TOKYO and NEW ORLEANS, May 17,
2015 /PRNewswire/ -- Astellas Pharma Inc. (TSE: 4503)
announced today that results from its Phase 3b BESIDE clinical
trial demonstrated solifenacin (SOLI) with mirabegron (MIRA) as an add-on therapy (ADD-ON) was
superior to solifenacin monotherapy in incontinent overactive
bladder (OAB) patients. The results of the BESIDE trial, which were
presented today at the 2015 annual meeting of the American
Urological Association (AUA), showed that the ADD-ON group achieved
its primary efficacy endpoints.
In the BESIDE trial, the mean number of daily incontinence
episodes was reduced by 1.80 episodes in OAB patients given
solifenacin 5 mg with mirabegron 50 mg (dosage was increased from
25 mg after 4 weeks) as an add-on therapy compared to a reduction
of 1.53 episodes seen with SOLI 5 mg monotherapy. The difference
between the two treatments of approximately 0.26 was statistically
significant (P=0.001). The mean number of daily micturitions was
reduced by 1.59 micturitions in the ADD-ON group compared to 1.14
micturitions with SOLI 5 mg (the difference of 0.45 was
statistically significant [P<0.001]).
In addition, ADD-ON treatment was both non-inferior and superior
to SOLI 10 mg for daily reduction in micturitions. ADD-ON treatment
also was superior to SOLI 5 mg and 10 mg monotherapy for
improvement in urine volume voided per micturition.
At least one treatment emergent adverse event (TEAE) was
reported by 35.9% receiving ADD-ON therapy, 39.4% receiving SOLI 10
mg and 33.1% receiving SOLI 5 mg, with the most common (occurring
in at least 2% of patients) being dry mouth, constipation and
peripheral edema. Serious adverse events (SAEs) were reported by
1.8% of patients receiving ADD-ON therapy, 2.1% receiving SOLI 10
mg and 1.2% receiving SOLI 5 mg. The ADD-ON group reported a lower
incidence of dry mouth than the SOLI 10 mg group (5.9% versus
9.5%), and a similar incidence as the SOLI 5 mg group (5.6%). The
incidence of constipation in the ADD-ON group was 4.6% versus 4.7%
and 3.0% for the SOLI 10 mg and SOLI 5 mg groups,
respectively.
"The BESIDE results appear to indicate that adding mirabegron
therapy, a Beta-3 adrenergic agonist, to solifenacin therapy, an
antimuscarinic, may offer relief from the burden of OAB," said
Professor Marcus Drake, MA, DM, FRCS (Urol), University of
Bristol and Bristol Urological
Institute, Bristol, UK. "Such a
combined use may help practitioners address the continued unmet
need for additional treatment options that can help people living
with this debilitating condition."
About the BESIDE Trial
The Phase 3b BESIDE study is a randomized, double-blind,
international study designed to evaluate the efficacy and safety of
mirabegron as add-on therapy to solifenacin in incontinent OAB
patients. Study patients received SOLI 5 mg monotherapy for 4
weeks; subjects with inadequate response to treatment (i.e.,
patients who still experienced one or more incontinence episodes
during a three-day diary period) were then randomized to either
SOLI 5 mg, SOLI 10 mg, or SOLI 5 mg in combination with
MIRA 25 mg, which was increased to
MIRA 50 mg after 4 weeks. Overall
2,174 patients were randomized to the ADD-ON group (n=727), SOLI 5
mg (n=728) or SOLI 10 mg (n=719). The primary efficacy endpoint was
change from baseline to the end of treatment (EoT) in mean number
of incontinence episodes/24 hours.
All three treatment arms investigated in this study appeared to
be well-tolerated, and the adverse event (AE) profile with ADD-ON
treatment was generally consistent with the known profiles of SOLI
and MIRA. Vital signs in this
group showed no additive or synergistic effects beyond those known
for either monotherapy.
ABOUT
MYRBETRIQ®/BETMIGA®/BETANIS®
(mirabegron)
Indication and Usage
Myrbetriq/Betmiga/Betanis (mirabegron) is a beta-3
adrenergic agonist indicated for the treatment of overactive
bladder (OAB) with symptoms of urge urinary incontinence, urgency,
and urinary frequency.
Important Safety Information
Myrbetriq can increase blood pressure. Periodic blood pressure
determinations are recommended, especially in hypertensive
patients. Myrbetriq is not recommended for use in severe
uncontrolled hypertensive patients (defined as systolic blood
pressure >/= 180mm Hg and/or diastolic blood
pressure >/= 110 mm Hg).
Urinary retention in patients with bladder outlet obstruction
(BOO) and in patients taking antimuscarinic medications for the
treatment of OAB has been reported in postmarketing experience in
patients taking mirabegron. A controlled clinical safety study in
patients with BOO did not demonstrate increased urinary retention
in Myrbetriq patients; however, Myrbetriq should be administered
with caution to patients with clinically significant BOO. Myrbetriq
should also be administered with caution to patients taking
antimuscarinic medications for the treatment of OAB.
Since Myrbetriq is a moderate CYP2D6 inhibitor, the systemic
exposure to CYP2D6 substrates such as metoprolol and desipramine is
increased when coadministered with Myrbetriq. Therefore,
appropriate monitoring and dose adjustment may be necessary,
especially with narrow therapeutic index drugs metabolized by
CYP2D6, such as thioridazine, flecainide, and propafenone.
Most commonly reported adverse reactions (>2% and
>placebo) for Myrbetriq 25 mg and 50 mg vs placebo,
respectively, were hypertension (11.3%, 7.5% vs 7.6%),
nasopharyngitis (3.5%, 3.9% vs 2.5%), urinary tract infection
(4.2%, 2.9% vs 1.8%), and headache (2.1%, 3.2% vs 3.0%).
For Full Prescribing Information for Myrbetriq (mirabegron)
extended–release tablets, please visit
http://www.myrbetriqHCP.com.
About VESIcare® (solifenacin succinate)
tablets
Indication and Dosage
VESIcare (solifenacin succinate) tablets are indicated for the
treatment of overactive bladder with symptoms of urge urinary
incontinence, urgency, and urinary frequency. The recommended dose
of VESIcare is 5 mg once daily. If the 5-mg dose is well tolerated,
the dose may be increased to 10 mg once daily.
Important Safety Information
VESIcare is contraindicated in patients with urinary retention,
gastric retention, uncontrolled narrow-angle glaucoma, and in
patients with hypersensitivity to the product.
Angioedema of the face, lips, tongue and/or larynx have been
reported with VESIcare. Cases of angioedema have been
reported to occur hours after the first dose or after multiple
doses. Angioedema associated with upper airway swelling may
be life threatening. If involvement of the tongue, hypopharynx, or
larynx occurs, VESIcare should be promptly discontinued and
appropriate therapy and/or measures necessary to ensure a patent
airway should be promptly provided. Anaphylactic reactions have
been reported rarely in patients treated with VESIcare. VESIcare
should not be used in patients with a known or suspected
hypersensitivity to solifenacin succinate. In patients who
develop anaphylactic reactions, VESIcare should be discontinued and
appropriate therapy and/or measures should be taken.
VESIcare should be administered with caution to patients with
clinically significant bladder outflow obstruction, decreased
gastrointestinal motility, controlled narrow-angle glaucoma, or
reduced renal or hepatic function. Doses of VESIcare higher than 5
mg are not recommended in patients with severe renal impairment,
moderate hepatic impairment, or when administered with ketoconazole
or other potent CYP3A4 inhibitors. Use of VESIcare in patients with
severe hepatic impairment is not recommended.
Anticholinergic central nervous system (CNS) effects have been
reported with VESIcare use, including headache, confusion,
hallucinations and somnolence. Patients should be monitored for
signs of anticholinergic CNS effects, particularly after beginning
treatment or increasing dose, and be advised not to drive or
operate heavy machinery until they know how VESIcare affects them.
If a patient experiences these effects, dose reduction or drug
discontinuation should be considered.
In placebo-controlled studies, for the 10-mg dose, three
intestinal serious adverse events were reported (one fecal
impaction, one colonic obstruction, and one intestinal
obstruction). For the 5-mg dose, one serious adverse event
(angioneurotic edema) was reported.
In placebo-controlled studies, the most common adverse reactions
reported by patients were dry mouth (10.9%, 27.6%, 4.2%),
constipation (5.4%, 13.4%, 2.9%), blurred vision (3.8%, 4.8%,
1.8%), and urinary tract infection (2.8%, 4.8%, 2.8%) with VESIcare
5 mg, 10 mg, and placebo, respectively.
For Full Prescribing Information for VESIcare (solifenacin
succinate) tablets, please visit http://www.vesicareHCP.com.
Myrbetriq, ® Betmiga,
® Betanis® and VESIcare®
are trademarks of Astellas Pharma Inc.
About Overactive Bladder (OAB)
Overactive bladder is a urine storage problem of urgency, with or
without urge urinary incontinence (leakage), often with urinary
frequency and nocturia.1 By 2018, an estimated 546
million people worldwide will be affected by OAB.2
For people with OAB, inappropriate signals are
sent to the muscles in the bladder causing them to contract before
the bladder is full. These bladder contractions may cause strong,
sudden urges, and a frequent need to go to the
bathroom.3
About Astellas
Astellas is a pharmaceutical company dedicated to improving the
health of people around the world through provision of innovative
and reliable pharmaceuticals. For more information on Astellas,
please visit our website at www.astellas.us, follow us on
Twitter at www.twitter.com/AstellasUS or like our
Facebook page at www.facebook.com/AstellasUS.
References:
1. Abrams P, Cardozo L, Fall M, et al. The
standardisation of terminology of lower urinary tract function:
report from the standardisation sub-committee of the international
continence society. Neurourology & Urodynamics. 2002;
21(2): 167–78.
2. Irwin DE, Kopp ZS, Agatep B, Milsom I, Abrams P.
Worldwide prevalence estimates of lower urinary tract symptoms,
overactive bladder, urinary incontinence and bladder outlet
obstruction. BJU Int. 2011;108(7):1132-1138.
3. It's Time to Talk about OAB. Urology Care
Foundation Web site. http://www.urologyhealth.org/OAB/patients.cfm.
Accessed May 4, 2015
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