Underactive Bladder MedDRA version: 21.1 Level: LLT Classification code 10021635 Term: Incomplete bladder emptying System Organ Class: 100000004857 MedDRA version: 21.0 Level: LLT Classification code 10060695 Term: Residual urine System Organ Class: 100000004857 MedDRA version: 20.1 Level: LLT Classification code 10005071 Term: Bladder retention System Organ Class: 100000004857 MedDRA version: 20.0 Level: LLT Classification code 10012549 Term: Detrusor muscle weakness System Organ Class: 100
Conditions
Sponsors
Astellas Pharma Europe B.V.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: At Study Entry – Screening (visit 1): 1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved written informed consent and privacy language as per national regulations must be obtained from the subject prior to any study-related procedures (including withdrawal of prohibited medication, if applicable). 2. Subject is considered an adult according to local regulation at the time of signing the informed consent form (ICF). 3. Subject is diagnosed with UAB, defined as a bothersome chronic incomplete bladder emptying: • clinical condition is present for = 6 months before screening, and • subject has a PVR = 75 mL (measured by ultrasound after uroflowmetry; V1_PVRUS1). 4. Subject on CIC should have been on CIC for at least 1 month and should be able to void spontaneously and not be completely dependent on CIC. 5. Female subject must either: •Be of non-childbearing potential: -Post-menopausal (defined as at least 1 year without any menses for which there is no other obvious pathological or physiological cause) prior to screening, or -Documented surgically sterile (e.g., hysterectomy, bilateral salpingectomy, bilateral oophorectomy). •Or, if of childbearing potential: -Agrees not to try to become pregnant during the study and for 28 days after the final study drug administration -Agrees to have a serum pregnancy test on all visits -And have a negative serum pregnancy test at the screening visit -And agrees to consistently use 1 form of highly effective birth control* starting at screening and throughout the study period and for 28 days after the final study drug administration. 6. Female subject must agree not to breastfeed starting at screening and throughout the study period, and for 28 days after the final study drug administration. 7. Female subject must not donate ova starting at screening and throughout the study period, and for 28 days after the final study drug administration. 8. A sexually active male subject with female partner(s) of childbearing potential (including breastfeeding partner(s)) is eligible if he agrees to use a male condom starting at screening and continue throughout study treatment and for 90 days after the final study drug administration. If the male subject has not had a vasectomy or is not sterile as defined below, his female partner(s) is utilizing 1 form of highly effective birth control*starting at screening and will continue throughout study treatment and for 90 days after the male subject receives the final study drug administration. 9. Male subject must not donate sperm starting at screening and throughout the study period and for 90 days after the final study drug administration. 10. Male subject with a pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy throughout the study period and for 28 days after the final study drug administration. *Highly effective forms of birth control include: • Consistent and correct usage of established hormonal contraceptives that inhibit ovulation • Established intrauterine device or intrauterine system • Bilateral tubal occlusion • Vasectomy (a vasectomy is a highly effective contraception method provided the absence of sperm has been confirmed. If not, an additional highly effective method of contraception should be used) • Male is sterile due to a bilateral orchiectomy • Sexual Abstinence is considered a highly effective method only if defined as refrai
Exclusion criteria
Exclusion criteria: At Study Entry – Screening (visit 1): Related to lower urinary tract: 1. Subject has significant BOO: •Clinically significant urethral stricture in the opinion of the investigator. •Female subject has uterine prolapse = Grade 2 Shaw’s system (down to or outside the introitus), moderate or severe cystocele (reaches or protrudes outside the introitus). •Male subject has a bladder outlet obstruction index (BOOI) = 40 on PFS (either performed on screening or within 12 months of the screening visit), or –if PFS is not available–a PV of > 40 mL (Europe) > 30 mL (Japan) on ultrasound (either performed on screening or within 6 months of the screening visit). Note: if PFS is available and PV is above the cut-off level, the subject is not to be excluded if BOOI is 430 ms for males or > 450 ms for females, a pre-existing long QT syndrome or hypokalemia. 16. Clinically significant abnormal 12-lead ECG. 17. Current or previous malignant disease of the pelvis. Subjects with a history of (non-pelvic) cancer are considered eligible if the subje
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To evaluate the efficacy of ASP8302 compared with placebo in subjects with UAB •To investigate the safety and tolerability of ASP8302 compared with placebo in subjects with UAB •To investigate the pharmacokinetics of ASP8302 in subjects with UAB •To support the development of the UAB - Patient Reported Outcome (PRO) ;Secondary Objective: Not applicable.;Primary end point(s): Efficacy Primary: •Change from baseline to visit 4 in PVR after standardized bladder filling measured by catheterization (PVRC2). ;Timepoint(s) of evaluation of this end point: Change from baseline visit 2 to visit 4. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary*: •VVST at site visits •BVEC2 (i.e., BVE calculated with PVRC2 and VVST) Exploratory*: •PVRUS1, PVRC1, PVRUS2 BVEUS1, BVEC1, BVEUS2 •Uroflowmetry parameters: Voiding time, flow time, Q (max and ave), time to Qmax (absolute, % of voiding time), BC and VV. •Urodynamic parameters (only applicable for PFS sub-study): including uroflow measurements done during PFS, Pdet (Opening, at Qmax, mu), Pves, Pabd, bladder capacity index (BCI; males only), Watts factor (max and AUC), VCE, t20-80, BOOI (males only), Schäfer grade, position in the Maastricht-Hannover Nomogram, volume at first sensation of bladder filling, volume at first desire and volume at urgent desire. •3-day micturition diary parameters: number of daily micturitions (waking, nocturnal, 24-h), VV per micturition, PPIUS/total urgency and frequency score, number of urgency episodes, i.e., PPIUS Grade 3 or 4, number of incontinence episodes and pads used; for subjects on CIC: number of CICs and catheterized volume. •Questionnaire data: International Consultation on Incontinence Modular Questionnaire– Underactive Bladder Patient Reported Outcome (ICIQ-UAB PRO) symptom score and sub scores, symptom and bother scores as assessed by International Consultation on Incontinence Modular Questionnaire-Male/Female Lower Urinary Tract Symptoms (ICIQ-MLUTS/FLUTS), European Quality of Life 5 Dimensions Questionnaire (EQ-5D), 12 Item Short Form Health Survey (SF-12), Patient Global Impression of Change (PGI-C), Patient Global Impression of Severity (PGI-S). Responder analysis*: •PVR responders: responders will be defined as subjects with = 30% reduction of PVR from baseline to EoT; a second definition of a PVR responder is a subject with = 50 mL reduction from baseline to EoT. •PGI-C responders: responders will be defined as subjects with a response “much improved” or “very much improved” at EoT. •CIC responders: responders will be defined as subjects who are on CIC at baseli | — |
Countries
Germany, Japan, Netherlands, Poland, Slovakia, United Kingdom
Contacts
Public ContactService Desk - Global Clinical Dev.
Astellas Pharma Europe B.V.
Outcome results
None listed