Myrbetriq™ (Mirabegron) to Improve Disordered Sleep in Subjects With Lower Urinary Tract Symptoms (LUTS)

Inclusion criteria

• Age ≥ 18.
• Subject is willing and able to complete the micturition diary and sleep questionnaires correctly.
• Symptoms of overactive bladder (OAB) (urinary frequency and urgency with or without urgency incontinence) for at least 3 months, with an IPSS ≥ 12.
• Moderate sleep disturbance with a mean score on the Jenkins Scale > 7.
• Micturitions/24 hrs ≥ 8; total excretory volume of <3L.
• Washout period of 2 weeks for any drugs not listed in the exclusions.

Exclusion criteria

• 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:

(i) Phytotherapy for benign prostatic hypertrophy (BPH) or a 5-alpha reductase inhibitor within 3 months.

(ii) Alpha blocker within 2 weeks. (iii) Taken an oral alpha agonist, tricyclic antidepressants, and anticholinergic or cholinergic medication within 2 weeks of the first screening visit with the following exception: topical anticholinergic eye drops used for glaucoma or inhaled anti-cholinergic used for chronic obstructive pulmonary disease (COPD).

(iv) Taken an estrogen, androgen, or any drug producing androgen suppression, or anabolic steroids within 3 months.

• Post void residual volume > 350 mL.
• 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.
• Any prior invasive intervention for LUTS (including bladder paralytics such as botulin toxin)
• 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.
• Known primary neurologic conditions such as multiple sclerosis, Parkinson's disease, diabetic neuropathy or any neurological diseases known to affect bladder function.
• 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.
• Two documented independent urinary tract infections of any type in the past year.
• Patient with a diagnosed sleep disorder (ie. Obstructive Sleep Apnea) undergoing evaluation and treatment requiring change in care within 30 days of screening visit.
• Subject has moderate to severe hepatic impairment [ALT (SGPT), AST (SGOT) or GGT value greater than 3 times the upper limit of normal in the clinical center lab; confirmed on a second measurement].
• Subject has severe renal impairment or End Stage Renal disease (i.e., creatinine greater than 2.0 mg/dl).
• PSA (prostate specific antigen) level greater than 10 ng/ml at the first screening visit (if male).
• Subject has severe uncontrolled hypertensionas defined by a systolic pressure ≥180 mmHg and/or diastolic pressure ≥120 mmHg.
• Subject has a clinically significant abnormal 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 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. Men with a history of prostate cancer regardless of curability are not eligible.
• 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.
• Unable to follow protocol directions due to organic brain or psychiatric disease.
• History of alcoholism or any other substance abuse, which, in the opinion of the investigator, would affect compliance with the protocol.