Clinical Study to Assess the Efficacy and Safety of THVD-201 in Patients With OAB

Study Overview
=================
Brief Summary
-----------------
The primary purpose of this study is to assess the efficacy and safety of THVD-201(Combination of tolterodine and pilocarpine) in patients with Overactive bladder during the period of treatment, 12 weeks. This study also includes an open label extension period of an additional 12 weeks following the treatment to assess long-term efficacy and safety of THVD-201 in patients with Overactive bladder.

Official Title
-----------------
Multicenter, Randomized, Double-blind, Parallel, Active Control, Phase III Clinical Study to Assess the Efficacy and Safety of THVD-201 in Patients With Overactive Bladder Including an Open-label, Extension Study

Conditions
-----------------
Overactive Bladder

Intervention / Treatment
-----------------
* Drug: THVD-201
* Drug: Placebo(For THVD-201)
* Drug: Detrusitol 2mg tablet
* Drug: Placebo(For Detrusitol 2mg tablet)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 20 - 85 years History of OAB (pure urge or mixed urinary incontinence with predominant urge incontinence) for ≥ 6 months. In the case of females, at least 2 years has passed since menopause. Or all pre-menopausal female subjects must have been using a highly effective method of birth control during the study. Subject of childbearing potential must have had a negative pregnancy test prior to enrollment. Exclusion Criteria: Predominate stress incontinence, insensate incontinence (those incapable of distinguishing discrete incontinence episodes) and overflow incontinence, as major reason for urine loss or urinary frequency as determined by the investigator. History of neurogenic bladder. PVR > 200mL History of clinically significant renal disease or estimated creatinine clearance defined by Cockcroft and Gault formula < 30 mL/min. History of malignant tumor within the past 5 years. History or presence of tachyarrhythmia or cardiac disease that in the opinion of the investigator might have confounded the results of the study or posed additional risk to the subject. Subjects who had a value for QTc > 450 msec at the Screening visit. Patient with asthma PSA ≥ 10 ng/mL in male who is 50 years and over.

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: THVD-201<br>1. Treatment period(12 weeks) Double dummy(A+B) A. THVD-201: capsule B. Placebo(For Detrusitol 2mg tablet) One capsule and One tablet bid on an empty stomach 2. Open-label extension period(An additional 12 weeks) Regardless of the previous type of arm, all patients only take THVD-201 during this period. One capsule bid on an empty stomach | Drug: THVD-201<br>* Combination of Tolterodine 2mg and Pilocarpine 9mg<br>Drug: Placebo(For Detrusitol 2mg tablet)<br> <br> |
| Active Comparator: Tolterodine (Detrusitol)<br>1. Treatment period(12 weeks) Double dummy(A+B) A. Placebo(For THVD-201): capsule B. Detrusitol 2mg tablet One capsule and One tablet bid on an empty stomach 2. Open-label extension period(An additional 12 weeks) Regardless of the previous type of arm , all patients only take THVD-201 during this period. One capsule bid on an empty stomach | Drug: THVD-201<br>* Combination of Tolterodine 2mg and Pilocarpine 9mg<br>Drug: Placebo(For THVD-201)<br> <br> Drug: Detrusitol 2mg tablet<br>* Tolterodine 2mg<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean daily micturition frequency | The change of Mean daily micturition frequency between 0 and 12 weeks | 12 weeks | 
| ADR Incidence of Dry mouth |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean daily micturition frequency | The change of Mean daily micturition frequency between 0 and 24 weeks | 24 weeks | 
| Mean daily Incontinence frequency(12 weeks) | The change of Mean daily Incontinence frequency between 0 and 12 weeks | 12 weeks | 
| Mean daily Incontinence frequency(24 weeks) | The change of Mean daily Incontinence frequency between 0 and 24 weeks | 24 weeks | 
| Mean daily Urgency frequency(12 weeks) | The change of Mean daily Urgency frequency between 0 and 12 weeks | 12 weeks | 
| Mean daily Urgency frequency(24 weeks) | The change of Mean daily Urgency frequency between 0 and 24 weeks | 24 weeks | 
| Mean daily Nocturia frequency(12 weeks) | The change of Mean daily Nocturia frequency between 0 and 12 weeks | 12 weeks | 
| Mean daily Nocturia frequency(24 weeks) | The change of Mean daily Nocturia frequency between 0 and 24 weeks | 24 weeks | 
| Mean daily Micturition volume(12 weeks) | The change of Mean daily Micturition volume between 0 and 12 weeks | 12 weeks | 
| Mean daily Micturition volume(24 weeks) | The change of Mean daily Micturition volume between 0 and 24 weeks | 24 weeks | 
| Score of OAB-SS questionnaire(12 weeks) | The change of the Score between 0 and 12 weeks | 12 weeks | 
| Score of OAB-SS questionnaire(24 weeks) | The change of the Score between 0 and 24 weeks | 24 weeks | 
| Score of OAB-q questionnaire(12 weeks) | The change of the Score between 0 and 12 weeks | 12 weeks | 
| Score of OAB-q questionnaire(24 weeks) | The change of the Score between 0 and 24 weeks | 24 weeks | 
| VAS score of dry mouth symptom(12 weeks) | The change of the Score between 0 and 12 weeks | 12 weeks | 
| VAS score of dry mouth symptom(24 weeks) | The change of the Score between 0 and 24 weeks | 24 weeks | 
| Score of Xerostomia Inventory questionnaire(12 weeks) | The change of the Score between 0 and 12 weeks | 12 weeks | 
| Score of Xerostomia Inventory questionnaire(24 weeks) | The change of the Score between 0 and 24 weeks | 24 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Overactive Bladder, Tolterodine (Detrusitol), Pilocarpine