Summary of the Study Results
Study Operator
(Corporation,
Kyorin Pharmaceutical Co., Ltd./ Ono Pharmaceutical Co., Ltd.
Institution)
Target Indication
Overactive bladder
Proprietary Name
(For approved drug)
Uritos® Tablets 0.1 mg/ Staybla® Tablets 0.1 mg
Active ingredient
Imidafenacin
Name of Study
Long-term study of imidafenacin in overactive bladder
Number of
Investigational Sites
38
Study Period
Undisclosed
Phase of Study
Phase III
Publication
Osamu Yamaguchi et al., Yakuri to Chiryo/ Japanese Pharmacology and
Therapeutics 2009; 37: 909-930
To assess the safety and efficacy of long-term treatment (52 weeks) of
Study Objectives
imidafenacin 0.2 mg/day or 0.4 mg/day (increased dose after 12-week
treatment with 0.2 mg/day) in a multicenter open-label uncontrolled
study in patients with overactive bladder.
Study methods
Multicenter open-label uncontrolled study
Planned: 300-350 patients to receive the study drug (at least 100 patients
Number of Subjects
to be assessed at 52 weeks after dose increase)
Analyzed: 435 patients enrolled and analyzed for safety, 338 patients
analyzed for efficacy (PPS)
Criteria for Subjects
[Main Inclusion Criteria]
1. Male and female patients at the age of 20 years or older
2. Urinary urgency, urinary frequency, or urge urinary incontinence
[Main Exclusion Criteria]
1. Genuine stress urinary incontinence
2. Concomitant diseases including bladder cancer, urinary calculus, and
urinary tract infection
3. Diseases in which anticholinergic drugs are contraindicated
4. Polyuria
Investigational New
Drug, Dose and
Normal dose: A 0.1 mg tablet of imidafenacin per dose was orally
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Administration
administered twice daily after breakfast and dinner.
Increased dose: Two 0.1 mg tablets of imidafenacin per dose were orally
administered twice daily after breakfast and dinner.
0.2 mg/day without dose increase: 52 weeks (Treatment period with the
normal dose: 52 weeks)
Treatment Period
0.4 mg/day including dose increase: 64 weeks (Treatment period with the
normal dose: 12 weeks; Treatment period with the increased dose: 52
weeks)
[Safety Endpoints]
Adverse
events,
adverse
drug
reactions,
laboratory
tests,
electrocardiogram (12-lead), blood pressure, pulse rate, and residual
urine volume.
Endpoints
[Efficacy Endpoints]
Number of urge urinary incontinence episodes, urinary incontinence
episodes, Micturitions, urgency episodes, mean voided volume per
micturition, QOL etc.
The following analyses were performed on data from treatment groups
that continued to receive 0.2 mg/day and that were switched to receive
0.4 mg/day after dose increase:
[Safety Analysis]
The safety analyses were performed using the safety population.The
incidences of adverse events and adverse drug reactions were calculated.
Summary statistics for measured value in blood pressure, pulse rate, and
Statistical Methods
residual urine volume were calculated per assessment period and
longitudinal changes for those parameters were examined. Summary
statistics were calculated for item of continuous quantity and frequency
distribution tables were created for item of ordinal scale for laboratory
values per assessment period. Also, the existence of abnormal findings
and the percentages of abnormal changes were calculated.
[Efficacy Analysis]
The efficacy analyses were performed using the Per Protocol Set (PPS).
The PPS was the primary analytical population.
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Summary statistics for measured values, change, and percentage change
for the efficacy endpoints were calculated per assessment period and
longitudinal changes for the efficacy endpoints were examined.
The dose increase to 0.4 mg of imidafenacin further improved symptoms
of overactive bladder and QOL in patients who did not respond
sufficiently to the normal dose (0.2 mg/day). The effect was maintained
without attenuation for one year after dose increase. While it was
Summary/Conclusion
supposed that close attention should be paid to the onset of adverse
events including dry mouth and constipation probably due to
anticholinergic effects, there was no increase in adverse drug reactions or
new clinically problematic adverse drug reaction arising from the
long-term treatment after dose increase, indicating that long-term
treatment can be safely performed.
Creation date of This
Summary
June 30, 2010
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