None listed
Conditions
Brief summary
This study will assess the safety of THVD-201 and how well it is tolerated. It will investigate the effects on your bladder symptoms of THVD-201 compared to tolterodine alone, and placebo. The study will also investigate whether the combination treatment reduces the unwanted side effects associated with taking tolterodine alone.
Interventions
THVD-201, a Combination of Tolterodine and a Muscarinic Agonist
Lead in period = 6 weeks duration: Toterodine 2 mg twice daily.
12 week double blind period where patients receive either of the following: THVD-201 twice daily; Tolterodine 2 mg twice daily; or Placebo twice daily. There are three periods of four weeks duration. Patients either take one of the three doses for 4 weeks and then cross over to either of the other two treatments at four weekly intervals.
Extension period (12 weeks dura
THVD-201, a Combination of Tolterodine and a Muscarinic Agonist Lead in period = 6 weeks duration: Toterodine 2 mg twice daily. 12 week double blind period where patients receive either of the following: THVD-201 twice daily; Tolterodine 2 mg twice daily; or Placebo twice daily. There are three periods of four weeks duration. Patients either take one of the three doses for 4 weeks and then cross over to either of the other two treatments at four weekly intervals. Extension period (12 weeks duration): Either, 4mg Tolterodine long acting once daily; or 3 mg THVD-201 twice daily.
Sponsors
TheraVida, Inc
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used)
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Females 18-75 years 2. Subject has a history of OAB (pure urge or mixed urinary incontinence with predominant urge incontinence) for equal to 6 months. Subject who is currently taking IR tolterodine (2 mg bid) for at least 5 weeks and who is considered to be a responder to this therapy (see below for number of micturitions and incontinence episodes per day). Depending on the anti-muscarinic treatment at screening, all subjects will need to have completed at least 1 to 5 weeks of 2 mg bid IR tolterodine prior to starting the baseline diary o Subjects may be converted from extended release tolterodine (at least 4 weeks of 4 mg QD) to tolterodine IR (2 mg bid) for at least 1 week prior to the start of the baseline diary. Subjects may be converted from a non-tolterodine OAB treatment to IR tolterodine (2 mg bid) for at least 5 weeks prior to initiation of the baseline diary. Subjects taking IR tolterodine 1 mg bid need to be treated with 2 mg bid tolterodine for at least 5 weeks prior to starting the baseline diary. 3. Subject meets the following criteria, based on the voiding and dry mouth VAS diary Urinary frequency less than 13 micturitions per day, as recorded in the subject diary with or without symptoms of urgency (i.e., sudden desire to micturate) Less than 4 incontinence episodes over a 3-day period VAS equal to or greater than 35 mm on a 100 mm scale for dry mouth 4. Subject is able and willing to correctly and independently complete the subject voiding diaries and VAS assessments for 3 consecutive days during the week before Visits 2, 3, 4 and 5. 5. Subject is able to use toilet without assistance 6. Subject of childbearing potential must have a negative pregnancy test prior to enrollment and should not be breast-feeding. All pre-menopausal subjects must be using a highly effective method of birth control during the study and for at least one month following the last dose of study medication. (Menopause defined as at least one year without menses.) A highly effective method of birth control is defined as one that results in a low failure rate (i.e., less than 1 percent per year) when used consistently and correctly, such as contraceptive implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence, or a vasectomized partner. 7. Subject is willing and able to consent to participate by signing an informed consent form following an explanation of the nature and purpose of this study.
Exclusion criteria
1. Subjects with 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 2. Subjects with history of neurogenic bladder 3. Subjects with clinically significant renal disease (estimated creatinine clearance defined by Cockcroft and Gault formula less than 30 ml per min) 4. Subject has elevated serum transaminases (ALT or AST greater than 1.3 times the upper limit of normal for the laboratory conducting the test) and no history of hepatic dysfunction 5. Subjects with uninvestigated haematuria 6. Subjects who develop acute urinary tract infections (UTI) during the baseline period following a negative urinalysis at screening visit, or subjects with recurrent UTI defined as receiving treatment for symptomatic UTI more than 2 times in the past year 7. Subjects with indwelling catheter or requiring intermittent catheterization 8. Subjects with bladder or lower urinary tract surgeries performed within the past 6 months, or those who had surgeries leading to complications such as fistula 9. Subjects diagnosed with bladder cancer, interstitial cystitis, or painful bladder syndrome within the past 6 months 10. Subjects taking diuretics or oestrogen therapy that was not part of a long-term stable program of at least 6 months 11. Subjects starting bladder retraining per bladder drill programs 12. Subjects who were anticipated to begin or change other bladder therapies (non-medicinal) such as biofeedback or kegels, during the course of the study 13. Subjects with malignancy within the past 6 months or prior pelvic malignancies requiring radiation therapy or whose surgery had led to complications such as fistulas, etc 14. Subjects with a history or presence of tachyarrhythmias or cardiac disease that in the opinion of the investigator might confound the results of the study or pose additional risk to the subject. Subjects with QTc greater than 470 msec should not be enrolled. 15. Subjects taking any medications that may interfere with lower urinary tract function or dry mouth, or affect the subject's suitability and r or effective participation in the trial (i.e., drugs that may have anti-muscarinic or anti-histaminic activity or induce or inhibit cytochrome P450 2D6 enzyme). 16. Subjects with the history or current untreated narrow angle glaucoma 17. Subjects with the history or current myasthenia gravis 18. Subjects with known or suspected biliary tract disease, active nephrolithiasis, cognitive or psychiatric disturbances, gastric retention, urinary retention, uncontrolled ulcerative colitis, toxic megacolon or other known medical condition, which in the opinion of the investigator would compromise the subject’s ability to participate in this trial (e.g., progressive malignant disease, HIV infection, major surgery within last 4 weeks). 19. Subjects with a history of chronic alcohol or drug abuse within last 6 months 20. Subjects with post void residual urine volume > 100 mL (non-invasive bladder scan) 21. Subject with known polyuria (3 L per day) 22. Subjects who drink grapefruit juice daily 23. Subjects with hypersensitivity to the components of the tolterodine and THVD-201 formulation 24. Subjects participating in another clinical trial or receiving a non-approved drug less than 30 days prior to the screening visit.
Outcome results
None listed