Efficacy and Safety Study of GSK1358820 in Japanese Patients With Urinary Incontinence Due to Neurogenic Detrusor Overactivity

Exclusion Criteria

• •Subject has a history or evidence of any diseases, functional abnormalities or bladder surgery, other than NDO, that may have affected bladder function including but not limited to:
• •1. Bladder stones (including bladder stone surgery) within 6 months prior to screening or confirmed occurrence of bladder stones at the screening phase
• •2. Surgery (including minimally invasive surgery) within 1 year of screening for stress incontinence or pelvic organ prolapse
• •3. Current use of an electrostimulation/neuromodulation device for treatment of urinary incontinence. Note: Use of any implantable device is prohibited within 4 weeks prior to initiation of Screening phase and throughout the study period. Use of any external device is discontinued at least 7 days prior to the start of the screening phase
• •4. Current use of a baclofen pump
• •5. History of interstitial cystitis, in the opinion of the investigator (or subinvestigator)
• •6. Past or current evidence of hematuria due to urological/renal pathology or uninvestigated hematuria. Subjects with investigated hematuria may enter the study if urological/renal pathology has been ruled out to the satisfaction by the investigator (or subinvestigator)
• •7. Past or current history of bladder cancer or other urothelial malignancy, positive result of urine cytology or uninvestigated suspicious urine cytology results at the Screening phase. Suspicious urine cytology abnormalities require that bladder cancer or other urothelial malignancy has been ruled out to the satisfaction of the investigator according to local site practice.
• •8. An active genital infection, other than genital warts, either concurrently or within 4 weeks prior to Screening
• •9. Male with previous or current diagnosis of prostate cancer or a prostate specific antigen (PSA) level of \>10 nanogram (ng)/milliliter (mL) at Screening. Subjects with a PSA level of \>= 4 ng/mL but \<= 10 ng/mL must have prostate cancer ruled out to the satisfaction of the investigator (or subinvestigator) according to local site practice.
• •10. Evidence of urethral and/or bladder outlet obstruction, in the opinion of the investigator (or subinvestigator)
• •Subject has a serum creatinine level \>2 times the upper limit of normal (ULN) at screening
• •Alanine aminotransferase (ALT) \> 2×ULN; and bilirubin \> 1.5×ULN (isolated bilirubin \>1.5×ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%) at screening
• •Subject has current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment). Notes:
• •1. Stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice, or cirrhosis
• •2. Chronic stable hepatitis B and C (example, presence of hepatitis B surface antigen \[HBsAg\] or positive hepatitis C antibody \[HCVAb\] test result within 3 months prior to first dose of study treatment) are acceptable if subject otherwise meets entry criteria
• •QTc \>450 milliseconds (msec) or QTc \>480 msec in subjects with Bundle Branch Block from the result of ECG at screening. Notes:
• •1. The QTc is the QT interval corrected for heart rate according to Bazett's formula (QTcB), Fridericia's formula (QTcF), and/or another method, machine-read or manually over-read
• •2. The specific formula that will be used to determine eligibility and discontinuation for an individual subject should be determined prior to initiation of the study. In other words, several different formulae cannot be used to calculate the QTc for an individual subject and then the lowest QTc value used to include or discontinue the subject from the trial
• •Subject has hemophilia or other clotting factor deficiencies or disorders that cause bleeding diathesis
• •Subject changes or initiates or discontinues anticholinergic, beta-3 adrenergic receptor agonist or any other medications or therapies to treat urinary incontinence due to NDO, within 6 days prior to the start of the screening phase
• •Subject has been treated with any intravesical pharmacologic agent (e.g., capsaicin, resiniferatoxin) for urinary incontinence due to NDO within 12 months prior to initiation of Treatment phase 1 (Week 0)
• •Subject has previous or current use of botulinum toxin therapy of any serotype for the treatment of any urological condition
• •Subject has previous use within 12 weeks prior to initiation of Treatment phase 1 (Week 0) or current use of botulinum toxin therapy of any serotype for any non-urological condition or beauty care
• •Subject has been immunized for botulinum toxin of any serotype
• •Subject cannot withhold any antiplatelet or anticoagulant therapy or medications with anticoagulative effects for 3 days prior to initiation of Treatment phase 1 (Week 0). Some medications may need to be withheld for \> 3 days, per clinical judgment of the investigator (or subinvestigator).
• •Subject without a urinary tract infection (UTI) as determined from the urinalysis or urine culture and/or investigator opinion, has not initiated prophylactic antibiotic medication 1 to 3 days prior to the initiation of Treatment phase 1 (Week 0). Subject with a UTI as determined from the urinalysis or urine culture and/or investigator opinion, has not initiated antibiotic medication at least 5 days prior to the initiation of Treatment phase 1 (Week 0)
• •Subject is symptomatic for UTI on day of treatment
• •Subject has a history of sensitivity to any of the study medications, medications used in the study (including anesthesia), or their components or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation
• •Subject has any medical condition that may put them at increased risk with exposure to GSK1358820 including diagnosed myasthenia gravis, Eaton-Lambert syndrome, or amyotrophic lateral sclerosis
• •Females who are pregnant, nursing or planning a pregnancy during the study
• •Subject has a post void residual urine volume above 200 mL for subjects who micturate or have a mixed catheterization/spontaneous micturition pattern. The post void residual measurement can be repeated once; the subject is to be excluded if the repeated measure is above 200 mL.
• •Subject has a 24-hour total volume of urine voided \>3000 mL of urine collected over 24 consecutive hours during the 3-day bladder diary collection period in the Screening phase
• •Subject is currently participating in or has previously participated in another therapeutic study within 30 days prior to the start of the Screening phase
• •Subject has any condition or situation which, in the investigator's (or sub-investigator's) opinion, puts the subject at significant risk, may confound the study results, or may interfere significantly with the subject's participation in the study.