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

Overactive Bladder Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01167257
• Other study ID #: TCGHUROL001
• Status: Completed
• Phase: Phase 2
• First received: July 20, 2010
• Last updated: September 19, 2014
• Start date: May 2010
• Est. completion date: December 2013

Study information

• Verified date: September 2014
• Source: Buddhist Tzu Chi General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Taiwan: Center for Drug EvaluationTaiwan: Department of HealthTaiwan: Research Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Adults with age of 20 years old or above

2. 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)

3. Free of active urinary tract infection

4. Free of bladder outlet obstruction on enrollment

5. Free of overt neurogenic bladder dysfunction

6. Having been treated with antimuscarinic agents for at least 4 weeks without effect or with intolerable adverse effects

7. Patient has not been treated with bladder surgery for OAB, such as enterocystoplasty, that might affect the therapeutic effect of test drug

8. Patient can record voiding diary for the urinary frequency and urgency

9. Patient or his/her legally acceptable representative has signed the written informed consent form

Exclusion Criteria:

1. Use of antimuscarinic agent and effective in treatment of lower urinary tract symptoms

2. Patients with severe cardiopulmonary disease and such as congestive heart failure, arrhythmia, poorly controlled hypertension, not able to receive regular follow-up

3. Patients with bladder outlet obstruction on enrollment

4. Patients with postvoid residual >150 mL

5. Patients with uncontrolled confirmed diagnosis of acute urinary tract infection

6. 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

7. Patients with any contraindication to be urethral catheterization during treatment

8. Female patients who is pregnant, lactating, or with child-bearing potential without contraception.

9. Myasthenia gravis, Eaton Lambert syndrome.

10. Patients with any other serious disease considered by the investigator not suitable for general anesthesia or in the condition to enter the trial

11. Patients participated investigational drug trial within 1 month before entering this study

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Overactive Bladder
• Urinary Bladder, Overactive

Intervention

Drug:
• Liposome encapsulated botulinum toxin A
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
• Normal saline instillation
Normal saline (BoNT-A/NS) 50 mL in single intravesical instillation

Locations

Country	Name	City	State
Taiwan	Buddhist Tzu Chi General Hospital	Hualien

Sponsors (1)

Lead Sponsor	Collaborator
Buddhist Tzu Chi General Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Baseline to 4 weeks after initial treatment	No
Secondary	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	Baseline to 4 weeks after initial treatment	No
Secondary	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	Baseline to 4 weeks after initial treatment	No
Secondary	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	Baseline to 4 weeks after initial treatment	No
Secondary	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	Baseline to 4 weeks after initial treatment	No
Secondary	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	Baseline to 4 weeks after initial treatment	No
Secondary	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	Baseline and 1 month after initial treatment	No
Secondary	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.	Baseline to 4 weeks after initial treatment	No
Secondary	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.	Baseline to 4 weeks after initial treatment	No