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Completed

NCT Number: NCT01908829

A Trial Comparing Combination Treatment (Solifenacin Plus Mirabegron) With One Treatment Alone (Solifenacin)

The purpose of this study was to see if adding a new type of medication recently approved to treat overactive bladder (mirabegron) to an antimuscarinic treatment (solifenacin) would be more effective in controlling incontinence than when using the antimuscarinic treatment alone.

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Key information

Conditions

Urinary Bladder Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Lower Urinary Tract Symptoms Male Urogenital Diseases Pathological Conditions, Signs and Symptoms Signs and Symptoms Urinary Bladder Overactive Urinary Bladder, Overactive Urinary Incontinence Urination Disorders Urogenital Diseases Urologic Diseases Urological Manifestations

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Site: 37402, Yerevan, Armenia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Main Inclusion at Screening:
  • Subject has symptoms of OAB (urinary frequency and urgency with urgency incontinence) for >= 3 months prior to the screening visit
  • Subject is willing and able to complete the micturition diary and questionnaires correctly, including collection and measurement of urine output for 3 days prior to each visit;
  • Subject has symptoms of "wet" OAB (urinary frequency and urgency with incontinence or mixed incontinence with predominant urgency incontinence), and reports an average of at least 2 incontinence episodes per day.
  • Main Inclusion at Run-in (Visit 2):
  • Subject experiences on average at least 1 episode of urgency (grade 3 or 4) with or without incontinence per 24-hour period during the 3-day micturition diary period.
  • Subject experiences on average at least 2 incontinence episodes per 24-hour period during the 3-day micturition diary period.
  • Subject experiences on average at least 8 micturitions (excluding incontinence episodes) per 24-hour period during the 3-day micturition diary period.
  • Main Inclusion at Randomization (Visit 3):
  • Subject experiences at least 1 incontinence episode during the 3-day micturition diary period and wishes to increase their treatment for OAB symptoms.

Exclusion criteria

  • Main Exclusion at Screening:
  • Subject in the opinion of the investigator has clinically significant Bladder Outlet Obstruction (BOO).
  • Subject has significant Post-void residual (PVR) volume (PVR > 150 ml).
  • Subject has significant stress incontinence or mixed stress/urgency incontinence where stress is the predominant factor as determined by the investigator
  • Subject has an indwelling catheter or practices intermittent self catheterization.
  • Subject has evidence of a UTI.
  • Subject has chronic inflammation such as interstitial cystitis, bladder stones, previous pelvic radiation therapy, or previous or current malignant disease of the pelvic organs
  • Subject has moderate to severe hepatic impairment
  • Subject has severe renal impairment or End Stage Renal disease
  • Subject has a clinically significant abnormal Electrocardiogram (ECG)
  • Subject has a concurrent malignancy or history of cancer (except noninvasive skin cancer) within the last 5 years prior to screening.
  • Subject has a QTcF interval > 450 ms for males or > 470 ms for females or is at risk of QT prolongation (e.g., family history of long QT syndrome, hypokalaemia).
  • Subject has received intravesical treatment in the past 12 months with e.g., botulinum toxin, resiniferatoxin, capsaicin.
  • Subject has severe uncontrolled hypertension, which is defined as a sitting average systolic blood pressure ≥ 180 mmHg and/or average diastolic blood pressure ≥ 110 mmHg.
  • Main Exclusion at Randomization (visit 3):
  • Subject has achieved 100% continence from Visit 2 to Visit 3 (no incontinence episodes are recorded in the 3 day diary administered for 3 days prior to Visit 3).
  • Subject does not desire an increase in study medication.
  • Subject has an average total daily urine volume > 3000ml as recorded in the micturition diary.
  • Subject has severe uncontrolled hypertension, which is defined as a sitting average systolic blood pressure ≥ 180 mmHg and/or average diastolic blood pressure ≥ 110 mmHg.
  • Subject has a clinically significant abnormal ECG

Treatment and study plan

Mirabegron 25 MG

Drug

Mirabegron was supplied as the marketed formulation in the 25 mg OCAS (Oral Controlled Absorption System) modified release tablets. Medication was taken orally with a glass of water, with or without food.

Other names: Betmiga, Myrbetriq, YM178, Betanis

Mirabegron 50 MG

Drug

Mirabegron was supplied as the marketed formulation in the 50 mg OCAS (Oral Controlled Absorption System) modified release tablets. Medication was taken orally with a glass of water, with or without food.

Other names: YM905, Vesitrim, Vesikur, Vesicare

Solifenacin 5 mg

Drug

Solifenacin was provided as the marketed formulation in the 5 mg strength. Medication was taken orally with a glass of water, with or without food.

Other names: Vesicare, Vesitrim, YM905, Vesikur

solifenacin 10 mg

Drug

Solifenacin was provided as the marketed formulation in the 10 mg strength. Medication was taken orally with a glass of water, with or without food.

Other names: Vesicare, Vesitrim, YM905, Vesikur

mirabegron 25 mg matching placebo

Drug

Matching placebo of mirabegron OCAS 25 mg tablets was supplied. Medication was taken orally with a glass of water, with or without food.

mirabegron 50 mg matching placebo

Drug

Matching placebo of mirabegron OCAS 50 mg tablets was supplied. Medication was taken orally with a glass of water, with or without food.

solifenacin 5 mg matching placebo

Drug

Matching placebo of solifenacin succinate 5 mg tablets was supplied. Medication was taken orally with a glass of water, with or without food.

solifenacin 10 mg matching placebo

Drug

Matching placebo of solifenacin succinate 10 mg tablets was supplied. Medication was taken orally with a glass of water, with or without food.

Primary outcomes

  1. Change From Baseline to End of Treatment (EoT) in Mean Number of Incontinence Episodes Per 24 Hours

    Time frame: Baseline and end of treatment (up to 12 weeks)

    The mean number of incontinence episodes (complaint of any involuntary leakage of urine) per day was derived from number of incontinence episodes recorded on valid diary days during the 3-day micturition diary period divided by the number of valid diary days during the 3-day micturition diary period. The analysis population consisted of the Full Analysis Set (FAS) which comprised of all the Randomized Analysis Set's (RAS) participants who met the following criteria: took at least 1 dose of double-blind study drug after randomization, reported at least 1 micturition in the baseline diary & at least 1 micturition postbaseline & reported at least 1 incontinence episode in the baseline diary. For participants who withdrew before EoT (week 12) and have no measurement available for that diary period, the Last Observation Carried Forward (LOCF) value during the double-blind study period was used as EoT value to derive the primary variable.

Secondary outcomes

  1. Change From Baseline to Weeks 4, 8 & 12 in Mean Number of Incontinence Episodes Per 24 Hours

    Time frame: Baseline and weeks 4, 8 & 12

    The mean number of incontinence episodes (complaint of any involuntary leakage of urine) per day was derived from number of incontinence episodes recorded on valid diary days during the 3-day micturition diary period divided by the number of valid diary days during the 3-day micturition diary period.

  2. Change From Baseline in Mean Number of Micturitions Per 24 Hours

    Time frame: Baseline and weeks 4, 8 & 12

    The average number of micturitions (voluntary urinations (excluding incontinence only episodes)) per 24 hours was derived from number of micturitions recorded on valid diary days during the 3-day micturition diary period divided by the number of valid diary days during the 3-day micturition diary period (excluding incontinence only episodes).

  3. Number of Incontinence Episodes Reported During the 3-Day Diary

    Time frame: Weeks 4, 8 and 12

    The number of incontinence episodes (complaint of any involuntary leakage of urine) per day was derived from total number of incontinence episodes on valid diary days recorded during the 3-day micturition diary period.

  4. Change From Baseline in Mean Volume Voided (MVV) Per Micturition

    Time frame: Baseline and weeks 4, 8 & 12

    MVV per micturition was defined as MVV (mL) per micturition during last 3 days of the 3-day micturition diary period. MVV per micturition was calculated as the sum of each volume voided for each record with volume voided > 0 on valid diary days divided by the total number of records with a volume voided > 0 on valid diary days during the 3-day micturition diary period.

  5. Change From Baseline to EoT in Corrected Micturition Frequency (CMF)

    Time frame: Baseline and EoT (up to 12 weeks)

    CMF was defined as the mean number of micturitions per 24 hours that participants would have at EoT if their fluid intake had remained unchanged since baseline. This was calculated by the MVV per Micturition at baseline multiplied by the mean number of micturitions per 24 hours at baseline divided by the MVV per micturition at EoT.

  6. Change From Baseline in Mean Number of Urgency Incontinence (UI) Episodes Per 24 Hours

    Time frame: Baseline and weeks 4, 8 & 12

    UI was defined as the complaint of involuntary urine leakage accompanied by or immediately preceded by urgency. UI was measured using the Patient Perception of Intensity of Urgency Scale (PPIUS), a patient reported outcome validated 5-point categorical scale rating the degree of associated urinary urgency severity (0=No urgency, I felt no need to empty my bladder, but did so for other reasons. 1=Mild, I could postpone voiding as long as necessary, without fear of wetting myself. 2= Moderate, I could postpone voiding for a short while, without fear of wetting myself. 3=Severe, I could not postpone voiding, but had to rush to the toilet in order not to wet myself. 4=Urgency incontinence, I leaked before arriving to the toilet). One urgency incontinence episode was counted for each record of the diary in which the following occurred: incontinence episode or 'both' was recorded & severity of urinary urgency recorded was 3 or 4.

  7. Number of UI Episodes Reported During the 3-Day Diary

    Time frame: Weeks 4, 8 and 12

    Number of UI episodes was calculated using the number of UI episodes recorded on valid diary days during the 3-day micturition diary period. NOTE: Only urgency incontinence episodes recorded on a valid diary day were counted.

  8. Change From Baseline in Mean Number of Urgency Episodes (Grade 3 and/or 4) Per 24 Hours

    Time frame: Baseline and weeks 4, 8 & 12

    An urgency episode was defined as the complaint of a sudden, compelling desire to pass urine, which is difficult to defer. The mean number of urgency episodes (severity of 3 or 4) per 24 hours was defined as the average number of times a participant recorded an urgency episode (severity of 3 or 4) with or without incontinence per day during the 3-day micturition diary period. Measured using the PPIUS scale. This was calculated using the sum of each record with an urgency episode (severity of 3 or 4) recorded on a valid diary day divided by the number of valid diary days during the 3-day micturition diary period.

  9. Change From Baseline in Mean Number of Pads Per 24 Hours

    Time frame: Baseline and weeks 4, 8 & 12

    The mean number of pads per 24 hours was defined as the average number of times a participant recorded a new pad used per day during the 3-day micturition diary period. This was calculated using the number of new pads used during valid diary days during the 3-day micturition diary period divided by the number of valid diary days during the 3-day micturition diary period.

  10. Number of Pads Used During the 3-Day Diary

    Time frame: Weeks 4, 8 and 12

    The number of pads used was defined as the number of times a participant recorded a new pad used during the 3-day micturition diary period. This was calculated using the sum of each record with new pad checked. Only records with new pad checked on a valid diary day were counted.

  11. Change From Baseline in Mean Number of Nocturia Episodes

    Time frame: Baseline and weeks 4, 8 & 12

    Mean number of nocturia episodes was defined as the number of times a participant urinated (excluding incontinence only episodes) while sleeping during the 3-day diary period, divided by the number of valid diary days during the diary period. Night time episode of incontinence only was not considered a nocturia episode. Nocturia episodes were counted for each micturition record which occurred between the date/time of going to bed with intention to sleep and the date/time of getting up with intention to stay awake on a valid diary day & which was accompanied by a sleep interruption. Nocturia only determined for those who were not night-shift workers.

  12. Number of Nocturia Episodes Reported Over 3-Day Diary

    Time frame: Weeks 4, 8 and 12

    The number of nocturia episodes was defined as the number of times a participant urinated (excluding incontinence only episodes) during sleeping time during the 3-day micturition diary period. This was calculated using the sum of each nocturia episode recorded on valid diary days during the 3-day micturition diary period.

  13. Number of Participants With Change From Baseline to EoT in Euroqol European Quality of Life-5 Dimensions (EQ-5D) Subscale Score: Mobility

    Time frame: Baseline and EoT (up to 12 weeks)

    The EQ-5D is an international, standardized, nondisease specific instrument for describing and valuing health status. It has 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels: level 1=no problem or none; level 2=slight problems; level 3=moderate problems; level 4=severe problems; level 5=unable to perform activity.

  14. Number of Participants With Change From Baseline to EoT in EQ-5D Subscale Score: Self-care

    Time frame: Baseline and EoT (up to 12 weeks)

    The EQ-5D is an international, standardized, nondisease specific instrument for describing and valuing health status. It has 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels: level 1=no problem or none; level 2=slight problems; level 3=moderate problems; level 4=severe problems; level 5=unable to perform activity.

  15. Number of Participants With Change From Baseline to EoT in EQ-5D Subscale Score: Usual Activities

    Time frame: Baseline and EoT (up to 12 weeks)

    The EQ-5D is an international, standardized, nondisease specific instrument for describing and valuing health status. It has 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels: level 1=no problem or none; level 2=slight problems; level 3=moderate problems; level 4=severe problems; level 5=unable to perform activity.

  16. Number of Participants With Change From Baseline to EoT in EQ-5D Subscale Score: Pain/Discomfort

    Time frame: Baseline and EoT (up to 12 weeks)

    The EQ-5D is an international, standardized, nondisease specific instrument for describing and valuing health status. It has 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels: level 1=no problem or none; level 2=slight problems; level 3=moderate problems; level 4=severe problems; level 5=unable to perform activity.

  17. Number of Participants With Change From Baseline to EoT in EQ-5D Subscale Score: Anxiety/Depression

    Time frame: Baseline and EoT (up to 12 weeks)

    The EQ-5D is an international, standardized, nondisease specific instrument for describing and valuing health status. It has 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels: level 1=no problem or none; level 2=slight problems; level 3=moderate problems; level 4=severe problems; level 5=unable to perform activity.

  18. Change From Baseline in Overactive Bladder Symptom (OAB-q) Symptom Bother Score

    Time frame: Baseline and weeks 4, 8 & 12

    The OAB-q was a self-reported questionnaire comprising 33-items each rated on a 6-point Likert scale. The questionnaire consisted of an 8-item symptom bother scale and 25 health-related QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). Symptom Bother score ranges from 0 (least severity) to 100 (worst severity).

  19. Change From Baseline in OAB-q Health-Related Quality of Life (HRQL) Total Score

    Time frame: Baseline and weeks 4, 8 & 12

    The OAB-q was a self-reported questionnaire comprising 33-items each rated on a 6-point Likert scale. The questionnaire consisted of an 8-item symptom bother scale and 25 health-related QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life).

  20. Change From Baseline in OAB-q HRQL Subscale Score: Coping

    Time frame: Baseline and weeks 4, 8 & 12

    The OAB-q was a self-reported questionnaire comprising 33-items each rated on a 6-point Likert scale. The questionnaire consisted of an 8-item symptom bother scale and 25 health-related QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life).

  21. Change From Baseline in OAB-q HRQL Subscale Score: Concern

    Time frame: Baseline and weeks 4, 8 & 12

    The OAB-q was a self-reported questionnaire comprising 33-items each rated on a 6-point Likert scale. The questionnaire consisted of an 8-item symptom bother scale and 25 health-related QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life).

  22. Change From Baseline in OAB-q HRQL Subscale Score: Sleep

    Time frame: Baseline and weeks 4, 8 & 12

    The OAB-q was a self-reported questionnaire comprising 33-items each rated on a 6-point Likert scale. The questionnaire consisted of an 8-item symptom bother scale and 25 health-related QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life).

  23. Change From Baseline in OAB-q HRQL Subscale Score: Social Interaction

    Time frame: Baseline and weeks 4, 8 & 12

    The OAB-q was a self-reported questionnaire comprising 33-items each rated on a 6-point Likert scale. The questionnaire consisted of an 8-item symptom bother scale and 25 health-related QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life).

  24. Change From Baseline in Treatment Satisfaction - Visual Analogue Scale (TS-VAS) Score

    Time frame: Baseline and weeks 4, 8 & 12

    The TS-VAS rated participant satisfaction with treatment on a scale from 0 (No, not at all) to 10 (Yes, completely).

  25. Change From Baseline in Patient Perception Bladder Control (PPBC) Score

    Time frame: Baseline and weeks 4, 8 & 12

    The PPBC was a validated, global assessment tool using a 6-point Likert scale on which participants rated their subjective impression of their current bladder condition. PPBC score: 1-no problem, 2- some very minor problems, 3-some minor problems, 4-moderate problems, 5-severe problems, 6-many severe problems.

  26. Number of Participants in Each Category of Patient and Clinician Global Impression of Change Scales (PGIC and CGIC)

    Time frame: End of treatment (up to 12 weeks)

    The PGIC was a 2-part questionnaire, assessing both the change in the participant's overall condition (Patient Impression in General Health (PIBS)) and change in bladder condition since the start of the study (Patient Impression in General Health (PIGH)) (from very much worse to very much improved). The CGIC was a single questionnaire assessing the participant's change in bladder condition since the beginning of the study (Clinician Impression in Bladder Symptoms (CIBS)).

  27. Percentage of Participants With at Least a 50% Decrease From Baseline in Mean Number of Incontinence Episodes Per 24 Hours

    Time frame: Weeks 4, 8 and 12

    Incontinence was defined as any involuntary leakage of urine.

  28. Percentage of Participants With Zero Incontinence Episodes Postbaseline

    Time frame: Weeks 4, 8 and 12

    Incontinence was defined as any involuntary leakage of urine.

  29. Percentage of Participants With a Mean of at Least 8 Micturitions Per 24 Hours at Baseline and Less Than 8 Micturitions Per 24 Hours Postbaseline

    Time frame: Weeks 4, 8 and 12

    Micturitions were defined as voluntary urinations (excluding incontinence only episodes).

  30. Percentage of Participants With at Least a 10-Point Improvement From Baseline in OAB-q Symptom Bother Score

    Time frame: Weeks 4, 8 and 12

    The OAB-q was a self-reported questionnaire comprising 33-items each rated on a 6-point Likert scale. The questionnaire consisted of an 8-item symptom bother scale and 25 health-related QoL (HRQL) items comprising 4 HRQL subscales (Coping, Concern, Sleep, and Social Interaction). Symptom Bother score ranges from 0 (least severity) to 100 (worst severity).

  31. Percentage of Participants With at Least a 10-Point Improvement From Baseline in HRQL Total Score

    Time frame: Weeks 4, 8 and 12

    HRQL subscales (coping, concern, sleep and social) and total score range from 0 (worst quality of life) to 100 (best quality of life).

  32. Percentage of Participants With at Least a 1-Point Improvement From Baseline in PPBC

    Time frame: Weeks 4, 8 and 12

    The PPBC was a validated, global assessment tool using a 6-point Likert scale on which participants rated their subjective impression of their current bladder condition.

  33. Percentage of Participants With Major (at Least 2-Point) Improvement From Baseline in PPBC

    Time frame: Weeks 4, 8 and 12

    The PPBC was a validated, global assessment tool using a 6-point Likert scale on which participants rated their subjective impression of their current bladder condition.

  34. Number of Participants With Adverse Events (AEs)

    Time frame: From first dose of double blind treatment until 30 days after last dose (up to 16 weeks)

    AE was defined as any untoward medical occurrence in a participant administered a study drug or has undergone study procedures & which does not necessarily have a causal relationship with this treatment. Treatment-Emergent Adverse Event (TEAE) referred to an adverse event which started or worsened in the period from first double-blind medication intake until 30 days after the last double-blind medication intake.

  35. Change From Baseline in Post Void Residual (PVR) Volume

    Time frame: Baseline and weeks 4, 8 & 12

    PVR Volume was assessed by bladder scan.

Sponsors and collaborators

Lead sponsor

Astellas Pharma Europe Ltd.

Industry

Registry information

Official study title

A Randomized, Double-Blind, Multi-Centre Study to Evaluate the Efficacy and Safety of Adding Mirabegron to Solifenacin in Incontinent OAB Subjects Who Have Received Solifenacin for 4 Weeks and Warrant Additional Relief for Their OAB Symptoms

Acronym: BESIDE

Important dates

Study start
2013
Primary completion
2014
Study completion
2014
First posted
Jul 26, 2013
Registry last updated
Oct 31, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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