Primary objective:* To evaluate the safety and tolerability of long-term combination treatment with solifenacin (5 mg)with mirabegron (50 mg) compared to solifenacin and mirabegron monotherapySecondary objectives:* To evaluate efficacy of long-term…
ID
Source
Brief title
Condition
- Bladder and bladder neck disorders (excl calculi)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary
Incidence and severity of treatment emergent adverse events (TEAEs)
Primary Efficacy Variables
* Change from baseline in mean number of incontinence episodes per 24 hours at
EoT
* Change from baseline in mean number of micturitions per 24 hours at EoT
Key Responder Variables
* Zero Incontinence Episodes: a responder is defined as a subject with 0
incontinence episodes
post-baseline in the last 3 days prior to Month 1, 3, 6, 9, 12, and EoT
* Responders for changes from baseline in Symptom Bother and health related QoL
scores as
assessed by OAB-q: a responder is defined as a subject with at least 10 points
improvement from
baseline to each visit (Month 1, 3, 6, 9, 12, and EoT)
* 50% Reduction in Incontinence Episodes: a responder is defined as a subject
with at least 50%
decrease from baseline in mean number of incontinence episodes per 24 hours
(Month 1, 3, 6, 9,
12, and EoT)
Secondary outcome
Secondary Safety Variables
* Vital signs: sitting systolic and diastolic blood pressure and pulse rate
(home measurements and
office measurements)
* Laboratory tests: hematology, biochemistry, and urinalysis
* ECG parameters
* PVR
Secondary Efficacy Variables
* Change from baseline in mean volume voided per micturition at EoT
* Change from baseline in Symptom Bother as assessed by Overactive Bladder
Questionnaire
(OAB-q) at EoT
* Change from baseline in subject assessment of Treatment Satisfaction * Visual
Analogue Scale
(TS-VAS) at EoT
* Number of incontinence episodes at Month 1, 3, 6, 9 12, and EoT and changes
from baseline
* Change from baseline in mean number of incontinence episodes at secondary
time points (after 1,
3, 6, 9 and 12 months of treatment)
* Change from baseline in mean number of micturitions at secondary time points
( after 1, 3, 6, 9
and 12 months of treatment)
* Change from baseline in mean volume voided at secondary time points (after 3,
6 and 12 months
of treatment)
* Number of urgency incontinence episodes during the 7-day observation period
prior to Month 1,
3, 6, 9, 12, and EoT and changes from baseline
* Change from baseline in mean number of urgency incontinence episodes per 24
hours (Month 1,
3, 6, 9, 12, and EoT)
* Change from baseline in mean number of urgency episodes (grade 3 and/or 4)/24
hours (PPIUS
scale) (Month 1, 3, 6, 9, 12, and EoT)
* Number of nocturia episodes during the 7-day observation period prior to
Month 1, 3, 6, 9, 12,
and EoT and changes from baseline
* Change from baseline in mean number of nocturia episodes per 24 hours (Month
1, 3, 6, 9, 12,
and EoT)
* Number of pads used during the 7-day observation period prior to Month 1, 3,
6, 9, 12, and EoT
and changes from baseline
* Change from baseline in mean number of pads used per 24 hours (Month 1, 3, 6,
9, 12, and EoT)
* Number of incontinence-free days during the 7-day diary period (Month 1, 3,
6, 9, 12, and EoT)
* Number of days with less than 8 micturitions during the 7-day diary period
(Month 1, 3, 6, 9, 12,
and EoT)
* Number of incontinence-free days with less than 8 micturitions during the
7-day diary period
(Month 1, 3, 6, 9, 12, and EoT)
* Change from baseline in PPBC (Month 1, 3, 6, 9, 12, and EoT)
* Change from baseline in Symptom Bother as assessed by the OAB-q at secondary
time points
(Month 1, 3, 6, 9, and 12)
* Change from baseline in health related QoL scores as assessed by the OAB-q
(including
subscales) (Month 1, 3, 6, 9, 12, and EoT)
* Patient Global Impression of Change (PGIC) scale (Month 12 and EoT)
* Change from baseline in scores as assessed by the European Quality of Life in
5 Dimensions
(EQ-5D) questionnaire (including subscales) (Month 1, 3, 6, 9, 12, and EoT)
* Change from baseline in scores as assessed by the Work Productivity and
Activity Impairment:
Specific Health Problem (WPAI:SHP) questionnaire (Month 6, 12, and EoT)
* Change from baseline in the subject's assessment of TS-VAS at secondary time
points (Month 1,
3, 6, 9, and 12)
Other Responder Variables
* Micturition Frequency Normalization: a responder is defined as a subject who
had at least 8
micturitions per 24 hours at baseline and less than 8 micturitions per 24 hours
post-baseline
(Month 1, 3, 6, 9, 12, and EoT)
* Zero Incontinence Episodes: a responder is defined as a subject with 0
incontinence episodes
post-baseline in the last 7 days prior to Month 1, 3, 6, 9, 12, and EoT
* Subjects with at least 1 point improvement from baseline in PPBC (Month 1, 3,
6, 9, 12, and EoT)
* Subjects with major (at least 2 points) improvement from baseline in PPBC
(Month 1, 3, 6, 9, 12,
and EoT)
* Double responder: 50% reduction in mean number of incontinence episodes per
24 hours
compared to baseline and MID reached (improvement by at least 10 points) on the
Symptom
Bother scale of the OAB-q (Month 1, 3, 6, 9, 12, and EoT)
* Double responder: 50% reduction in mean number of incontinence episodes per
24 hours
compared to baseline and MID reached (improvement by at least 10 points) on the
HRQL Total
score of the OAB-q (Month 1, 3, 6, 9, 12, and EoT)
* Double responder: 50% reduction in mean number of incontinence episodes per
24 hours
compared to baseline and at least 1 point improvement from baseline in PPBC
(Month 1, 3, 6, 9,
12, and EoT)
* Triple responder: 50% reduction in mean number of incontinence episodes per
24 hours
compared to baseline, MID reached (improvement by at least 10 points) on the
Symptom Bother
scale of the OAB-q, and at least 1 point improvement from baseline in PPBC
(Month 1, 3, 6, 9,
12, and EoT)
* Triple responder: 50% reduction in mean number of incontinence episodes per
24 hours
compared to baseline, MID reached (improvement by at least 10 points) on the
HRQL Total score
of the OAB-q, and at least 1 point improvement from baseline in PPBC (Month 1,
3, 6, 9, 12, and
EoT)
Background summary
To evaluate the safety and tolerability of long-term combination treatment with
solifenacin (5 mg)
with mirabegron (50 mg) compared to solifenacin and mirabegron monotherapy
Study objective
Primary objective:
* To evaluate the safety and tolerability of long-term combination treatment
with solifenacin (5 mg)
with mirabegron (50 mg) compared to solifenacin and mirabegron monotherapy
Secondary objectives:
* To evaluate efficacy of long-term combination treatment with solifenacin and
mirabegron
* To evaluate Patient Reported Outcomes (PRO) during long-term combination
treatment with
solifenacin and mirabegron
Study design
This is a multinational, multi-center, randomized, double-blind,
parallel-group, active controlled phase 3 study.
The study will comprise a single-blind, 2-week placebo run-in period followed
by a randomized, double-blind, active controlled, 52-week treatment period
followed by a 2-week follow-up period. Subjects will visit the clinic at
Screening (Visit 1), at the end of the placebo run-in period (Visit 2/
Randomization), after 1, 3, 6, 9 and 12 months of double-blind treatment (Visit
3, 4, 5, 6 and 7) and 2
weeks after End of Trial (EoT), for a follow-up visit (Visit 8).
Intervention
Investigational Product and Dose:
* Combination of 5 mg solifenacin + 50 mg mirabegron
Comparative Drug and Dose:
* Solifenacin succinate 5 mg
* Mirabegron OCAS 50 mg
Study burden and risks
Based on the data available for the monotherapies and combination treatment, it
is expected that the potential benefits of participating in the trial outweigh
the risk.
Sylviusweg 62
Leiden 2333 BE
NL
Sylviusweg 62
Leiden 2333 BE
NL
Listed location countries
Age
Inclusion criteria
* Subject is male or female and at least 18 years of age;;* Subject is willing and able to complete the micturition diary and questionnaires correctly and able to measure his/her vital signs at home at stipulated time points, using the device provided by the study personnel, and to adequately record the readings;;* Subject has symptoms of *wet* OAB for at least three months
Exclusion criteria
* Subject has neurological cause for detrusor overactivity (e.g. neurogenic bladder, diabetic neuropathy with autonomic component or bladder involvement, or systemic or central neurological disease such as multiple sclerosis and Parkinson's disease with autonomic component or bladder involvement). An autonomic component can be inferred when autonomic functions are affected, including heart rate, blood pressure, perspiration and digestion.;* Subject has chronic inflammation such as bladder pain syndrome / interstitial cystitis, symptomatic bladder stones or any previous or current radiation cystitis.;* Subject has moderate to severe hepatic impairment;* Subject has severe renal impairment;* Subject has a clinically significant abnormal ECG;* Subject has a concurrent malignancy or history of cancer (except noninvasive skin cancer) within the last 5 years prior to screening.;* Subject has an average QTcF interval > 450 ms for males or > 470 ms for females based on the triplicate ECGs completed at Screening or is at risk of QT prolongation (e.g., family history of long QT syndrome, hypokalaemia).;* Subject has severe hypertension, which is defined as a sitting average systolic blood pressure * 180 mmHg and/or average diastolic blood pressure * 110 mmHg.;* In the opinion of the investigator the subject has clinically significant bladder outflow obstruction at risk of urinary retention;;* Subject has significant PVR volume (> 150 mL); ;* Subject has significant stress incontinence or mixed stress/urgency incontinence where stress is the predominant factor as determined by the investigator;;* Subject has an indwelling catheter or practices intermittent self-catheterization;;* Subject has evidence of urinary tract infection (UTI), chronic inflammation such as interstitial cystitis, bladder stones, previous pelvic radiation therapy or previous or current malignant disease of the pelvic organs;;* Subject has had intravesical treatment in the past 12 months with e.g., botulinum toxin, resiniferatoxin, capsaicin;
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2012-005736-29-NL |
| CCMO | NL45587.018.13 |