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CompletedNCT03175029Updated Jan 20, 2025Results posted

Exploratory Study of TAC-302 in Detrusor Underactivity Patients With Overactive Bladder.

A Phase 2 interventional study of TAC-302 and Placebo in Detrusor Underactivity and Overactive Bladder, sponsored by Taiho Pharmaceutical Co., Ltd.. Completed at 1 site in Japan. Open to participants aged 20 Years and older. Per ClinicalTrials.gov, last updated 2025-01-20.

Sponsored by Taiho Pharmaceutical Co., Ltd. · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
195
Allocation
Randomized
Ages
20 Years and older
Sex
All
01

Study summary

The purpose of this study is to evaluate the efficacy and safety of TAC-302 in detrusor underactivity patients with overactive bladder.

Read the detailed description

The main purpose of this study is to assess the efficacy of TAC-302 for 12 weeks in detrusor underactivity patients with overactive bladder by measuring the following parameters of pressure-flow study.

  • Male; bladder contractility index (BCI)
  • Female; projected isovolumetric pressure (PIP) 1
02

Conditions studied

  • Detrusor Underactivity
  • Overactive Bladder

Keywords

  • Lower Urinary Tract Symptoms
03

Who can participate

Ages eligible
20 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Key Inclusion Criteria:

  • To have Lower Urinary Tract Symptoms for at least 12 weeks prior to study entry
  • To have at least 1 urinary urgency episodes per day, and diurnal urinary frequency of 8 or more per day.
  • To meet the detrusor underactivity criteria by urodynamic study

Key Exclusion Criteria:

  • Neurogenic bladder by the central nervous system diseases.
  • StageIII or more cystocele of pelvic organ prolapse quantification system (women)
  • Prostate volume ≥30mL (Men)
  • Any symptoms of Urinary tract infection (UTI)
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
195 participants (actual)

Study arms

  • Experimental
    TAC-302

    Drug: TAC-302

  • Placebo comparator
    Placebo

    Drug: Placebo

Interventions

  • DrugTAC-302

    TAC-302 200 mg administered orally twice per day after meals, for 12 weeks.

  • DrugPlacebo

    Placebo administered orally twice per day after meals, for 12 weeks.

05

What researchers measure

Primary outcomes

  1. Changes in the Mean BCI for Male From Baseline to Week 12

    BCI indicates maxim um detrusor pressure at peak urine flow (PdetQmax) + 5 × peak urine flow rate (Qmax): PdetQmax and Qmax denotes detrusor pressure at maximum flow and maximum flow rate in pressure flow study, respectively. This index is used to assess detrusor contractility in men, with a higher value indicating greater detrusor contractility. Contractility can be divided into strong \> 150, normal 100-150, and weak \< 100. No theoretical minimum and maximum value of the scale range exists.

    Time frame: Baseline to Week 12

  2. Changes in the Mean PIP1 for Female From Baseline to Week 12

    PIP1 indicates PdetQma x + Qmax: PdetQmax and Qmax denotes detrusor pressure at maximum flow and maximum flow rate in pressure flow study, respectively. This index is used to assess detrusor contractility in women, with a higher value indicating greater detrusor contractility. Contractility can be divided into strong \> 75, normal 30-75, and weak \< 30. No theoretical minimum and maximum value of the scale range exists.

    Time frame: Baseline to Week 12

Secondary outcomes

  1. Changes in the Mean BVE From Baseline to Week 12 (Overall)

    BVE indicates Voided volume / (voided volume + post void residual): calculated from the voided volume measured by uroflowmetry and the post void residual measured by ultrasonography.

    Time frame: Baseline to Week 12

  2. Changes in the Mean BVE From Baseline to Week 12 (In the Subgroup of Patients With Post Void Residual ≥ 50 mL at Baseline)

    BVE indicates Voided volume / (voided volume + post void residual): calculated from the voided volume measured by uroflowmetry and the post void residual measured by ultrasonography.

    Time frame: Baseline to Week 12

  3. Changes in the Mean BVE for Female From Baseline to Week 12 (In the Subgroup of Patients With Post Void Residual ≥ 100 mL at Baseline)

    BVE indicates Voided volume / (voided volume + post void residual): calculated from the voided volume measured by uroflowmetry and the post void residual measured by ultrasonography.

    Time frame: Baseline to Week 12

  4. Number of Micturitions Per 24 Hours at Baseline and Week 12

    On the basis of information from bladder diary records in the 3 days directly before each evaluation timepoint, an average of urinations per 24 hours was calculated. The patients with at least 8 urinations per 24 hours at registration were included in this study.

    Time frame: Baseline to Week 12

  5. Number of Urinary Urgency Episodes Per 24 Hours at Baseline and Week 12

    On the basis of information from bladder diary records in the 3 days directly before each evaluation timepoint, an average of urinary urgency episodes per 24 hours was calculated. The patients with at least one urinary urgency episode per 24 hours at registration were included in this study.

    Time frame: Baseline to Week 12

  6. Overactive Bladder Symptom Score (OABSS) Total Score at Baseline and Week 12

    Overactive bladder symptoms were evaluated using the OABSS. The OABSS Total Score is the sum of four symptom scores: daytime frequency (score 0-2), nighttime frequency (score 0-3), urgency (score 0-5), and urgency incontinence (score 0-5). The range of scores is from 0 to 15 points with a higher score indicating greater severity. A score ≤ 5 was determined to be mild, a score of 6 to 11 was determined to be moderate and a score ≥ 12 was determined to be severe.

    Time frame: Baseline to Week 12

  7. Number of Participants With Adverse Events

    In tabulation of adverse events, the diagnoses entered on eCRFs were coded using the medical dictionary for regulatory activities (MedDRA) ver.22.1, and were presented as MedDRA preferred terms.

    Time frame: Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)

  8. Number of Participants With Adverse Drug Reactions

    Time frame: Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)

  9. Number of Participants With Serious Adverse Events

    In tabulation of adverse events, the diagnoses entered on eCRFs were coded using the medical dictionary for regulatory activities (MedDRA) ver.22.1, and were presented as MedDRA preferred terms.

    Time frame: Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)

  10. Number of Participants With Adverse Events Leading to Death

    Time frame: Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)

  11. Number of Participants With Adverse Events Leading to Dose Discontinuation

    Time frame: Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)

  12. Number of Participants With Adverse Events Leading to Dose Interruption

    In tabulation of adverse events, the diagnoses entered on eCRFs were coded using the medical dictionary for regulatory activities (MedDRA) ver.22.1, and were presented as MedDRA preferred terms.

    Time frame: Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)

06

Results

Posted Jan 20, 2025

Participant flow

This study was conducted at 21 medical institutions in Japan and the study period was from September 9, 2017 to November 14, 2019. Of the 213 patients who gave informed consent and received screening tests, 18 patients were withdrawn at screening. The number of patients enrolled in the observation period was 195 patients, but after the end of the observation period, 76 patients were determined to be eligible for enrollment in the treatment period.

Participant flow — Overall Study
MilestoneTAC-302Placebo
Started5224
Completed4923
Not completed31
Withdrew: Withdrawal by subject21
Withdrew: Study treatment becomes impossible due to changing hospital or other reasons10

Outcome measures

PrimaryChanges in the Mean BCI for Male From Baseline to Week 12

BCI indicates maxim um detrusor pressure at peak urine flow (PdetQmax) + 5 × peak urine flow rate (Qmax): PdetQmax and Qmax denotes detrusor pressure at maximum flow and maximum flow rate in pressure flow study, respectively. This index is used to assess detrusor contractility in men, with a higher value indicating greater detrusor contractility. Contractility can be divided into strong \> 150, normal 100-150, and weak \< 100. No theoretical minimum and maximum value of the scale range exists.

Time frame:
Baseline to Week 12
Reported as:
Mean · Score on a scale
Changes in the Mean BCI for Male From Baseline to Week 12
Score on a scaleTAC-302Placebo
BCI at baseline64.604 ± 16.56961.339 ± 16.629
BCI at Week 1275.156 ± 21.07660.513 ± 16.708
Statistical analysis
  • TAC-302 · t-test, 2 sided · p = <0.001 · Mean difference (final values): 10.552 · 95% CI 5.514 to 15.590
  • Placebo · t-test, 2 sided · p = 0.819 · Mean difference (final values): -0.826 · 95% CI -8.676 to 7.023
  • TAC-302 vs Placebo · t-test, 2 sided · p = 0.015 · Mean difference (final values): 11.378 · 95% CI 2.345 to 20.411
PrimaryChanges in the Mean PIP1 for Female From Baseline to Week 12

PIP1 indicates PdetQma x + Qmax: PdetQmax and Qmax denotes detrusor pressure at maximum flow and maximum flow rate in pressure flow study, respectively. This index is used to assess detrusor contractility in women, with a higher value indicating greater detrusor contractility. Contractility can be divided into strong \> 75, normal 30-75, and weak \< 30. No theoretical minimum and maximum value of the scale range exists.

Time frame:
Baseline to Week 12
Reported as:
Mean · Score on a scale
Changes in the Mean PIP1 for Female From Baseline to Week 12
Score on a scaleTAC-302Placebo
PIP1 at baseline18.769 ± 6.59120.561 ± 7.524
PIP1 at Week 1229.373 ± 9.36925.487 ± 9.581
Statistical analysis
  • TAC-302 · t-test, 2 sided · p = <0.001 · Mean difference (final values): 10.604 · 95% CI 5.753 to 15.455
  • Placebo · t-test, 2 sided · p = 0.138 · Mean difference (final values): 4.926 · 95% CI -2.121 to 11.973
  • TAC-302 vs Placebo · t-test, 2 sided · p = 0.157 · Mean difference (final values): 5.678 · 95% CI -2.375 to 13.731
SecondaryChanges in the Mean BVE From Baseline to Week 12 (Overall)

BVE indicates Voided volume / (voided volume + post void residual): calculated from the voided volume measured by uroflowmetry and the post void residual measured by ultrasonography.

Time frame:
Baseline to Week 12
Reported as:
Mean · percentage
Changes in the Mean BVE From Baseline to Week 12 (Overall)
percentageTAC-302Placebo
BVE at baseline55.43 ± 26.8263.71 ± 21.80
BVE at Week 1266.79 ± 27.0465.69 ± 28.98
Statistical analysis
  • TAC-302 · t-test, 2 sided · p = 0.006 · Mean difference (final values): 10.91 · 95% CI 3.22 to 18.59
  • Placebo · t-test, 2 sided · p = 0.570 · Mean difference (final values): 2.42 · 95% CI -6.27 to 11.10
  • TAC-302 vs Placebo · t-test, 2 sided · p = 0.178 · Mean difference (final values): 8.49 · 95% CI -3.96 to 20.95
SecondaryChanges in the Mean BVE From Baseline to Week 12 (In the Subgroup of Patients With Post Void Residual ≥ 50 mL at Baseline)

BVE indicates Voided volume / (voided volume + post void residual): calculated from the voided volume measured by uroflowmetry and the post void residual measured by ultrasonography.

Time frame:
Baseline to Week 12
Reported as:
Mean · percentage
Changes in the Mean BVE From Baseline to Week 12 (In the Subgroup of Patients With Post Void Residual ≥ 50 mL at Baseline)
percentageTAC-302Placebo
BVE at baseline42.77 ± 24.6655.95 ± 23.70
BVE at Week 1261.66 ± 30.4558.83 ± 26.15
Statistical analysis
  • TAC-302 · t-test, 2 sided · p = <0.001 · Mean difference (final values): 18.41 · 95% CI 9.13 to 27.69
  • Placebo · t-test, 2 sided · p = 0.489 · Mean difference (final values): 2.88 · 95% CI -5.81 to 11.58
  • TAC-302 vs Placebo · t-test, 2 sided · p = 0.031 · Mean difference (final values): 15.53 · 95% CI 1.48 to 29.58
SecondaryChanges in the Mean BVE for Female From Baseline to Week 12 (In the Subgroup of Patients With Post Void Residual ≥ 100 mL at Baseline)

BVE indicates Voided volume / (voided volume + post void residual): calculated from the voided volume measured by uroflowmetry and the post void residual measured by ultrasonography.

Time frame:
Baseline to Week 12
Reported as:
Mean · percentage
Changes in the Mean BVE for Female From Baseline to Week 12 (In the Subgroup of Patients With Post Void Residual ≥ 100 mL at Baseline)
percentageTAC-302Placebo
BVE at baseline32.10 ± 20.1644.03 ± 19.42
BVE at Week 1254.71 ± 33.7846.13 ± 18.72
Statistical analysis
  • TAC-302 · t-test, 2 sided · p = <0.001 · Mean difference (final values): 23.57 · 95% CI 11.26 to 35.88
  • Placebo · t-test, 2 sided · p = 0.708 · Mean difference (final values): 2.10 · 95% CI -10.19 to 14.40
  • TAC-302 vs Placebo · t-test, 2 sided · p = 0.025 · Mean difference (final values): 21.47 · 95% CI 2.96 to 39.98
SecondaryNumber of Micturitions Per 24 Hours at Baseline and Week 12

On the basis of information from bladder diary records in the 3 days directly before each evaluation timepoint, an average of urinations per 24 hours was calculated. The patients with at least 8 urinations per 24 hours at registration were included in this study.

Time frame:
Baseline to Week 12
Reported as:
Mean · Events
Number of Micturitions Per 24 Hours at Baseline and Week 12
EventsTAC-302Placebo
Number of micturitions per 24 hours at baseline11.753 ± 3.06511.764 ± 3.145
Number of micturitions per 24 hours at Week 1210.830 ± 3.95010.174 ± 2.348
SecondaryNumber of Urinary Urgency Episodes Per 24 Hours at Baseline and Week 12

On the basis of information from bladder diary records in the 3 days directly before each evaluation timepoint, an average of urinary urgency episodes per 24 hours was calculated. The patients with at least one urinary urgency episode per 24 hours at registration were included in this study.

Time frame:
Baseline to Week 12
Reported as:
Mean · Events
Number of Urinary Urgency Episodes Per 24 Hours at Baseline and Week 12
EventsTAC-302Placebo
Number of urinary urgency episodes per 24 hours at baseline5.452 ± 4.5745.701 ± 3.878
Number of urinary urgency episodes per 24 hours at Week 124.469 ± 6.0952.493 ± 3.600
SecondaryOveractive Bladder Symptom Score (OABSS) Total Score at Baseline and Week 12

Overactive bladder symptoms were evaluated using the OABSS. The OABSS Total Score is the sum of four symptom scores: daytime frequency (score 0-2), nighttime frequency (score 0-3), urgency (score 0-5), and urgency incontinence (score 0-5). The range of scores is from 0 to 15 points with a higher score indicating greater severity. A score ≤ 5 was determined to be mild, a score of 6 to 11 was determined to be moderate and a score ≥ 12 was determined to be severe.

Time frame:
Baseline to Week 12
Reported as:
Mean · points
Overactive Bladder Symptom Score (OABSS) Total Score at Baseline and Week 12
pointsTAC-302Placebo
OABSS total score at baseline8.7 ± 2.98.9 ± 2.4
OABSS total score at Week 126.5 ± 3.27.3 ± 3.0
SecondaryNumber of Participants With Adverse Events

In tabulation of adverse events, the diagnoses entered on eCRFs were coded using the medical dictionary for regulatory activities (MedDRA) ver.22.1, and were presented as MedDRA preferred terms.

Time frame:
Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
Reported as:
Count of participants · Participants
Number of Participants With Adverse Events
ParticipantsTAC-302Placebo
Any adverse events249
Deafness neurosensory01
Constipation12
Dental caries01
Diarrhea20
Diverticulum intestinal haemorrhagic01
Glossitis01
Haematochezia01
Nausea01
Vomiting01
Pyrexia20
Bacteriuria10
Bronchitis11
Cystitis11
Gastroenteritis10
Herpes virus infection01
Influenza10
Nasopharyngitis21
Periodontitis01
Pharyngitis11
Pyuria20
Urinary tract infection10
Vulvitis10
Enteritis infectious20
Enterocolitis viral10
Compression fracture10
Fracture10
Subdural haematoma10
Contusion10
Post procedural haematuria10
Meniscus injury10
Tooth dislocation10
Blood creatinine phosphokinase increased10
Back pain20
Pain in extremity01
Headache20
Dysuria10
Renal colic10
Urethral pain10
Prostatitis10
Cough01
Dermatitis contact01
Miliaria10
Rash01
Orthostatic hypotension01
SecondaryNumber of Participants With Adverse Drug Reactions
Time frame:
Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
Reported as:
Count of participants · Participants
Number of Participants With Adverse Drug Reactions
ParticipantsTAC-302Placebo
Number of Participants With Adverse Drug Reactions00
SecondaryNumber of Participants With Serious Adverse Events

In tabulation of adverse events, the diagnoses entered on eCRFs were coded using the medical dictionary for regulatory activities (MedDRA) ver.22.1, and were presented as MedDRA preferred terms.

Time frame:
Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
Reported as:
Count of participants · Participants
Number of Participants With Serious Adverse Events
ParticipantsTAC-302Placebo
Any serious adverse events21
Prostatitis10
Subdural haematoma10
Diverticulum intestinal haemorrhagic01
SecondaryNumber of Participants With Adverse Events Leading to Death
Time frame:
Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
Reported as:
Count of participants · Participants
Number of Participants With Adverse Events Leading to Death
ParticipantsTAC-302Placebo
Number of Participants With Adverse Events Leading to Death00
SecondaryNumber of Participants With Adverse Events Leading to Dose Discontinuation
Time frame:
Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
Reported as:
Count of participants · Participants
Number of Participants With Adverse Events Leading to Dose Discontinuation
ParticipantsTAC-302Placebo
Number of Participants With Adverse Events Leading to Dose Discontinuation00
SecondaryNumber of Participants With Adverse Events Leading to Dose Interruption

In tabulation of adverse events, the diagnoses entered on eCRFs were coded using the medical dictionary for regulatory activities (MedDRA) ver.22.1, and were presented as MedDRA preferred terms.

Time frame:
Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
Reported as:
Count of participants · Participants
Number of Participants With Adverse Events Leading to Dose Interruption
ParticipantsTAC-302Placebo
Any adverse events leading to dose interruption21
Enteritis infectious10
Enterocolitis viral10
Diverticulum intestinal haemorrhagic01

Adverse events

Collected over Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period). Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
TAC-3020/52 (0%)2/52 (3.8%)24/52 (46.2%)
Placebo0/24 (0%)1/24 (4.2%)9/24 (37.5%)
Most frequent serious events
Most frequent serious events
EventTAC-302Placebo
Diverticulum intestinal haemorrhagicGastrointestinal disorders0/521/24
Subdural haematomaInjury, poisoning and procedural complications1/520/24
ProstatitisReproductive system and breast disorders1/520/24
Most frequent other events
Showing 10 of 41
Most frequent other events
EventTAC-302Placebo
ConstipationGastrointestinal disorders1/522/24
Deafness neurosensoryEar and labyrinth disorders0/521/24
Dental cariesGastrointestinal disorders0/521/24
GlossitisGastrointestinal disorders0/521/24
HaematocheziaGastrointestinal disorders0/521/24
NauseaGastrointestinal disorders0/521/24
VomitingGastrointestinal disorders0/521/24
BronchitisInfections and infestations1/521/24
CystitisInfections and infestations1/521/24
Herpes virus infectionInfections and infestations0/521/24

Baseline characteristics

Per protocol set (PPS) was used for the analysis. PPS included all patients in the Full analysis set (FAS) with no inclusion/exclusion criteria violations, who were compliant for ≥ 80% of the treatment period, were not administered any prohibited concomitant medication or therapy during the study period, and had a week 12 evaluation of the primary endpoint. FAS included all patients who took the study drug at least once and had ≥ 1 efficacy measurement before and during the treatment period.

Age, Continuous
Age, Continuous(years)TAC-302PlaceboTotal
Mean71.0 ± 10.770.4 ± 9.170.8 ± 10.2
Age, Continuous
Age, Continuous(years)TAC-302PlaceboTotal
Median74.0 (46 to 90)73.5 (44 to 84)74.0 (44 to 90)
Sex: Female, Male
Sex: Female, Male(Participants)TAC-302PlaceboTotal
Female15722
Male271138
Race (NIH/OMB)
Race (NIH/OMB)(Participants)TAC-302PlaceboTotal
American Indian or Alaska Native000
Asian421860
Native Hawaiian or Other Pacific Islander000
Black or African American000
White000
More than one race000
Unknown or Not Reported000
Duration of lower urinary tract symptoms
Duration of lower urinary tract symptoms(months)TAC-302PlaceboTotal
Mean92.2 ± 95.172.9 ± 71.186.4 ± 88.4
Duration of lower urinary tract symptoms
Duration of lower urinary tract symptoms(months)TAC-302PlaceboTotal
Median79.0 (4 to 483)45.5 (12 to 264)68.0 (4 to 483)
Bladder voiding efficiency (BVE)
Bladder voiding efficiency (BVE)(%)TAC-302PlaceboTotal
Mean58.38 ± 26.7463.11 ± 24.1359.82 ± 25.86
Bladder voiding efficiency (BVE)
Bladder voiding efficiency (BVE)(%)TAC-302PlaceboTotal
Median65.15 (0.6 to 88.6)73.46 (11.7 to 89.6)69.18 (0.6 to 89.6)

4 further baseline measures are reported on the registry.

07

Study locations

1 site
  • Taiho Pharmaceutical Co., Ltd selected site
    Kumamoto, Japan
08

References and documents

Publications

  • Yoshida M, Gotoh M, Yokoyama O, Kakizaki H, Yamanishi T, Yamaguchi O. Efficacy of TAC-302 for patients with detrusor underactivity and overactive bladder: a randomized, double-blind, placebo-controlled phase 2 study. World J Urol. 2022 Nov;40(11):2799-2805. doi: 10.1007/s00345-022-04163-4. Epub 2022 Oct 7. PubMed 36205739 ↗

Study documents

  • Study protocol · Sep 19, 2018
  • Statistical analysis plan · Jan 8, 2020

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT03175029
Lead sponsor
Taiho Pharmaceutical Co., Ltd.
Responsible party
Sponsor
First posted
Jun 5, 2017
Start date
Sep 9, 2017
Primary completion
Nov 1, 2019
Completion
Mar 27, 2020
Results posted
Jan 20, 2025
Last update
Jan 20, 2025

Study contacts

Taiho Pharmaceutical Co., Ltd
study director · Taiho Pharmaceutical Co., Ltd.

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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