Study Evaluating the Safety, Tolerability, and Efficacy of Dexmecamylamine (TC-5214) for Treatment of Overactive Bladder

Study Overview
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Brief Summary
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Overactive bladder (OAB) is a syndrome characterized by symptoms of a sudden need to urinate with or without incontinence (leaking). The purpose of this study is to test whether dexmecamylamine is safe and effective compared to placebo for the treatment of symptoms of OAB.

Detailed Description
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The study included a three- or five-week screening period, followed by a 12-week treatment period during which patients received either one of three doses of dexmecamylamine or placebo twice daily, randomized in a ratio of 2:1:1:1 (placebo, low dose, mid dose, high dose), with a two-week follow-up period. A total of 768 subjects with overactive bladder were randomized into the double-blind treatment period of the study.

Conditions
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Overactive Bladder

Intervention / Treatment
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* Drug: dexmecamylamine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Verified medical history of overactive bladder for at least 6 months Capable of walking unassisted to use the bathroom Able to measure voided urine volume and complete the diary without assistance If the subject is currently being treated with an OAB medication, the subject is willing to discontinue OAB medications while participating in this study Exclusion Criteria: Diagnosis of a neurological disease affecting bladder function Stress incontinence, insensate incontinence, overflow incontinence or incontinence due to urinary fistula History of incomplete bladder emptying, bladder outflow obstruction or post-void residual bladder volume > 150 mL Males with benign prostatic hyperplasia or with a prostate-specific antigen (PSA) of 4 ng/mL or more Other urinary tract pathology such as malignancy, ureteric reflux, bladder stone, uninvestigated hematuria, urethral stricture, or cystitis Prior treatment with intravesical or intraprostatic botulinum toxin in the last 2 years Myasthenia gravis Angle closure glaucoma Current implantation of interstim electrodes or vaginal surgical mesh Presence of a clinically significant medical condition at any time during the study Presence of clinically significant abnormalities in laboratory findings, physical exam findings or vital signs Participated in an investigational drug trial within 3 months of screening

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>One tablet of placebo to be administered orally twice a day. | Drug: Placebo<br> <br> |
| Experimental: 0.5 mg dexmecamylamine (TC-5214)<br>One tablet of 0.5 mg dexmecamylamine to be administered orally twice a day. | Drug: dexmecamylamine<br> <br> * Other names: TC-5214;|
| Experimental: 1 mg dexmecamylamine (TC-5214)<br>One tablet of 1 mg dexmecamylamine to be administered orally twice a day. | Drug: dexmecamylamine<br> <br> * Other names: TC-5214;|
| Experimental: 2 mg dexmecamylamine (TC-5214)<br>One tablet of 2 mg dexmecamylamine to be administered orally twice a day. | Drug: dexmecamylamine<br> <br> * Other names: TC-5214;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in micturition frequency per 24 hours | Micturition: Any voiding episode recorded by the patient as urinated either with or without incontinence. | 12 weeks | 
| Change from baseline in urinary urge incontinence (UUI) episodes per 24 hours |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the volume voided per micturition |  | 12 weeks | 
| Change from baseline in nocturia per 24 hours | Nocturia: A micturition that wakes the subject from sleep between the time the subject went to bed and the time the subject woke up. | 12 weeks | 
| Clinical Global Impression of Improvement (CGI-I) |  | 12 weeks | 
| Change from baseline in Patient Perception of Bladder Condition (PPBC) |  | 12 weeks | 
| Change from baseline in the Urgency Questionnaire |  | 12 weeks | 
| Change from baseline in disease specific quality of life (OABq) |  | 12 weeks |