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    The EU Clinical Trials Register currently displays   42732   clinical trials with a EudraCT protocol, of which   7035   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2015-004036-36
    Sponsor's Protocol Code Number:178-MA-1008
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2016-05-06
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedGermany - BfArM
    A.2EudraCT number2015-004036-36
    A.3Full title of the trial
    A Phase 4, Double-Blind, Randomized, Placebo-controlled, Multi-
    Center Study to Evaluate the Efficacy, Safety, and Tolerability of
    Mirabegron in Men with Overactive Bladder (OAB) Symptoms
    While Taking the Alpha Blocker Tamsulosin Hydrochloride for
    Lower Urinary Tract Symptoms (LUTS) due to Benign Prostatic
    Hyperplasia (BPH)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study to evaluate the efficacy and safety of combined use of tamsulosin and mirabegron in men who have enlarged prostate and an overactive bladder
    A.4.1Sponsor's protocol code number178-MA-1008
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorAstellas Pharma Global development, Inc
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportAstellas Pharma Global Development, Inc
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAstellas Pharma Europe B.V.
    B.5.2Functional name of contact pointService Desk
    B.5.3 Address:
    B.5.3.1Street AddressSylviusweg 62
    B.5.3.2Town/ cityLeiden
    B.5.3.3Post code2333BE
    B.5.3.4CountryNetherlands
    B.5.4Telephone number+31(0)715455878
    B.5.5Fax number+31(0)715455224
    B.5.6E-mailraymond.vanaarle@astellas.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Betmiga
    D.2.1.1.2Name of the Marketing Authorisation holderAstellas Pharma Europe B.V.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameBetmiga
    D.3.2Product code PRD746368
    D.3.4Pharmaceutical form Prolonged-release tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Betmiga
    D.2.1.1.2Name of the Marketing Authorisation holderAstellas Pharma Europe B.V.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameBetmiga
    D.3.2Product code PRD746368
    D.3.4Pharmaceutical form Prolonged-release tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboProlonged-release tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboProlonged-release tablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Over active bladder (OAB) in men with Lower Urinary Tract Symptoms (LUTS) due to Benign Prostatic Hyperplasia (BPH)
    E.1.1.1Medical condition in easily understood language
    Over active bladder in men who also have an enlarged prostate with voiding problems
    E.1.1.2Therapeutic area Diseases [C] - Male diseases of the urinary and reproductive systems [C12]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level PT
    E.1.2Classification code 10046543
    E.1.2Term Urinary incontinence
    E.1.2System Organ Class 10038359 - Renal and urinary disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To study the efficacy of mirabegron versus placebo in men with OAB symptoms while taking tamsulosin hydrochloride for LUTS due to BPH.
    E.2.2Secondary objectives of the trial
    To assess safety and tolerability of mirabegron versus placebo in men with OAB symptoms while
    taking tamsulosin hydrochloride for LUTS due to BPH.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Institutional Review Board (IRB)/ Independent Ethics Committee (IEC)-approved written Informed Consent and privacy language as per national regulations (e.g., HIPAA Authorization for US sites) must be obtained from the subject or legally authorized representative prior to any study-related procedures (including withdrawal of prohibited medication, if applicable).
    2. Men ≥40 years of age with history of OAB symptoms (urinary frequency and urgency with or without incontinence) while taking tamsulosin hydrochloride 0.4 mg daily for at least 2 months to treat LUTS due to BPH.
    3. Subject has symptoms of OAB (frequency of ≥8 micturitions per day and urgency episodes of ≥2 per day) for ≥3 months prior to Screening.
    4. Subject has an IPSS score ≥8.
    5. Subject has Prostate-Specific Antigen (PSA) <4 ng/mL OR PSA ≥4 but <10 ng/mL with a prostate biopsy that is negative for cancer in the past two years.
    6. Subject is willing and able to complete the 3-day diary (including urine volumes, vital sign measurements), and Quality of Life questionnaires.
    7. Subject and their spouses/partners who are of childbearing potential must be using a highly effective method of birth control, which includes established use of oral, injected or implanted hormonal methods of contraception, placement of an IUD or IUS. Birth control must be practiced from Screening and continue throughout the study and for 30 days after the final study drug administration. In addition, sperm donation will not be allowed throughout the study and for 30 days after the final study drug administration.
    8. Subject agrees not to participate in another interventional study while on treatment.
    Inclusion Criteria assessed at Visit 2 (Baseline) based on the 3-day diary:
    9. Subject continues to meet all inclusion criteria of Visit 1 (Screening).
    10. Subject must experience an average of 8 or more micturitions per day over the 3-day diary period.
    11. Subject must experience an average of 2 episodes of urgency per day (grade 3 or 4) over the 3-day diary period.
    E.4Principal exclusion criteria
    1. Subject has PVR >200 mL.
    2. Subject has Qmax <5.0 mL/second with a minimum voided volume of 125 mL.
    3. Subject has hematuria >3 rbc/hpf that has not been fully evaluated.
    4. Subject has evidence of UTI.
    5. Subject has neurogenic bladder (spinal cord injury, multiple sclerosis, Parkinson’s etc.).
    6. Subject has diabetic neuropathy.
    7. Previous open, robotic or minimally invasive prostate surgery (including transurethral
    procedures). Planned (scheduled) pelvic or prostate surgery planned during the study
    period.
    8. Planned (scheduled) cataract surgery during the study period.
    9. Subject with significant stress incontinence as determined by the Investigator.
    10. Subject with clinically significant bladder outlet obstruction as determined by the
    Investigator.
    11. Subject has an indwelling catheter or practices intermittent self-catheterization.
    12. Subject has experienced 3 or more episodes of recurrent urinary tract infection within the last 12 months.
    13. Subject has a symptomatic urinary tract infection, prostatitis, chronic inflammation such as interstitial cystitis, bladder stones, previous pelvic radiation therapy, or previous or current malignant disease of the pelvic organs (i.e., within the confines of the pelvis including the bladder, prostate and rectum; organs of the lower gastrointestinal tract are not necessarily considered pelvic organs as the distal ascending colon, the full transverse colon and proximal portion of the descending colon are in the abdomen).
    14. Subject has received intravesical injection in the past 12 months with botulinum toxin, resiniferatoxin, or capsaicin.
    15. Subject has ever received electro-stimulation therapy for OAB (e.g. sacral nerve stimulation or Percutaneous Tibial Nerve Stimulation [PTNS]).
    16. Subject began or has changed a bladder training program or pelvic floor exercises less than 30 days prior to Screening.
    17. Subject has postural hypotension or syncope or postural orthostatic tachycardia.
    18. Subject has moderate or severe hepatic impairment defined as Child-Pugh Class B or C.
    19. Subject has severe renal impairment defined as estimated creatinine clearance less than 29 mL/min/1.73m2 as determined by central laboratory calculation of eGFR. A subject with End Stage Renal Disease (ESRD) or undergoing dialysis is also not a candidate for the study.
    20. Subject has severe uncontrolled hypertension, which is defined as a sitting systolic blood pressure ≥180 mmHg and/or diastolic blood pressure ≥110 mmHg.
    21. Subjects has baseline resting pulse rate <60 BPM or >90 BPM.
    22. Subject has evidence of QT prolongation on Screening (Visit 1) or Baseline (Visit 2) electrocardiogram (ECG) defined as QTcF >450 msec.
    23. Subject has any clinically significant ECG abnormality, as determined by the Investigator.
    24. Subject has AST or ALT >2x upper limit of normal (ULN), or y-GT >3x ULN and considered clinically significant by the Investigator.
    25. Subject has a hypersensitivity to any components of mirabegron, tamsulosin hydrochloride, or any of the inactive ingredients.
    26. Subject has a history of angioedema.
    27. Subject has any clinically significant condition, which in the opinion of the Investigator makes the subject unsuitable for study participation.
    28. Subject has been treated with an experimental device within 28 days or received an investigational agent within 28 days or 5 half-lives, whichever is longer, prior to Screening.
    29. Subject has a concurrent malignancy or history of any malignancy (within the past 5 years), except non-metastatic basal or squamous cell carcinoma of the skin that has been treated successfully.
    30. Subject has ongoing alcohol and/or drug abuse.
    31. Subject is using prohibited medications defined in Appendix 1, Part A within 30 days prior to Screening (Visit 1) through Follow-Up Phone Call (Visit 6).
    32. Subject has stopped, started or changed the dose of a restricted medication (defined in Appendix 1, Part B) within 30 days prior to Screening (Visit 1) through Follow-Up Phone Call (Visit 6).
    33. Subject has participated in an interventional trial within 30 days prior to Screening (Visit 1).
    34. Subject is involved in the conduct of the study as an employee of the Astellas group, third party associated with the study, or the study site team.
    35. Subject has previously received mirabegron in the 6 months prior to Screening (Visit 1).
    Exclusion Criteria assessed at Visit 2 (Baseline):
    36. Subject was non-compliant during the 4-week tamsulosin hydrochloride run-in period, defined as taking less than 80% or greater than 120% of study medication.
    37. Subject had an average total daily urine volume >3000mL as recorded in the 3-day diary.
    E.5 End points
    E.5.1Primary end point(s)
    Change from Baseline (Visit 2) to Week 12/ End of Treatment (Visit 5) in mean number of micturitions per day based on a 3-day diary.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Week 12
    E.5.2Secondary end point(s)
    ● Change from Baseline (Visit 2) to Week 4, Week 8, and Week 12/End of Treatment (Visit 5) in mean volume voided per micturition.
    ● Change from Baseline (Visit 2) to Week 4, Week 8, and Week 12/End of Treatment (Visit 5) in mean number of incontinence episodes per day (FAS-I).
    ● Change from Baseline (Visit 2) to Week 4, Week 8, and Week 12/End of Treatment (Visit 5) in mean number of urgency episodes (grade 3 and 4) per day.
    ● Change from Baseline (Visit 2) to Week 4, Week 8, and Week 12/End of Treatment (Visit 5) in IPSS total score and subscales (Voiding, Storage, and Quality of Life).
    ● Change from Baseline (Visit 2) to Week 4, Week 8, and Week 12/End of Treatment (Visit 5) in mean number of urgency incontinence episodes per day (FAS-I).
    ● Change from Baseline (Visit 2) to Week 4, Week 8, and Week 12/End of Treatment (Visit 5) in Symptom Bother Total Health Related Quality of Life and subscale
    (coping, concern, sleep, social interaction, and symptom bother) scores as assessed by OAB-q questionnaire.
    ● Change from Baseline (Visit 2) to Week 4, Week 8, and Week 12/End of Treatment (Visit 5) as assessed by EQ-5D-5L questionnaire.
    ● Change from Baseline (Visit 2) to Week 4, Week 8, and Week 12/End of Treatment (Visit 5) in PPBC.
    ● Change from Baseline (Visit 2) to Week 4, Week 8, and Week 12/End of Treatment (Visit 5) in Total Urgency and Frequency Score (TUFS) using PPIUS (Grade 3 or 4).
    ● Change from Baseline (Visit 2) to Week 4, Week 8, and Week 12/End of Treatment (Visit 5) in mean number of nocturia episodes per day.
    ● Change from Baseline (Visit 2) to Week 4, Week 8, and Week 12/End of Treatment (Visit 5) in TS-VAS scores.
    ● Change from Baseline (Visit 2) to Week 4, Week 8, and Week 12/End of Treatment (Visit 5) in the number of protective garments (e.g. absorbent pads, incontinence
    briefs, disposable underwear).
    E.5.2.1Timepoint(s) of evaluation of this end point
    Week 4, 8 and 12
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) Yes
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned7
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA50
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Canada
    United States
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of trial in all participating countries is defined as the Last Subject’s Last Visit.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months6
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 328
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 657
    F.2 Gender
    F.2.1Female No
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state120
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 600
    F.4.2.2In the whole clinical trial 985
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    After study is ended, standard clinical practises apply.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2016-07-11
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-06-08
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2018-09-12
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