This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback
Trial record 1 of 1 for:    178-MA-1008
Previous Study | Return to List | Next Study

A Study to Evaluate the Efficacy, Safety, and Tolerability of Mirabegron in Men With OAB Symptoms While Taking Tamsulosin Hydrochloride for Lower Urinary Tract Symptoms (LUTS) Due to Benign Prostatic Hyperplasia (BPH)

This study is currently recruiting participants.
See Contacts and Locations
Verified May 2017 by Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
ClinicalTrials.gov Identifier:
NCT02757768
First received: April 15, 2016
Last updated: May 9, 2017
Last verified: May 2017
  Purpose
The purpose of the study is to assess the efficacy, safety, and tolerability of mirabegron versus placebo in men with overactive bladder (OAB) symptoms while taking tamsulosin hydrochloride for lower urinary tract symptoms (LUTS) due to Benign Prostatic Hyperplasia (BPH).

Condition Intervention Phase
Benign Prostatic Hyperplasia Overactive Bladder Drug: Mirabegron Drug: Placebo Drug: Tamsulosin Hydrochloride Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Investigator
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. ):

Primary Outcome Measures:
  • Change from Baseline to Week 12 (End of Treatment) in mean number of micturitions per day based on a 3-day diary [ Time Frame: Baseline and Week 12 ]

Secondary Outcome Measures:
  • Change from Baseline to Week 4, Week 8, and Week 12 (End of Treatment) in mean volume voided per micturition [ Time Frame: Baseline and Weeks 4, 8 and 12 ]
  • Change from Baseline to Week 4, Week 8, and Week 12 (End of Treatment) in mean number of incontinence episodes per day [ Time Frame: Baseline and Weeks 4, 8 and 12 ]
  • Change from Baseline to Week 4, Week 8, and Week 12 (End of Treatment) in mean number of urgency episodes (grade 3 or 4) per day [ Time Frame: Baseline and Weeks 4, 8 and 12 ]
  • Change from Baseline to Week 4, Week 8, and Week 12 (End of Treatment) in International Prostate Symptom Score (IPSS) Total score [ Time Frame: Baseline and Weeks 4, 8 and 12 ]
  • Change from Baseline to Week 4, Week 8, and Week 12 (End of Treatment) in International Prostate Symptom Score (IPSS) subscale Voiding score [ Time Frame: Baseline and Weeks 4, 8 and 12 ]
  • Change from Baseline to Week 4, Week 8, and Week 12 (End of Treatment) in International Prostate Symptom Score (IPSS) subscale Storage score [ Time Frame: Baseline and Weeks 4, 8 and 12 ]
  • Change from Baseline to Week 4, Week 8, and Week 12 (End of Treatment) in International Prostate Symptom Score (IPSS) subscale Quality of Life score [ Time Frame: Baseline and Weeks 4, 8 and 12 ]
  • Change from Baseline to Week 4, Week 8, and Week 12 (End of Treatment) in mean number of urgency incontinence episodes per day [ Time Frame: Baseline and Weeks 4, 8 and 12 ]
  • Change from Baseline to Week 12 (End of Treatment) in Symptom Bother Score as assessed by Overactive Bladder- questionnaire (OAB-q) [ Time Frame: Baseline and Week 12 ]
    Overactive bladder symptoms will be assessed using the Symptom Bother Scale of the Overactive Bladder quesionnaire.

  • Change from Baseline to Week 12 (End of Treatment) in Health Related Quality of Life (HRQL) subscale Coping score as assessed by Overactive Bladder-questionnaire (OAB-q) [ Time Frame: Baseline and Week 12 ]
  • Change from Baseline to Week 12 (End of Treatment) in Health Related Quality of Life (HRQL) subscale Sleep score as assessed by Overactive Bladder-questionnaire (OAB-q) [ Time Frame: Baseline and Week 12 ]
  • Change from Baseline to Week 12 (End of Treatment) in Health Related Quality of Life (HRQL) Social Interaction score as assessed by Overactive Bladder-questionnaire (OAB-q) [ Time Frame: Baseline and Week 12 ]
  • Change from Baseline to Week 4, Week 8, and Week 12 (End of Treatment) as assessed by Measure of Health Status Questionnaire developed by the EuroQol Group (EQ-5D-5L questionnaire) [ Time Frame: Baseline and Weeks 4, 8 and 12 ]
  • Change from Baseline to Week 4, Week 8, and Week 12 (End of Treatment) in Patient Perception of Bladder Condition (PPBC) [ Time Frame: Baseline and Weeks 4, 8 and 12 ]
  • Change from Baseline to Week 4, Week 8, and Week 12 (End of Treatment) in Total Urgency and Frequency Score (TUFS) using Patient Perception of Intensity of Urgency Scale (PPIUS) (Grade 3 or 4) [ Time Frame: Baseline and Weeks 4, 8 and 12 ]
  • Change from Baseline to Week 4, Week 8, and Week 12 (End of Treatment) in mean number of nocturia episodes per day [ Time Frame: Baseline and Weeks 4, 8 and 12 ]
  • Change from Baseline to Week 4, Week 8, and Week 12 (End of Treatment) in Treatment Satisfaction Visual Analog Scale (TS-VAS) scores [ Time Frame: Baseline and Weeks 4, 8 and 12 ]
  • Change from Baseline to Week 4, Week 8, and Week 12 (End of Treatment) in number of protective garments (e.g., absorbent pads, incontinence briefs, disposable underwear) [ Time Frame: Baseline and Weeks 4, 8 and 12 ]
  • Change from Baseline to Week 12 (End of Treatment) in Total Health Related Quality of Life (HRQL) Score as assessed by Overactive Bladder-questionnaire (OAB-q) [ Time Frame: Baseline and Week 12 ]
    HRQL will be assessed by the subscale scores (coping, concern, sleep and social interaction) of the OAB-q. The total score will be calculated by adding the 4 subscale scores.

  • Change from Baseline to Week 12 (End of Treatment) in HRQL subscale Concern score as assessed by Overactive Bladder questionnaire (OAB-q) [ Time Frame: Baseline and Week 12 ]

Estimated Enrollment: 856
Actual Study Start Date: April 30, 2016
Estimated Study Completion Date: March 31, 2018
Estimated Primary Completion Date: March 3, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Mirabegron
Continued treatment with tamsulosin hydrochloride after adding mirabegron
Drug: Mirabegron
Oral
Other Names:
  • Myrbetriq
  • Betmiga
  • YM178
Drug: Tamsulosin Hydrochloride
Oral
Other Names:
  • Flomax
  • Omnic
Placebo Comparator: Placebo
Continued treatment with tamsulosin hydrochloride after adding placebo
Drug: Placebo
Oral
Drug: Tamsulosin Hydrochloride
Oral
Other Names:
  • Flomax
  • Omnic

Detailed Description:

At Screening (Visit 1), subjects will enter into a 4-week open label tamsulosin hydrochloride 0.4 mg QD run-in period prior to being randomized into the 12-week double-blind treatment period (Visit 2). At conclusion of the 4-week tamsulosin hydrochloride run-in period, subjects will complete a 3-day diary just prior to Baseline (Visit 2). Approximately 7 days prior to Visit 2 subjects will receive a phone call reminding them about the diary and to answer any questions.

If subjects meet all entry criteria at the end of the tamsulosin hydrochloride run-in period, subjects will be randomized to 1 of 2 treatment groups (mirabegron or placebo) for 12 weeks of treatment in addition to the continuation of tamsulosin hydrochloride 0.4 mg QD. Those subjects randomized to mirabegron will start at 25 mg and will increase to 50 mg after 4 weeks. Those subjects randomized to placebo will start blinded product matched to the mirabegron 25 mg tablet and will increase to blinded product matched to 50 mirabegron after 4 weeks. Once a subject has increased dose, the subject will remain on that dose for the remainder of the study unless for safety reasons is required to discontinue study drug.

A training diary will be completed in the first 2 weeks of the tamsulosin hydrochloride run-in period. During this evaluation period at least one telephone contact will take place with the subject. Diaries will be completed at home, using the electronic patient-reported outcome (ePRO) device, for 3 consecutive days prior to each visit: Baseline (Visit 2), Week 4 (Visit 3), Week 8 (Visit 4), and Week 12/End of Treatment (Visit 5). Site staff will contact the subject approximately 7 days prior to the scheduled visit to remind the subject to complete the electronic diary, review completion instruction and review changes to concomitant medications and adverse events (if applicable).

Three days before Visits 2 (Baseline), 3 (Week 4), 4 (Week 8), and 5 (Week 12), subjects will complete a 3-day diary, using the ePRO device in which the subject will record micturition frequency, urgency (PPIUS), incontinence and volume voided. In addition, the diary will capture morning and evening blood pressure and pulse rate measurements via Home Blood Pressure Monitoring (HBPM). At Visit 1, International Prostate Symptom Score (IPSS) will be completed. At Visits 2, 3, 4, and 5, subjects will complete the IPSS, EQ-5D-5L, OAB-q, PPBC, and TS-VAS. Maximum urinary flow (Qmax) will be measured at Visit 1 (Screening/tamsulosin hydrochloride run-in) and Visit 5 (Week 12/End of Treatment). Post-void residual volume (PVR) will be assessed at Screening/tamsulosin hydrochloride run-in (Visit 1), Baseline (Visit 2) and at Week 4 (Visit 3), Week 8 (Visit 4), and Week 12/End of Treatment (Visit 5). A follow-up phone call (Visit 6) will be conducted 4-weeks after End of Treatment (Visit 5). Total study participation is approximately 20 weeks.

  Eligibility

Ages Eligible for Study:   40 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria assessed at Visit 1 (Screening):

  • Men ≥40 years of age with history of overactive bladder (OAB) symptoms (frequency of ≥8 micturitions per day and urgency episodes of ≥2 per day) while taking tamsulosin hydrochloride for at least 2 months to treat LUTS due to BPH.
  • Subject has symptoms of OAB (urinary frequency and urgency with or without incontinence) for ≥3 months prior to Screening.
  • Subject has an International Prostate Symptom Score (IPSS) score ≥8.
  • Subject has Prostate-Specific Antigen (PSA) <4 ng/mL.
  • Subject is willing and able to complete the 3-day diary (including urine volumes, vital signs measurements), and Quality of Life questionnaires.
  • Subject and the subject's spouses/partners who are of childbearing potential must be using a highly effective birth control, which includes established use of oral, injected or implanted hormonal methods of contraception, placement of an intrauterine device (IUD) or intrauterine system (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.
  • 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:

  • Subject continues to meet all inclusion criteria of Visit 1 (Screening).
  • Subject must experience an average of 8 or more micturitions per day over the 3-day diary period.
  • Subject must experience an average of 2 episodes of urgency per day (grade 3 or 4) over the 3-diary period

Exclusion Criteria assessed at Visit 1 (Screening):

  • Subject has post-void residual volume (PVR) >200 mL.
  • Subject has maximum urinary flow (Qmax) <5.0 mL/second with a minimum voided volume of 125 mL.
  • Subject has hematuria >3 rbc/hpf that has not been fully evaluated.
  • Subject has evidence of Urinary Tract Infection (UTI). Urine culture and sensitivity will be performed for positive leukocytes, nitrites, or turbidity and will be confirmed with a culture greater than 100,000 cfu/mL. If a subject has a UTI, at Screening (Visit 1) the subject may be rescreened after successful treatment of the UTI (confirmed by a laboratory result of negative urine culture).
  • Subject has neurogenic bladder (spinal cord injury, multiple sclerosis, Parkinson's, etc.).
  • Subject has diabetic neuropathy.
  • Previous open, robotic or minimally invasive prostate surgery (including transurethral procedures). Planned (scheduled) pelvic or prostate surgery during the study period.
  • Planned (scheduled) cataract surgery.
  • Subject with significant stress incontinence
  • Subject with clinically significant bladder outlet obstruction.
  • Subject has an indwelling catheter or practices intermittent self-catheterization.
  • Subject has experienced 3 or more episodes of recurrent urinary tract infection within the last 12 months.
  • 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 such as the distal ascending colon, the full transverse colon and proximal portion of the descending colon are in the abdomen).
  • Subject has received intravesical injection in the past 12 months with botulinum toxin, resiniferatoxin, or capsaicin.
  • Subject has ever received electro-stimulation therapy for OAB (e.g. sacral nerve stimulation or Percutaneous Tibial Nerve Stimulation [PTNS]).
  • Subject began or has changed a bladder training program or pelvic floor exercises less than 30 days prior to Screening.
  • Subject has postural hypotension or syncope or postural orthostatic tachycardia.
  • Subject has moderate or severe hepatic impairment defined as Child-Pugh Class B or C.
  • Subject has severe renal impairment defined as estimated creatinine clearance less than 29 mL/min/1.73 m2 as determined by hospital laboratory calculation of eGFR. A subject with End Stage Renal Disease (ESRD) or undergoing dialysis is also not a candidate for the study.
  • Subject has severe uncontrolled hypertension, which is defined as a sitting systolic blood pressure ≥180 mmHg and/or diastolic blood pressure ≥110 mmHg.
  • Subject has baseline resting pulse rate <60 BPM or >90 BPM.
  • Subject has evidence of QT prolongation on Screening (Visit 1) or Baseline (Visit 2) electrocardiogram (ECG) defined as QTcF >450 msec.
  • Subject has any clinically significant ECG abnormality.
  • Subject has AST or ALT >2x upper limit of normal (ULN), or γ-GT >3x ULN and considered clinically significant.
  • Subject has a hypersensitivity to any components of mirabegron, tamsulosin hydrochloride, or any of the inactive ingredients.
  • Subject has a history of angioedema.
  • Subject has any clinical significant condition which makes the subject unsuitable for study participation.
  • 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.
  • 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.
  • Subject has ongoing alcohol and/or drug abuse.
  • Subject is using prohibited medications within 30 days prior to Screening (Visit 1) through Follow-Up Phone Call (Visit 6).
  • Subject has stopped, started or changed the dose of a restricted medication within the 30 days prior to Screening (Visit 1) through Follow-Up Phone Call (Visit 6)
  • Subject has participated in an interventional trial within 30 days prior to Screening (Visit 1).
  • 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.
  • Subject has previously received mirabegron in the 6 months prior to Screening (Visit 1).

Exclusion Criteria assessed at Visit 2 (Baseline):

  • 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.
  • Subject had an average total daily urine volume >3000 mL as recorded in the 3-day diary.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02757768

Contacts
Contact: Astellas Pharma Global Development 800-888-7704 ext 5473 astellas.registration@astellas.com

  Show 102 Study Locations
Sponsors and Collaborators
Astellas Pharma Global Development, Inc.
Investigators
Study Director: Medical Director Astellas Pharma Global Development, Inc., Medical Affairs, Americas
  More Information

Responsible Party: Astellas Pharma Global Development, Inc.
ClinicalTrials.gov Identifier: NCT02757768     History of Changes
Other Study ID Numbers: 178-MA-1008
2015-004036-36 ( EudraCT Number )
Study First Received: April 15, 2016
Last Updated: May 9, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. ):
Myrbetriq
Lower Urinary Tract Symptoms
Benign Prostatic Hyperplasia
Overactive Bladder
Betmiga
Mirabegron
Tamsulosin Hydrochloride

Additional relevant MeSH terms:
Hyperplasia
Urinary Bladder, Overactive
Prostatic Hyperplasia
Lower Urinary Tract Symptoms
Pathologic Processes
Urinary Bladder Diseases
Urologic Diseases
Urological Manifestations
Signs and Symptoms
Prostatic Diseases
Genital Diseases, Male
Tamsulosin
Mirabegron
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Urological Agents
Adrenergic beta-3 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists

ClinicalTrials.gov processed this record on July 26, 2017