A Study to Evaluate the Efficacy and Safety of Mirabegron Compared to Solifenacin in Patients With Overactive Bladder Who Were Previously Treated With Another Medicine But Were Not Satisfied With That Treatment.
- Conditions
- Urologic DiseasesUrinary Bladder, OveractiveUrinary Bladder Diseases
- Interventions
- Registration Number
- NCT01638000
- Lead Sponsor
- Astellas Pharma Europe Ltd.
- Brief Summary
The purpose of the study was to assess the efficacy, safety and tolerability of mirabegron 50 mg versus (vs) solifenacin 5 mg in the treatment of patients with OAB who were dissatisfied with their treatment due to lack of efficacy.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1887
- Subject is willing and able to complete the micturition diary and questionnaires correctly
- Subject has symptoms of OAB (urinary frequency and urgency with or without urgency incontinence) for at least 3 months
- Subject is currently or has previously received at least one antimuscarinic agent intended to treat their OAB. The last antimuscarinic must have been taken for at least 4 weeks and taken within 6 months prior to the Screening Visit
- Female subject is breastfeeding, pregnant, intends to become pregnant during the study, or of childbearing potential is sexually active and not practicing a highly reliable method of birth control
- Subject has neurogenic bladder
- Subject has significant stress incontinence or mixed stress/urgency incontinence where stress is the predominant factor as determined by the investigator (for female subjects confirmed by a cough provocation test)
- Subject has an indwelling catheter or practices intermittent self-catheterization
- Subject has diabetic neuropathy
- Subject has evidence of a symptomatic urinary tract infection, chronic inflammation such as interstitial cystitis, bladder stones, previous pelvic radiation therapy or previous or current malignant disease of the pelvic organs
- Subject has uncontrolled narrow angle glaucoma, urinary or gastric retention, severe ulcerative colitis, toxic megacolon, myasthenia gravis or any other medical condition which makes the use of anticholinergics contraindicated
- The subject is currently receiving or has a history of treatment with intravesical botulinum toxin (cosmetic use is acceptable) or resiniferatoxin within 9 months prior to screening
- Subject receives non-drug treatment including electro-stimulation therapy (with the exception of a bladder training program or pelvic floor exercises which started more than 30 days prior to screening)
- Subject has moderate to severe hepatic impairment
- Subject has severe renal impairment or end stage renal disease
- Subject has severe uncontrolled hypertension
- Subject has a clinically significant abnormal electrocardiogram (ECG) or has a known history of QT prolongation or currently taking medication known to prolong the QT interval
- Subject has a known or suspected hypersensitivity to solifenacin, mirabegron or any of the inactive ingredients
- Subject has a concurrent malignancy or history of cancer (except noninvasive skin cancer) within the last 5 years prior to screening
- Subject has been treated with an experimental device within 30 days or received an experimental agent within the longer of 30 days or five half-lives
- Subject is using prohibited medications which cannot be stopped safely at the Screening Visit. Subject is excluded if using restricted medications not meeting protocol-specified criteria
- Subject's last antimuscarinic treatment was solifenacin
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Mirabegron 50 mg Mirabegron Participants who received mirabegron 50 mg once daily for 12 weeks. Solifenacin 5 mg Solifenacin succinate Participants who received solifenacin 5 mg once daily for 12 weeks.
- Primary Outcome Measures
Name Time Method Change From Baseline to Final Visit in the Mean Number of Micturitions Per 24 Hours Baseline and final visit (up to Week 12) A micturition is any voluntary urination (excluding incontinence only episodes). The mean number of micturitions per 24 hours were calculated from the data recorded by the participant during the 3-day micturition diary period.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Zero Incontinence Episodes at Weeks 4, 8, 12 and Final Visit Week 4, Week 8, Week 12 A responder is defined as a participant who reported incontinence episodes at baseline and reported no incontinence episodes during the treatment period at specified visit.
Percentage of Participants Reporting at Least One Treatment-emergent Adverse Event of Dry Mouth, Constipation or Blurred Vision During Double-blind Treatment Period From first dose of study drug up to 30 days after last dose of study drug (up to 16 weeks) A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE; defined as any untoward medical occurrence in a patient administered a study drug) that started or worsened in the period from the first double-blind medication intake until 30 days after the last double-blind medication intake. The following TEAEs were selected for inclusion in the analysis: Dry mouth (aptyalism, dry mouth, dry throat), constipation (constipation), blurred vision (vision blurred, myopia, refraction disorder, accommodation disorder).
Change From Baseline to 4, 8 and 12 Weeks of Treatment in Mean Number of Micturitions Per 24 Hours Baseline and Week 4, Week 8, Week 12 Number of Incontinence Episodes at 4, 8 and 12 Weeks of Treatment and at the Final Visit Week 4, Week 8, Week 12 An incontinence episode is any involuntary leakage of urine. The total number of incontinence episodes per 24 hours were calculated from the data recorded by the participant during the 3-day micturition diary period prior to each visit.
Change From Baseline to 4, 8 and 12 Weeks of Treatment in Mean Number of Incontinence Episodes Per 24 Hours Baseline and Week 4, Week 8, Week 12 An incontinence episode is any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours were calculated from the data recorded by the participant during the 3-day micturition diary period.
Number of Urgency Incontinence Episodes at 4, 8 and 12 Weeks of Treatment and at the Final Visit Week 4, Week 8, Week 12 An urgency incontinence episode is any involuntary leakage of urine accompanied by or immediately proceeded by urgency. The total number of urgency incontinence episodes per 24 hours were calculated from the data recorded by the participant during the 3-day micturition diary period prior to each visit.
Change From Baseline to 4, 8 and 12 Weeks of Treatment in Mean Number of Urgency Incontinence Episodes Per 24 Hours Baseline and Week 4, Week 8, Week 12 An urgency incontinence episode is any involuntary leakage of urine accompanied by or immediately proceeded by urgency. The mean number of urgency incontinence episodes per 24 hours were calculated from the data recorded by the participant during the 3-day micturition diary period.
Change From Baseline to 4, 8 and 12 Weeks of Treatment and at the Final Visit in Mean Number of Urgency Episodes (Grade 3 or 4) Per 24 Hours Baseline and Week 4, Week 8, Week 12 An urgency episode is a sudden compelling desire to pass urine immediately followed by an incontinent event or the patient having to rush to the toilet and make it in time; severity recorded as 3 (severe urgency) or 4 (urgency incontinence) on the Patient Perception of the Intensity of Urgency Scale (PPIUS) validated scale. The mean number of urgency episodes per 24 hours were calculated from the data recorded by the participant during the 3-day micturition diary period.
Change From Baseline to 4, 8 and 12 Weeks of Treatment and at the Final Visit in Mean Level of Urgency Baseline and Week 4, Week 8, Week 12 Urgency level was rated by the participant during the 3-day micturition diary period using the PPIUS 5-point categorical scale: 0. No urgency; 1. Mild urgency; 2. Moderate urgency; 3. Severe urgency; 4. Urgency incontinence.
Number of Pads Used at 4, 8 and 12 Weeks of Treatment and at the Final Visit Week 4, Week 8, Week 12 The total number of pads per 24 hours were calculated from the data recorded by the participant during the 3-day micturition diary period prior to each visit.
Change From Baseline in Mean Number of Pads Used Per 24 Hours After 4, 8 and 12 Weeks of Treatment Baseline and Week 4, Week 8 , Week 12 The mean number of pads per 24 hours were calculated from the data recorded by the participant during the 3-day micturition diary period.
Number of Nocturia Episodes at 4, 8 and 12 Weeks of Treatment and at the Final Visit Week 4, Week 8, Week 12 A nocturia episode is defined as waking at night ≥1 times to void (i.e., any voiding associated with sleep disturbance between the time the patient 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 total number of nocturia episodes were calculated from the data recorded by the participant during the 3-day micturition diary period prior to each visit.
Change From Baseline in Mean Number of Nocturia Episodes Per 24 Hours After 4, 8 and 12 Weeks of Treatment Baseline and Week 4, Week 8, Week 12 A nocturia episode is defined as waking at night ≥1 times to void (i.e., any voiding associated with sleep disturbance between the time the patient 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 were calculated from the data recorded by the participant during the 3-day micturition diary period.
Percentage of Participants With Normalization of Micturitions at Weeks 4, 8, 12 and Final Visit Week 4, Week 8, Week 12 A responder is defined as a participant who has ≥8 micturitions at baseline and has \<8 micturitions per 24 hours during the treatment period at each specified visit, where change from baseline is \<0.
Percentage of Participants With 50% Reduction in Incontinence Episodes at Weeks 4, 8, 12 and Final Visit Week 4, Week 8, Week 12 A responder is defined as a participant with at least 50% decrease from baseline in mean number of incontinence episodes per 24 hours during the treatment period at specified visit.
Change From Baseline to Week 4 in Mobility Scores as Assessed by the European Quality of Life 5-Dimensions (EQ-5D-5L) Questionnaire Baseline and Week 4 The European Quality of Life 5-Dimensions Questionnaire (EQ-5D-5L) is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform \[extreme problems\]).
Change From Baseline to Week 4 in Self-care Scores as Assessed by the EQ-5D-5L Questionnaire Baseline and Week 4 The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform \[extreme problems\]).
Change From Baseline to Week 4 in Usual Activities Scores as Assessed by the EQ-5D-5L Questionnaire Baseline and Week 4 The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform \[extreme problems\]).
Change From Baseline to Week 4 in Pain/Discomfort Scores as Assessed by the EQ-5D-5L Questionnaire Baseline and Week 4 The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform \[extreme problems\]).
Change From Baseline to Week 4 in Anxiety/Depression Scores as Assessed by the EQ-5D-5L Questionnaire Baseline and Week 4 The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform \[extreme problems\]).
Change From Baseline to Week 8 in Mobility Scores as Assessed by the EQ-5D-5L Questionnaire Baseline and Week 8 The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform \[extreme problems\]).
Change From Baseline to Week 8 in Self-care Scores as Assessed by the EQ-5D-5L Questionnaire Baseline and Week 8 The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform \[extreme problems\]).
Change From Baseline to Week 8 in Usual Activities Scores as Assessed by the EQ-5D-5L Questionnaire Baseline and Week 8 The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform \[extreme problems\]).
Change From Baseline to Week 8 in Pain/Discomfort Scores as Assessed by the EQ-5D-5L Questionnaire Baseline and Week 8 The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform \[extreme problems\]).
Change From Baseline to Week 8 in Anxiety/Depression Scores as Assessed by the EQ-5D-5L Questionnaire Baseline and Week 8 The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform \[extreme problems\]).
Change From Baseline to Week 12 in Mobility Scores as Assessed by the EQ-5D-5L Questionnaire Baseline and Week 12 The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform \[extreme problems\]).
Change From Baseline to Week 12 in Self-care Scores as Assessed by the EQ-5D-5L Questionnaire Baseline and Week 12 The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform \[extreme problems\]).
Change From Baseline to Week 12 in Usual Activities Scores as Assessed by the EQ-5D-5L Questionnaire Baseline and Week 12 The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform \[extreme problems\]).
Change From Baseline to Week 12 in Pain/Discomfort Scores as Assessed by the EQ-5D-5L Questionnaire Baseline and Week 12 The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform \[extreme problems\]).
Change From Baseline to Week 12 in Anxiety/Depression Scores as Assessed by the EQ-5D-5L Questionnaire Baseline and Week 12 The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform \[extreme problems\]).
Change From Baseline to Final Visit in Mobility Scores as Assessed by the EQ-5D-5L Questionnaire Baseline and final visit (up to Week 12) The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform \[extreme problems\]).
Change From Baseline to Final Visit in Self-care Scores as Assessed by the EQ-5D-5L Questionnaire Baseline and final visit (up to Week 12) The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform \[extreme problems\]).
Change From Baseline to Final Visit in Usual Activities Scores as Assessed by the EQ-5D-5L Questionnaire Baseline and final visit (up to Week 12) The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform \[extreme problems\]).
Percentage of Participants With Improvement in Symptom Bother Score as Assessed by the OAB-q: ≥ 10 Points Improvement in OAB-q at Week 12 and Final Visit Baseline to Week 12 A responder is defined as a participant with ≥10 points improvement in symptom bother from baseline.
Change From Baseline to Final Visit in Pain/Discomfort Scores as Assessed by the EQ-5D-5L Questionnaire Baseline and final visit (up to Week 12) The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform \[extreme problems\]).
Change From Baseline to Final Visit in Anxiety/Depression Scores as Assessed by the EQ-5D-5L Questionnaire Baseline and final visit (up to Week 12) The EQ-5D-5L is a standardized nondisease specific (i.e., generic) instrument for use as a measure of health outcome. It has 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension has 5 response levels (e.g., no problems with performing activity, slight problems, moderate problems, severe problems, unable to perform \[extreme problems\]).
Change From Baseline to Weeks 4, 8, 12, and at the Final Visit in Symptom Bother Score as Assessed by the Overactive Bladder Questionnaire (OAB-q) Baseline and Week 4, Week 8, 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 8 items, scored from 1 to 6. The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 (least severity) to 100 (worst severity). A negative change from baseline indicates an improvement.
Change From Baseline to Weeks 4, 8, 12, and at the Final Visit in Total Health-Related Quality of Life (HRQoL) Score as Assessed by the OAB-q Baseline and Week 4, Week 8, Week 12 The 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). The 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.
Change From Baseline to Weeks 4, 8, 12, and at the Final Visit in Patient Perception of Bladder Condition (PPBC) Baseline and Week 4, Week 8, Week 12 The Patient Perception of Bladder Condition (PPBC) questionnaire is a single-item questionnare used to assess participants' perceptions and impressions of their bladder condition. Participants assessed their bladder condition using a 6-point categorical scale: 1. Does not cause me any problems at all; 2. Causes me some very minor problems; 3. Causes me some minor problems; 4. Causes me (some) moderate problems; 5. Causes me severe problems; 6. Causes me many severe problems.
Change From Baseline to Week 12 and the Final Visit in the Patient's Assessment of Treatment Satisfaction (TS)-Visual Analog Scale (VAS) Baseline and Week 12 The Treatment Satisfaction (TS)-Visual Analogue Scale (VAS) was a self-rated scale with the participant answering the question "Are you satisfied with your treatment?" and placing a vertical mark on a line from 0 (No, not at all) to 10 (Yes, completely).
Percentage of Participants With Improvement in HRQoL Scales as Assessed by the OAB-q: ≥10 Points Improvement in OAB-q at Week 12 and Final Visit Baseline to Week 12 A responder is defined as a participant with \>=10 points improvement in the total HRQL score from baseline.
Percentage of Participants With Improvement in PPBC: ≥1 Point Improvement at Week 12 and Final Visit Baseline to Week 12 A responder is defined as a participant with ≥1 point improvement in PPBC from baseline.
Change From Baseline to Week 12 and the Final Visit in the Patient's Assessment of Treatment Satisfaction Questionnaire-Likert Scale Baseline and Week 12 The Treatment Satisfaction (TS)-Likert Scale was a self-rated scale with the participant answering the question "How satisfied were you with your treatment?" with on a scale from 1 (extremely dissatisfied) to 7 (extremely satisfied).
Percentage of Participants With Improvement of Treatment Satisfaction Questionnaire - Likert Scale: ≥1, ≥2, ≥3, ≥4, ≥5, and 6-point Improvement From Baseline to Week 12 Baseline to Week 12 A responder is defined as a participant with ≥1, ≥2, ≥3, ≥4, ≥5 or 6-point improvement from baseline in TS-Likert scale.
Percentage of Participants With Improvement in Treatment Satisfaction Questionnaire - Likert Scale: ≥1, ≥2, ≥3, ≥4, ≥5, and 6-point Improvement From Baseline to Final Visit Baseline to final visit (up to Week 12) A responder is defined as a participant with \>=1 or \>=2 or \>=3 or \>=4 or \>=5 or 6-point improvement from baseline in TS-Likert scale.
Percentage of Participants With Major Improvement in PPBC: ≥2 Point Improvement at Week 12 and Final Visit Baseline to Week 12 A responder is defined as a participant with ≥2 point improvement in PPBC from baseline.
Trial Locations
- Locations (217)
Site: 37404
🇦🇲Yerevan, Armenia
Site: 37402
🇦🇲Yerevan, Armenia
Site: 43013
🇦🇹Linz, Austria
Site: 43005
🇦🇹Oberwart, Austria
Site: 43011
🇦🇹Vienna, Austria
Site: 43003
🇦🇹Wels, Austria
Site: 43002
🇦🇹Vienna, Austria
Site: 37501
🇧🇾Minsk, Belarus
Site: 36005
🇭🇺Csongrad, Hungary
Site: 35306
🇮🇪Dublin, Ireland
Site: 37101
🇱🇻Riga, Latvia
Site: 35104
🇵🇹Lisbon, Portugal
Site: 36003
🇭🇺Budapest, Hungary
Site: 37406
🇦🇲Yerevan, Armenia
Site: 36004
🇭🇺Budapest, Hungary
Site: 43015
🇦🇹Innsbruck, Austria
Site: 35801
🇫🇮Oulu, Finland
Site: 35804
🇫🇮Tampere, Finland
Site: 77705
🇰🇿Almaty, Kazakhstan
Site: 48001
🇵🇱Lublin, Poland
Site: 48005
🇵🇱Wroclaw, Poland
Site: 35105
🇵🇹Lisbon, Portugal
Site: 42104
🇸🇰Galanta, Slovakia
Site: 36006
🇭🇺Nyiregyhaza, Hungary
Site: 35901
🇧🇬Lovech, Bulgaria
Site: 35903
🇧🇬Sofia, Bulgaria
Site: 99502
🇬🇪Tbilisi, Georgia
Site: 42103
🇸🇰Piestany, Slovakia
Site: 42101
🇸🇰Poprad, Slovakia
Site: 35302
🇮🇪Dublin, Ireland
Site: 36002
🇭🇺Szekszard, Hungary
Site: 35301
🇮🇪Dublin, Ireland
Site: 47002
🇳🇴Hamar, Norway
Site: 35103
🇵🇹Porto, Portugal
Site: 35101
🇵🇹Setubal, Portugal
Site: 38604
🇸🇮Ljubljana, Slovenia
Site: 38606
🇸🇮Novo Mesto, Slovenia
Site: 48006
🇵🇱Krakow, Poland
Site: 48004
🇵🇱Piaseczno, Poland
Site: 42105
🇸🇰Trencin, Slovakia
Site: 42102
🇸🇰Zilina, Slovakia
Site: 41001
🇨🇭Frauenfeld, Switzerland
Site: 33004
🇫🇷Orleans Cedex 2, France
Site: 34002
🇪🇸Barcelona, Spain
Site: 34012
🇪🇸Valencia, Spain
Site: 37403
🇦🇲Yerevan, Armenia
Site: 43006
🇦🇹Baden, Austria
Site: 37401
🇦🇲Yerevan, Armenia
Site: 37502
🇧🇾Minsk, Belarus
Site: 37504
🇧🇾Vitebsk, Belarus
Site: 32008
🇧🇪Deurne, Belgium
Site: 32006
🇧🇪Brussels, Belgium
Site: 32004
🇧🇪Gent, Belgium
Site: 32001
🇧🇪Edegem, Belgium
Site: 32005
🇧🇪Liege, Belgium
Site: 35902
🇧🇬Burgas, Bulgaria
Site: 32007
🇧🇪Leuven, Belgium
Site: 35909
🇧🇬Haskovo, Bulgaria
Site: 35905
🇧🇬Plovdiv, Bulgaria
Site: 10003
🇨🇦Brampton, Canada
Site: 10010
🇨🇦Abbotsford, Canada
Site: 10001
🇨🇦Bathurst, Canada
Site: 10002
🇨🇦Montreal, Canada
Site: 10005
🇨🇦Brantford, Canada
Site: 10007
🇨🇦Kingston, Canada
Site: 10009
🇨🇦Sherbrooke, Canada
Site: 10008
🇨🇦Victoria, Canada
Site: 42004
🇨🇿Bohumin, Czechia
Site: 42003
🇨🇿Brno, Czechia
Site: 42001
🇨🇿Hradec Kralove, Czechia
Site: 42006
🇨🇿Plzen-Lochotin, Czechia
Site: 42002
🇨🇿Jihlava, Czechia
Site: 42005
🇨🇿Prague 1, Czechia
Site: 42007
🇨🇿Prague 4, Czechia
Site: 45001
🇩🇰Aarhus N, Denmark
Site: 45002
🇩🇰Aalborg, Denmark
Site: 45005
🇩🇰Frederiksbjerg, Denmark
Site: 42008
🇨🇿Prague, Czechia
Site: 45003
🇩🇰Odense C, Denmark
Site: 45004
🇩🇰Hvidovre, Denmark
Site: 33010
🇫🇷Angers, France
Site: 35802
🇫🇮Jyvaskyla, Finland
Site: 33007
🇫🇷Colmar Cedex, France
Site: 33011
🇫🇷Dijon, France
Site: 33002
🇫🇷Marseille, France
Site: 33001
🇫🇷Paris Cedex 20, France
Site: 33006
🇫🇷Marseille, France
Site: 33015
🇫🇷Valence, France
Site: 99503
🇬🇪Tbilisi, Georgia
Site: 33017
🇫🇷Tours, France
Site: 30009
🇬🇷Athens, Greece
Site: 30008
🇬🇷Larisa, Greece
Site: 30010
🇬🇷Thessaloniki, Greece
Site: 35305
🇮🇪Waterford, Ireland
Site: 35304
🇮🇪Cork, Ireland
Site: 39001
🇮🇹Avellino, Italy
Site: 35303
🇮🇪Tralee, Ireland
Site: 39005
🇮🇹Catanzaro, Italy
Site: 39002
🇮🇹Florence, Italy
Site: 39010
🇮🇹Pavia, Italy
Site: 39003
🇮🇹Cinisello Balsamo, Italy
Site: 39008
🇮🇹Milan, Italy
Site: 39007
🇮🇹Treviglio, Italy
Site: 77703
🇰🇿Astana, Kazakhstan
Site: 96103
🇱🇧Achrafieh, Lebanon
Site: 96102
🇱🇧Jbeil, Lebanon
Site: 37103
🇱🇻Liepaja, Latvia
Site: 77702
🇰🇿Astana, Kazakhstan
Site: 37003
🇱🇹Vilnius, Lithuania
Site: 31005
🇳🇱Eindhoven, Netherlands
Site: 31006
🇳🇱Zwolle, Netherlands
Site: 37001
🇱🇹Kaunas, Lithuania
Site: 31004
🇳🇱Enschede, Netherlands
Site: 31001
🇳🇱Tilburg, Netherlands
Site: 31007
🇳🇱Nijmegen, Netherlands
Site: 31008
🇳🇱Utrecht, Netherlands
Site: 47001
🇳🇴Tonsberg, Norway
Site: 47005
🇳🇴Trondheim, Norway
Site: 48007
🇵🇱Kolbuszowa Dolna, Poland
Site: 70001
🇷🇺Moscow, Russian Federation
Site: 70009
🇷🇺Saint Petersburg, Russian Federation
Site: 70012
🇷🇺Saint Petersburg, Russian Federation
Site: 70004
🇷🇺St. Petersburg, Russian Federation
Site: 38603
🇸🇮Ljubljana, Slovenia
Site: 34009
🇪🇸Bilbao, Spain
Site: 38601
🇸🇮Maribor, Slovenia
Site: 34001
🇪🇸Barcelona, Spain
Site: 38602
🇸🇮Maribor, Slovenia
Site: 34005
🇪🇸Madrid, Spain
Site: 34010
🇪🇸San Sebastian, Spain
Site: 34013
🇪🇸Murcia, Spain
Site: 34014
🇪🇸Sevilla, Spain
Site: 46007
🇸🇪Gothenburg, Sweden
Site: 46003
🇸🇪Norrtalje, Sweden
Site: 46005
🇸🇪Karlshamn, Sweden
Site: 41003
🇨🇭Zurich, Switzerland
Site: 90007
🇹🇷Diyarbakir, Turkey
Site: 90004
🇹🇷Istanbul, Turkey
Site: 90001
🇹🇷Izmir, Turkey
Site: 90008
🇹🇷Izmir, Turkey
Site: 38002
🇺🇦Kiev, Ukraine
Site: 38001
🇺🇦Kharkov, Ukraine
Site: 90009
🇹🇷Manisa, Turkey
Site: 38004
🇺🇦Dnepropetrovsk, Ukraine
Site: 44023
🇬🇧Harrow, United Kingdom
Site: 44029
🇬🇧Birmingham, United Kingdom
Site: 44001
🇬🇧Edgbaston, United Kingdom
Site: 44017
🇬🇧London, United Kingdom
Site: 44008
🇬🇧Liverpool, United Kingdom
Site: 44006
🇬🇧Kent, United Kingdom
Site: 44019
🇬🇧Leicester, United Kingdom
Site: 44022
🇬🇧Northwood, United Kingdom
Site: 44013
🇬🇧Newcastle upon Tyne, United Kingdom
Site: 44007
🇬🇧Reading, United Kingdom
Site: 44009
🇬🇧Plymouth, United Kingdom
Site: 44026
🇬🇧Taunton, United Kingdom
Site: 44024
🇬🇧West Yorkshire, United Kingdom
Site: 70006
🇷🇺Moscow, Russian Federation
Site: 70002
🇷🇺Moscow, Russian Federation
Site: 33013
🇫🇷Nimes, France
Site: 99501
🇬🇪Tbilisi, Georgia
Site: 30001
🇬🇷Athens, Greece
Site: 10004
🇨🇦Toronto, Canada
Site: 10011
🇨🇦Barrie, Canada
Site: 42106
🇸🇰Martin, Slovakia
Site: 43014
🇦🇹Graz, Austria
Site: 35908
🇧🇬Sofia, Bulgaria
Site: 35906
🇧🇬Sofia, Bulgaria
Site: 33005
🇫🇷Paris Cedex 20, France
Site: 33003
🇫🇷Rouen, France
Site: 33014
🇫🇷Suresnes Cedex, France
Site: 49006
🇩🇪Bad Ems, Germany
Site: 49009
🇩🇪Halle Saale, Germany
Site: 30005
🇬🇷Alexandroupoli, Greece
Site: 30007
🇬🇷Athens, Greece
Site: 30006
🇬🇷Herakleion, Greece
Site: 30004
🇬🇷Patras, Greece
Site: 30002
🇬🇷Thessaloniki, Greece
Site: 36001
🇭🇺Salgotarjan, Hungary
Site: 39006
🇮🇹Perugia, Italy
Site: 77706
🇰🇿Almaty, Kazakhstan
Site: 37102
🇱🇻Riga, Latvia
Site: 31010
🇳🇱Amsterdam, Netherlands
Site: 35102
🇵🇹Matosinhos, Portugal
Site: 48003
🇵🇱Warsaw, Poland
Site: 70007
🇷🇺Moscow, Russian Federation
Site: 70008
🇷🇺Moscow, Russian Federation
Site: 70005
🇷🇺Moscow, Russian Federation
Site: 70011
🇷🇺Moscow, Russian Federation
Site: 70003
🇷🇺Moscow, Russian Federation
Site: 70010
🇷🇺Saint Petersburg, Russian Federation
Site: 70013
🇷🇺Saint Petersburg, Russian Federation
Site: 34003
🇪🇸Madrid, Spain
Site: 34004
🇪🇸Madrid, Spain
Site: 34011
🇪🇸Mendaro, Spain
Site: 46004
🇸🇪Halmstad, Sweden
Site: 46001
🇸🇪Stockholm, Sweden
Site: 46006
🇸🇪Uppsala, Sweden
Site: 46002
🇸🇪Stockholm, Sweden
Site: 90005
🇹🇷Ankara, Turkey
Site: 90003
🇹🇷Ankara, Turkey
Site: 90011
🇹🇷Denizli, Turkey
Site: 38007
🇺🇦Chernivtsi, Ukraine
Site: 90010
🇹🇷Sivas, Turkey
Site: 44027
🇬🇧Aberdeen, United Kingdom
Site: 44030
🇬🇧Chichester, United Kingdom
Site: 44028
🇬🇧Croydon, United Kingdom
Site: 44025
🇬🇧Cambridge, United Kingdom
Site: 44003
🇬🇧Devon, United Kingdom
Site: 44012
🇬🇧Leeds, United Kingdom
Site: 44011
🇬🇧Glasgow, United Kingdom
Site: 44010
🇬🇧London, United Kingdom
Site: 44021
🇬🇧Nottingham, United Kingdom
Site: 44005
🇬🇧Sheffield, United Kingdom
Site: 44020
🇬🇧Southampton, United Kingdom
Site: 44002
🇬🇧West Yorkshire, United Kingdom
Site: 38003
🇺🇦Lviv, Ukraine