Underactive Bladder
Conditions
Keywords
Underactive Bladder, ASP8302
Brief summary
The study objectives of this study are to evaluate the efficacy of ASP8302 compared with placebo in participants with underactive bladder (UAB), to investigate the safety and tolerability of ASP8302 compared with placebo in participants with UAB, to investigate the pharmacokinetics of ASP8302 in participants with UAB and to support the development of the UAB - Patient Reported Outcome (PRO).
Detailed description
The study will comprise a screening visit, followed by a treatment period and a 2-week follow-up period, in total 8 weeks. Participants will visit the clinic at screening (visit 1) and every 2 weeks (visit 2, 3, 4, and 5). During the course of the study assessments will be performed at the visits.
Interventions
DRUGASP8302
Oral Capsule
DRUGPlacebo
Oral Capsule
Sponsors
Astellas Pharma Europe B.V.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
At visit 1: * 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). * Subject on clean intermittent catheterization (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. * 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, 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. * 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. * Female subject must not donate ova starting at screening and throughout the study period, and for 28 days after the final study drug administration. * A sexually active male subject with female partner(s) of childbearing potential 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, 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. * Male subject must not donate sperm starting at screening and throughout the study period and for 90 days after the final study drug administration. * 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. * Subject agrees not to participate in another interventional study while participating in this study. At visit 2: * Subject has a PVR ≥ 100 mL (measured by catheterization, i.e., PVRC2). * Subject has a VVST ≥ 50 mL and a bladder voiding efficiency ((BVE) (V2\_BVE)) ≥ 10%. The VVST and V2\_PVRC2 will be used to calculate V2\_BVE = \[VVST/(V2\_PVRC2 + VVST)\] times 100.
Exclusion criteria
At visit 1: Related to lower urinary tract: * Subject has significant BOO: * Subject has clinically significant urethral stricture (e.g., requiring surgery). * Female subject has uterus prolapse ≥ Grade 2 Shaw's system (up 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 cm H2O on pressure flow study (PFS) (either performed on screening or within 12 months of the screening visit), or -if PFS is not available-a prostate volume (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 bladder outlet obstruction index (BOOI) is \< 40. * Other condition that constitutes significant BOO. * Subject is known to have urgency urinary incontinence that is clinically significant. * Subject is known to have 1 or more bladder diverticuli that is/are clinically significant. * Subject is known to have vesico-ureteral/renal reflux that is clinically significant. * Subject has a urinary catheter in situ (including suprapubic catheters). * Subject is known to have 1 of the following conditions as a primary cause for subject's UAB, or a condition that could potentially influence treatment outcome: * Neurological lesion or condition, including cerebrovascular accident, spinal lumbar disc hernia, spinal cord injury, multiple sclerosis, Parkinson's disease, Guillain-Barré syndrome, pudendal, hypogastric or pelvic nerve lesion. Diabetes mellitus is allowed if controlled with or without medical treatment (e.g., HbA1C \< 7%). * Increased pelvic floor muscle activity during voiding (e.g., dyssynergic striated sphincteric activity/striated sphincteric activity during voiding, Fowler syndrome and pelvic floor muscle spasm). * Previous bladder surgery (e.g., bladder augmentation or reduction surgery, latissimus dorsi detrusor myoplasty). Prior Benign Prostatic Obstruction surgery or pelvic organ prolapse surgery is allowed if performed more than 6 months prior to screening. * Previous implant surgery for incontinence still in situ (e.g., tape, sling or artificial sphincter) * Significant active urological pain syndrome. * Previous pelvic radiation therapy. * Dependence on use of a manual assistance method intended to improve bladder emptying (e.g., Credé's maneuver or suprapubic tapping). Related to (previous or current) treatment and/or study drug: * Subject is receiving 1 or more of the following non-medication therapies: * Electrostimulation therapy, e.g., neurostimulation/modulation or sacral nerve stimulation in the past 3 months. * Intravesical or injection based treatment (e.g., botulinum toxin injections in urethra or bladder in the past 12 months). * An ongoing bladder training program and/or pelvic floor muscle exercises, which started within 6 weeks prior to visit 1. * Muscle-derived stem cell injection in the bladder or urethra or bladder transplantation at any time prior to screening. * Subject is using prohibited medications or subject is using restricted medications under conditions different to those specified in the concomitant medication section. * Subject has a known or suspected hypersensitivity to ASP8302 or any of the inactive ingredients. Related to concomitant conditions: (Please note that these
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in PVR After Standardized Bladder Filling Measured by Catheterization (PVRc2) at Week 4 | Baseline and week 4 | Volume of urine in the bladder after standardized bladder filling measured by catheterization (PVRc2). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Voided Volume After Standardized Bladder Filling (VV_St) at Week 4 | Week 4 | VVst is thought to increase as the bladder emptying is improved. Standardizing the bladder filling is thought to increase accuracy in comparison with normal spontaneous bladder filling which will differ between time points. No multiplicity correction will be performed. |
| Bladder Voiding Efficiency Calculated With PVRc2 and VV-St (BVEc2) at Week 4 | Week 4 | Bladder voiding efficiency (BVE) is defined as the percentage of the total bladder capacity (BC) that is voided using the following formula: BVE = \[volume voided (VV) / (PVR + VV)\] x 100. BVEc2: BVE calculated for PVRc2 parameter i.e. BVEc2 = \[VV\_St / (PVRc2 + VV\_St)\] x 100. |
Countries
Germany, Japan, Netherlands, Poland, Slovakia, United Kingdom
Outcome results
None listed