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

• Mirabegron (Drug), also known as Myrbetriq: 25 mg PO per day for four weeks. if tolerated then uptitrated to 50 mg PO per day for the remaining 8 weeks

Primary outcomes

• • Improvement from baseline on the PROMIS Sleep Disturbance scale at the 12 week follow-up. [12 weeks]
• • Improvement from baseline in the number micturitions/24 hours at the 12 week follow-up. [12 weeks]

Secondary outcomes

• • Improvement from baseline on the Jenkins sleep scale at the 12 week follow-up. [12 weeks]
• • Improvement of nocturia (nocturnal voiding) based on the amount of voids that disrupt patient sleep in the voiding diary. [12 weeks]

Other outcomes

• • Improvement from baseline on the International Prostate Symptom Score (IPSS)/American Urological Society Symptom Index (AUA-SI) scale at the 12 week follow-up. [at 12 week follow-up]: exploratory endpoint

Sex: All, ages: 18 Years to any

Inclusion Criteria:

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

Exclusion Criteria:

1. 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.
2. Post void residual volume > 350 mL.
3. 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.
4. Subject has neurogenic bladder.
5. Any prior invasive intervention for LUTS (including bladder paralytics such as botulin toxin)
6. 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).
7. Subject has an indwelling catheter or practices intermittent self-catheterization.
8. Known primary neurologic conditions such as multiple sclerosis, Parkinson's disease, diabetic neuropathy or any neurological diseases known to affect bladder function.
9. 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.
10. Two documented independent urinary tract infections of any type in the past year.
11. Patient with a diagnosed sleep disorder (ie. Obstructive Sleep Apnea) undergoing evaluation and treatment requiring change in care within 30 days of screening visit.
12. Subject has moderate to severe hepatic impairment \[ALT (SGPT), AST (SGOT) or GGT value greater than 3 times the upper limit of normal in the clinical center lab; confirmed on a second measurement\].
13. Subject has severe renal impairment or End Stage Renal disease (i.e., creatinine greater than 2.0 mg/dl).
14. PSA (prostate specific antigen) level greater than 10 ng/ml at the first screening visit (if male).
15. Subject has severe uncontrolled hypertensionas defined by a systolic pressure ≥180 mmHg and/or diastolic pressure ≥120 mmHg.
16. 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.
17. Subject has a known or suspected hypersensitivity to Mirabegron or any of the inactive ingredients.
18. 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.
19. 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.
20. Unable to follow protocol directions due to organic brain or psychiatric disease.
21. History of alcoholism or any other substance abuse, which, in the opinion of the investigator, would affect compliance with the protocol.

• Kevin McVary, MD, Principal investigator, Southern Illinois University