| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Neurogenic overactive bladder disaese in patients with multiple sclerosis | |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.1 | | E.1.2 | Level | LLT | | E.1.2 | Classification code | 10059617 | | E.1.2 | Term | Overactive bladder | |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial | | to evaluate accidental evidence (casuistic findings) in more detail and to show efficacy of darifenacin in the treatment of multiple sclerosis patients with neurogenic overactive bladder | |
| E.2.2 | Secondary objectives of the trial | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria | At Screening
• Male and female patients aged 18 years with the diagnosis of multiple sclerosis
• Neurogenic detrusor overactivity without DSD as confirmed by the baseline
urodynamics during this study.
• Symptoms of OAB as defined by
- micturitions/day 8 and more, respectively
- urgency episodes per day 1 and more, respectively
• Patients capable of understanding the given information and having signed
Patient Informed Consent Form after full discussion of the research nature of the
treatment and its risks and benefits
• Patients capable of independently completing the bladder diary
• Patients capable of independent toileting
• Patients able to swallow the study medication in accordance to the protocol
• Body Mass Index equal to or greater than 18.5 kg/m2 and less than 35.0 kg/m2
| |
| E.4 | Principal exclusion criteria | At Screening
• Treatment with drugs known to affect mainly the urinary bladder function
• Participation in a bladder-training program or any electro stimulation therapy
within the 2 weeks prior to Visit 1
• Low compliance bladder (Compliance < 20 mL/cm H2O),
• Indwelling catheter or intermittent self-catheterization
• Patients with post-void residual (PVR) urinary volume >200 mL at Baseline
• Urinary retention or clinically significant bladder outlet obstruction
• Low pressure reflux
• Clinically predominant and bothersome stress urinary incontinence
• Neurological diseases other than multiple sclerosis affecting
• Any clinically significant congenital or acquired disorder of the urogenital tract
• Any urogenital surgery within 12 months prior to Visit 1
• Any history of pelvic radiation therapy
• Females with urinary symptoms secondary to cystocele or pelvic organ prolapse
greater than stage 2
• Chronic persistent local pathology that in the opinion of the investigator may lead
to urinary symptoms, such as one of the genito-urinary pain syndromes, interstitial
cystitis; fecal impaction and severe constipation
• Three or more urinary tract infections per year over the preceding 12 months
• Unexplained haematuria
• Any history of carcinoma of the urogenital tract.
• Concomitant diseases in which the use of darifenacin is contraindicated
• Significant medical problems, including but not limited to the following: uncontrolled
severe hypertension, uncontrolled severe heart failure, myocardial infarction in the
last 6 months, uncontrolled thyroid disease (unless the patient is on controlled
thyroid hormone for at least 3 months), or evidence (from direct questioning
and/or physical examination) of any clinically significant systemic disease that in
the investigator’s opinion makes the patient unfit to participate in the study
• Evidence, based on laboratory tests done at Visit 1, of:
Hepatic disorder (ALT or AST > 1.5 x upper normal limit [ULN]; bilirubin > 1.2 x ULN
unless secondary to Gilbert’s disease in the opinion of the investigator)
Blood coagulation disorder (e.g. haemophilia)
Anemia (haemoglobin > 2 g/dL [20 g/L] below the lower limit of normal)
• Currently receiving or have received the following medications within two weeks
prior to Visit 2 and at any time during the study:
- Cholinergic agonists and cholinesterase inhibitors e.g. bethanecol, donepezil,
rivastigmine
- Potent inhibitors of cytochrome CYP3A4 and potent P-glycoprotein inhibitors such
as cyclosporine and verapamil.
• Treatment with an unstable dose of any drug having the potential for significant
anticholinergic side effects in the last 4 weeks prior to Visit 1
• Women of child-bearing potential defined as all women physiologically capable of
becoming pregnant, unless they are using one or more of the following acceptable
methods of contraception: surgical sterilization (e.g. bilateral tubal ligation,
vasectomy), hormonal contraception (implantable, patch, oral), and double-barrier
methods (any double combination of: hormonal IUD, male or female condom with
spermicidal gel, diaphragm, sponge, cervical cap). Acceptable methods of
contraception may also include total abstinence at the discretion of the
investigator. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-
ovulation methods) and withdrawal are not acceptable methods of contraception.
Reliable contraception should be maintained throughout the study
• Pregnant or nursing (lactating) women
• Any investigational drug during the 30 days or five times the plasma half-life (if
known), whichever is longer, preceding Visit 1 and at any time during the study
• History of hypersensitivity to darifenacin or to drugs with similar chemical structures
• Abusers of alcohol and/or other drugs which in the judgment of the investigator
would interfere with participation in the study
Concomitant Medication
• Treatment with drugs known to affect mainly the urinary bladder function
• Treatment with an unstable dose of any drug having the potential for significant
anticholinergic side effects in the last 4 weeks prior to Visit 1
• Cholinergic agonists and cholinesterase inhibitors e.g. bethanecol, donepezil,
rivastigmine.
• Potent inhibitors of cytochrome CYP3A4 and potent P-glycoprotein inhibitors
• Any investigational drug (including placebo) within 30 days of Visit 1
| |
| E.5 End points |
| E.5.1 | Primary end point(s) | | • volume at first detrusor contraction | |
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 | The trial involves single site in the Member State concerned | No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 14 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 | Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
