCAS 0.4 mg | Patient Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Much Improved | 85 participants |
| TOCAS 0.4 mg | Patient Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Very Much Improved | 14 participants |
| FDC 0.4 mg/6 mg | Patient Global Impression Scale at End of Treatment: Overall Bladder Symptoms | No Change | 46 participants |
| FDC 0.4 mg/6 mg | Patient Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Very Much Improved | 20 participants |
| FDC 0.4 mg/6 mg | Patient Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Much Improved | 95 participants |
| FDC 0.4 mg/6 mg | Patient Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Minimally Improved | 124 participants |
| FDC 0.4 mg/6 mg | Patient Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Minimally Worse | 2 participants |
| FDC 0.4 mg/6 mg | Patient Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Much Worse | 0 participants |
| FDC 0.4 mg/6 mg | Patient Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Very Much Worse | 0 participants |
| FDC 0.4 mg/9 mg | Patient Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Minimally Improved | 105 participants |
| FDC 0.4 mg/9 mg | Patient Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Very Much Worse | 0 participants |
| FDC 0.4 mg/9 mg | Patient Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Much Worse | 1 participants |
| FDC 0.4 mg/9 mg | Patient Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Much Improved | 105 participants |
| FDC 0.4 mg/9 mg | Patient Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Very Much Improved | 23 participants |
| FDC 0.4 mg/9 mg | Patient Global Impression Scale at End of Treatment: Overall Bladder Symptoms | Minimally Worse | 9 participants |
| FDC 0.4 mg/9 mg | Patient Global Impression Scale at End of Treatment: Overall Bladder Symptoms | No Change | 38 participants |
Comparison: Difference vs TOCAS.p-value: <0.001Chi-squared
Comparison: Difference vs TOCAS.p-value: <0.001Chi-squared
Comparison: Difference vs placebo.p-value: <0.001Chi-squared
Comparison: Difference vs placebo.p-value: <0.001Chi-squared
Comparison: Difference vs placebo.p-value: 0.058Chi-squared
Secondary
Percentage of Participants Who Were OAB-q Responders at End of Treatment
A OAB-q responder was defined as a participant with an improvement from baseline in HRQoL subscale total score ≥ 10.
Time frame: Week 12 (end of 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Were OAB-q Responders at End of Treatment | 40.8 percentage of participants |
| TOCAS 0.4 mg | Percentage of Participants Who Were OAB-q Responders at End of Treatment | 42.9 percentage of participants |
| FDC 0.4 mg/6 mg | Percentage of Participants Who Were OAB-q Responders at End of Treatment | 45.5 percentage of participants |
| FDC 0.4 mg/9 mg | Percentage of Participants Who Were OAB-q Responders at End of Treatment | 47.5 percentage of participants |
Comparison: Difference vs TOCAS (superiority test).p-value: 0.874Chi-squared
Comparison: Difference vs TOCAS (superiority test).p-value: 0.24Chi-squared
Comparison: Difference vs placebo (superiority test).p-value: 0.324Chi-squared
Comparison: Difference vs placebo (superiority test).p-value: 0.043Chi-squared
Comparison: Difference vs placebo (superiority test).p-value: 0.407Chi-squared
Secondary
Time of Maximum Concentration at Steady State (Tmaxss) of Tamsulosin
Time frame: Week 4, Week 8 and Week 12
Population: PKAS population. N indicates the number of participants with available data at each timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Time of Maximum Concentration at Steady State (Tmaxss) of Tamsulosin | Week 8 [N= 255; 259; 248] | 5.09 h | Geometric Coefficient of Variation 3.4 |
| Placebo | Time of Maximum Concentration at Steady State (Tmaxss) of Tamsulosin | Week 4 [N= 263; 281; 274] | 5.04 h | Geometric Coefficient of Variation 4.1 |
| Placebo | Time of Maximum Concentration at Steady State (Tmaxss) of Tamsulosin | Week 12 [N= 163; 167; 166] | 5.10 h | Geometric Coefficient of Variation 3.6 |
| TOCAS 0.4 mg | Time of Maximum Concentration at Steady State (Tmaxss) of Tamsulosin | Week 8 [N= 255; 259; 248] | 5.10 h | Geometric Coefficient of Variation 3.3 |
| TOCAS 0.4 mg | Time of Maximum Concentration at Steady State (Tmaxss) of Tamsulosin | Week 4 [N= 263; 281; 274] | 5.06 h | Geometric Coefficient of Variation 4 |
| TOCAS 0.4 mg | Time of Maximum Concentration at Steady State (Tmaxss) of Tamsulosin | Week 12 [N= 163; 167; 166] | 5.09 h | Geometric Coefficient of Variation 3.6 |
| FDC 0.4 mg/6 mg | Time of Maximum Concentration at Steady State (Tmaxss) of Tamsulosin | Week 4 [N= 263; 281; 274] | 5.08 h | Geometric Coefficient of Variation 3.6 |
| FDC 0.4 mg/6 mg | Time of Maximum Concentration at Steady State (Tmaxss) of Tamsulosin | Week 12 [N= 163; 167; 166] | 5.09 h | Geometric Coefficient of Variation 3.3 |
| FDC 0.4 mg/6 mg | Time of Maximum Concentration at Steady State (Tmaxss) of Tamsulosin | Week 8 [N= 255; 259; 248] | 5.11 h | Geometric Coefficient of Variation 3.4 |
Secondary
Tmaxss of Solifenacin
Time frame: Week 4, Week 8 and Week 12
Population: PKAS population. N indicates the number of participants with available data at each timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Tmaxss of Solifenacin | Week 4 [N= 281; 273] | 5.47 h | Geometric Coefficient of Variation 1.41 |
| Placebo | Tmaxss of Solifenacin | Week 8 [N= 258; 248] | 5.48 h | Geometric Coefficient of Variation 0.9 |
| Placebo | Tmaxss of Solifenacin | Week 12 [N= 166; 167] | 5.48 h | Geometric Coefficient of Variation 0.9 |
| TOCAS 0.4 mg | Tmaxss of Solifenacin | Week 4 [N= 281; 273] | 5.47 h | Geometric Coefficient of Variation 1.2 |
| TOCAS 0.4 mg | Tmaxss of Solifenacin | Week 8 [N= 258; 248] | 5.48 h | Geometric Coefficient of Variation 0.9 |
| TOCAS 0.4 mg | Tmaxss of Solifenacin | Week 12 [N= 166; 167] | 5.48 h | Geometric Coefficient of Variation 0.9 |