Mirabegron and Urinary Urgency Incontinence

• Sponsor: Loyola University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02495389
• Collaborator: Astellas Pharma US, Inc. (Industry)
• Enrollment: 84
• Location: 1
• Arm: 1
• Actual Duration (Months): 48
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

This study is for women diagnosed with urinary urgency incontinence (UUI) or overactive bladder (OAB). Some patients continue to have symptoms even while taking medication for OAB. The purpose of this study is to estimate the number of women who respond to a medication called mirabegron and estimate change in symptom severity over 12 weeks of therapy. A secondary goal is to correlate the female urinary microbiome (FUM) with response to treatment and change in symptom severity over 12 weeks of therapy.

Condition or Disease	Intervention/Treatment	Phase
Overactive Bladder	Drug: Mirabegron	Phase 4

Detailed Description

Mirabegron is an FDA-approved medication for urgency incontinence. Evaluation of mirabegron's influence on clinical symptoms may need to take into account the effect of the female urinary microbiome (FUM) on a patient's response to treatment. Compared to asymptomatic patients, several bacterial species are more common in patients with overactive bladder.

Currently, physicians have limited ability to personalize a patient's urinary urgency incontinence treatment and, consequently, the prescribed medication may provide minimal symptom relief. Since the FUM can be assessed prior to treatment, this study proposes to determine if baseline FUM assessment can provide insight into future symptom relief with mirabegron treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 84 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: All patients receive mirabegron daily for 12 weeksAll patients receive mirabegron daily for 12 weeks
• Masking: None (Open Label)
• Masking Description: There is no masking scheme
• Primary Purpose: Treatment
• Official Title: Mirabegron and Urinary Urgency Incontinence: The Clinical Response and the Female Urinary Microbiome
• Actual Study Start Date: Jan 28, 2015
• Actual Primary Completion Date: Jan 29, 2019
• Actual Study Completion Date: Jan 29, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Mirabegron Participants received mirabegron (Myrbetriq) daily for 12 weeks	Drug: Mirabegron; Mirabegron is a medication for the treatment of overactive bladder. It was developed by Astellas Pharma and was approved by the United States Food and Drug Administration (FDA) in July 2012.; Other Names: Myrbetriq Betmiga

Outcome Measures

Primary Outcome Measures

1. Response to Therapy [12 weeks]

   Response to therapy was measured using the Patient Perception of Bladder Control (PPBC) questionnaire which measures patients' perceived bladder condition on a 6-point ordinal scale ranging from 1 (no problems at all) to 6 (many severe problems). Women reporting a PPBC score of 4 or 5 by week 12 responded to therapy. Women reporting a PPBC score of 1, 2, or 3 by week 12 did not respond to therapy.

Secondary Outcome Measures

1. Change in Overactive Bladder Questionnaire (OAB-q) Health Related Quality of Life (HRQL) [12 weeks]

   The Overactive Bladder Questionnaire (OAB-q) Health Related Quality of Life (HRQL) score is a measure of patients' bladder symptom severity. It ranges from 25 to 150 where higher scores indicate greater quality of life.

2. Change in Urinary Distress Inventory (UDI) [12 weeks]

   The Urinary Distress Inventory is a 29-item questionnaire that asks patients to report how bothered they are by symptoms of urinary urgency on a scale from 1 (not at all) to 4 (quite a bit). The total score ranges from 0 to 300 where higher scores indicate worsening symptom severity.

3. Change in Pelvic Organ Prolapse Distress Inventory (POPDI) Score [12 weeks]

   The Pelvic Organ Prolapse Distress Inventory (POPDI) is a 16-item questionnaire that asks patients to report how bothered they are by symptoms of urinary urgency on a scale from 1 (not at all) to 4 (quite a bit). The total score ranges from 0 to 300 where higher scores indicate worsening symptom severity.

4. Change in Colo-Rectal-Anal Distress Inventory (CRADI) [12 weeks]

   The Colo-Rectal-Anal Distress Inventory (CRADI) is a 17-item questionnaire that asks patients to report how bothered they are by symptoms of urinary urgency on a scale from 1 (not at all) to 4 (quite a bit). The total score ranges from 0 to 400 where higher scores indicate worsening symptom severity.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Bothersome idiopathic (non-neurologic) urgency urinary incontinence (UUI) who recall ≥ 5 urgency predominant urinary incontinence episodes in the prior week (urgency urinary incontinence or mixed urinary incontinence-urgency predominant)

• No contraindications to taking mirabegron

• Patients on current OAB therapy will undergo a two-week drug washout period prior to baseline assessment

Exclusion Criteria:

• Neurologic disease known to affect the lower urinary tract

• Systemic immunologic deficiency

• Current urinary tract infection (UTI) (based on dipstick assessment) or recurrent culture-proven UTIs

• History or current pelvic malignancy or radiation

• Untreated symptomatic pelvic organ prolapse (POP) > POP-Q Stage II

• A contraindication to receiving mirabegron

• Women of childbearing potential who are pregnant or nursing or intend to become pregnant during the study, or who are not practicing a reliable method of contraception

• Must not have taken any antibiotics in the 4 weeks prior to enrollment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Loyola University Medical Center	Maywood	Illinois	United States	60153

Sponsors and Collaborators

• Loyola University
• Astellas Pharma US, Inc.

Investigators

• Principal Investigator: Alan Wolfe, PhD, Loyola Univerity Medical Center

Study Documents (Full-Text)

• Informed Consent Form - Jan 17, 2018
• Study Protocol - Sep 8, 2015

More Information

Publications

• Barber MD, Chen Z, Lukacz E, Markland A, Wai C, Brubaker L, Nygaard I, Weidner A, Janz NK, Spino C. Further validation of the short form versions of the Pelvic Floor Distress Inventory (PFDI) and Pelvic Floor Impact Questionnaire (PFIQ). Neurourol Urodyn. 2011 Apr;30(4):541-6. doi: 10.1002/nau.20934. Epub 2011 Feb 22.
• Brubaker L, Nager CW, Richter HE, Visco A, Nygaard I, Barber MD, Schaffer J, Meikle S, Wallace D, Shibata N, Wolfe AJ. Urinary bacteria in adult women with urgency urinary incontinence. Int Urogynecol J. 2014 Sep;25(9):1179-84. doi: 10.1007/s00192-013-2325-2. Epub 2014 Feb 11.
• Chapple CR, Cardozo L, Nitti VW, Siddiqui E, Michel MC. Mirabegron in overactive bladder: a review of efficacy, safety, and tolerability. Neurourol Urodyn. 2014 Jan;33(1):17-30. doi: 10.1002/nau.22505. Epub 2013 Oct 11. Review.
• Chapple CR, Nitti VW, Khullar V, Wyndaele JJ, Herschorn S, van Kerrebroeck P, Blauwet MB, Siddiqui E. Onset of action of the β3-adrenoceptor agonist, mirabegron, in Phase II and III clinical trials in patients with overactive bladder. World J Urol. 2014 Dec;32(6):1565-72. doi: 10.1007/s00345-014-1244-2. Epub 2014 Jan 24.
• 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):563-74.
• Coyne KS, Matza LS, Kopp Z, Abrams P. The validation of the patient perception of bladder condition (PPBC): a single-item global measure for patients with overactive bladder. Eur Urol. 2006 Jun;49(6):1079-86. Epub 2006 Jan 24.
• de Boer TA, Salvatore S, Cardozo L, Chapple C, Kelleher C, van Kerrebroeck P, Kirby MG, Koelbl H, Espuna-Pons M, Milsom I, Tubaro A, Wagg A, Vierhout ME. Pelvic organ prolapse and overactive bladder. Neurourol Urodyn. 2010;29(1):30-9. doi: 10.1002/nau.20858. Review.
• Fouts DE, Pieper R, Szpakowski S, Pohl H, Knoblach S, Suh MJ, Huang ST, Ljungberg I, Sprague BM, Lucas SK, Torralba M, Nelson KE, Groah SL. Integrated next-generation sequencing of 16S rDNA and metaproteomics differentiate the healthy urine microbiome from asymptomatic bacteriuria in neuropathic bladder associated with spinal cord injury. J Transl Med. 2012 Aug 28;10:174. doi: 10.1186/1479-5876-10-174.
• Haylen BT, de Ridder D, Freeman RM, Swift SE, Berghmans B, Lee J, Monga A, Petri E, Rizk DE, Sand PK, Schaer GN. An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction. Int Urogynecol J. 2010 Jan;21(1):5-26. doi: 10.1007/s00192-009-0976-9. Epub 2009 Nov 25. Review.
• Haylen BT, de Ridder D, Freeman RM, Swift SE, Berghmans B, Lee J, Monga A, Petri E, Rizk DE, Sand PK, Schaer GN; International Urogynecological Association; International Continence Society. An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction. Neurourol Urodyn. 2010;29(1):4-20. doi: 10.1002/nau.20798. Review.
• Hilt EE, McKinley K, Pearce MM, Rosenfeld AB, Zilliox MJ, Mueller ER, Brubaker L, Gai X, Wolfe AJ, Schreckenberger PC. Urine is not sterile: use of enhanced urine culture techniques to detect resident bacterial flora in the adult female bladder. J Clin Microbiol. 2014 Mar;52(3):871-6. doi: 10.1128/JCM.02876-13. Epub 2013 Dec 26.
• Irwin DE, Kopp ZS, Agatep B, Milsom I, Abrams P. Worldwide prevalence estimates of lower urinary tract symptoms, overactive bladder, urinary incontinence and bladder outlet obstruction. BJU Int. 2011 Oct;108(7):1132-8. doi: 10.1111/j.1464-410X.2010.09993.x. Epub 2011 Jan 13.
• Kenton K, Fitzgerald MP, Brubaker L. What is a clinician to do-believe the patient or her urinary diary? J Urol. 2006 Aug;176(2):633-5; discussion 635.
• Khasriya R, Sathiananthamoorthy S, Ismail S, Kelsey M, Wilson M, Rohn JL, Malone-Lee J. Spectrum of bacterial colonization associated with urothelial cells from patients with chronic lower urinary tract symptoms. J Clin Microbiol. 2013 Jul;51(7):2054-62. doi: 10.1128/JCM.03314-12. Epub 2013 Apr 17.
• Lowenstein L, Rickey L, Kenton K, Fitzgerald MP, Brubaker L, Tulke M, Fordham J, Mueller ER. Reliability and responsiveness of the Urgency Severity and Life Impact Questionnaire (USIQ). Int Urogynecol J. 2012 Feb;23(2):193-6. doi: 10.1007/s00192-011-1531-z. Epub 2011 Aug 18.
• Michel MC, Chapple CR. Basic mechanisms of urgency: roles and benefits of pharmacotherapy. World J Urol. 2009 Dec;27(6):705-9. doi: 10.1007/s00345-009-0446-5. Review.
• Mostwin JL. Pathophysiology: the varieties of bladder overactivity. Urology. 2002 Nov;60(5 Suppl 1):22-6; discussion 27. Review.
• Pearce MM, Hilt EE, Rosenfeld AB, Zilliox MJ, Thomas-White K, Fok C, Kliethermes S, Schreckenberger PC, Brubaker L, Gai X, Wolfe AJ. The female urinary microbiome: a comparison of women with and without urgency urinary incontinence. mBio. 2014 Jul 8;5(4):e01283-14. doi: 10.1128/mBio.01283-14.
• Sajadi KP, Vasavada SP. Overactive bladder after sling surgery. Curr Urol Rep. 2010 Nov;11(6):366-71. doi: 10.1007/s11934-010-0136-2.
• Siddiqui H, Nederbragt AJ, Lagesen K, Jeansson SL, Jakobsen KS. Assessing diversity of the female urine microbiota by high throughput sequencing of 16S rDNA amplicons. BMC Microbiol. 2011 Nov 2;11:244. doi: 10.1186/1471-2180-11-244.
• Smith HS, Hughes JP, Hooton TM, Roberts P, Scholes D, Stergachis A, Stapleton A, Stamm WE. Antecedent antimicrobial use increases the risk of uncomplicated cystitis in young women. Clin Infect Dis. 1997 Jul;25(1):63-8.
• Tincello DG, Owen RK, Slack MC, Abrams KR. Validation of the Patient Global Impression scales for use in detrusor overactivity: secondary analysis of the RELAX study. BJOG. 2013 Jan;120(2):212-216. doi: 10.1111/1471-0528.12069. Epub 2012 Nov 27.
• Wolfe AJ, Toh E, Shibata N, Rong R, Kenton K, Fitzgerald M, Mueller ER, Schreckenberger P, Dong Q, Nelson DE, Brubaker L. Evidence of uncultivated bacteria in the adult female bladder. J Clin Microbiol. 2012 Apr;50(4):1376-83. doi: 10.1128/JCM.05852-11. Epub 2012 Jan 25.

• Responsible Party: Alan J. Wolfe, Professor, Loyola University
• ClinicalTrials.gov Identifier: NCT02495389
• Other Study ID Numbers: 207102
• First Posted: Jul 13, 2015
• Last Update Posted: Nov 13, 2020
• Last Verified: Oct 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Alan J. Wolfe, Professor, Loyola University: Urinary Urgency Incontinence; Mirabegron; Myrbetriq; Betmiga
• Additional relevant MeSH terms: Urinary Bladder, Overactive; Mirabegron

Study Results

Participant Flow

Recruitment Details	Patients were recruited from January 2015 through October 2018 (46 months) from a tertiary care female pelvic medicine and reconstructive surgery practice.

Arm/Group Title	Mirabegron
Arm/Group Description	This arm comprises women who received mirabegron
Period Title: Overall Study
STARTED	84
COMPLETED	44
NOT COMPLETED	40

Baseline Characteristics

Arm/Group Title	Mirabegron
Arm/Group Description	This arm comprises women who received mirabegron
Overall Participants	84
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.67 (12.46)
Sex: Female, Male (Count of Participants)
Female	84 100%
Male	0 0%
Race/Ethnicity, Customized (Count of Participants)
Caucasian or White	65 77.4%
African American or Black	11 13.1%
Asian	1 1.2%
Multiracial	1 1.2%
Other	4 4.8%
Not Reported	2 2.4%
Region of Enrollment (Count of Participants)
United States	84 100%
Hormone Replacement Therapy (Count of Participants)
Taking hormone replacement therapy	7 8.3%
Not taking hormone replacement therapy	75 89.3%
Unknown	2 2.4%
Type II Diabetes Status (Count of Participants)
Diabetic	16 19%
Non-Diabetic	67 79.8%
Not reported	1 1.2%
Smoker Status (Count of Participants)
Smoker	8 9.5%
Non-smoker	74 88.1%
Not reported	2 2.4%
Hypertension Status (Count of Participants)
Hypertensive	43 51.2%
Non-hypertensive	40 47.6%
Not reported	1 1.2%
Cardiovascular Status (Count of Participants)
Heart disease	12 14.3%
No heart disease	71 84.5%
Not reported	1 1.2%
Chronic Obstructive Pulmonary Disease (COPD) (Count of Participants)
Positive	4 4.8%
Negative	78 92.9%
Not reported	2 2.4%
Asthma Status (Count of Participants)
Positive	13 15.5%
Negative	69 82.1%
Not reported	2 2.4%

Outcome Measures

1. Primary Outcome

Title	Response to Therapy
Description	Response to therapy was measured using the Patient Perception of Bladder Control (PPBC) questionnaire which measures patients' perceived bladder condition on a 6-point ordinal scale ranging from 1 (no problems at all) to 6 (many severe problems). Women reporting a PPBC score of 4 or 5 by week 12 responded to therapy. Women reporting a PPBC score of 1, 2, or 3 by week 12 did not respond to therapy.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

This analysis comprises women who received mirabegron and completed 12 weeks of therapy

Arm/Group Title	Mirabegron
Arm/Group Description	This arm comprises women who received mirabegron
Measure Participants	44
Responded to therapy	15 17.9%
Did not respond to therapy	29 34.5%

2. Secondary Outcome

Title	Change in Overactive Bladder Questionnaire (OAB-q) Health Related Quality of Life (HRQL)
Description	The Overactive Bladder Questionnaire (OAB-q) Health Related Quality of Life (HRQL) score is a measure of patients' bladder symptom severity. It ranges from 25 to 150 where higher scores indicate greater quality of life.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

This analysis comprises women who received mirabegron for 12 weeks and completed the Overactive Bladder Questionnaire at baseline and after 12 weeks of therapy

Arm/Group Title	Mirabegron
Arm/Group Description	This arm comprises women who received mirabegron
Measure Participants	40
Baseline	50.92 (26.14)
After 12 weeks of therapy	74.88 (25.35)
Change Score	23.96 (17.54)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron
	Comments	The null hypothesis is that there is no change in patients' baseline Overactive Bladder Questionnaire (OAB-q) Health Related Quality of Life (HRQL) score after 12 weeks of therapy.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	t-test, 2 sided
	Comments	A two-sided paired t-test was used for this analysis.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	23.96
	Confidence Interval	(2-Sided) 95%; 18.35 to 29.57
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.7741
	Estimation Comments

3. Secondary Outcome

Title	Change in Urinary Distress Inventory (UDI)
Description	The Urinary Distress Inventory is a 29-item questionnaire that asks patients to report how bothered they are by symptoms of urinary urgency on a scale from 1 (not at all) to 4 (quite a bit). The total score ranges from 0 to 300 where higher scores indicate worsening symptom severity.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

This analysis comprises women who received mirabegron for 12 weeks and completed the Urinary Distress Inventory at baseline and after 12 weeks of therapy

Arm/Group Title	Mirabegron
Arm/Group Description	This arm comprises women who received mirabegron
Measure Participants	44
Baseline	121.25 (51.19)
After 12 weeks of therapy	69.62 (46.75)
Change Score	-51.62 (40.85)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron
	Comments	The null hypothesis is that there is no change in patients' baseline Urinary Distress Inventory score after 12 weeks of therapy.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	t-test, 2 sided
	Comments	A two-sided paired t-test was used for this analysis.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-51.62
	Confidence Interval	(2-Sided) 95%; -64.04 to -39.20
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.1584
	Estimation Comments

4. Secondary Outcome

Title	Change in Pelvic Organ Prolapse Distress Inventory (POPDI) Score
Description	The Pelvic Organ Prolapse Distress Inventory (POPDI) is a 16-item questionnaire that asks patients to report how bothered they are by symptoms of urinary urgency on a scale from 1 (not at all) to 4 (quite a bit). The total score ranges from 0 to 300 where higher scores indicate worsening symptom severity.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

This analysis comprises women who received mirabegron for 12 weeks and completed the Prolapse Distress Inventory at baseline and after 12 weeks of therapy

Arm/Group Title	Mirabegron
Arm/Group Description	This arm comprises women who received mirabegron
Measure Participants	44
Baseline	77.85 (64.80)
After 12 weeks of therapy	48.55 (50.91)
Change Score	-29.30 (36.28)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron
	Comments	The null hypothesis is that there is no change in patients' baseline Pelvic Organ Prolapse Distress Inventory score after 12 weeks of therapy.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	t-test, 2 sided
	Comments	A two-sided paired t-test was used for this analysis.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-29.30
	Confidence Interval	(2-Sided) 95%; -40.33 to -18.27
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.4701
	Estimation Comments

5. Secondary Outcome

Title	Change in Colo-Rectal-Anal Distress Inventory (CRADI)
Description	The Colo-Rectal-Anal Distress Inventory (CRADI) is a 17-item questionnaire that asks patients to report how bothered they are by symptoms of urinary urgency on a scale from 1 (not at all) to 4 (quite a bit). The total score ranges from 0 to 400 where higher scores indicate worsening symptom severity.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

This analysis comprises women who received mirabegron for 12 weeks and completed the Colo-Rectal-Anal Distress Inventory at baseline and after 12 weeks of therapy

Arm/Group Title	Mirabegron
Arm/Group Description	This arm comprises women who received mirabegron
Measure Participants	44
Baseline	94.50 (82.18)
After 12 weeks of therapy	62.50 (68.17)
Change Score	-32.00 (40.61)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mirabegron
	Comments	The null hypothesis is that there is no change in patients' baseline Colo-Rectal-Anal Distress Inventory score after 12 weeks of therapy.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	t-test, 2 sided
	Comments	A two-sided paired t-test was used for this analysis.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-32.00
	Confidence Interval	(2-Sided) 95%; -44.35 to -19.65
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.1226
	Estimation Comments

Adverse Events

Time Frame	Adverse event data were collected for 26 weeks
Arm/Group Title	Mirabegron
Arm/Group Description	This arm comprises women who received mirabegron
All Cause Mortality
	Mirabegron
	Affected / at Risk (%)	# Events
Total	0/84 (0%)
Serious Adverse Events
	Mirabegron
	Affected / at Risk (%)	# Events
Total	2/84 (2.4%)
Immune system disorders
Breast Cancer	1/84 (1.2%)	1
Nervous system disorders
Stroke	1/84 (1.2%)	1
Other (Not Including Serious) Adverse Events
	Mirabegron
	Affected / at Risk (%)	# Events
Total	12/84 (14.3%)
Gastrointestinal disorders
Constipation	1/84 (1.2%)	1
Diarrhea	3/84 (3.6%)	3
Abdominal Cramping	1/84 (1.2%)	1
General disorders
Somnolence	1/84 (1.2%)	1
Leg pain	1/84 (1.2%)	1
Nausea	1/84 (1.2%)	1
Infections and infestations
Bacterial Infection	1/84 (1.2%)	1
Product Issues
Allergic Reaction to mirabegron	1/84 (1.2%)	1
Vascular disorders
Elevated Systolic Blood Pressure	2/84 (2.4%)	2

Limitations/Caveats

There are no limitations or caveats to report

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.