Mixed Urinary Incontinence
Conditions
Interventions
Product Name: Litoxetine
Product Code: Litoxetine
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: LITOXETINE
CAS Number: 86811-0
Sponsors
IXALTIS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Willing to provide written informed consent 2. Have symptoms of urinary incontinence for at least 3 consecutive months 3. Have at least 7 incontinence episodes per week in the diary entries for the Screening Period of which at least 3 episodes per week are defined as stress urinary incontinence. The PPIUS will be completed when subjects report an event in the electronic diary (e-diary) 4. Have an Investigator-confirmed urinary leakage from the urethral meatus synchronous with effort, eg, coughing or straining as an objective evidence of the stress component of incontinence. The urge incontinence component must be confirmed by the subject diaries during the Screening Period, using the PPIUS 5. Subject is ambulatory and able to use the toilet independently 6. If subjects use pelvic floor exercises, subjects must have been on a stable exercise and activity regime for at least 3 months prior to Screening and that regime must remain stable during the treatment period 7. Subject has a body mass index = 19 kg/m2 but =65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: 1. History of anti-incontinence surgery in past 12 months 2. Use of Botox for urge urinary incontinence in the past 12 months 3. Grade III/IV pelvic organ prolapse; defined per clinical practice 4. History of interstitial cystitis or bladder-related pain 5. History of pelvic prolapse repair (cystocele or rectocele) or urethral diverticulectomy within 12 months of Screening 6. Subjects with concurrent (at Screening), recent (within 30 days), chronic, or recurrent (> 4 per year) urinary tract infections (positive dipstick for urinary tract infection and abnormal microscopic evaluation, signs and symptoms) or unevaluated microhematuria 7. History of diagnosed gastrointestinal obstructive disorders 8. Chronic severe constipation 9. History of radiation cystitis or history of pelvic irradiation 10. Electrostimulation, biofeedback, or bladder training therapy (behavioural therapy), during the previous month prior to Screening, or the intention to initiate such therapies during the study. Pessaries and implants are also excluded. 11. Postvoid residual (PVR) urine volume > 150 mL 12. Diagnosis of dementia 13. Diagnosis of epilepsy 14. Diagnosis of acute narrow-angle glaucoma 15. History of mania or diagnosis of bipolar disorder, and/or seizures 16. Subjects with uncontrolled hypertension 17. Documented history of myocardial infarction, unstable angina, and/or has undergone coronary artery bypass surgery and/or percutaneous transluminal coronary angioplasty in the past year 18. Congestive heart failure (New York Heart Association Class III or IV heart failure 19. Any concurrent condition or any clinically significant abnormality on the Screening physical examination, laboratory tests, electrocardiogram (ECG; including ischemic heart disease), Hepatitis B or C, which, in the opinion of the Investigator, may affect the interpretation of efficacy or safety data, or which otherwise contraindicates participation in a clinical study with litoxetine: a. Hypersensitivity to litoxetine or any of its ingredients b. History of clinically significant drug hypersensitivity c. Subjects with current (within 2 years) urogenital neoplasms or malignancies including bladder, uterine or cervical cancer d. Subjects with neuropathology that could affect the lower urinary tract or nerve supply, including but not limited to multiple sclerosis, stroke, Parkinsonism, or spinal cord injury e. Subjects with diabetes insipidus f. Clinically significant or unstable, endocrine, hepatic, renal, immunologic, or lung disease (ie, active chronic obstructive pulmonary disease, active seasonal allergic rhinitis), or malignancy other than nonmelanomatous skin cancer 20. Severe renal impairment (estimated glomerular filtration rate < 30 mL/min/1.73m2) 21. Severe hepatic impairment (Child-Pugh B or greater) 22. Subjects who are on current treatment for depression 23. Use of the following medications: nonselective irreversible monoamineoxidase inhibitors, cytochrome P450 (CYP)1A2 inhibitors (such as fluvoxamine, ciprofloxacin, or
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy of 3 doses of litoxetine (10 mg, 20 mg, 40 mg) versus placebo administered orally twice daily (BID) for 12 weeks in female subjects with a diagnosis of MUI;Secondary Objective: To evaluate the safety and tolerability of 3 doses of litoxetine (10 mg, 20 mg, 40 mg BID) compared to placebo in female subjects with a diagnosis of MUI.;Primary end point(s): Percentage change from the end of the Placebo Run-in Period to Week 12 in the weekly average of number of incontinence episodes/24 hours (Number of incontinence episodes/24 hours will be computed as Total Number of incontinence episodes recorded over the 7 days/7);Timepoint(s) of evaluation of this end point: Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Absolute change from the end of the Placebo Run-in Period to Week 12 in the number of incontinence episodes/24 hours • Dose response of study drug on the primary endpoint • Proportion of subjects who become continent at Week 4, Week 8, and Week 12 • Change in the Kings Health Questionnaire total score and 3 sub-domain scores at Week 12 • Change from end of the Placebo Run-in Period in subject’s rating of improvement using the PGI-I at Week 12 • Change from end of the Placebo Run-in Period in PPBC score at Weeks 4, 8, and 12 • Percentage change from end of the Placebo Run-in Period to Week 4 and Week 8 in incontinence episodes/24 hours • Percentage change from end of the Placebo Run-in Period to Week 4, Week 8, and Week 12 in: - Weekly average of number of stress incontinence episodes/24 hours - Weekly average of number of urge incontinence episodes/24 hours - Weekly average of number of micturitions/24 hours - Weekly average of number of nocturia episodes/24 hours • Proportion of subjects with at least a 50% reduction from end of the Placebo Run-in Period to Week 4, Week 8, and Week 12 in weekly average incontinence episodes/24 hours • Proportion of subjects with at least a 50% reduction from end of the Placebo Run-in Period to Week 12 in weekly average stress incontinence episodes/24 hours • Proportion of subjects with at least a 50% reduction from end of the Placebo Run-in Period to Week 12 in weekly average urge incontinence episodes/24 hours • Proportion of subjects with < 8 micturitions/24 hours at Week 12 • Proportion of subjects with no urgency at Week 12 • Proportion of subjects reporting nocturia at end of the Placebo Run-in Period with no nocturia at Week 4, Week | — |
Countries
Canada, France, Georgia, Poland, Ukraine, United Kingdom
Contacts
Public ContactElisabeth Svanberg
IXALTIS
Outcome results
None listed