MedPath

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

Registration Number
NCT01908829
Lead Sponsor
Astellas Pharma Europe Ltd.
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
2174
Inclusion Criteria
  • Main Inclusion at Screening:

    1. Subject has symptoms of OAB (urinary frequency and urgency with urgency incontinence) for >= 3 months prior to the screening visit
    2. 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;
    3. 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):

    1. 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.
    2. Subject experiences on average at least 2 incontinence episodes per 24-hour period during the 3-day micturition diary period.
    3. 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):

    1. 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:

    1. Subject in the opinion of the investigator has clinically significant Bladder Outlet Obstruction (BOO).
    2. Subject has significant Post-void residual (PVR) volume (PVR > 150 ml).
    3. Subject has significant stress incontinence or mixed stress/urgency incontinence where stress is the predominant factor as determined by the investigator
    4. Subject has an indwelling catheter or practices intermittent self catheterization.
    5. Subject has evidence of a UTI.
    6. Subject has chronic inflammation such as interstitial cystitis, bladder stones, previous pelvic radiation therapy, or previous or current malignant disease of the pelvic organs
    7. Subject has moderate to severe hepatic impairment
    8. Subject has severe renal impairment or End Stage Renal disease
    9. Subject has a clinically significant abnormal Electrocardiogram (ECG)
    10. Subject has a concurrent malignancy or history of cancer (except noninvasive skin cancer) within the last 5 years prior to screening.
    11. 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).
    12. Subject has received intravesical treatment in the past 12 months with e.g., botulinum toxin, resiniferatoxin, capsaicin.
    13. 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):

    1. 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).
    2. Subject does not desire an increase in study medication.
    3. Subject has an average total daily urine volume > 3000ml as recorded in the micturition diary.
    4. 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.
    5. Subject has a clinically significant abnormal ECG

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Combination (solifenacin + mirabegron)solifenacin 10 mg matching placeboParticipants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period.
Solifenacin 5 mgmirabegron 50 mg matching placeboParticipants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period
Solifenacin 10 mgsolifenacin 5 mg matching placeboParticipants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.
Solifenacin 10 mgmirabegron 50 mg matching placeboParticipants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.
Solifenacin 5 mgmirabegron 25 mg matching placeboParticipants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period
Solifenacin 10 mgsolifenacin 10 mgParticipants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.
Solifenacin 10 mgmirabegron 25 mg matching placeboParticipants received solifenacin 5 mg matching placebo, mirabegron 25 mg matching placebo and solifenacin 10 mg once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period.
Combination (solifenacin + mirabegron)mirabegron 25 mgParticipants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period.
Combination (solifenacin + mirabegron)mirabegron 50 mgParticipants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period.
Combination (solifenacin + mirabegron)solifenacin 5 mgParticipants received solifenacin 5 mg, mirabegron 25 mg and solifenacin 10 mg matching placebo once daily for the first 4 weeks of double-blind period. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron tablet was replaced by a 50 mg mirabegron tablet. Placebo was given for the 2 week single-blind safety follow-up period.
Solifenacin 5 mgsolifenacin 5 mgParticipants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period
Solifenacin 5 mgsolifenacin 10 mg matching placeboParticipants received solifenacin 5 mg, mirabegron 25 mg matching placebo and solifenacin 10 mg matching placebo once daily. For the last 8 weeks of the double-blind treatment period, the 25 mg mirabegron matching placebo tablet was replaced by a 50 mg mirabegron matching placebo tablet (to maintain the blind). Placebo was given for the 2 week single-blind safety follow-up period
Primary Outcome Measures
NameTimeMethod
Change From Baseline to End of Treatment (EoT) in Mean Number of Incontinence Episodes Per 24 HoursBaseline 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 Outcome Measures
NameTimeMethod
Change From Baseline in Mean Number of Pads Per 24 HoursBaseline 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.

Number of Pads Used During the 3-Day DiaryWeeks 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.

Change From Baseline in Mean Number of Nocturia EpisodesBaseline 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.

Number of Nocturia Episodes Reported Over 3-Day DiaryWeeks 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.

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

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

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

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

Change From Baseline in OAB-q HRQL Subscale Score: ConcernBaseline 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).

Change From Baseline in Mean Number of Micturitions Per 24 HoursBaseline 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).

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

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

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

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

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

Number of UI Episodes Reported During the 3-Day DiaryWeeks 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.

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

Percentage of Participants With Zero Incontinence Episodes PostbaselineWeeks 4, 8 and 12

Incontinence was defined as any involuntary leakage of urine.

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

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

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

Change From Baseline in OAB-q HRQL Subscale Score: CopingBaseline 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).

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

Change From Baseline in OAB-q HRQL Subscale Score: SleepBaseline 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).

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

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

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

Number of Participants With Adverse Events (AEs)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.

Change From Baseline in Post Void Residual (PVR) VolumeBaseline and weeks 4, 8 & 12

PVR Volume was assessed by bladder scan.

Change From Baseline in OAB-q HRQL Subscale Score: Social InteractionBaseline 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).

Percentage of Participants With at Least a 50% Decrease From Baseline in Mean Number of Incontinence Episodes Per 24 HoursWeeks 4, 8 and 12

Incontinence was defined as any involuntary leakage of urine.

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

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

Percentage of Participants With a Mean of at Least 8 Micturitions Per 24 Hours at Baseline and Less Than 8 Micturitions Per 24 Hours PostbaselineWeeks 4, 8 and 12

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

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

Trial Locations

Locations (217)

Urology Center of Central Florida

🇺🇸

Kissimmee, Florida, United States

Alliance Urology Specialists

🇺🇸

Greensboro, North Carolina, United States

Site: 47005

🇳🇴

Bekkestua, Norway

Site: 48006

🇵🇱

Krakow, Poland

Site: 43005

🇦🇹

Vienna, Austria

Site: 43011

🇦🇹

Vienna, Austria

Site: 42113

🇸🇰

Michalovce, Slovakia

Site: 35310

🇮🇪

Dublin, Ireland

Site: 43006

🇦🇹

Innsbruck, Austria

Site: 35306

🇮🇪

Limerick, Ireland

Site: 47003

🇳🇴

Trondheim, Norway

Site: 43007

🇦🇹

Linz, Austria

Site: 43002

🇦🇹

Vienna, Austria

Site: 45008

🇩🇰

Aarhus N, Denmark

Advanced Urology Centers of New York

🇺🇸

Garden City, New York, United States

Site: 42021

🇨🇿

Plzen, Czechia

Site: 42016

🇨🇿

Prague 1, Czechia

Site: 61001

🇦🇺

Kogarah, Sydney, Australia

Palmetto Professional Research

🇺🇸

Hialeah, Florida, United States

The American Institute of Research

🇺🇸

Los Angeles, California, United States

Genova Clinical Research

🇺🇸

Tucson, Arizona, United States

Associated Pharmaceutical Research Center, Inc.

🇺🇸

Buena Park, California, United States

Bayview Research Group

🇺🇸

Valley Village, California, United States

Best Quality Research Inc.

🇺🇸

Hialeah, Florida, United States

Private Practice

🇺🇸

West Palm Beach, Florida, United States

PMG Research of Raleigh, dba PMG Research of Cary

🇺🇸

Cary, North Carolina, United States

Quality Clinical Research

🇺🇸

Omaha, Nebraska, United States

Herman Clinical Research

🇺🇸

Suwanee, Georgia, United States

First Urology, PSC

🇺🇸

Jeffersonville, Indiana, United States

Deaconess Gateway Health Center

🇺🇸

Newburgh, Indiana, United States

Premier Medical Group of the Hudson Valley PC

🇺🇸

Poughkeepsie, New York, United States

PMG Research of Winston-Salem, LLC

🇺🇸

Winston-Salem, North Carolina, United States

MedStar Health Research Institute

🇺🇸

Hyattsville, Maryland, United States

The Clinical Trial Center

🇺🇸

Jenkintown, Pennsylvania, United States

Beyer Research

🇺🇸

Kalamazoo, Michigan, United States

Albuquerque Clinical Trials, Inc.

🇺🇸

Albuquerque, New Mexico, United States

Health Concepts

🇺🇸

Rapid City, South Dakota, United States

Site: 61016

🇦🇺

Victoria, Australia

Site: 43010

🇦🇹

Vienna, Austria

Alexandria Clinical Research

🇺🇸

Alexandria, Virginia, United States

Jean Brown Research

🇺🇸

Salt Lake City, Utah, United States

Site: 37402

🇦🇲

Yerevan, Armenia

Site: 37403

🇦🇲

Yerevan, Armenia

Site: 37405

🇦🇲

Yerevan, Armenia

Site: 43008

🇦🇹

Graz, Austria

Site: 43001

🇦🇹

Innsbruck, Austria

Site: 43004

🇦🇹

Vienna, Austria

Site: 43012

🇦🇹

Vienna, Austria

Site: 43003

🇦🇹

Wels, Austria

Site: 49008

🇩🇪

Bad Ems, Germany

Site: 36002

🇭🇺

Nyiregyhaza, Hungary

Site: 42022

🇨🇿

Praha 4, Czechia

Site: 32007

🇧🇪

Anderlecht, Belgium

Site: 15007

🇨🇦

Kitchener, Canada

Site: 15019

🇨🇦

Sherbrooke, Canada

Site: 15012

🇨🇦

Toronto, Canada

Site: 33018

🇫🇷

Bordeaux Cedex, France

Site: 32013

🇧🇪

Deurne, Belgium

Site: 32009

🇧🇪

Edegem, Belgium

Site: 32003

🇧🇪

Gent, Belgium

Site: 42004

🇨🇿

Plzen, Czechia

Site: 15018

🇨🇦

Victoriaville, Canada

Site: 15001

🇨🇦

Barrie, Canada

Site: 32008

🇧🇪

Liege, Belgium

Site: 35804

🇫🇮

Helsinki (hus), Finland

Site: 42017

🇨🇿

Praha 2, Czechia

Site: 42007

🇨🇿

Praha 4, Czechia

Site: 15009

🇨🇦

Bathurst, Canada

Site: 15006

🇨🇦

Brampton, Canada

Site: 15015

🇨🇦

Granby, Canada

Site: 45003

🇩🇰

Frederiksberg, Denmark

Site: 45011

🇩🇰

Odense C, Denmark

Site: 15014

🇨🇦

Kelowna, Canada

Site: 15047

🇨🇦

Victoria, Canada

Site: 42015

🇨🇿

Brno, Czechia

Site: 42020

🇨🇿

Melnik, Czechia

Site: 42018

🇨🇿

Nachod, Czechia

Site: 32014

🇧🇪

Roeselare, Belgium

Site: 45009

🇩🇰

Herlev, Denmark

Site: 49004

🇩🇪

Hamburg, Germany

Site: 99502

🇬🇪

T'bilisi, Georgia

Site: 33017

🇫🇷

Marseille, France

Site: 49018

🇩🇪

Henningsdorf, Germany

Site: 34004

🇪🇸

Madrid, Spain

Site: 49022

🇩🇪

Berlin, Germany

Site: 30002

🇬🇷

Patras, Greece

Site: 30001

🇬🇷

Athens, Greece

Site: 30005

🇬🇷

Heraklion, Crete, Greece

Site: 39010

🇮🇹

Firenze, Italy

Site: 36011

🇭🇺

Hajduszoboszlo, Hungary

Site: 36008

🇭🇺

Salgotarjan, Hungary

Site: 42109

🇸🇰

Zilina, Slovakia

Site: 34015

🇪🇸

Madrid, Spain

Site: 35304

🇮🇪

Tralee, Ireland

Site: 97203

🇮🇱

Petach Tikva, Israel

Site: 35313

🇮🇪

Mullingar, Ireland

Site: 97205

🇮🇱

Petach Tikva, Israel

Site: 39009

🇮🇹

Varese, Italy

Site: 38601

🇸🇮

Ljubljana, Slovenia

Site: 38606

🇸🇮

Maribor, Slovenia

Site: 38607

🇸🇮

Maribor, Slovenia

Site: 34001

🇪🇸

Getafe (Madrid), Spain

Site: 34023

🇪🇸

Mendaro, Spain

Site: 34016

🇪🇸

Bilbao, Spain

Site: 34012

🇪🇸

Barcelona, Spain

Site: 38610

🇸🇮

Ptuj, Slovenia

Site: 34018

🇪🇸

San Sebastian de los Reyes, Spain

Site: 34007

🇪🇸

Sevilla, Spain

Site: 46004

🇸🇪

Halmstad, Sweden

Site: 90005

🇹🇷

Ankara, Turkey

Site: 34014

🇪🇸

Vigo, Spain

Site: 44019

🇬🇧

Coventry, United Kingdom

Site: 44015

🇬🇧

Cheltenham, United Kingdom

Site: 41008

🇨🇭

Baden, Switzerland

Site: 44016

🇬🇧

Kings Lynn, United Kingdom

Site: 46014

🇸🇪

Norrtalje, Sweden

Site: 46001

🇸🇪

Stockholm, Sweden

Site: 90003

🇹🇷

Izmir, Turkey

Site: 90007

🇹🇷

Kocaeli, Turkey

Site: 90004

🇹🇷

Manisa, Turkey

Site: 90006

🇹🇷

Sivas, Turkey

Site: 44007

🇬🇧

Bristol, United Kingdom

Site: 44017

🇬🇧

London, United Kingdom

Site: 44011

🇬🇧

West Yorkshire, United Kingdom

Site: 44013

🇬🇧

Taunton, United Kingdom

Wake Research Associates LLC

🇺🇸

Raleigh, North Carolina, United States

Stedman Clinical Trials

🇺🇸

Tampa, Florida, United States

Site: 44012

🇬🇧

Cambridge, United Kingdom

Site: 35104

🇵🇹

Lisbon, Portugal

Site: 42112

🇸🇰

Piestany, Slovakia

Meridien Research

🇺🇸

Tampa, Florida, United States

Innovative Research of West FL

🇺🇸

Clearwater, Florida, United States

Meridian Clinical Research, LLC

🇺🇸

Savannah, Georgia, United States

North Idaho Urology

🇺🇸

Coeur d'Alene, Idaho, United States

Bay State Clinical Trials, Inc.

🇺🇸

Watertown, Massachusetts, United States

Brooklyn Urology Research Group

🇺🇸

Brooklyn, New York, United States

The Urology Group

🇺🇸

Cincinnati, Ohio, United States

Providence Health Partners

🇺🇸

Dayton, Ohio, United States

Site: 61006

🇦🇺

Adelaide, Australia

Site: 32005

🇧🇪

Gent, Belgium

Site: 15013

🇨🇦

Toronto, Canada

Site: 15016

🇨🇦

Victoria, Canada

Site: 42008

🇨🇿

Prague, Czechia

Site: 35805

🇫🇮

Tampere, Finland

Site: 49020

🇩🇪

Reutlingen, Germany

Site: 49021

🇩🇪

Hagenow, Germany

Site: 49011

🇩🇪

Halle (Saale), Germany

Site: 49009

🇩🇪

Hettstedt, Germany

Site: 49003

🇩🇪

Lutherstadt Eisleben, Germany

Site: 49017

🇩🇪

Koblenz, Germany

Site: 49014

🇩🇪

Sangerhausen, Germany

Site: 36003

🇭🇺

Csongrad, Hungary

Site: 36009

🇭🇺

Szekszard, Hungary

Site: 35303

🇮🇪

Cork, Ireland

Site: 35301

🇮🇪

Dublin, Ireland

Site: 35309

🇮🇪

Dublin, Ireland

Site: 35305

🇮🇪

Waterford, Ireland

Site: 97202

🇮🇱

Jerusalem, Israel

Site: 97201

🇮🇱

Haifa, Israel

Site: 97207

🇮🇱

Kfar Saba, Israel

Site: 39002

🇮🇹

Cantanzaro, Italy

Site: 39007

🇮🇹

Avellino, Italy

Site: 39013

🇮🇹

Treviglio (BG), Italy

Site: 97206

🇮🇱

Tel Hashomer, Israel

Site: 39006

🇮🇹

Perugia, Italy

Site: 96101

🇱🇧

Beirut, Lebanon

Site: 31008

🇳🇱

Amsterdam, Netherlands

Site: 47002

🇳🇴

Tonsberg, Norway

Site: 48002

🇵🇱

Kolbuszowa Dolna, Poland

Site: 48005

🇵🇱

Piaseczno, Poland

Site: 48010

🇵🇱

Lublin, Poland

Site: 48001

🇵🇱

Warszawa, Poland

Site: 35105

🇵🇹

Lisbon, Portugal

Site: 48008

🇵🇱

Warszawa, Poland

Site: 35102

🇵🇹

Matosinhos, Portugal

Site: 35103

🇵🇹

Porto, Portugal

Site: 35101

🇵🇹

Setubal, Portugal

Site: 40012

🇷🇴

Craiova, Romania

Site: 35106

🇵🇹

Tomar, Portugal

Site: 40016

🇷🇴

Bucharest, Romania

Site: 40019

🇷🇴

Craiova, Romania

Site: 40018

🇷🇴

Bucharest, Romania

Site: 40017

🇷🇴

Oradea, Romania

Site: 40003

🇷🇴

Judetul Ilfov, Romania

Site: 70008

🇷🇺

Moscow, Russian Federation

Site: 70011

🇷🇺

Moscow, Russian Federation

Site: 70004

🇷🇺

Moscow, Russian Federation

Site: 70005

🇷🇺

Moscow, Russian Federation

Site: 70003

🇷🇺

Moscow, Russian Federation

Site: 40020

🇷🇴

Timisoara, Romania

Site: 70013

🇷🇺

Rostove-on-Don, Russian Federation

Site: 70010

🇷🇺

Moscow, Russian Federation

Site: 70002

🇷🇺

Saint Petersburg, Russian Federation

Site: 70012

🇷🇺

Moscow, Russian Federation

Site: 70024

🇷🇺

Moscow, Russian Federation

Site: 70007

🇷🇺

Saint Petersburg, Russian Federation

Site: 70006

🇷🇺

Saint Petersburg, Russian Federation

Site: 70025

🇷🇺

Saratov, Russian Federation

Site: 70009

🇷🇺

Saint Petersburg, Russian Federation

Site: 42114

🇸🇰

Kosice, Slovakia

Site: 42111

🇸🇰

Nove Zamky, Slovakia

Site: 42110

🇸🇰

Bratislava, Slovakia

Site: 42108

🇸🇰

Poprad, Slovakia

Site: 34021

🇪🇸

Miranda de Ebro, Spain

Site: 34013

🇪🇸

San Sebastian, Spain

Site: 34020

🇪🇸

Sevilla, Spain

Site: 41001

🇨🇭

Frauenfeld, Switzerland

Site: 46013

🇸🇪

Lund, Sweden

Site: 46012

🇸🇪

Stockholm, Sweden

Site: 90008

🇹🇷

Ankara, Turkey

Site: 90002

🇹🇷

Izmir, Turkey

Site: 46015

🇸🇪

Umea, Sweden

Site: 44009

🇬🇧

Garston, United Kingdom

Site: 44010

🇬🇧

Nottingham, United Kingdom

Site: 44008

🇬🇧

Plymouth, United Kingdom

Site: 44018

🇬🇧

Northampton, United Kingdom

Site: 32015

🇧🇪

Kortrijk, Belgium

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