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Underactive BladderPhase 2NCT03702777

A Study of ASP8302 in Participants With Underactive Bladder

A Phase 2 study testing ASP8302 in people with Underactive Bladder, run by Astellas Pharma Europe B.V. at 29 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Underactive Bladder
What is being tested?
ASP8302
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
135 participants
Where
29 sitesin 6 countries
Study dates
20 Nov 2018to 28 Apr 2020
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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.

Who cannot join

  • 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.
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  • 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 (γ-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.

Trial locations and contacts

29 sites in 6 countries.

29 sites in 6 countries

Japan14 sites

  • Site JP81006

    Asahikawa, Hokkaido

  • Site JP81003

    Fukuoka

  • Site JP81002

    Kobe, Hyōgo

  • Site JP81004

    Kumamoto

  • Site JP81012

    Kurashiki, Okayama-ken

  • Site JP81009

    Nagoya, Aichi-ken

  • Site JP81008

    Ōbu, Aichi-ken

  • Site JP81010

    Saga

  • Site JP81005

    Sapporo, Hokkaido

  • Site JP81015

    Sapporo, Hokkaido

  • Site JP81011

    Sayama, Osaka

  • Site JP81001

    Shimotsuga-gun, Tochigi

  • Site JP81013

    Shizuoka

  • Site JP81007

    Yoshida-gun, Fukui

Other trials in Japan

Germany4 sites

  • Site DE49001

    Duisburg

  • Site DE49002

    Duisburg

  • Site DE49004

    Gronau

  • Site DE49003

    Mönchengladbach

Other trials in Germany

Poland4 sites

  • Site PL48004

    Mysłowice

  • Site PL48003

    Piaseczno

  • Site PL48002

    Szczecin

  • Site PL48001

    Warsaw

Other trials in Poland

Netherlands3 sites

  • Site NL31003

    Eindhoven

  • Site NL31002

    Maastricht

  • Site NL31001

    Rotterdam

Other trials in Netherlands

Slovakia3 sites

  • Site SK42103

    Košice

  • Site SK42101

    Nitra

  • Site SK42102

    Trenčín

Other trials in Slovakia

United Kingdom1 site

  • Site UK44002

    Bristol

Other trials in United Kingdom

About this study

Official title: A Randomized, Double-blind, Placebo-controlled, Multicenter, Phase 2a, Proof-of-Concept Study of ASP8302 in Subjects With Underactive Bladder

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).

Read the 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.

Being tested
ASP8302, Placebo
Keywords
Underactive Bladder, ASP8302
Medical subject headings
Urinary Bladder, Underactive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ASP8302Drug

    Oral Capsule

  • PlaceboDrug

    Oral Capsule

Study groups in NCT03702777
Study groupRoleWhat they receive
ASP8302 100mgExperimentalParticipants will receive ASP8302 100mg capsules orally once daily for up to 4 weeks.
Receives: Drug: ASP8302
PlaceboPlacebo comparatorParticipants will receive ASP8302 matching placebo orally once daily for up to 4 weeks.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change From Baseline in PVR After Standardized Bladder Filling Measured by Catheterization (PVRc2) at Week 4

    Volume of urine in the bladder after standardized bladder filling measured by catheterization (PVRc2).

    Measured: Baseline and week 4

Secondary outcomes (2)

  1. Voided Volume After Standardized Bladder Filling (VV_St) at 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.

    Measured: Week 4

  2. Bladder Voiding Efficiency Calculated With PVRc2 and VV-St (BVEc2) at 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.

    Measured: Week 4

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Oct 2018
  2. Study start20 Nov 2018
  3. Primary completion28 Apr 2020
  4. Study completion28 Apr 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
135 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03702777
Sponsor's protocol ID
8302-CL-0201
Other IDs
2017-003693-13, 2017
Status last verified
Nov 2024
First submitted
5 Oct 2018
Last updated
21 Nov 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.

Publications

  • van Till JWO, Arita E, Kuroishi K, Croy R, Oelke M, van Koeveringe GA, Chapple CR, Yamaguchi O, Abrams P. Muscarinic-3-receptor positive allosteric modulator ASP8302 in patients with underactive bladder. A randomized controlled trial. Neurourol Urodyn. 2022 Jun;41(5):1139-1148. doi: 10.1002/nau.24931. Epub 2022 Apr 14.

    PubMed 35419807

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ASP8302 in people with Underactive Bladder, run by Astellas Pharma Europe B.V. at 29 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 50 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 29 sites in Japan, Germany, Poland, Netherlands, Slovakia and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in PVR After Standardized Bladder Filling Measured by Catheterization (PVRc2) at Week 4 (time frame: Baseline and week 4). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03702777, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Nov 2024.

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