Clinical trial NCT04545580: Clinical Study to Evaluate the Treatment Effect and Safety of BAY1817080 in Patients With Overactive Bladder (OAB)
Official title: A Randomized, Placebo-controlled, Double-blind, Parallel-group, Multi-center, Proof-of-concept Study to Assess the Efficacy and Safety of BAY 1817080 in Patients With Overactive Bladder (OAB) Over a 12-week Treatment Period
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Overactive Bladder
Keywords: Urinary Bladder, Overactive
OAB
Urinary incontinence
Urinary urgency
Urgency
Micturition
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2020-09-11
Enrollment: 99
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of the study is to determine how well the drug BAY1817080 works in OAB patients with urgency urinary incontinence (UUI), defined as involuntary leakage of urine, accompanied or immediately preceded by a sudden compelling desire to void.

BAY1817080 is a new drug under development which blocks proteins expressed on the sensory nerves in the bladder. These nerves seem to overreact in OAB patients.

This study will test if the treatment with BAY1817080 will reduce the frequency of OAB symptoms. The frequency of OAB symptoms before the treatment and the frequency after 4, 8 and 12 weeks of treatment will be compared.

Another important objective of this study will be the assessment of BAY1817080 safety and tolerability in this patient population.

BAY1817080 will be compared to a "placebo". A placebo tablet looks like the study drug but does not have any medicine in it. Using a placebo helps to learn if the study drug works. Each participant is expected to take part in the study for about 5 months (around 20-22 weeks).


Eligibility criteria: Inclusion Criteria:

at screening：

* Adults ≥ 18 years of age at the time of signing the informed consent
* Have "wet" OAB symptoms (urgency, frequency and urinary incontinence) for ≥ 3 months prior to screening visit
* Women of childbearing potential (WOCBP) must agree to use acceptable effective or highly effective contraceptive methods
* Capable of giving signed informed consent
* Willing and able to complete the electronic bladder diary and questionnaires

at baseline (to be checked at V3, prior to randomization):

* Completion of all 3 days of 3-day electronic bladder diary during run-in phase
* Compliance of ≥80% with intake of study intervention during run-in
* Frequency of micturition on average ≥ 8 episodes/24 hours during the run-in phase according to 3-day electronic bladder diary
* Frequency of urgency urinary incontinence on average ≥ 1 episode/24 hours during the run-in phase according to 3-day electronic bladder diary

Exclusion Criteria:

* 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
* Significant stress incontinence or mixed stress/urgency incontinence
* Post-void residual volume (PVR) \> 150 mL at Visit 1 or at Visit 3
* In need of catheterization (indwelling or intermittent)
* Clinically significant urinary outflow obstruction
* Previous pelvic radiation, or previous or current malignant disease of pelvic organs
* Neurogenic bladder
* Bladder pain syndrome/interstitial cystitis
* Recurrent and/or symptomatic bladder stones
* 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
* Unexplained macro- or micro-hematuria
* Diabetes insipidus
* Diabetes mellitus with inadequate glycemic control as indicated by HbA1C result of \> 8% at screening
* Clinically significant cardiovascular or cerebrovascular disease
* Systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg
* Clinically significant abnormal electrocardiogram (ECG) at screening
* Moderate-to-severe hepatic impairment defined as Child-Pugh Class B or C
* 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
* 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) OR
  * Positive hepatitis B virus surface antigen (HBsAg) OR
  * Positive hepatitis C virus antibodies (anti-HCV) and detection of mRNA (HCV-mRNA, only tested if hepatitis C virus antibodies were detected)
* Severe renal impairment as defined by estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73 m\^2 calculated by Modification of Diet in Renal Disease (MDRD) formula
* 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., excessively low body weight, Chronic bowel disease, Crohn's disease and ulcerative colitis)
* 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
* 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)
* 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
* 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)

Primary outcomes:
measure: 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
timeFrame: From baseline up to 12 weeks
Secondary outcomes:
measure: Change from baseline to Week 12 (EoT) based on electronic bladder diary in mean number of UUI episodes/24 hours
timeFrame: From baseline up to 12 weeks
measure: Change from baseline to Week 12 (EoT) based on electronic bladder diary in mean number of urinary incontinence (UI) episodes/24 hours
timeFrame: From baseline up to 12 weeks
measure: Change from baseline to Week 12 (EoT) based on electronic bladder diary in mean number of micturition episodes/24 hours
timeFrame: From baseline up to 12 weeks
measure: Change from baseline to Week 12 (EoT) based on electronic bladder diary in mean number of urgency episodes (Grade 3 or 4)/24 hours
timeFrame: From baseline up to 12 weeks
measure: Change from baseline to Week 12 (EoT) based on electronic bladder diary in mean number of nocturia episodes/24 hours
timeFrame: From baseline up to 12 weeks
measure: Change from baseline to Week 12 (EoT) based on electronic bladder diary in mean volume voided per micturition
timeFrame: From baseline up to 12 weeks
measure: Incidence of adverse events
timeFrame: From the start of study intervention (at start of run-in) until the follow-up visit (up to 18 weeks)
Other outcomes:
Locations:
city: Botany
country: Australia
facility: Emeritus Research
state: New South Wales
city: Camberwell
country: Australia
facility: Emeritus Research
state: Victoria
city: Graz
country: Austria
facility: Medizinische Universität Graz
state: Steiermark
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck
city: Benesov
country: Czechia
facility: Afimed s.r.o
city: Cheb
country: Czechia
facility: Gynekologie Cheb s.r.o.
city: Olomouc
country: Czechia
facility: G-Centrum Olomouc s.r.o. Dr. Skrivanek
city: Plzen
country: Czechia
facility: GynCare MUDr. Michael Svec s.r.o.
city: Praha 2
country: Czechia
facility: Urocentrum Praha, s.r.o.
city: Praha 6
country: Czechia
facility: Androgeos - private center of urology and andrology
city: Praha 8
country: Czechia
facility: Fakultní nemocnice Bulovka
city: Duisburg
country: Germany
facility: Urologicum Duisburg - Praxis Walsum
state: Nordrhein-Westfalen
city: Mettmann
country: Germany
facility: Überörtliche Gemeinschaftspraxis "Urologie Neandertal"
state: Nordrhein-Westfalen
city: Halle
country: Germany
facility: Praxis Hr. Dr. M. Markov
state: Sachsen-Anhalt
city: Lutherstadt Eisleben
country: Germany
facility: Urologicum
state: Sachsen-Anhalt
city: Christchurch
country: New Zealand
facility: Canterbury Urology Research Trust
city: Tauranga
country: New Zealand
facility: Tauranga Urology Research Limited
city: Krakow
country: Poland
facility: Medico Praktyka Lekarska
city: Lublin
country: Poland
facility: NZOZ NOVITA, Specjalistyczne Gabinety Lekarskie S.C
city: Myslowice
country: Poland
facility: Centrum Urologiczne Sp. z o.o.
city: Piaseczno
country: Poland
facility: NZOZ Heureka
city: Skierniewice
country: Poland
facility: Przychodnia Lekarska Eskulap
city: Lisboa
country: Portugal
facility: CHULN - Hospital Santa Maria
city: Porto
country: Portugal
facility: Centro Hospitalar Universitario do Porto
city: Porto
country: Portugal
facility: CHUSJ - Hospital Sao Joao
city: Singapore
country: Singapore
facility: KK Women's and Children's Hospital
city: Göteborg
country: Sweden
facility: Göteborgs Urologmottagning
city: Solna
country: Sweden
facility: Urogyn
Study officials:
References:
citation: Fletcher MC. Selectivity of the P2X3 receptor antagonist Eliapixant, and its potential use in the treatment of endometriosis. Purinergic Signal. 2022 Mar;18(1):1-3. doi: 10.1007/s11302-021-09831-5. Epub 2022 Jan 3. No abstract available.