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Trial registered on ANZCTR


Registration number
ACTRN12610001093077
Ethics application status
Approved
Date submitted
10/12/2010
Date registered
13/12/2010
Date last updated
21/11/2011
Type of registration
Prospectively registered

Titles & IDs
Public title
Comparison of THVD-201 with Tolterodine and Placebo for Overactive Bladder Symptoms
Scientific title
Comparison of THVD-201, a Combination of Tolterodine and a Muscarinic Agonist vs. Tolterodine Alone vs. Placebo to measure the tolerability in Subjects with Overactive Bladder (OAB) Symptoms
(Protocol No.: THVD-201-002)
Secondary ID [1] 253265 0
THVD -201-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Symptoms of overactive bladder. 258796 0
Condition category
Condition code
Renal and Urogenital 258947 258947 0 0
Other renal and urogenital disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 257729 0
Treatment: Drugs
Comparator / control treatment
In the double blind phase the comparator is Tolterodine 2mg twice daily verses the study drug verses placebo.

In the extension phase the comparator is 4mg Tolterodine (long acting) verses 3mg THVD-201 (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.
Control group
Active

Outcomes
Primary outcome [1] 259799 0
Determine the tolerability of the combination of tolterodine and pilocarpine (THVD-201) in OAB subjects.
Timepoint [1] 259799 0
A subject diary will be completed documenting the average daily number of micturitions; the average daily number of incontinence episodes and the average daily VAS scores of dry mouth at baseline, Week 4, Week 8 and Week 12 of the double blind period and week 6 and week 12 in the open label extension period.
Secondary outcome [1] 268599 0
Determine the effect of THVD 201 vs tolterodine alone vs. placebo on the symptoms of overactive bladder in subjects who have some degree of dry mouth on toterodine monotherapy.
Timepoint [1] 268599 0
A subject diary will be completed documenting the average daily number of micturitions; the average daily number of incontinence episodes and the average daily VAS scores of dry mouth at baseline, Week 4, Week 8 and Week 12 of the double blind period and week 6 and week 12 in the open label extension period.

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
75 Years
Sex
Females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation involves contacting the holder of the allocation schedule who is "off-site" .
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Three treatment triple crossover
Phase
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
15/01/2011
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
120
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 3082 0
New Zealand
State/province [1] 3082 0
Country [2] 3083 0
Korea, Republic Of
State/province [2] 3083 0

Funding & Sponsors
Funding source category [1] 258190 0
Self funded/Unfunded
Name [1] 258190 0
TheraVida, Inc.
Country [1] 258190 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
TheraVida, Inc
Address
400S, ElCamino Real Suite 1200
San Mateo, California 94402
Country
United States of America
Secondary sponsor category [1] 257365 0
Commercial sector/Industry
Name [1] 257365 0
Novotech (Australia) Pty Ltd
Address [1] 257365 0
Level 3 19 Harris Street
Pyrmont, NSW 2009
Country [1] 257365 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 260181 0
Flinders Clinical Research Ethics Committee
Ethics committee address [1] 260181 0
Ethics committee country [1] 260181 0
Australia
Date submitted for ethics approval [1] 260181 0
22/10/2010
Approval date [1] 260181 0
20/11/2010
Ethics approval number [1] 260181 0
1/10/0428

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 32004 0
Address 32004 0
Country 32004 0
Phone 32004 0
Fax 32004 0
Email 32004 0
Contact person for public queries
Name 15251 0
Andreas Kroemer
Address 15251 0
Novotech (Australia) Pty Limited
Level 3, 19 Harris Street
Pyrmont, NSW 2009
Country 15251 0
Australia
Phone 15251 0
+61 2 8569 1400
Fax 15251 0
+61 2 8569 1498
Email 15251 0
[email protected]
Contact person for scientific queries
Name 6179 0
Mehdi Paborji
Address 6179 0
TheraVida, Inc.
400 S. El Camino Real Suite 1200
San Mateo, California 94402
Country 6179 0
United States of America
Phone 6179 0
+1 650903 2225
Fax 6179 0
Email 6179 0
[email protected]

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What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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