OVADER: Clinical Study to Evaluate the Treatment Effect and Safety of BAY1817080 in Patients With Overactive Bladder (OAB)

Sponsor

Bayer (Industry)

Overall Status

Completed

CT.gov ID

NCT04545580

Collaborator

(none)

Enrollment

Locations

Arms

16.2

Actual Duration (Months)

3.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Overactive Bladder	Drug: Placebo Drug: BAY1817080	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

99 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Sep 16, 2020

Actual Primary Completion Date :

Dec 22, 2021

Actual Study Completion Date :

Jan 21, 2022

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Treatment period: Placebo This arm consists of participants who complete the run-in period, and are still eligible, according to all in- and exclusion criteria for diagnosis of OAB with UUI based on bladder diary baseline data. Participants will be randomized to 12 weeks of double-blind treatment with matching placebo.	Drug: Placebo Matching placebo for BAY1817080, will be taken twice daily orally as tablet(s)
Experimental: Treatment period: BAY1817080 This arm consists of participants who complete the run-in period, and are still eligible, according to all in- and exclusion criteria for diagnosis of OAB with UUI based on bladder diary baseline data. Participants will be randomized to 12 weeks of double-blind treatment with BAY1817080.	Drug: BAY1817080 BAY1817080 will be taken twice daily orally as tablet(s)

Arm

Intervention/Treatment

Placebo Comparator: Treatment period: Placebo

This arm consists of participants who complete the run-in period, and are still eligible, according to all in- and exclusion criteria for diagnosis of OAB with UUI based on bladder diary baseline data. Participants will be randomized to 12 weeks of double-blind treatment with matching placebo.

Drug: Placebo

Matching placebo for BAY1817080, will be taken twice daily orally as tablet(s)

Experimental: Treatment period: BAY1817080

Drug: BAY1817080

BAY1817080 will be taken twice daily orally as tablet(s)

Outcome Measures

Primary Outcome Measures

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 [From baseline up to 12 weeks]

Secondary Outcome Measures

Change from baseline to Week 12 (EoT) based on electronic bladder diary in mean number of UUI episodes/24 hours [From baseline up to 12 weeks]
Change from baseline to Week 12 (EoT) based on electronic bladder diary in mean number of urinary incontinence (UI) episodes/24 hours [From baseline up to 12 weeks]
Change from baseline to Week 12 (EoT) based on electronic bladder diary in mean number of micturition episodes/24 hours [From baseline up to 12 weeks]
Change from baseline to Week 12 (EoT) based on electronic bladder diary in mean number of urgency episodes (Grade 3 or 4)/24 hours [From baseline up to 12 weeks]
Change from baseline to Week 12 (EoT) based on electronic bladder diary in mean number of nocturia episodes/24 hours [From baseline up to 12 weeks]
Change from baseline to Week 12 (EoT) based on electronic bladder diary in mean volume voided per micturition [From baseline up to 12 weeks]
Incidence of adverse events [From the start of study intervention (at start of run-in) until the follow-up visit (up to 18 weeks)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.
1. use of any drug treatment after start of study intervention intended for the OAB/UI symptoms other than the study intervention
1. neuromodulation therapy and intravesical treatment - less than 12 months prior to screening or at any time during the study
1. use of any treatment intended for other conditions but which can affect urinary bladder function during the study
1. 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Emeritus Research	Botany	New South Wales	Australia	2019
2	Emeritus Research	Camberwell	Victoria	Australia	3124
3	Medizinische Universität Graz	Graz	Steiermark	Austria	8036
4	Medizinische Universität Innsbruck	Innsbruck		Austria	6020
5	Afimed s.r.o	Benesov		Czechia	256 01
6	Gynekologie Cheb s.r.o.	Cheb		Czechia	350 02
7	G-Centrum Olomouc s.r.o. Dr. Skrivanek	Olomouc		Czechia	772 00
8	GynCare MUDr. Michael Svec s.r.o.	Plzen		Czechia	326 00
9	Urocentrum Praha, s.r.o.	Praha 2		Czechia	120 00
10	Androgeos - private center of urology and andrology	Praha 6		Czechia	160 00
11	Fakultní nemocnice Bulovka	Praha 8		Czechia	180 00
12	Urologicum Duisburg - Praxis Walsum	Duisburg	Nordrhein-Westfalen	Germany	47179
13	Überörtliche Gemeinschaftspraxis "Urologie Neandertal"	Mettmann	Nordrhein-Westfalen	Germany	40822
14	Praxis Hr. Dr. M. Markov	Halle	Sachsen-Anhalt	Germany	06132
15	Urologicum	Lutherstadt Eisleben	Sachsen-Anhalt	Germany	06295
16	Canterbury Urology Research Trust	Christchurch		New Zealand	8013
17	Tauranga Urology Research Limited	Tauranga		New Zealand	3112
18	Medico Praktyka Lekarska	Krakow		Poland	31-315
19	NZOZ NOVITA, Specjalistyczne Gabinety Lekarskie S.C	Lublin		Poland	20-632
20	Centrum Urologiczne Sp. z o.o.	Myslowice		Poland	41-400
21	NZOZ Heureka	Piaseczno		Poland	05-500
22	Przychodnia Lekarska Eskulap	Skierniewice		Poland	96-100
23	CHULN - Hospital Santa Maria	Lisboa		Portugal	1649-035
24	CHUP - Hospital Santo Antonio	Porto		Portugal	4050
25	CHUSJ - Hospital Sao Joao	Porto		Portugal	4200-319
26	KK Women's and Children's Hospital	Singapore		Singapore	229899
27	Göteborgs Urologmottagning	Göteborg		Sweden	411 36
28	Urogyn	Solna		Sweden	170 73