Study to evaluate the efficacy and safety of combined use of tamsulosin and mirabegron in men who have enlarged prostate and an overactive bladder

Phase 1

• Conditions: Therapeutic area: Diseases [C] - Male diseases of the urinary and reproductive systems [C12]; Over active bladder (OAB) in men with Lower Urinary Tract Symptoms (LUTS) due to Benign Prostatic Hyperplasia (BPH); MedDRA version: 20.1Level: PTClassification code 10046543Term: Urinary incontinenceSystem Organ Class: 10038359 - Renal and urinary disorders

• Registration Number: EUCTR2015-004036-36-CZ
• Lead Sponsor: Astellas Pharma Global development, Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-05-04
• Last Update Posted: 22 October 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 985

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 < 10ng/mL with a prostate biopsy that is negative for cancer in te past two year
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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 328
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 657

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 or glaucoma 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 concu

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Primary 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.;Timepoint(s) of evaluation of this end point: Week 12;Main Objective: To study the efficacy of mirabegron versus placebo in men with OAB symptoms while taking tamsulosin hydrochloride for LUTS due to BPH.;Secondary Objective: To assess safety and tolerability of mirabegron versus placebo in men with OAB symptoms while<br>taking tamsulosin hydrochloride for LUTS due to BPH.