| 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 | 13.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10059617 |
| E.1.2 | Term | Overactive bladder |
| E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
|
| 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 the efficacy of four combinations of solifenacin succinate (2.5 mg or 5 mg) plus mirabegron (25 mg
or 50 mg) vs. solifenacin succinate 5 mg monotherapy |
|
| E.2.2 | Secondary objectives of the trial |
To investigate the dose-response surface of combinations of solifenacin succinate (0 mg, 2.5 mg, 5 mg and 10
mg) and mirabegron (0 mg, 25 mg and 50 mg) doses;
To compare the safety and tolerability of six combinations of solifenacin succinate and mirabegron vs. solifenacin
succinate monotherapy, mirabegron monotherapy, and placebo;
To investigate the population pharmacokinetics (PK) and PK/pharmacodynamic (PD) relationship of
six combinations of solifenacin succinate and mirabegron and the mirabegron and solifenacin succinate
monotherapies. |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
FARMACOCINETICA/FARMACODINAMICA: Versione:1 Data:2010/12/06 Titolo:Studio dose-ranging, multicentrico, randomizzato, in doppio cieco, fattoriale, a gruppi paralleli, con controllo attivo e verso placebo per valutare l’efficacia, la sicurezza e la tollerabilita` di sei combinazioni di dose di solifenacina succinato e mirabegron rispetto alle monoterapie con mirabegron e solifenacina succinato nel trattamento della vescica iperattiva Obiettivi:Lo studio di farmacocinetica e` parte di questo protocollo.Ai soggetti sara` chiesto di partecipare ad un addizionale sottostudio di farmacocinetica (PK) che comportera` la valutazione delprofilo PK aggiuntivo, in occasione di una visita. Si prevede che a questo studio parteciperanno 120 soggetti (10 per braccio di trattamento). Nota:quando 1200 soggetti saranno randomizzati nel protocollo e se meno di 120 soggetti saranno arruolati nel sottostudio , potrebbe essere presa la decisione di arruolare soggetti solo nel sottostudio o di chiudere la partecipazione al sottostudio.
|
|
| E.3 | Principal inclusion criteria |
Inclusion Criteria at Visit 1/Screening
1.Subject is male or female and at least 18 years of age;
2.Subject has a Body Mass Index (BMI) of between 18 and 35 kg/m2 and a total body weight between 50 and 95
kg;
3.Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent
and privacy language as per national regulations has been obtained from the subject prior to any study-related
procedures (including discontinuation of prohibited medication, if applicable);
4. Subject is willing and able to complete the micturition diary and questionnaires correctly and is willing and
able to measure his/her vital signs at home at stipulated time points, using the device provided by the study
personnel, and to adequately record the readings
5. Subject has symptoms of OAB (urinary frequency, urgency and/or urgency incontinence) for at least 3 months
Inclusion Criteria at Visit 2/Placebo Run-In
6. Subject must still fulfill all inclusion criteria and none of the exclusion criteria for Visit 1;
7. Subject is willing and able to complete the micturition diary correctly and is willing and able to measure
his/her vital signs at home at stipulated time points, using the device provided by the study personnel, and to
adequately record the readings
Inclusion Criteria at Visit 3/Baseline
8. Subject continues to meet all inclusion criteria and none of the exclusion criteria for Visit 1;
9. Subject has experienced frequency of micturition on average ≥ 8 times per 24-hour period during the 3-day
micturition diary period (incontinence episode should not be counted as a micturition);
10. Subject must experience at least 1 episode of urgency (grade 3 or 4) per 24-hour period (with or without
urgency incontinence) during the 3 day micturition diary period. |
|
| E.4 | Principal exclusion criteria |
Exclusion Criteria at Visit 1/Screening
1. Subject is breastfeeding, pregnant or intends to become pregnant during the study. The pregnancy test (β-HCG
in serum) at Screening must be negative in women of childbearing potential;
2. Female subjects of childbearing potential and not using a highly effective method of birth control during the
study and for 30 days after final study drug administration.
3. Male subjects (unless surgically sterile) with female spouses/partners who are of childbearing potential, and not
using a barrier method of contraception during the study and for 30 days after final study drug administration. In
addition, female spouses/partners of male subjects and who are of childbearing potential should also use a highly
effective method of birth control during the study and for 30 days after final study drug administration. Highly
effective methods of birth control are defined as those, alone or in combination, that result in a low failure rate
(i.e. less than 1% per year) when used consistently and correctly.
4. In the opinion of the Investigator, the subject has clinically significant bladder outflow obstruction at risk of
urinary retention;
5. Subject has significant PVR volume (> 150 mL);
6. Subject has significant stress incontinence or mixed stress/urgency incontinence where stress is the
predominant factor as determined by the Investigator (for female subjects confirmed by the cough provocation
test
7. Subject has a neurological cause for detrusor overactivity;
8. Subject has an indwelling catheter or practices intermittent self-catheterization;
9. Subject has diabetic neuropathy;
10. Subject has chronic inflammation such as interstitial cystitis, bladder stones, previous pelvic radiation therapy
or previous or current malignant disease of the pelvic organs;
11. Subject has had previous lower urinary tract or pelvic floor surgery (except cystoscopy);
12. Subject has had intravesical treatment in the past 12 months with e.g., botulinum toxin, resiniferatoxin,
capsaicin;
13. Subject has uncontrolled narrow angle glaucoma, urinary or gastric retention, severe ulcerative colitis
or Crohn’s Disease, toxic megacolon, myasthenia gravis or any other condition which makes the use of
anticholinergics contraindicated;
14. Subject has clinically significant cardiovascular or cerebrovascular diseases within 6 months prior to
Screening, such as myocardial infarction, uncontrolled angina, significant ventricular arrhythmias, heart failure
and stroke;
15. Subject is receiving current non-drug treatment including electro-stimulation therapy (with the exception of a
bladder training program or pelvic floor exercises which started more than 30 days prior to Screening);
16. Subject is using medications intended to treat OAB or prohibited medications. Subject is excluded if using
restricted medications under conditions different to those specified in the “Concomitant Medication” section;
17. Subject has known or suspected hypersensitivity to solifenacin succinate, mirabegron or any of their
excipients;
18. Subject has any significant neurological disease or defect affecting bladder function (e.g., neurogenic bladder,
systemic or central neurological disease such as multiple sclerosis [MS] and Parkinson’s disease);
19. Subject has severe hypertension which is defined as a sitting average systolic blood pressure ≥ 180 mmHg
and/or an average diastolic blood pressure ≥ 110 mmHg; |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change from baseline in mean volume voided per micturition after 12 weeks of treatment |
|
| 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 | Yes |
| 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 | No |
| 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) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| - same IMP used at different dosage |
|
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 106 |
| 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 | 9 |
| 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 | 9 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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