| Eligibility |
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 exclusion criteria do not require specific diagnostic evaluation
during the screening visit, unless the subject presents with signs and symptoms suggesting
the presence of this condition that were not present earlier.)
- Subject is known to have inflammatory bowel disease or clinically significant
diarrhea.
- Subject is known to be immunocompromised due to conditions such as human
immunodeficiency virus/acquired immune deficiency syndrome or hepatitis C.
- Subject has been diagnosed with clinically significant cardiovascular or
cerebrovascular diseases within 6 months prior to visit 1, such as myocardial
infarction, uncontrolled angina/coronary artery disease, significant ventricular
arrhythmias and heart failure (New York Heart Association class III/IV).
- Subject has been diagnosed with clinically significant asthma, chronic bronchitis
and/or chronic obstructive pulmonary disease.
- Subject is known to have a mean Fridericia corrected QT interval (QTcF) > 430 ms for
males or > 450 ms for females, a pre-existing long QT syndrome or hypokalemia.
- Subject has a clinically significant abnormal 12-lead ECG.
- Subject has current or previous malignant disease of the pelvis. Subjects with a
history of (non-pelvic) cancer are considered eligible if the subject has undergone
therapy and the subject has been considered disease free for at least 5 years. Subject
with completely excised basal cell carcinoma or squamous cell carcinoma of the skin
and completely excised cervical cancer in situ are also considered eligible.
- Subject is known to have moderate to severe hepatic impairment (i.e., Child-Pugh class
B or C).
- Subject is known to have severe renal impairment defined as estimated glomerular
filtration rate (eGFR) < 30 mL/min/1.73 m^2.
- Subject is known to have current or history of alcohol and/or drug abuse within the
last 24 months prior to screening.
- Subject has clinical signs and symptoms of a urinary tract infection (UTI), which is
combined with a result of urine test (e.g., positive urine culture containing >
100,000 cfu/mL in midstream urine). If a UTI is confirmed in the visit 1 sample, the
run-in period should be stopped. After successful treatment of the UTI, the subject
can be rescreened and if eligible enroll in the study. If the subject has asymptomatic
bacteriuria (i.e., a positive urine culture without clinical signs and symptoms of a
UTI), the subject should not be excluded.
- Subject has any of the following abnormal liver or kidney function parameters (as
assessed in visit 1 sample):
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST) or bilirubin
increased to > 1.5 times the upper limit of normal (ULN).
- Gamma glutamyltransferase (?-GT) increased to > 3 times the ULN.
- eGFR < 45 mL/min/1.73 m^2 based on the Modification of Diet in Renal Disease
formula.
General:
- Subject has received investigational therapy within 28 days or 5 half-lives, whichever
is longer, prior to screening.
- Subject is known to have any condition, which makes the subject unsuitable for study
participation.
At visit 2:
- Subject meets any of the exclusion criteria of visit 1.
- Subject has severe overactive bladder (OAB), i.e., experienced 3 or more episodes of
urgency (Patient Perception of Intensity of Urgency Scale (PPIUS) grade 3 or 4),
during the 3-day micturition diary period prior to visit 2.
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