E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
A condition that causes sudden, uncontrolled need or urge to urinate and in some cases may lead to urinary leakage |
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E.1.1.2 | Therapeutic area | Diseases [C] - Symptoms and general pathology [C23] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10059617 |
E.1.2 | Term | Overactive bladder |
E.1.2 | System Organ Class | 100000004857 |
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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 BAY1817080 125 mg twice a day (BID) in comparison to placebo in the treatment of OAB with urgency urinary incontinence (UUI) over a 12-week treatment period |
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E.2.2 | Secondary objectives of the trial |
To further evaluate the efficacy of BAY1817080 125 mg BID in comparison to placebo in the treatment of OAB with urgency urinary incontinence (UUI) over a 12-week treatment period
To evaluate the safety and tolerability of BAY1817080 125 mg BID in comparison to placebo over a treatment period of up to 12-weeks |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria at screening:
1. Adults ≥ 18 years of age at the time of signing the informed consent
2. Have “wet” OAB symptoms (urgency, frequency and urinary incontinence) for ≥ 3 months prior to screening visit
3. Women of childbearing potential (WOCBP) must agree to use acceptable effective or highly effective contraceptive methods
4. Capable of giving signed informed consent
5. Willing and able to complete the electronic bladder diary and questionnaires
Inclusion criteria at baseline (to be checked at V3, prior to randomization):
6. Completion of all 3 days of 3-day electronic bladder diary during run-in phase
7. Compliance of ≥80% with intake of study intervention during run-in
8. Frequency of micturition on average ≥ 8 episodes/24 hours during the run-in phase according to 3-day electronic bladder diary
9. Frequency of urgency urinary incontinence on average ≥ 1 episode/24 hours during the run-in phase according to 3-day electronic bladder diary |
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E.4 | Principal exclusion criteria |
1. Polyuria known or based on the clinical evidence during the run-in phase recorded in the 3-day electronic bladder diary and the investigator´s clinical judgement
2. Significant stress incontinence or mixed stress/urgency incontinence
3. Post-void residual volume (PVR) > 150 mL at Visit 1 or at Visit 3
4. In need of catheterization (indwelling or intermittent)
5. Clinically significant urinary outflow obstruction
6. Previous pelvic radiation, or previous or current malignant disease of pelvic organs
7. Neurogenic bladder
8. Bladder pain syndrome/interstitial cystitis
9. Recurrent and/or symptomatic bladder stones
10. Current symptomatic or recent (within 30 days prior to Visit 1), or recurrent (2 or more infections within 6 months, or > 3 infections within 12 months) urinary tract infection
11. Unexplained macro- or micro-hematuria
12. Diabetes insipidus
13. Diabetes mellitus with inadequate glycemic control as indicated by HbA1C result of > 8% at screening
14. Clinically significant cardiovascular or cerebrovascular disease
15. Uncontrolled hypertension, despite treatment with antihypertensive(s), indicated by a sitting systolic blood pressure ≥ 180 mmHg and/or diastolic blood pressure ≥ 110 mmHg
16. Clinically significant abnormal electrocardiogram (ECG) at screening
17. Moderate-to-severe hepatic impairment defined as Child-Pugh Class B or C
18. Laboratory values outside the inclusion range (as specified in the laboratory manual and in the reports from the central laboratory) before start of study intervention, and considered clinically relevant
19. At screening:
- ALT above 2xULN OR
- AST above 2xULN OR
- total bilirubin greater than ULN OR
- AP above 2x ULN OR
- INR greater than ULN (unless on vitamin K antagonist treatment)
20. Severe renal impairment as defined by estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 calculated by Modification of Diet in Renal Disease (MDRD) formula
21. Any other diseases or conditions that according to the investigator can compromise the function of the body systems and could result in altered absorption, excessive accumulation, impaired metabolism, or altered excretion of the study intervention (e.g., Chronic bowel disease, Crohn’s disease and ulcerative colitis)
22. Any severe or unstable diseases or medical conditions including psychiatric disorders that might interfere with the conduct of the study, or could jeopardize the safety of the participant, or the interpretation of the results
23. History of major depression within 2 years prior to screening, or a history of other major psychiatric disorder at any time (e.g., schizophrenia, bipolar disorder)
24. Concurrent malignancy or history of cancer (except for adequately treated basal cell or squamous cell carcinoma of the skin) within the last 5 years prior to screening
25. Intake of prohibited medication due to potential drug-drug interaction Use of other treatments that might interfere with the conduct of the study or the interpretation of the results e.g.
a) use of any drug treatment after start of study intervention intended for the OAB/UI symptoms other than the study intervention
b) neuromodulation therapy and intravesical treatment – less than 12 months prior to screening or at any time during the study
c) use of any treatment intended for other conditions but which can affect urinary bladder function during the study
d) Non-drug treatment (e.g. physical treatment or acupuncture) – permitted only if initiated ≥4 weeks prior to Screening and planned to be continued during the study) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Average change from baseline over Week 4, 8 and 12 (end of treatment [EoT]) in mean number of urgency urinary incontinence (UUI) episodes/24 hours based on electronic bladder diary |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline up to 12 weeks |
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E.5.2 | Secondary end point(s) |
1. Change from baseline to Week 12 (EoT) based on electronic bladder diary in mean number of Urgency urinary incontinence (UUI) episodes/24 hours
2. Change from baseline to Week 12 (EoT) based on electronic bladder diary in mean number of Urinary incontinence (UI) episodes/24 hours
3. Change from baseline to Week 12 (EoT) based on electronic bladder diary in mean number of micturition episodes/24 hours
4. Change from baseline to Week 12 (EoT) based on electronic bladder diary in mean number of urgency episodes (Grade 3 or 4)/24 hours
5. Change from baseline to Week 12 (EoT) based on electronic bladder diary in mean number of nocturia episodes/24 hours
6. Change from baseline to Week 12 (EoT) based on electronic bladder diary in mean volume voided per micturition
7. The incidence of adverse events, drug-related adverse events and taste related adverse events
8. The maximum intensity of adverse events per participant |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-6: From baseline up to 12 weeks
7-8: From the start of study intervention (at start of run-in) until the follow-up visit (up to 18 weeks). |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 | No |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 12 |