Neurogenic detrusor overactivity in patients with spinal cord injury
Conditions
Interventions
Trade Name: Detrusitol
Product Name: Detrol
Pharmaceutical Form: Tablet
INN or Proposed INN: Tolterodine tartrate
Other descriptive name: Detrol
Concentration unit: mg milligram(s)
Concentration type:
Sponsors
Pfizer
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patients aged 18-65 years, with urodynamic evidence of neurogenic detrusor overactivity (phasic or uninhibited detrusor contraction) arising as a consequence of spinal cord injury or pathology. 2. Evidence of phasic uninhibited detrusor contraction on fast fill cystometry at the beginning of Period 1. 3. Demonstrable provoked uninhibited detrusor contraction following force fill at the beginning of Period 1. 4. Subjects capable of understanding and giving written informed consent after full discussion concerning the nature of the research. 5. Female subjects must have a negative pregnancy test. 6. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the trial. 7. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Subjects who do not provide written consent to participate in the study 2. Subjects who have a medical condition that would impair their ability to participate reliably in the study. 3. Subjects who are pregnant or lactating. 4. Subjects with a recent history of autonomic dysreflexia (AD) or AD which is associated with urodynamic investigations 5. Treatment within 7 days (or 5x plasma half-life, if longer) preceding the study, or expected to start treatment during the study with: a. anticholinergic drugs b. drugs with significant anticholinergic effects such as tricyclic antidepressants c. drug treatment for overactive bladder. Estrogen treatment initiated more than 2 months prior to randomization is allowed. 6. Use of inhibitors of the metabolism of tolterodine: a. Potent cytochrome P450 3A4 inhibitors such as macrolide antibiotics (erythromycin and clarithromycin), antifungal agents (ketoconazole and itraconazole), cimetidine, MAOIs, and protease inhibitors. Drugs and/or herbal preparations capable of inducing hepatic enzyme metabolism (e.g., barbiturates, rifampin, carbamazepine, phenytoin, primidone or St. John’s Wort). These must be discontinued within 30 days (or 5 half-lives of inducing/inhibiting agent, whichever is longer) of enrollment in the study. b. Fluoxetine must be discontinued at least 5 weeks before first dose of study medication. c. Have consumed grapefruit or grapefruit-containing products within 7 days prior to the first dose of study medication 7. Subject on a variable dosage of any drug with anticholinergic side effects, or subject expected to start such treatment during the study. 8. Have a known history of hypersensitivity, allergy, severe adverse drug reaction or intolerance to anticholinergic drugs, including tolterodine. 9. Have contraindications to the use of anticholinergic drugs, e.g., uncontrolled narrow-angle glaucoma, urinary retention, significant urinary outflow obstruction (not including sphincter dyssynergia), gastric retention. Significant urinary outflow obstruction is defined as being a urinary pressure/flow study in the obstructed range of the Abrams/Griffiths nomogram or a maximum urinary flow rate 1+ on dipstick test unless fully investigated prior to randomization to exclude significant urological disease). 13. Have a clinically significant ECG abnormality at screening, except those with non-clinically significant sinus tachycardia or sinus bradycardia. Screening 12-lead ECG demonstrating QTC>430 msec (males) and QTc>450 msec (females). 14. History or evidence of major hematological, renal or hepatic abnormalities (subjects with clinically significant hepatic (Child Pugh C classification) or significant renal impairment serum creatinine 3xULN).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To compare a single oral dose of tolterodine (2 mg) with placebo on the reduction of uninhibited detrusor contractions induced by provocation testing.;Secondary Objective: 1. To evaluate the safety of tolterodine administration in patients with spinal cord injury and pathology. 2. To explore relationships of the efficacy variables with serum concentrations of tolterodine and/or its active metabolite, DD 01.;Primary end point(s): 1. Area under the pressure curve of the provoked detrusor contraction | — |
Countries
Iceland
Outcome results
None listed