Clinical trial NCT02916693
Conditions: Erectile Dysfunction Overactive Bladder Urinary Incontinence
Keywords: Mirabegron Overactive Bladder Erectile Dysfunction Beta 3 agonist
Sponsor: Johns Hopkins University
Start date: 2017-08-01; Completion date: 2020-01-01
Enrollment: 20 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The only class of oral erectile dysfunction (ED) medication on the market are the phosphodiesterase Type 5 inhibitors (PDE5i). This pilot study is being done to evaluate the effect of Mirabegron, an oral beta-3 adrenergic agonist, on men with both Overactive Bladder (OAB) symptoms and mild to moderate ED.

Detailed description:
ED affects up to 30 million men in the United States. The only class of oral medication approved for ED is PDE5i. These include sildenafil, tadalafil, vardenafil and avanafil. Other pharmacologic options in the treatment of ED are delivered as an intraurethral suppository (alprostadil) or intracavernosal injection (alprostadil, papaverine, phentolamine, atropine). These are more invasive routes of administration. Men who fail to obtain benefit from a PDE5i or those who have a contraindication to this class of medication may ultimately avoid further pharmacologic treatment options. An alternative class of oral medication to treat ED may prove to be of benefit to a large population of underserved men.

There is in vitro evidence that beta-3 adrenergic receptors exist in human corpus cavernosum tissue. Activation of these receptors results in vasorelaxation, suggesting a potential pro-erectogenic effect is possible in vivo. Additionally, nebivolol, a beta-blocker, has pro-erectogenic effects noted in several studies. There is evidence that nebivolol exerts beta-3 adrenergic agonism, which may explain the mechanism by which these effects occur.

Mirabegron is the only available beta-3 adrenergic agonist in the United States. Its favorable safety profile and the potential for therapeutic efficacy in ED make it suitable for further investigation.

It is hypothesized that beta-3 adrenergic activation offers a pharmacologic target for the treatment of ED. Men with mild, mild to moderate, or moderate ED and symptoms of OAB can be recruited with pre- and post- Mirabegron administration assessment of their ED to determine the validity of this hypothesis. Men with severe ED will be excluded as historical data shows they are less likely to benefit from oral pharmacologic therapy alone. Mirabegron is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adults with OAB.

Arms: arm 1: Participants take 25- 50mg oral Mirabegron tablets daily for 12 weeks,
Interventions: intervention 1: Mirabegron
Intervention descriptions: intervention 1: FDA-approved, beta 3 agonist for over active bladder

Protocol documents:
Prot_SAP_000.pdf: 
 
 
P.I.: Arthur L. Burnett M.D., M.B.A 
 
 
Application Number: IRB00097439 
 
                                                                                                   Date: May 23, 2016 
 
COVER PAGE 
 
NCT number: 02916693  
 
Official Title: Mirabegron for Erectile Dysfunction 
 
Document date: May 23,2016 
 
Principal Investigator: Arthur L. Burnett 
 
Participating Site: Johns Hopkins University, Baltimore, 
MD, USA 
 
 
 
 
 
 
 
 
 
 


 
 
P.I.: Arthur L. Burnett M.D., M.B.A 
 
 
Application Number: IRB00097439 
 
                                                                                                   Date: May 23, 2016 
 
Erectile dysfunction (ED) affects up to 30 million men in the United States. The only class of oral 
medication approved for ED is phosphodiesterase type 5 inhibitors (PDE5i). These include 
sildenafil, tadalafil, vardenafil and avanafil. Other pharmacologic options in the treatment of ED 
are delivered as an intraurethral suppository (alprostadil) or intracavernosal injection 
(alprostadil, papaverine, phentolamine, atropine). These are more invasive routes of 
administration. Men who fail to obtain benefit from a PDE5i or those who have a 
contraindication to this class of medication may ultimately avoid further pharmacologic 
treatment options. An alternative class of oral medication to treat ED may prove to be of 
benefit to a large population of underserved men.  
 
There is in vitro evidence that beta-3 adrenergic receptors exist in human corpus cavernosum 
tissue. Activation of these receptors results in vasorelaxation, suggestion a potential pro-
erectogenic effect is possible in vivo. Additionally, nebivolol, a beta-blocker, has pro-
erectogenic effects noted in several studies. There is evidence that nebivolol exerts beta-3 
adregenergic agonism, which may explain the mechanism by which these effects occur. 
 
Mirabegron is the only available beta-3 adrenergic agonist in the United States. Its favorable 
safety profile and the potential for therapeutic efficacy in ED make it suitable for further 
investigation.  
 
We hypothesize that beta-3 adrenergic activation offers a pharmacologic target for the 
treatment of ED. Men with mild, mild to moderate, or moderate ED and symptoms of 
overactive bladder (OAB) can be recruited with pre- and post- Mirabegron administration 
assessment of their ED to determine the validity of this hypothesis. Men with sever ED will be 
excluded as historical data shows they are less likely to benefit from oral pharmacologic 
therapy alone. Mirabegron is approved by the U.S. Food and Drug Administration (FDA) for the 
treatment of adults with OAB. Therefore, recruiting men with concurrent ED and OAB (rather 
than men with ED alone) will avoid the need for off-label administration of Mirabegron. 
We propose a pilot study to be initiated at Johns Hopkins to investigate this hypothesis. If 
measurable positive effect on erectile function is noted, this can guide further investigation in a 
randomized, placebo-controlled blinded clinical trial.  
For the observational pilot study, we will recruit 20 men with mild, mild to moderate, or 
moderate ED and symptoms of OAB who present routinely to the urology clinic at Johns 
Hopkins. This initial group of patients will allow a clinical assessment of Mirabegron’s possible 
in vivo effect on erectile function.  


 
 
P.I.: Arthur L. Burnett M.D., M.B.A 
 
 
Application Number: IRB00097439 
 
                                                                                                   Date: May 23, 2016 
 
• Screening of erectile function status will be performed using the International Index of 
Erectile Function Questionnaire (IIEF). The Overactive Bladder questionnaire (OAB-q) 
will be used to assess the bother of OAB symptoms and its impact on health related 
quality of life. Currently, questionnaires such as the IIEF and the Sexual Health Inventory 
for Men (SHIM) are the primary tools guiding diagnosis and medical therapy of ED. 
Other validated tools or measurable physiologic correlates of ED are not yet available in 
current Urology clinical practice. More objective testing via a penile Doppler ultrasound 
is performed only for surgical candidates and does not guide medical therapy.  
• Inclusion criteria will be: (1) men 18 to 70 years old, (2) presence of mild (score 22-25 
out of 30 on the IIEF-Erectile Function domain), mild to moderate (score 17-21) or 
moderate (score 11-16) ED, (3) presence of OAB symptoms for at least 3 months with at 
least 3 micturitions per day and at least 3 episodes of urgency in a 3-day period. Past use 
of anticholinergic medications is acceptable.  
• Exclusion criteria will be: (1) concurrent ED therapy, (2) prior pelvic surgery (including 
prostatectomy, cystectomy, transurethral procedures), (3) prior penile surgery (4) 
history of priapism, (5) history of neurologic disease (such as spinal cord injury, 
Parkinson’s disease, multiple sclerosis), (6) uncontrolled hypertension (systolic blood 
pressure > 140mmHg or diastolic blood pressure > 90mmHg), (7) chronic kidney disease 
stage 4 or 5 (estimate creatinine clearance rate < 30ml/min), (8) moderate or severe 
hepatic impairment (Child-Pugh Class B or C) (9) concomitant use of CYP2D6-
metabolized drugs (metoprolol, desipramine, thioridazine, flecainide, propafenone) or 
digoxin (10) post void residual greater than 150 ml, or (11) evidence of urinary tract 
infection on urinalysis and/or urine culture.  
 
Internal review board approval will be obtained prior to patient screening. Following this, 
patients being seen routinely in the clinic setting will be screened for possible study 
participation. The initial clinic visit will consist of medical and surgical history, a physical exam 
(including blood pressure, postvoid residual measurement using a portable ultrasound machine 
specifically for this purpose as is routinely done in Urology clinical practice and urinalysis and/or 
urine culture) and administration of the IIEF and OAB-q questionnaires. A physician or clinical 
nurse participating in the pilot study will perform these tasks. Results will be recorded. A 
schematic of the protocol study design is shown below. 
 
Baseline 
Week 2 
Week 4 
Week 8 
Week 12 
Vital Signs 
X 
X 
X 
X 
X 
Postvoid 
Residual 
(Ultrasound) 
X 
 
X 
X 
X 
Urinalysis 
X 
X 
X 
X 
X 


 
 
P.I.: Arthur L. Burnett M.D., M.B.A 
 
 
Application Number: IRB00097439 
 
                                                                                                   Date: May 23, 2016 
 
IIEF 
X 
X 
X 
X 
X 
OAB-q 
X 
X 
X 
X 
X 
Clinical 
Interview 
X 
X 
X 
X 
X 
 
• Patients who meet inclusion criteria, do not meet exclusion criteria and are interested in 
participating in the study will discuss the risks and benefits of trial participation in detail. 
Informed consent will be obtained without monetary compensation. 
• Time 0: Study participants will be provided with daily Mirabegron 25mg for 14 days (2 
weeks. Astellas will supply the medication. Instruction for participants will include 
careful monitoring for any adverse effects of the medication, including those related to 
elevated blood pressure, nasal congestion, urinary tract infection, headache or other 
changes from baseline. Participants will receive contact information with 24-hour access 
to report any adverse reactions and to receive medical advice. Any concerning 
symptoms (at any stage of the study) will result in immediate discontinuation of the 
provided medication, medical assessment and recording of these findings. The FDA’s 
MedWatch program and Astellas will be contacted to report such findings as well.  
• Week 2: Study participants will return for evaluation by a physician or clinical nurse. Any 
noted adverse reactions will be recorded. Blood pressure and postvoid residual will be 
measured. IIEF and OAB-q questionnaires will be administered. If no adverse findings 
are noted, the participants will have the opportunity to dose-escalate if required to 
assess optimal benefit from use of the medication, Accordingly, they may either 
continue on Mirabegron 25 mg daily or proceed to receive Mirabegron 50mg daily to be 
taken for the next 10 weeks. Reduction in dosing will also be permitted during the 
course of the study (resumption of 25mg daily dosing) and will be recorded. Instructions 
to report any adverse reactions will be reinforced, as previously.  
• Weeks 4 and 8: Study participants will return for interim evaluation by physician or 
clinical nurse. Reassessment of adverse reactions and clinical monitoring (blood 
pressure, postvoid residual) will be repeated, followed by re-administration of IIEF and 
OAB-q questionnaires. 
• Week 12: Study participants will return for final evaluation by a physician or clinical 
nurse. Adverse reactions will be recorded. Blood pressure, postvoid residual IIEF and 
OAB-q questionnaires will again be assessed. Participants will be encouraged to contact 
study investigators with any concern of adverse effects following the conclusion of their 
participation.  
Results from 20 subjects will be carefully tabulated. Adverse events will be recorded. Changes 
in blood pressure and postvoid residual will be evaluated. IIEF and OAB-q scores will be 
reviewed. The primary endpoint will be the change in IIEF-Erectile Function domain score 


 
 
P.I.: Arthur L. Burnett M.D., M.B.A 
 
 
Application Number: IRB00097439 
 
                                                                                                   Date: May 23, 2016 
 
between Time 0, Week 2 and Weeks 4, 8 and 12. A measurable positive effect will be noted by 
a total mean increase of 4 or more points in the IIEF-Erectile Function domain score. Secondary 
endpoints will include OAB improvement, as reflected by a 10 point decrease in OAB-q 
symptom severity score. 
This non-randomized single arm study will enroll 20 men with mild to moderate ED by IIEF 
criteria (scores 11-25) and symptoms of OAB. Pre-treatment IIEF and OAB scores will be 
compared to post-treatments scores at 4, 8, and 12 weeks. The primary analysis for both IIEF 
and OAB scores will be repeated measures analysis of variance (RMANOVA) if there are no 
missing time points, otherwise a mixed model will be used. The primary endpoint will be the 
TIME effect, i.e. to test for a change from pre-treatment value of IIEF or OAB. The minimum 
change considered clinically relevant is an increase in IIEF of 4 units, and a decrease in OAB of 
10 units. In addition to absolute change I IIEF or OAB scores, we will also evaluate models of 
percentage change from pre-treatment value. If the overall effect of TIME is statististically 
significant we will use paired t-tests comparing pre-treatment to each of the post-treatment 
values, with a Bonferroni p-value adjustment, to determine the time at which an increase in IIEF 
of at least 4 points or a decrease in OAB of at least 10 points can first be detected. Covariates to 
be evaluated as potential confounding factors include age, comorbidity or cause of ED, body 
mass index, and other medications.  
Although this is a pilot study and there are no data to suggest the magnitude of the effect of 
Mirabegron on ED, we performed power calculations for various scenarios of change in IIEF or 
OAB. The scenarios used a pattern of means with an absolute increase from pre-treatment to 
12 weeks of 4 units for IIEF and absolute decrease of 10 units for OAB, and plausible 
conservative (higher than expected) values for the within-subject standard deviation that were 
increased until power fell below 80%. For both IIEF and OAB we evaluated power if the pre-
treatment mean was the midpoint of the range of values eligible for study: IIEF = 18 (range 11-
25), OAB = 50 (range 0-100). However, the power was not sensitive to the pre-treatment mean, 
and showed little variation according to the specific changes in mean score between time 
points, for a fixed overall change from pre-treatment to 12 weeks. The table below shows 
power to detect a 4 unit increase in IIEF and 10 unit decrease in OAB, with 20 patients 
evaluated at 4 time points, α = 0.05, within-subject standard deviation and autocorrelation 
both constant over time. Power calculations were performed using PASS v. 11 (NCSS Software, 
Inc., Kaysville, UT), according to the method of Mueller (Mueller 1989).  
Pattern of means over 4 time points 
Within-
subject SD 
Power 
Pre-test 
4 weeks 
8 weeks 
12 weeks 
IIEF 
 
 
18 
20 
20 
22 
2 
>0.99 
18 
20 
20 
22 
3.5 
0.88 
18 
20 
20 
22 
3.8 
0.81 


 
 
P.I.: Arthur L. Burnett M.D., M.B.A 
 
 
Application Number: IRB00097439 
 
                                                                                                   Date: May 23, 2016 
 
OAB 
 
 
60 
56 
52 
50 
5 
>0.99 
60 
56 
52 
50 
8 
0.87 
60 
56 
52 
50 
10 
0.84 
 
Thus, despite the small size of the study, power is likely to be more than adequate to detect the 
minimum changes in IIEF (increase 4 units) and OAB (decrease 10 units) considered clinically 
relevant.  
Should a measurable positive effect be noted, a more extensive randomized, placebo 
controlled, blinded and possibly multi-institutional trial be considered. The information 
obtained from the pilot study an help guide future studies if appropriate.  
Rationale for the proposed drug doses: 
Per the Mirabegron US package insert, 2015: The approved therapeutic dose of Mirabegron for 
OAB in the United States is 25mg once daily which may be increased to 50mg once daily based 
on individual tolerability. Mirabegron has been studied at doses ranging from 25mg to 200mg 
once daily in OAB patients and 25mg demonstrated statistical superiority compared to placebo 
for incontinence episodes and frequency.  
Rationale for 12-week observation period: 
Mirabegron has been studied extensively for at least a 12-week time period as this was the 
approximate time other classes of OAB drugs (eg. Antimuscarinics) were discontinued due to 
low tolerability (eg. Dry mouth). Mirabegron was found to be both efficacious and tolerable 
within this time frame. 
Rationale for open label study design: 
The proposed study is an observational pilot investigation. Results from this preliminary 
investigation will dictate the utility of a more resource consuming, future randomized 
controlled trial.  
Discussion of the clinical effects and adverse effects of Mirabegron for its approved 
indication: 
The approved indication is the treatment of OAB and the safety of the drug has been well 
characterized in phase 2 and 3 studies. 
Potential adverse effects include QT prolongation with supratherapeutic doses or in high risk 
populations, increased heart rate and increased blood pressure, the risks of which are greater 
with increasing exposure. Cutaneous hypersensitivity reactions are also a potential risk. 
Changes in pulse rate and blood pressure are reversible upon discontinuation of the drug. The 


 
 
P.I.: Arthur L. Burnett M.D., M.B.A 
 
 
Application Number: IRB00097439 
 
                                                                                                   Date: May 23, 2016 
 
most commonly reported adverse events include: hypertension, nasopharyngitis, urinary tract 
infection and headache. Other adverse events: constipation, upper respiratory infection, 
arthralgia, diarrhea, abdominal pain and fatigue. 
 
Drugs that may interact with Mirabegron include: 
Moderate to strong CYP2D6 inhibitors with narrow therapeutic index may interact with 
Mirabegron including: thioridazine, flecainide, propafenone, amitryptiyline, paroxetine, 
aripiprazole, donepezil, tramadol, imipramine, des/venlafaxine and terbinafine 
Moderate to strong CYP3A4 inhibitors may also interact including: indinavir, nelfinavir, 
ritonavir, clarithromycin, itraconazole, ketoconazole, Nefazadone, Saquinavir, 
Telithromycin,Cimetidine, Clotrimazole, Cyclosporine, Erythromycin, Fluconazole, Itraconazole 
 
References 
1. National Institutes of Health (NIH) Consensus Conference. NIH Consensus Development 
Panel on Impotence. Impotence Journal of the American Medical Association. 
1993;270:83-90 
• Provides epidemiological data on ED in the United States 
2. Cirino G, Sorrentino R, di Villa Blanca Rd, Popolo Am Palmieri A, Imbimbo C, Fusco F, 
Longo N, Tajana G, Ignarro LJ, Mirone V. Involvement of beta 3 adrenergic receptor 
activation via cyclic GMP-but not NO-dependent mechanisms in human corpus 
cavernosum function. Proc Nati Acad Sci U.S.A. 2003 Apr 29;100(9):5531-6 
• Describes the present of beta-3 adrenergic receptors in human corpus 
cavernosum tissue. Also discusses the in vitro effect of activation of these 
receptors. 
3. Nitti VW, Chapple CR, Walters C, Blauwet MB, Herchorn S, Milsom, Auerbach S, 
Radziszewski P. Safety and tolerability of beta-3 adrenoceptor agonist Mirabegron, for 
the treatment of overactive bladder: results of a prospective pooled analusis of three 
12-week randomized Phase III trials and of a 1-year randomized Phase III trial. Int J Clin 
Pract. 2014 Aug;68(8):972-85 
• Describes the adverse effect profile of Mirabegron 25, 50 and 100mg 
administration, in comparison with placebo.  
4. Gauthier C, Trochu JN. Nebivolol: the first vasodilatory beta-blocker with a beta-3 
adrenergic agonist activity [article in French]. Ann Cardiol Angelol (Paris). 2010 
Jun;59(3(:155-9 
• Provides evidence of beta-3 adrenergic agonism by nebivolol. This hints at the 
potential underlying mechanism by which Nebivolol has apparent pro-
erectogenic effects.  
5. Martinez-Salamanca JI, La Fuente JM, Cardoso J, Fernandez A, Cuevas P, Wright HM, 
Angulo J. Nebivolol Potentiates the Efficacy of PDE5 Inhibitors to Relax Corpus 


 
 
P.I.: Arthur L. Burnett M.D., M.B.A 
 
 
Application Number: IRB00097439 
 
                                                                                                   Date: May 23, 2016 
 
Cavernosum and Penile Arteries from Diabetic Patients by Enhancing the NO/cGMP 
Pathway. J Sex Med 21014; 11:1182-1192 
• Describes the potential pro-erectogenic effect of nebivolol. Also mentions that 
“The mechanism by which nebivolol activates NO/cGMP pathway could 
include…β3-adrnegergic receptor activation” (see page 1189). 
6. Baumhakel M, Schlimmer N, Buyukafsar K, Arikan O, Bohm M. Nebivolol, but not 
Metoprolol, Improves Endothelial Function of the Corpus Cavernosum in Apolipoprotein 
E-Knockout Mice. J Pharmacol Exp Ther. 2008 Jun:325(3):818-23 
• Potential pro-erectogenic effect noted by nebivolol (which has evidence of beta-
3 adrenergic agonism) but not metoprolol (which does not appear to have beta-3 
adrenergic agonism effects). 
7. Reidenbach C, Schwinger RHG, Stenritz D, Kehe K, Thierman H, Klotz T, Sommer F, Bloch 
W, Brixius K. Nebivolol induces eNOS activation and NO-liberation in murine corpus 
cavernosum. Life Sci. 2007 Jun 6;80(26):2421-7 
• Further evidence of pro-erectogenic effects of nebivolol.  
8. Tobilli JE, Cao G, Casas G, Mazza ON. In vivo and in vitro effects of nebivolol on penile 
structures in hypertensive rats. Am J Hypertens. 2006 Dec;19(12):1226-32 
• Further evidence of pro-erectogenic effects of nebivolol.  
9. Brixius K, Middeke M, Lichtenthal A, Jahn E, Schwinger RH. Nitric oxide, erectile 
dysfunction and beta-blocker treatment (MR NOED study): benefit of nebivolol versus 
metoprolol in hypertensive men. Clin Exp Pharmacol Physiol. 2007 Apr;34(4):327-31 
• Further evidence of pro-erectogenic effects of nebivolol.  
10. Coyne K, Revicki D, Hunt T, Corey R, Stewart W. Bentkover J, Kurth H, Abrams P. 
Psychometric validation of an overactive bladder symptom and health-related quality of 
life questionnaire: the OAB-q. Qual Life Res. 2002 Sep;11(6):564-74 
• Describes the development and validation of the OAB-q 
11. MYRBETRIQ [Prescribing information]. Northbrook, IL: Astellas Pharma US, Inc.;2015. 
• Prescribing information for Myrbetriq. 
12. Mueller KE, Barton CN. Approximate power for repeated-measures ANOVA lacking 
sphericity. JASA 1989; 84:549-55. 
• Reference for statistical analysis 
13. Rosen RC, Riley A, Wagner G, Osterloh IH, Kirkpatrick J, Mishra A. The international 
Index of Erectile Function (IIEF): a multidimensional scale for assessment of erectile 
dysfunction. Urology 1997; 49:822-30. 
• Description of the IEF as a validated tool in the assessment of Erectile 
Dysfunction 
14. Rosen RC, Allen KR, Ni X, Araujo AB. Minimally clinically important differences in the 
erectile function domain of the International Index of Erectile Function Scale. Eur 
Urology 2011: 60: 1010-6 


 
 
P.I.: Arthur L. Burnett M.D., M.B.A 
 
 
Application Number: IRB00097439 
 
                                                                                                   Date: May 23, 2016 
 
• Evaluation that the 4-point score change is clinically meaningful across 
dimensions including ED etiology and severity. 
15. Yang M, Ni X, Sontag A, Litman HJ, Rosen RC. Nonresponders, partial responders, and 
complete responders to PDE5 inhibitors therapy according to IIEF criteria: validation of 
an anchor-based treatment responder classification. J Sex Med 2013; 10:3029-37 
• Further evaluation of the 4-point score changes as clinically meaningful  

ICF_001.pdf: 
Do not use this form for consenting research 
participants unless the Johns Hopkins Medicine 
Logo appears here. 
Date: March 12, 2018  
Principal Investigator: Arthur L. Burnett II M.D., M.B.A. 
Application No.: IRB00097439  
 
Page 1 of 10 
Combined Informed Consent/Authorization June 2015 Version 15 
 
 
 
 
COVER PAGE 
 
NCT number: 02916693  
 
Official Title: Mirabegron for Erectile Dysfunction 
 
Document date: March 12, 2018 
 
Principal Investigator: Arthur L. Burnett 
 
Participating Site: Johns Hopkins University, Baltimore, MD, 
USA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Do not use this form for consenting research 
participants unless the Johns Hopkins Medicine 
Logo appears here. 
Date: March 12, 2018  
Principal Investigator: Arthur L. Burnett II M.D., M.B.A. 
Application No.: IRB00097439  
 
Page 2 of 10 
Combined Informed Consent/Authorization June 2015 Version 15 
 
 
 
 
 
 
 
 
 
 
RESEARCH PARTICIPANT INFORMED CONSENT AND PRIVACY 
AUTHORIZATION FORM 
 
Protocol Title:  
 
 
Mirabegron for Erectile Dysfunction 
 
Application No.:   
 
IRB00097439  
 
Sponsor: 
 
Astellas Pharma Global Development, Inc.  
 
Principal Investigator (P.I.): Arthur L. Burnett II M.D., M.B.A. 
P.I. Address:  
 
 
The James Buchanan Brady Urological Institute 
    
 
 
The Johns Hopkins School of Medicine 
    
 
 
600 N Wolfe Street, Marburg 407 
                           
 
 
Baltimore, MD 21287-2101 
P.I. Telephone: 410-614-3986 
P.I. Fax: 410-614-3695 
  
 
1. 
What you should know about this study:   
• You are being asked to join a research study. This consent form explains the research study and your 
part in it. Please read it carefully and take as much time as you need. Ask your study doctor or the 
study team to explain any words or information that you do not understand. 
• You are a volunteer.  If you join the study, you can change your mind later.  There will be no penalty 
or loss of benefits if you decide to quit the study.   
• During the study, we will tell you if we learn any new information that might affect whether you 
wish to continue to participate. 
• If we think your participation in this study may affect your clinical care, information about your 
study participation will be included in your medical record, which is used throughout Johns Hopkins.   
Doctors outside of Johns Hopkins may not have access to this information.  You can ask the research 
team to send this information to any of your doctors. 
• When Johns Hopkins is used in this consent form, it includes The Johns Hopkins University, The 
Johns Hopkins Hospital, Johns Hopkins Bayview Medical Center, Howard County General Hospital, 
Johns Hopkins Community Physicians, Suburban Hospital, Sibley Memorial Hospital and All 
Children’s Hospital.  
• Biospecimens (urine) will be collected in this study.  Most biospecimens contain DNA, which is the 
genetic code for each person. 
• A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by 
U.S. Law.  This Web site will not include information that can identify you. At most, the Web site 
will include a summary of the results. You can search this Web site at any time.  
If you are using Epic for this study, fax a copy 
of the signed consent form to 410-367-7382. 
 
 
 
 
 
Patient I.D. Plate 
                                 


Do not use this form for consenting research 
participants unless the Johns Hopkins Medicine 
Logo appears here. 
Date: March 12, 2018  
Principal Investigator: Arthur L. Burnett II M.D., M.B.A. 
Application No.: IRB00097439  
 
Page 3 of 10 
Combined Informed Consent/Authorization June 2015 Version 15 
• If you would like to review the information for this study, or a summary of the results, ask the study 
team doctor for the ClinicalTrials.gov study registration number. 
 
2. 
Why is this research being done? 
This research is being done to discover if the study drug, Mirabegron is effective in improving 
symptoms of Erectile Dysfunction (ED) and Overactive Bladder Disease (OAB) in adult men. 
 
Mirabegron is approved by the Food and Drug Administration (FDA) for the treatment of Overactive 
Bladder Disease.  It is not approved for use in Erectile Dysfunction and its use in the study is considered 
investigational.  The FDA is allowing the use of Mirabegron in this research study.  
 
• Standard care for ED usually involves taking medication by mouth. However, these medications 
do not always work for everyone. If the oral medication does not produce results, the patient can 
take other medications that are either injected into the penis or inserted as a suppository. Some 
men find these medications uncomfortable to take. Vacuum pump devices and penile prostheses 
are also alternative treatments for ED.  
 
 
Mirabegron can be taken by mouth. In this study, we would like to evaluate if taking Mirabegron is 
helpful for men with ED symptoms.  
 
 
Men may join the study if: 
• Are between the ages of 18 and 70 
• Have mild to moderate erectile dysfunction 
• Are not taking any drugs for erectile dysfunction 
• Have had overactive bladder disease symptoms for at least 3 months 
• Has never had pelvic surgery including on the penis 
• Do not have high blood pressure, stage 4 or 5 kidney disease or moderate to severe liver disease 
• Are  not using certain drugs 
• Do not have a urinary tract infection 
 
How many people will be in this study?  
About 20 participants will be enrolled in this study at Johns Hopkins. 
 
3. 
What will happen if you join this study? 
If you agree to be in this study, we will ask you to do the following things: 
 
1. Come to the clinic of the study doctor where he, another study doctor or a study nurse will conduct 
the initial clinic visit.  
• You will be asked about your medical history which includes any drugs (prescribed, over-
the-counter and recreational) you are currently taking or have taken in the past. You will be 
asked about surgeries you may have had, any other illnesses you may have or had in the past 
and the treatment for those illnesses. You will also be asked if any diseases run in your 
family including cancer. 
• Your blood pressure and heart rate will be measured. 
• You will be asked to provide a urine sample so that it can be checked for signs of infection.  
• After you have provided your sample, the amount of urine left in your bladder (the post void 
residual) will be measured using a small ultrasound machine while you are laying down.  


Do not use this form for consenting research 
participants unless the Johns Hopkins Medicine 
Logo appears here. 
Date: March 12, 2018  
Principal Investigator: Arthur L. Burnett II M.D., M.B.A. 
Application No.: IRB00097439  
 
Page 4 of 10 
Combined Informed Consent/Authorization June 2015 Version 15 
• You will also be asked to complete 2 questionnaires. 
• You will be provided with daily study drug tablets, enough for 14 days (2 weeks) but by the 
end of the study you would have taken the study drug for 12 weeks.  
2. Take one tablet daily for 2 weeks and call any member of the study team at any time if you 
experience any side effects, for example headache or abdominal pain.  
3. After 14 days, return to the clinic for re-evaluation which involves: 
• Have your blood pressure, heart rate and post void residual re-measured. 
• Fill out the same 2 questionnaires from the initial visit again 
• Let a study team member know if you have experienced any side effects 
• You will be given enough daily study drug for 2 weeks 
4. After taking the study drug for 14 more days (2 weeks), return to the clinic for re-evaluation and you 
will be given enough daily study drug for 28 days 
5. After taking the study drug for 28 days (4 weeks) since you last came to the clinic, you will be asked 
to return for re-evaluation and given enough study drug for a final 28  days (4 weeks). 
6. After taking the drug for the last 4 weeks, you will be asked to return to the clinic for the final 
evaluation. You will be encouraged to call any of the study team members after the completion of 
the study if you have any concerns about side effects 
 
 
How long will you be in the study? 
You will be in this study for 12 weeks. 
 
Incidental Findings 
The ultrasound you are having as part of this research study will be reviewed by a qualified person just 
as it would be if you were having the ultrasound as part of your routine medical care. 
 
There is a possibility that while reviewing your ultrasound we may see an abnormality that we did not 
expect to see in this study. This is what is called an “incidental finding.” 
 
We will let you know ultrasound if we see such an incidental finding.  Depending on the type of 
incidental finding, we may contact you by mail or by phone. In the case of a potential serious 
emergency, someone may go to your home. 
 
A qualified person (usually a member of the research team) will talk to you if there is an incidental 
finding. You do not have an option to decline information about an incidental finding. 
 
If you want, we will give information about this incidental finding to your primary doctor or we will 
refer you to an appropriate doctor for further evaluation. 
• An incidental finding may cause you to feel anxious.   
• Since an incidental finding will be part of your medical record, it may affect your current or 
future life or health insurance coverage.  This risk will vary depending on the type of insurance 
plan involved.  
 
The costs for any care that will be needed to diagnose or treat an incidental finding would not be paid for 
by this research study.  These costs would be your responsibility. 
 
4. 
What are the risks or discomforts of the study? 
The study drug, Mirabegron, may cause: 
• An increase in blood pressure or make  blood pressure worse if there is a  history of high blood 
pressure 
• Inability to empty the  bladder or cause  a weak urine stream 


Do not use this form for consenting research 
participants unless the Johns Hopkins Medicine 
Logo appears here. 
Date: March 12, 2018  
Principal Investigator: Arthur L. Burnett II M.D., M.B.A. 
Application No.: IRB00097439  
 
Page 5 of 10 
Combined Informed Consent/Authorization June 2015 Version 15 
• Symptoms similar to the common cold  
• Urinary tract infection 
• Headache 
• An allergic reaction that may be serious 
If any of these or any other side effect occurs, please contact any member of the study team as soon as 
possible.  
 
There are no known harmful effects from the ultrasound used for medical testing. 
 
There is the risk that information about you may become known to people outside this study. To protect 
against this, the study information will be kept in password-protected computers in locked rooms 
accessible only to study staff.     
 
5. 
Are there benefits to being in the study? 
There may or may not be a direct benefit to you from being in this study. If you take part in this study, 
you may help others in the future. 
 
6. 
What are your options if you do not want to be in the study? 
• Alternative erectile dysfunction and overactive bladder disease treatments are available but are 
being withheld in this study so that the study team can properly evaluate the effect of Mirabegron 
alone on ED and OAB.   
• If you decide not to join this study, other options are available.  You do not have to join this 
study to get treatment.  Other treatments for erectile dysfunction include: Tadalafil, Sildenafil 
and Vardenafil which can be taken by mouth. Alprostadil is another treatment that can either be 
injected into the penis or inserted as a suppository. Vacuum pump devices and penile prostheses 
are also alternative treatments for ED.  
• Other oral treatments for overactive bladder disease include: Oxybutynin, Tolterodine, 
Darifenacin, Solifenacin and Fesoterodine. 
• You do not have to join this study.  If you do not join, your care at Johns Hopkins will not be 
affected. 
 
7. 
Will it cost you anything to be in this study? 
You will receive a separate Insurance and Research Participant Financial Responsibility Information 
Sheet (Sheet).  
 
This Sheet will give you the following information: 
 
• The procedures, tests, drugs or devices that are part of this research and that will be paid for by 
the study (no cost to you).   
 
• The procedures, tests, drugs or devices that will be billed to you and/or your health insurer.  If 
you have health insurance, you will be responsible for any co-pays or deductibles not covered by 
your insurance.  
 
8. 
Will you be paid if you join this study? 
No. Parking will be provided for visits 2 through 5 
 
9. 
Can you leave the study early? 
• You can agree to be in the study now and change your mind later. 


Do not use this form for consenting research 
participants unless the Johns Hopkins Medicine 
Logo appears here. 
Date: March 12, 2018  
Principal Investigator: Arthur L. Burnett II M.D., M.B.A. 
Application No.: IRB00097439  
 
Page 6 of 10 
Combined Informed Consent/Authorization June 2015 Version 15 
• If you wish to stop, please tell us right away. 
• Leaving this study early will not stop you from getting regular medical care.  
 
If you leave the study early, Johns Hopkins may use or give out your health information that it has 
already collected if the information is needed for this study or any follow-up activities.  
 
10. 
Why might we take you out of the study early? 
You may be taken out of the study if: 
• Staying in the study would be harmful. 
• You need treatment not allowed in the study. 
• You fail to follow instructions. 
• There may be other reasons to take you out of the study that we do not know at this time.  
 
If you are taken out of the study early, Johns Hopkins may use or give out your health information that it 
has already collected if the information is needed for this study or any follow-up activities. 
 
11. 
How will your privacy be protected?  
We have rules to protect information about you.  Federal and state laws and the federal medical Privacy 
Rule also protect your privacy.  By signing this form you provide your permission, called your 
“authorization,” for the use and disclosure of information protected by the Privacy Rule. 
 
The research team working on the study will collect information about you.  This includes things learned 
from the procedures described in this consent form.  They may also collect other information including 
your name, address, date of birth, and information from your medical records (which may include 
information about HIV status, drug, alcohol or STD treatment, genetic test results, or mental health 
treatment). 
 
The research team will know your identity and that you are in the research study.  Other people at Johns 
Hopkins, particularly your doctors, may also see or give out your information. We make this information 
available to your doctors for your safety.    
 
People outside of Johns Hopkins may need to see or receive your information for this study.  Examples 
include government agencies (such as the Food and Drug Administration), safety monitors, other sites in 
the study and companies that sponsor the study.  
 
If you are in a cancer study that receives federal funding, the National Cancer Institute (NCI) now 
requires that we report identifiable information (such as, zip code) about your participation.  You may 
contact the NCI if you have questions about how this information is used.  
 
We cannot do this study without your authorization to use and give out your information.  You do not 
have to give us this authorization.  If you do not, then you may not join this study. 
 
We will use and disclose your information only as described in this form and in our Notice of Privacy 
Practices; however, people outside Johns Hopkins who receive your information may not be covered by 
this promise or by the federal Privacy Rule.  We try to make sure that everyone who needs to see your 
information keeps it confidential – but we cannot guarantee that your information will not be re-
disclosed. 
 
The use and disclosure of your information has no time limit. You may revoke (cancel) your permission 
to use and disclose your information at any time by notifying the Principal Investigator of this study by 


Do not use this form for consenting research 
participants unless the Johns Hopkins Medicine 
Logo appears here. 
Date: March 12, 2018  
Principal Investigator: Arthur L. Burnett II M.D., M.B.A. 
Application No.: IRB00097439  
 
Page 7 of 10 
Combined Informed Consent/Authorization June 2015 Version 15 
phone or in writing.  If you contact the Principal Investigator by phone, you must follow-up with a 
written request that includes the study number and your contact information.  The Principal 
Investigator’s name, address, phone and fax information are on page one of this consent form.  
 
If you do cancel your authorization to use and disclose your information, your part in this study will end 
and no further information about you will be collected. Your revocation (cancellation) would not affect 
information already collected in the study, or information we disclosed before you wrote to the Principal 
Investigator to cancel your authorization. 
 
12. 
What treatment costs will be paid if you are injured in this study? 
Johns Hopkins does not have a program to pay you if you are hurt or have other bad results from being 
in the study.  However, medical care at Johns Hopkins is open to you as it is to all sick or injured people. 
 
The study sponsor, Astellas Pharma Global Development, Inc., has agreed to pay the usual and standard 
costs of treatment or hospital care you receive as a direct result of a study-related injury that are not 
covered by a health insurer (provided the costs are not the result of care required to treat your underlying 
disease or condition).  
 
Any costs that are not covered by the study sponsor or a health insurer will be billed to you. 
 
By signing this form you will not give up any rights you have to seek compensation for injury.  
 
13. 
What other things should you know about this research study? 
a. What is the Institutional Review Board (IRB) and how does it protect you?  
The Johns Hopkins Medicine IRB is made up of: 
• Doctors 
• Nurses 
• Ethicists 
• Non-scientists 
• and people from the local community.  
 
The IRB reviews human research studies. It protects the rights and welfare of the people taking part 
in those studies.  You may contact the IRB if you have questions about your rights as a participant or 
if you think you have not been treated fairly.  The IRB office number is 410-955-3008. You may 
also call this number for other questions, concerns or complaints about the research. 
 
When the Johns Hopkins School of Medicine Institutional Review Board (IRB) reviews a study at 
another site, that site (institution) is solely responsible for the safe conduct of the study and for 
following the protocol approved by the Johns Hopkins IRB.   
 
b. What do you do if you have questions about the study?    
Call the principal investigator, Dr. Burnett at 410-614-3986. If you wish, you may contact the 
principal investigator by letter or by fax.  The address and fax number are on page one of this 
consent form. If you cannot reach the principal investigator or wish to talk to someone else, call the 
IRB office at 410-955-3008.   
 
c. What should you do if you are injured or ill as a result of being in this study?  
If you think you are injured or ill because of this study, call the Principal Investigator, Dr. Arthur 
Burnett at 410-614-3986 during regular office hours.  
 


Do not use this form for consenting research 
participants unless the Johns Hopkins Medicine 
Logo appears here. 
Date: March 12, 2018  
Principal Investigator: Arthur L. Burnett II M.D., M.B.A. 
Application No.: IRB00097439  
 
Page 8 of 10 
Combined Informed Consent/Authorization June 2015 Version 15 
If you have an urgent medical problem related to your taking part in this study, call Dr. Arthur 
Burnett at 410-614-3986 during regular office hours and at 410-614-3986 after hours and on weekends. 
 
d. What happens to Data and Biospecimens that are collected in the study?  
Johns Hopkins and our research partners work to understand and cure diseases.  The biospecimens 
and/or data you provide are important to this effort. 
 
 
If you join this study, you should understand that you will not own your biospecimens or data, and 
should researchers use them to create a new product or idea, you will not benefit financially.  
 
With appropriate protections for privacy, Johns Hopkins may share your biospecimens and 
information with our research sponsors and partners. 
 
 


Do not use this form for consenting research 
participants unless the Johns Hopkins Medicine 
Logo appears here. 
Date: March 12, 2018  
Principal Investigator: Arthur L. Burnett II M.D., M.B.A. 
Application No.: IRB00097439  
 
Page 9 of 10 
Combined Informed Consent/Authorization June 2015 Version 15 
 
14. 
What does your signature on this consent form mean?  
Your signature on this form means that: You understand the information given to you in this form; you accept the 
provisions in the form and you agree to join the study. You will not give up any legal rights by signing this 
consent form.  
 
WE WILL GIVE YOU A COPY OF THIS SIGNED AND DATED CONSENT FORM 
 
________________________________________________________________________________________________________________________ 
Signature of Participant                                                                           (Print Name)                                                 
 
Date/Time  
 
________________________________________________________________________________________________________________________ 
Signature of Person Obtaining Consent                                                  (Print Name)                                               
 
Date/Time 
 
 
I have received the separate Insurance and Research Participant Financial Responsibility Information Sheet.   
 
________________________________________________________________________________________________________________________ 
Signature of Participant, LAR or Parent/Guardian                               (Print Name)                                                         
 
Date/Time 
 
NOTE: A COPY OF THE SIGNED, DATED CONSENT FORM MUST BE KEPT BY THE PRINCIPAL INVESTIGATOR; A COPY MUST BE GIVEN 
TO THE PARTICIPANT; IF YOU ARE USING EPIC FOR THIS STUDY A COPY MUST BE FAXED TO 410-367-7382; IF YOU ARE NOT USING EPIC 
A COPY MUST BE PLACED IN THE PARTICIPANT’S MEDICAL RECORD (UNLESS NO MEDICAL RECORD EXISTS OR WILL BE CREATED).  
 
ONLY CONSENT FORMS THAT INCLUDE THE JOHNS HOPKINS MEDICINE LOGO CAN BE USED TO OBTAIN THE CONSENT OF RESEARCH 
PARTICIPANTS. 
 
 


Do not use this form for consenting research 
participants unless the Johns Hopkins Medicine 
Logo appears here. 
Date: March 12, 2018  
Principal Investigator: Arthur L. Burnett II M.D., M.B.A. 
Application No.: IRB00097439  
 
Page 10 of 10 
Combined Informed Consent/Authorization June 2015 Version 15 
 
DOCUMENTATION OF PHYSICIAN/MID-LEVEL PROVIDER CONSENT 
 
My signature below indicates that I have discussed the risks, benefits, and alternatives, answered any 
questions, and believe the participant is able to make an informed choice to join the study. 
 
________________________________________________________________________________________________________________________ 
Signature of Physician/Mid-Level Provider                     (Print Name)                                                                     
 
Date/Time   
 
 
________________________________________________________________________________________________________________________ 
Signature of Participant                                                    (Print Name)                                                                    
 
Date/Time     
 
 
NOTE: A COPY OF THE SIGNED, DATED CONSENT FORM MUST BE KEPT BY THE PRINCIPAL INVESTIGATOR; A COPY MUST BE GIVEN 
TO THE PARTICIPANT; IF YOU ARE USING EPIC FOR THIS STUDY A COPY MUST BE FAXED TO 410-367-7382; IF YOU ARE NOT USING EPIC 
A COPY MUST BE PLACED IN THE PARTICIPANT’S MEDICAL RECORD (UNLESS NO MEDICAL RECORD EXISTS OR WILL BE CREATED).  
 
 
ONLY CONSENT FORMS THAT INCLUDE THE JOHNS HOPKINS MEDICINE LOGO CAN BE USED TO OBTAIN THE CONSENT OF RESEARCH 
PARTICIPANTS.