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Effects and Safety of Liposome Encapsulated Botulinum Toxin A for Overactive Bladder Syndrome

Primary Purpose

Overactive Bladder

Status

Completed

Phase

Phase 2

Locations

Taiwan

Study Type

Interventional

Intervention

Liposome encapsulated botulinum toxin A

Normal saline instillation

About this trial

This is an interventional treatment trial for Overactive Bladder focused on measuring Overactive bladder, Detrusor overactivity, Liposome, Botulinum toxin A

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Adults with age of 20 years old or above
Patients with symptoms of urgency frequency and/or urge incontinence and a urgency severity scale (USS) of at least 2, with or without urodynamically proven detrusor overactivity (DO) (defined by the International Continence Society (ICS) recommendation as: spontaneous detrusor contraction occurring during bladder filling phase or occurring before uninhibited detrusor contraction voiding at bladder capacity in the urodynamic study)
Free of active urinary tract infection
Free of bladder outlet obstruction on enrollment
Free of overt neurogenic bladder dysfunction
Having been treated with antimuscarinic agents for at least 4 weeks without effect or with intolerable adverse effects
Patient has not been treated with bladder surgery for OAB, such as enterocystoplasty, that might affect the therapeutic effect of test drug
Patient can record voiding diary for the urinary frequency and urgency
Patient or his/her legally acceptable representative has signed the written informed consent form

Exclusion Criteria:

Use of antimuscarinic agent and effective in treatment of lower urinary tract symptoms
Patients with severe cardiopulmonary disease and such as congestive heart failure, arrhythmia, poorly controlled hypertension, not able to receive regular follow-up
Patients with bladder outlet obstruction on enrollment
Patients with postvoid residual >150 mL
Patients with uncontrolled confirmed diagnosis of acute urinary tract infection
Patients have laboratory abnormalities at screening including:
Alanine aminotransferase (ALT) >3 x upper limit of normal range Aspartate aminotransferase (AST) >3 x upper limit of normal range Patients have abnormal serum creatinine level >2 x upper limit of normal range
Patients with any contraindication to be urethral catheterization during treatment
Female patients who is pregnant, lactating, or with child-bearing potential without contraception.
Myasthenia gravis, Eaton Lambert syndrome.
Patients with any other serious disease considered by the investigator not suitable for general anesthesia or in the condition to enter the trial
Patients participated investigational drug trial within 1 month before entering this study

Sites / Locations

Buddhist Tzu Chi General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Experimental arm

Control arm

Arm Description

Liposome encapsulated BoNT-A ( mixed BOTOX 200 U/10 mL in Liposome 80 mg/40 mL) in single intravesical instillation Liposome encapsulated botulinum toxin A'

Normal saline 50 mL in single intravesical instillation Normal saline instillation'

Outcomes

Primary Outcome Measures

Mean Change of the Total Frequency Per 3 Days

Efficacy: Mean change of the total frequency per 3 days from baseline to 4 weeks after the treatment day based on the 3-day voiding diary. Change = Week 4 minus Baseline value

Secondary Outcome Measures

Mean Change of the Urgency Episodes Per 3 Days

Efficacy: Mean change of the Urgency episodes per 3 days from baseline to 4 weeks after the treatment day based on the 3-day voiding diary. Change = Week 4 minus Baseline value

Mean Change of the Urgency Urinary Incontinence (UUI) Per 3 Days

Efficacy: Mean change of the urgency urinary incontinence (UUI) per 3 days from baseline to 4 weeks after the treatment day based on the 3-day voiding diary. Change = Week 4 minus Baseline value

Net Change of the Overactive Bladder Symptom Score (OABSS)

Efficacy:(measured the net change of variables from baseline to 1 month) Overactive bladder symptom score (OABSS) The OABSS is a 4-item questionnaire developed to evaluate OAB symptoms. The maximal scores are 2, 3, 5 and 5 for daytime frequency, nighttime frequency, urgency and urgency in continence, respectively. The OABSS range = 0 to 15 ((asymptomatic to very symptomatic). Change = Week 4 minus Baseline value

Net Change of the Functional Bladder Capacity (FBC)

Efficacy:(measured the net change of variables from baseline and 1 month) Functional bladder capacity (FBC) Change = Week 4 minus Baseline value

Net Change of the Maximum Flow Rate (Qmax)

Efficacy:(measured the net change of variables from baseline and 1 month) Maximum flow rate (Qmax) Change = Week 4 minus Baseline value

Net Change of the Postvoid Residual Volume (PVR)

Efficacy:(measured the net change of variables from baseline and 1 month) Postvoid residual volume (PVR) Change = Week 4 minus Baseline value

Net Change of the Urgency Severity Score (USS) Within 3 Days

Efficacy:(measured the net change of variables from baseline and 1 month) Urgency severity score (USS) within 3 days. The USS have 1-point scale ranging from 0 to 4. The USS grades urgency per toilet void as none, mild, moderate or severe.

Net Change of the Global Response Assessment (GRA)

Efficacy:(measured the net change of variables from baseline and 1 month) The Global response assessment (GRA) have seven point scale is centered at zero (no change): markedly worse; moderately worse; slightly worse; no change; slightly improved; moderately improved; and markedly improved.

Full Information

NCT ID

NCT01167257

First Posted

July 20, 2010

Last Updated

September 19, 2014

Sponsor

Buddhist Tzu Chi General Hospital

1. Study Identification

Unique Protocol Identification Number

NCT01167257

Brief Title

Effects and Safety of Liposome Encapsulated Botulinum Toxin A for Overactive Bladder Syndrome

Official Title

Comparative Study of the Efficacy and Safety of Liposome Encapsulated Botulinum Toxin-A (Lipotoxin) Versus Normal Saline Instillation in Treatment of Patients With Refractory Overactive Bladder Syndrome

Study Type

Interventional

2. Study Status

Record Verification Date

September 2014

Overall Recruitment Status

Completed

Study Start Date

May 2010 (undefined)

Primary Completion Date

December 2013 (Actual)

Study Completion Date

December 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Buddhist Tzu Chi General Hospital

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Overactive bladder (OAB) is a bothered symptom syndrome. Traditional medication for OAB is antimuscarinic agent. However, adverse events such as dry mouth, constipation, blurred vision, and dizziness may prohibit patient to take this drug for OAB. Intravesical botulinum toxin A (BoNT-A) is a novel treatment however, BoNT-A can cause acute urinary retention and large postvoid residual. In this grant we will evaluate liquid liposome delivery of BoNT-A (Liposome encapsulated BoNT-A) into the bladder without the need for cystoscopic-guided needle injection for refractory OAB.

Detailed Description

Overactive bladder (OAB) is a symptom syndrome characterized by urgency frequency with or without urgency incontinence, usually no metabolic or anatomical disorders can be found and it may have great impact on quality of life. Traditional medication for OAB is antimuscarinic agent which targets at the muscarinic receptors. There are several adverse events such as dry mouth, constipation, blurred vision, and dizziness related to antimuscarinics, therefore, some patients cannot tolerated this treatment. Intravesical botulinum toxin A (BoNT-A) has recently emerged as novel treatment for OAB refractory to antimuscarinics, however, BoNT-A injection can cause acute urinary retention and large postvoid residual. Urinary tract infection usually occurred following large postvoid residual and urinary retention. If we can deliver BoNT-A through the urothelium to the suburothelial space, but not into the detrusor layer, we might have therapeutic effects on the urothelial sensory nerves without compromising the detrusor contractility. This treatment will enable us to prevent the undesired detrusor underactivity after BoNT-A injection, especially in the elderly patients who had impaired detrusor contractility and OAB. Liposomes are vesicles, composed of concentric phospholipid bilayers separated by aqueous compartments. Because liposomes adsorb to cell surfaces and fuse with cells, they are being used as vehicles for drug delivery and gene therapy. In this grant we will evaluate liquid liposome delivery of BoNT-A (Liposome encapsulated BoNT-A) into the bladder without the need for cystoscopic-guided needle injection for refractory OAB, and study the mechanism of action of intravesical liposomal drug delivery. If successful, we will leverage our technology transfer expertise and bring the science from the bench top to the bed side to apply for a physician sponsored Investigational New Drug (IND) trial using liposome-BoNT in patients with OAB or DO.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Overactive Bladder

Keywords

Overactive bladder, Detrusor overactivity, Liposome, Botulinum toxin A

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

62 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Experimental arm

Arm Type

Experimental

Arm Description

Liposome encapsulated BoNT-A ( mixed BOTOX 200 U/10 mL in Liposome 80 mg/40 mL) in single intravesical instillation Liposome encapsulated botulinum toxin A'

Arm Title

Control arm

Arm Type

Placebo Comparator

Arm Description

Normal saline 50 mL in single intravesical instillation Normal saline instillation'

Intervention Type

Drug

Intervention Name(s)

Liposome encapsulated botulinum toxin A

Other Intervention Name(s)

Lipotoxin

Intervention Description

Liposome encapsulated BoNT-A ( mixed BOTOX 200 U/10 mL water in Liposome 80 mg/40 mL water) in single intravesical instillation, one time treatment at the treatment day

Intervention Type

Drug

Intervention Name(s)

Normal saline instillation

Other Intervention Name(s)

N/S

Intervention Description

Normal saline (BoNT-A/NS) 50 mL in single intravesical instillation

Primary Outcome Measure Information:

Title

Mean Change of the Total Frequency Per 3 Days

Description

Efficacy: Mean change of the total frequency per 3 days from baseline to 4 weeks after the treatment day based on the 3-day voiding diary. Change = Week 4 minus Baseline value

Time Frame

Baseline to 4 weeks after initial treatment

Secondary Outcome Measure Information:

Title

Mean Change of the Urgency Episodes Per 3 Days

Description

Efficacy: Mean change of the Urgency episodes per 3 days from baseline to 4 weeks after the treatment day based on the 3-day voiding diary. Change = Week 4 minus Baseline value

Time Frame

Baseline to 4 weeks after initial treatment

Title

Mean Change of the Urgency Urinary Incontinence (UUI) Per 3 Days

Description

Efficacy: Mean change of the urgency urinary incontinence (UUI) per 3 days from baseline to 4 weeks after the treatment day based on the 3-day voiding diary. Change = Week 4 minus Baseline value

Time Frame

Baseline to 4 weeks after initial treatment

Title

Net Change of the Overactive Bladder Symptom Score (OABSS)

Description

Time Frame

Baseline to 4 weeks after initial treatment

Title

Net Change of the Functional Bladder Capacity (FBC)

Description

Efficacy:(measured the net change of variables from baseline and 1 month) Functional bladder capacity (FBC) Change = Week 4 minus Baseline value

Time Frame

Baseline to 4 weeks after initial treatment

Title

Net Change of the Maximum Flow Rate (Qmax)

Description

Efficacy:(measured the net change of variables from baseline and 1 month) Maximum flow rate (Qmax) Change = Week 4 minus Baseline value

Time Frame

Baseline to 4 weeks after initial treatment

Title

Net Change of the Postvoid Residual Volume (PVR)

Description

Efficacy:(measured the net change of variables from baseline and 1 month) Postvoid residual volume (PVR) Change = Week 4 minus Baseline value

Time Frame

Baseline and 1 month after initial treatment

Title

Net Change of the Urgency Severity Score (USS) Within 3 Days

Description

Time Frame

Baseline to 4 weeks after initial treatment

Title

Net Change of the Global Response Assessment (GRA)

Description

Time Frame

Baseline to 4 weeks after initial treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Adults with age of 20 years old or above Patients with symptoms of urgency frequency and/or urge incontinence and a urgency severity scale (USS) of at least 2, with or without urodynamically proven detrusor overactivity (DO) (defined by the International Continence Society (ICS) recommendation as: spontaneous detrusor contraction occurring during bladder filling phase or occurring before uninhibited detrusor contraction voiding at bladder capacity in the urodynamic study) Free of active urinary tract infection Free of bladder outlet obstruction on enrollment Free of overt neurogenic bladder dysfunction Having been treated with antimuscarinic agents for at least 4 weeks without effect or with intolerable adverse effects Patient has not been treated with bladder surgery for OAB, such as enterocystoplasty, that might affect the therapeutic effect of test drug Patient can record voiding diary for the urinary frequency and urgency Patient or his/her legally acceptable representative has signed the written informed consent form Exclusion Criteria: Use of antimuscarinic agent and effective in treatment of lower urinary tract symptoms Patients with severe cardiopulmonary disease and such as congestive heart failure, arrhythmia, poorly controlled hypertension, not able to receive regular follow-up Patients with bladder outlet obstruction on enrollment Patients with postvoid residual >150 mL Patients with uncontrolled confirmed diagnosis of acute urinary tract infection Patients have laboratory abnormalities at screening including: Alanine aminotransferase (ALT) >3 x upper limit of normal range Aspartate aminotransferase (AST) >3 x upper limit of normal range Patients have abnormal serum creatinine level >2 x upper limit of normal range Patients with any contraindication to be urethral catheterization during treatment Female patients who is pregnant, lactating, or with child-bearing potential without contraception. Myasthenia gravis, Eaton Lambert syndrome. Patients with any other serious disease considered by the investigator not suitable for general anesthesia or in the condition to enter the trial Patients participated investigational drug trial within 1 month before entering this study

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Hann-Chorng Kuo, M.D.

Organizational Affiliation

Department of Urology, Buddhist Tzu Chi General Hospital and Tzu Chi University

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Yao-Chi Chuang, M.D.

Organizational Affiliation

Department of Urology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan

Official's Role

Principal Investigator

Facility Information:

Facility Name

Buddhist Tzu Chi General Hospital

City

Hualien

ZIP/Postal Code

970

Country

Taiwan

12. IPD Sharing Statement

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Effects and Safety of Liposome Encapsulated Botulinum Toxin A for Overactive Bladder Syndrome

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