37 research outputs found
EFFICACY, SAFETY, AND TOLERABILITY OF MIRABEGRON IN PATIENTS AGED ā„65 YR WITH OVERACTIVE BLADDER WET: A PHASE IV, DOUBLE-BLIND, RANDOMISED, PLACEBOCONTROLLED STUDY (PILLAR)
Pozadina: VeÄina bolesnika s prekomjerno aktivnim mokraÄnim mjehurom (PAMM) starija je od 65 godina. Dosad nije bilo prospektivnih ispitivanja kojima bi se ocijenila djelotvornost lijeÄenja agonistom Ī²3-adrenoreceptora mirabegronom u ovoj specifi Änoj dobnoj skupini. Cilj: Ispitivanje faze IV u kojem se usporeÄuju mirabegron u fl eksibilnoj dozi i placebo u starijih bolesnika s PAMM om i urgentnom inkontinencijom. Dizajn, uvjeti i sudionici: Bolesnici iz lokalne zajednice koji imaju ā„ 65 godina i PAMM u trajanju od ā„ 3 mjeseca. Intervencija: Nakon 2 tjednog uvodnog razdoblja tijekom kojeg se primjenjivao placebo bolesnici s jednom ili viÅ”e epizoda inkontinencije, tri ili viÅ”e epizoda urgencije i prosjeÄno osam ili viÅ”e mokrenja tijekom 24 h bili su randomizirani u omjeru 1:1 za dvostruko zaslijepljenu primjenu 25 mg mirabegrona ili odgovarajuÄe formulacije placeba na dan tijekom 12 tjedana. Nakon 4. ili 8. tjedna doza se prema odluci bolesnika i ispitivaÄa mogla poveÄati na 50 mg mirabegrona/odgovarajuÄe formulacije placeba na dan. Mjere ishoda i statistiÄka analiza: Primarne mjere ishoda: promjena srednjeg broja mokrenja tijekom 24 h i srednjeg broja epizoda inkontinencije tijekom 24 h od poÄetka ispitivanja do zavrÅ”etka lijeÄenja. Sekundarne mjere ishoda: promjena srednjeg izmokrenog volumena nakon mokrenja, srednjeg broja epizoda urgencije tijekom 24 h i srednjeg broja epizoda urgentne inkontinencije tijekom 24 h od poÄetka ispitivanja do zavrÅ”etka lijeÄenja. Za ocjenu srednjeg broja mokrenja tijekom 24 h, srednjeg izmokrenog volumena nakon mokrenju i srednjeg broja epizoda urgencije tijekom 24 h koristila se analiza kovarijance (ANCOVA). Za ocjenu srednjeg broja epizoda inkontinencije tijekom 24 h i srednjeg broja epizoda urgentne inkontinencije tijekom 24 h koristila se stratifi cirana rang ANCOVA. Rezultati i ograniÄenja: Uz mirabegron su opažena statistiÄki znaÄajna poboljÅ”anja u odnosu na placebo s obzirom na promjenu srednjeg broja mokrenja tijekom 24 h, srednjeg broja epizoda inkontinencije tijekom 24 h, srednjeg izmokrenog volumena nakon mokrenja, srednjeg broja epizoda urgencije tijekom 24 h i srednjeg broja epizoda urgentne inkontinencije tijekom 24 h od poÄetka ispitivanja do zavrÅ”etka lijeÄenja. Sigurnost i podnoÅ”ljivost odgovarale su poznatom sigurnosnom profi lu mirabegrona. ZakljuÄci: PotvrÄene su djelotvornost, sigurnost i podnoÅ”ljivost mirabegrona tijekom 12 tjedana u bolesnika s PAMM om i inkontinencijom u dobi od ā„ 65 godina.
Sažetak za bolesnike: Ispitivali smo uÄinak mirabegrona u usporedbi s placebom u osoba u dobi od 65 ili viÅ”e godina
s prekomjerno aktivnim mokraÄnim mjehurom i inkontinencijom. Mirabegron je ublažio simptome prekomjerno aktivnog mokraÄnog mjehura u usporedbi s placebom. Opažene nuspojave bile su sliÄne poznatim nuspojavama mirabegrona.Background: The majority of patients with overactive bladder (OAB) are aged >65 yr. There has been no prospectively designed study assessing treatment effi cacy with the b3-adrenoreceptor agonist, mirabegron, specifi cally in this age group. Objective: A phase IV study comparing fl exibly dosed mirabegron versus placebo in elderly patients with OAB and urgency incontinence. Design, setting, and participants: Community-dwelling patients aged ā„65 yr with OAB for ā„3 mo. Intervention: Following a 2-wk placebo run in, patients with one or more incontinence episodes, three or more urgency episodes, and an average of eight or more micturitions/ 24 h were randomised 1:1 to double-blind 25 mg/d mirabegron or matched placebo, for 12 wk. After week 4 or 8, the dose could be increased to 50 mg/d mirabegron/matched placebo based on patient and investigator discretion. Outcome measurements and statistical analysis: Coprimary endpoints: change from baseline to end of treatment (EOT) in the mean numbers of micturitions/24 h and incontinence episodes/24 h. Secondary endpoints: change from baseline to EOT in the mean volume voided/micturition, mean number of urgency episodes/24 h, and mean number of urgency incontinence episodes/24 h. Analysis of covariance (ANCOVA) was used for the mean number of micturitions/24 h, mean volume voided/micturition, and mean number of urgency episodes/24 h. Stratifi ed rank ANCOVA was used for the
mean numbers of incontinence episodes/24 h and urgency incontinence episodes/24 h. Results and limitations: Statistically signifi cant improvements were observed for mirabegron versus placebo in change from baseline to EOT in the mean number of micturitions/24 h, mean number of incontinence episodes/24 h, mean volume voided/micturition, mean number of urgency episodes/24 h, and mean number of urgency incontinence episodes/24 h. Safety and tolerability were consistent with the known mirabegron safety profi le. Conclusions: Mirabegron effi cacy, safety, and tolerability over 12 wk were confi rmed in patients aged ā„65 yr with OAB and incontinence
EFFICACY, SAFETY, AND TOLERABILITY OF MIRABEGRON IN PATIENTS AGED ā„65 YR WITH OVERACTIVE BLADDER WET: A PHASE IV, DOUBLE-BLIND, RANDOMISED, PLACEBOCONTROLLED STUDY (PILLAR)
Pozadina: VeÄina bolesnika s prekomjerno aktivnim mokraÄnim mjehurom (PAMM) starija je od 65 godina. Dosad nije bilo prospektivnih ispitivanja kojima bi se ocijenila djelotvornost lijeÄenja agonistom Ī²3-adrenoreceptora mirabegronom u ovoj specifi Änoj dobnoj skupini. Cilj: Ispitivanje faze IV u kojem se usporeÄuju mirabegron u fl eksibilnoj dozi i placebo u starijih bolesnika s PAMM om i urgentnom inkontinencijom. Dizajn, uvjeti i sudionici: Bolesnici iz lokalne zajednice koji imaju ā„ 65 godina i PAMM u trajanju od ā„ 3 mjeseca. Intervencija: Nakon 2 tjednog uvodnog razdoblja tijekom kojeg se primjenjivao placebo bolesnici s jednom ili viÅ”e epizoda inkontinencije, tri ili viÅ”e epizoda urgencije i prosjeÄno osam ili viÅ”e mokrenja tijekom 24 h bili su randomizirani u omjeru 1:1 za dvostruko zaslijepljenu primjenu 25 mg mirabegrona ili odgovarajuÄe formulacije placeba na dan tijekom 12 tjedana. Nakon 4. ili 8. tjedna doza se prema odluci bolesnika i ispitivaÄa mogla poveÄati na 50 mg mirabegrona/odgovarajuÄe formulacije placeba na dan. Mjere ishoda i statistiÄka analiza: Primarne mjere ishoda: promjena srednjeg broja mokrenja tijekom 24 h i srednjeg broja epizoda inkontinencije tijekom 24 h od poÄetka ispitivanja do zavrÅ”etka lijeÄenja. Sekundarne mjere ishoda: promjena srednjeg izmokrenog volumena nakon mokrenja, srednjeg broja epizoda urgencije tijekom 24 h i srednjeg broja epizoda urgentne inkontinencije tijekom 24 h od poÄetka ispitivanja do zavrÅ”etka lijeÄenja. Za ocjenu srednjeg broja mokrenja tijekom 24 h, srednjeg izmokrenog volumena nakon mokrenju i srednjeg broja epizoda urgencije tijekom 24 h koristila se analiza kovarijance (ANCOVA). Za ocjenu srednjeg broja epizoda inkontinencije tijekom 24 h i srednjeg broja epizoda urgentne inkontinencije tijekom 24 h koristila se stratifi cirana rang ANCOVA. Rezultati i ograniÄenja: Uz mirabegron su opažena statistiÄki znaÄajna poboljÅ”anja u odnosu na placebo s obzirom na promjenu srednjeg broja mokrenja tijekom 24 h, srednjeg broja epizoda inkontinencije tijekom 24 h, srednjeg izmokrenog volumena nakon mokrenja, srednjeg broja epizoda urgencije tijekom 24 h i srednjeg broja epizoda urgentne inkontinencije tijekom 24 h od poÄetka ispitivanja do zavrÅ”etka lijeÄenja. Sigurnost i podnoÅ”ljivost odgovarale su poznatom sigurnosnom profi lu mirabegrona. ZakljuÄci: PotvrÄene su djelotvornost, sigurnost i podnoÅ”ljivost mirabegrona tijekom 12 tjedana u bolesnika s PAMM om i inkontinencijom u dobi od ā„ 65 godina.
Sažetak za bolesnike: Ispitivali smo uÄinak mirabegrona u usporedbi s placebom u osoba u dobi od 65 ili viÅ”e godina
s prekomjerno aktivnim mokraÄnim mjehurom i inkontinencijom. Mirabegron je ublažio simptome prekomjerno aktivnog mokraÄnog mjehura u usporedbi s placebom. Opažene nuspojave bile su sliÄne poznatim nuspojavama mirabegrona.Background: The majority of patients with overactive bladder (OAB) are aged >65 yr. There has been no prospectively designed study assessing treatment effi cacy with the b3-adrenoreceptor agonist, mirabegron, specifi cally in this age group. Objective: A phase IV study comparing fl exibly dosed mirabegron versus placebo in elderly patients with OAB and urgency incontinence. Design, setting, and participants: Community-dwelling patients aged ā„65 yr with OAB for ā„3 mo. Intervention: Following a 2-wk placebo run in, patients with one or more incontinence episodes, three or more urgency episodes, and an average of eight or more micturitions/ 24 h were randomised 1:1 to double-blind 25 mg/d mirabegron or matched placebo, for 12 wk. After week 4 or 8, the dose could be increased to 50 mg/d mirabegron/matched placebo based on patient and investigator discretion. Outcome measurements and statistical analysis: Coprimary endpoints: change from baseline to end of treatment (EOT) in the mean numbers of micturitions/24 h and incontinence episodes/24 h. Secondary endpoints: change from baseline to EOT in the mean volume voided/micturition, mean number of urgency episodes/24 h, and mean number of urgency incontinence episodes/24 h. Analysis of covariance (ANCOVA) was used for the mean number of micturitions/24 h, mean volume voided/micturition, and mean number of urgency episodes/24 h. Stratifi ed rank ANCOVA was used for the
mean numbers of incontinence episodes/24 h and urgency incontinence episodes/24 h. Results and limitations: Statistically signifi cant improvements were observed for mirabegron versus placebo in change from baseline to EOT in the mean number of micturitions/24 h, mean number of incontinence episodes/24 h, mean volume voided/micturition, mean number of urgency episodes/24 h, and mean number of urgency incontinence episodes/24 h. Safety and tolerability were consistent with the known mirabegron safety profi le. Conclusions: Mirabegron effi cacy, safety, and tolerability over 12 wk were confi rmed in patients aged ā„65 yr with OAB and incontinence
Modeling dose-response relationships of the effects of fesoterodine in patients with overactive bladder
<p>Abstract</p> <p>Background</p> <p>Fesoterodine is an antimuscarinic for the treatment of overactive bladder, a syndrome of urgency, with or without urgency urinary incontinence (UUI), usually with increased daytime frequency and nocturia. Our objective was to develop predictive models to describe the dose response of fesoterodine.</p> <p>Methods</p> <p>Data from subjects enrolled in double-blind, placebo-controlled phase II and III trials were used for developing longitudinal dose-response models.</p> <p>Results</p> <p>The models predicted that clinically significant and near-maximum treatment effects would be seen within 3 to 4 weeks after treatment initiation. For a typical patient with 11 micturitions per 24 hours at baseline, predicted change was -1.2, -1.7, and -2.2 micturitions for placebo and fesoterodine 4 mg and 8 mg, respectively. For a typical patient with 2 UUI episodes per 24 hours at baseline, predicted change was -1.05, -1.26, and -1.43 UUI episodes for placebo and fesoterodine 4 mg and 8 mg, respectively. Increase in mean voided volume was estimated at 9.7 mL for placebo, with an additional 14.2 mL and 28.4 mL for fesoterodine 4 mg and 8 mg, respectively.</p> <p>Conclusions</p> <p>A consistent dose response for fesoterodine was demonstrated for bladder diary endpoints in subjects with overactive bladder, a result that supports the greater efficacy seen with fesoterodine 8 mg in post hoc analyses of clinical trial data. The dose-response models can be used to predict outcomes for doses not studied or for patient subgroups underrepresented in clinical trials.</p> <p>Trial Registration</p> <p>The phase III trials used in this analysis have been registered at ClinicalTrials.gov (NCT00220363 and NCT00138723).</p