| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| 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 compare the effect of three different doses of ONO-8539 with placebo in the mean change of the number of micturitions per 24h from baseline to 12 weeks |
|
| E.2.2 | Secondary objectives of the trial |
•To compare the effect of three different doses of ONO-8539 and Tolterodine versus placebo on the number of micturitions per 24h, frequency of urinary urgency incontinence episodes per 24h, number of urgency episodes per 24h, severity of urgency, mean volume voided per micturition, number of micturitions during daytime, number of micturitions during sleeping time and number of continent days (among incontinent patients), during the course of treatment;
•To compare the effect of three different doses of ONO-8539 and Tolterodine versus placebo on subjective scales of treatment effect and Quality of Life, during the course of treatment;
•To compare the safety and tolerability of three different doses of ONO-8539 and Tolterodine versus placebo
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1.Male and female patients aged between 18 and 80 years old inclusive
2.Patients have overactive bladder as defined by the standardization subcommittee of the International Continence Society (ICS) as urgency, with or without urgency incontinence, usually with frequency and nocturia, in the absence of local pathological or metabolic factors for >= 6 months.
3.During the placebo run-in, patients will have demonstrated:
a. Urinary frequency defined as at least 8 micturitions per 24 hrs on each diary day of the 3-day diary period and
b. Urinary urgency defined as at least 1 episode per 24hrs on each diary day and at least 6 episodes per 72 hrs of the 3-day diary period. ‘Urgency’ is defined as the event of grade 3 (Severe urgency) or grade 4 (urge incontinence) using the Patient Perception of Intensity of Urgency Scales (PPIUS); or
c. Urinary urgency incontinence defined as at least 1 urgency incontinence episode (involuntary loss of urine associated with urgency) per 24 hrs on each diary day of the 3-day diary period. ‘Urinary urgency incontinence’ is defined as the event of grade 4 (urge incontinence) using the PPIUS.
4. If male, patients must agree for themselves or their partner to use an adequate method of contraception from Visit 1 until 1 month after their follow up study visit.
5. If female, the patient must be post-menopausal, sterile or practice adequate contraception whenever sexually active for a period of at least 28 days before Visit 1 and agree to use a double barrier method to prevent pregnancy from Visit 1 until at least 1 month after the follow up visit.
6. The patient is able to read and understand the Patient Information Sheet and study procedures
7. The patient is able and willing to give written informed consent.
8. The patient must be at least 80% compliant with the drug dosing during the 2 weeks of placebo-run-in phase
9. The patient is capable of independently completing the bladder diary. |
|
| E.4 | Principal exclusion criteria |
1. The patient has the following pathological or metabolic conditions that may be the responsible for urgency or incontinence:
a. Stress incontinence or mixed incontinence where stress incontinence is the predominant component
b. Require in dwelling (intermittent) catheter
c. Genitourinary conditions other than overactive bladder that may cause urinary incontinence or affect urinary frequency
d. History of interstitial cystitis, pelvic or perineal pain, or haematuria that has not been evaluated to rule out malignant diseases within 12 months of Visit 1
e. Undergone electrostimulation therapy or bladder training within 14 days of the screening visit or are planning to do so during the study period
f. Undergone prostate surgery within the last 12 months of Visit 1 or had any type of operative procedure for urinary incontinence, or anterior colporrhaphy within the last 12 months of Visit 1
g. Past history of, or current neurological disease or injury that could affect the lower urinary tract function or its nerve supply
h. Requirement for ambulatory assistance or incapable of independent toileting
i. Difficulty emptying the bladder, or history of obstructive uropathy or urinary retention
j. Residual urine volume of >200 mL
k. Bladder outlet obstruction
l. Polyuria defined as total voided urine volume of >3000 ml on at least one day (24 h) (within the 3-day diary period)
m. Clinically suspected low bladder compliance or patient has an urodynamics evidence of low bladder compliance (<20mL/cm H20) within 6 months of Visit 1.
2. The patient has any medical condition contraindicating the use of antimuscarinic medication
3. The patient has a history of malignancy within the past 5 years of the screening visit. However, patients who have been adequately treated within the past 5 years for their basal cell or squamous carcinoma of the skin are not excluded
4. The patient has a medical history of :
a. Liver disease
b. Acromegaly or treatment with growth hormone or similar drugs
c. Major gastrointestinal surgery
5. The patient has one of the following cardiovascular conditions:
a. Angina. However, patients who are well controlled on their regular medication with no clinical symptoms or those patients who require occasional nitrates, such as nitroglycerin on exertion, are not excluded.
b. Congestive heart failure (CHF) with symptoms that occur at rest or minimal activity
c. History of myocardial infarction within the past 6 months of sceening visit
d. Coronary angioplasty or coronary artery bypass graft (CABG) within the past 6 months of screening visit
e. Abnormal blood pressure.
Note: subjects with medically controlled blood pressure (stable for at least three months) may participate
f. QTc interval (corrected by the Frederica formula: i.e. QTcF) is > 450 msec for male patients and > 470msec for female patients on 12-lead ECG prior to randomisation visit
6. The patient has a history of and/or current alcoholism or drug abuse (within the past 2 years)
7. The patient has a history or presence of other significant diseases, which might compromise the patient’s safety or the evaluation of the study results
8. The patient has acute gastrointestinal symptoms, except constipation, within 14 days of Visit 1
9. The patient has undergone botulinum toxin detrusor injection and vanilloids drugs within 12 months of Visit 1
10. The patient has taken any prohibited concomitant medication (as per study protocol) within the defined period prior to screening visit or throughout the study. Or the patient has changed the dose of a permitted medication required to be at a stable dose (as per study protocol) within the defined period prior to screening visit or throughout the study
11. The patient has received treatment with a drug with a known and frequent toxicity to a major organ system within the past 3 months of the screening visit
12. The patient has participated in a clinical trial involving IMP within 3 months or 5 half lives, whichever is the longer, prior to screening visit
13. The patient has donated one unit (400 mL) or more of blood, has had significant blood loss equaling at least one unit of blood within the past 12 weeks or a blood transfusion within the past 8 weeks of screening visit
14. The patient has a clinically significant laboratory abnormality, confirmed by repeat measurements that may interfere with the assessment of safety and/or efficacy of the study drug.
15. The patient has a positive result at screening for hepatitis, alcohol and/or drug of abuse
16. The patient is pregnant or breast feeding or is planning to become pregnant during the course of the study
17. The patient has inadequate vision or manual dexterity to use the patient diary
18. The patient is unlikely to comply with the clinical study protocol, communicate reliably with the investigator or is unsuitable for any reason
19. The patient has previously received ONO-8539 |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The mean change from baseline in the number of micturitions per 24 hrs at 12 weeks. |
|
| 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 | No |
| 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 | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| 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) | Yes |
| E.8.2.2 | Placebo | Yes |
| 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 | 7 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 64 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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 | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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