TOVIAZ® (fesoterodine fumarate) 14 CLINICAL STUDIES

(fesoterodine fumarate)

Prescribing Information

14 CLINICAL STUDIES

14.1 Adult Overactive Bladder

The efficacy of Toviaz extended-release tablets was evaluated in two, Phase 3, randomized, double-blind, placebo-controlled, 12-week studies for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency. Entry criteria required that patients have symptoms of overactive bladder for ≥6-months duration, at least 8 micturitions per day, and at least 6 urinary urgency episodes or 3 urge incontinence episodes per 3-day diary period. Patients were randomized to a fixed dose of Toviaz 4 or 8 mg/day or placebo. In one of these studies, 290 patients were randomized to an active control arm (an oral antimuscarinic agent). For the combined studies, a total of 554 patients received placebo, 554 patients received Toviaz 4 mg/day, and 566 patients received Toviaz 8 mg/day. The majority of patients were Caucasian (91%) and female (79%) with a mean age of 58 years (range 19–91 years).

The primary efficacy endpoints were the mean change in the number of urge urinary incontinence episodes per 24 hours and the mean change in the number of micturitions (frequency) per 24 hours. An important secondary endpoint was the mean change in the voided volume per micturition.

Results for the primary endpoints and for mean change in voided volume per micturition from the two 12-week clinical studies of Toviaz are reported in Table 10.

Table 10: Mean Baseline and Change From Baseline to Week 12 for Urge Urinary Incontinence Episodes, Number of Micturitions, and Volume Voided per Micturition
	Study 1			Study 2
Parameter	Placebo N=279	Toviaz 4mg/day N=265	Toviaz 8mg/day N=276	Placebo N=266	Toviaz 4mg/day N=267	Toviaz 8mg/day N=267
vs. = versus
* Only those patients who were urge incontinent at baseline were included for the analysis of number of urge incontinence episodes per 24 hours: In Study 1, the number of these patients was 211, 199, and 223 in the placebo, Toviaz 4 mg/day and Toviaz 8 mg/day groups, respectively. In Study 2, the number of these patients was 205, 228, and 218, respectively.
Number of urge incontinence episodes per 24 hours*
Baseline	3.7	3.8	3.7	3.7	3.9	3.9
Change from baseline	-1.20	-2.06	-2.27	-1.00	-1.77	-2.42
p-value vs. placebo	-	0.001	<0.001	-	<0.003	<0.001
Number of micturitions per 24 hours
Baseline	12.0	11.6	11.9	12.2	12.9	12.0
Change from baseline	-1.02	-1.74	-1.94	-1.02	-1.86	-1.94
p-value vs. placebo	-	<0.001	<0.001	-	0.032	<0.001
Voided volume per micturition (mL)
Baseline	150	160	154	159	152	156
Change from baseline	10	27	33	8	17	33
p-value vs. placebo	-	<0.001	<0.001	-	0.150	<0.001

Figures 1–4: The following figures show change from baseline over time in number of micturitions and urge urinary incontinence episodes per 24 h in the two studies.

A reduction in number of urge urinary incontinence episodes per 24 hours was observed for both doses as compared to placebo as early as two weeks after starting Toviaz therapy.

14.2 Pediatric Neurogenic Detrusor Overactivity

The efficacy of Toviaz was evaluated in Study 3 (NCT01557244), a Phase 3, randomized, open-label study consisting of a 12-week efficacy phase followed by a 12-week safety extension phase in pediatric patients from 6 years to 17 years of age. Two cohorts were studied. Cohort 1 (patients weighing greater than 25 kg) received a fixed dose of Toviaz 4 mg or Toviaz 8 mg tablets orally once daily, or once daily. In the safety extension phase, patients randomized to the active comparator were switched to Toviaz 4 mg or Toviaz 8 mg once daily. For study inclusion, patients were required to have stable neurological disease and clinically or urodynamically-demonstrated NDO. Cohort 2 patients weighing less than 25 kg received an investigational fesoterodine formulation.

During the 12-week efficacy phase, 124 patients (69 males and 55 females) were randomized to receive Toviaz 4 mg (N=42), Toviaz 8 mg (N=42), or active comparator (N=40) orally once daily. The majority of patients were Caucasian (52%) or Asian (44%) with a mean age of 11 years (range 6 years to 17 years) and a mean weight of 42.8 kg (range 25.1 to 96.0 kg).

Primary Endpoint

The primary efficacy endpoint was the mean change from baseline in maximum cystometric bladder capacity (MCBC) at Week 12.

Treatment with Toviaz 4 mg or 8 mg daily resulted in improvements from baseline to Week 12 in the primary efficacy endpoint, MCBC, for pediatric patients, with numerically higher changes from baseline for Toviaz 8 mg daily than for Toviaz 4 mg daily.

Results for the primary endpoint MCBC are reported in Table 11.

Table 11: Mean Baseline and Change From Baseline to Week 12 for Maximum Cystometric Bladder Capacity (mL) in Pediatric NDO Patients Receiving Toviaz 4 mg or Toviaz 8 mg and Weighing More Than 25 kg in Study 3
CI = confidence interval
Baseline is defined as the last available measurement prior to the start of treatment.
N is the number of patients who took at least one dose and provided a valid value for MCBC at baseline.
* Least squares mean change and 95% CI are based on an analysis of covariance model with terms for treatment group, baseline maximum cystometric bladder capacity and baseline weight. Last observation carried forward/baseline observation carried forward was used for imputing missing values at Week 12.
	Toviaz 4 mg	Toviaz 8 mg
N	41	41
Baseline	195.1	173.3
Change from baseline (95% CI)*	58.1 (28.8, 87.4)	83.4 (54.2, 112.5)

Secondary Endpoints

Results for other urodynamic secondary efficacy endpoints and selected secondary efficacy endpoints derived from patient urinary diaries are reported in Tables 12 and 13, respectively.

Table 12: Summary of Baseline and Change From Baseline to Week 12 in Secondary Urodynamic Endpoints in Pediatric NDO Patients Weighing Greater Than 25 kg in Study 3
	Toviaz 4 mg	Toviaz 8 mg
CI = confidence interval; IDC = involuntary detrusor contractions
Baseline is defined as the last available measurement prior to the start of treatment.
N is the number of patients who took at least one dose and provided valid endpoint data at baseline .
* Least squares mean change and 95% CI are based on an analysis of covariance model with terms for treatment group, baseline (for the endpoint being analyzed) and baseline weight. Last observation carried forward/baseline observation carried forward was used for imputing missing values at Week 12.
Detrusor pressure at maximum bladder capacity (cmH2O)
N	40	41
Baseline	26.5	27.2
Change from Baseline (95% CI)*	-2.9 (-7.6, 1.9)	-1.6 (-6.3, 3.1)
Number and percentage of patients with IDC at Baseline but not at Week 12 (n (%))
N	41	41
n (%)	9 (22.0)	18 (43.9)
Bladder volume at first IDC (mL)
N	26	36
Baseline	88.6	88.5
Change from Baseline (95% CI)*	30.5 (2.4, 58.6)	26.1 (2.2, 49.9)
Bladder compliance (mL/cmH20)
N	40	40
Baseline	13.8	10.1
Change from Baseline (95% CI)*	6.4 (-0.5, 13.3)	5.4 (-1.5, 12.3)

Table 13: Mean Baseline and Change From Baseline to Week 12 in Selected Secondary Bladder-Diary Endpoints in Pediatric NDO Patients Weighing Greater Than 25 kg in Study 3
	Toviaz 4 mg	Toviaz 8 mg
CI = confidence interval
Baseline is defined as the last available measurement prior to the start of treatment.
N is the number of patients who took at least one dose and provided valid endpoint data at baseline.
* Only patients with >0 incontinence episodes at baseline are included. † Least squares mean change and 95% CI are based on an analysis of covariance model with terms for treatment group, baseline (for the endpoint being analyzed) and baseline weight. Last observation carried forward/baseline observation carried forward was used for imputing missing values at Week 12.
Number of incontinence episodes per 24 hours*
N	33	33
Baseline	2.8	2.7
Change from Baseline (95% CI)†	-0.5 (-0.9, 0.0)	-0.9 (-1.4, -0.4)
Maximum catheterized urine volume per 24 hours (mL)
N	36	32
Baseline	222.5	164.7
Change from Baseline (95% CI)†	31.6 (-9.3, 72.6)	51.0 (8.1, 93.8)

Medication Guide

MEDICATION GUIDE

Patient Information TOVIAZ® (TOH-vee-as) (fesoterodine fumarate) extended-release tablets, for oral use
Read the Patient Information that comes with TOVIAZ before you start taking it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your healthcare provider about your medical condition or your treatment.
What is TOVIAZ? TOVIAZ is a prescription medicine used: • in adults to treat symptoms of a condition called overactive bladder (OAB), including urge urinary incontinence (leaking or wetting accidents due to a strong need to urinate), urinary urgency (having a strong need to urinate right away), or urinary frequency (having to urinate too often). • in children 6 years of age and older with a body weight greater than 55 pounds (25 kg) to treat neurogenic detrusor overactivity (NDO). TOVIAZ is used to increase the amount of urine your bladder can hold and reduce urine leakage. It is not known if TOVIAZ is safe and effective in children younger than 6 years of age or with a body weight 55 pounds (25-kg) or less.
Who should not take TOVIAZ? Do not take TOVIAZ if you: • are allergic to TOVIAZ or any of its ingredients. See the end of this leaflet for a complete list of ingredients. • are allergic to tolterodine tartrate tablets or tolterodine tartrate extended-release capsules. • are not able to empty your bladder (urinary retention). • have delayed or slow emptying of your stomach (gastric retention). • have an eye problem called uncontrolled narrow-angle glaucoma.
Before you take TOVIAZ, tell your healthcare provider about all your medical conditions, including if you: • have problems emptying your bladder or you have a weak urine stream. • have any stomach or intestinal problems, or problems with constipation. • are receiving treatment for an eye problem called narrow-angle glaucoma. • have a condition called Myasthenia Gravis. • have kidney problems. • have liver problems. • are pregnant or plan to become pregnant. It is not known if TOVIAZ will harm your unborn baby. Talk to your healthcare provider if you are pregnant or plan to become pregnant. • are breastfeeding or plan to breastfeed. It is not known if TOVIAZ passes into your breast milk. You should talk to your healthcare provider about the best way to feed your baby while taking TOVIAZ. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal products. TOVIAZ may affect the way other medicines work, and other medicines may affect how TOVIAZ works. Especially tell your healthcare provider if you are taking antimuscarinic, antibiotics, or antifungal medicines. Know all the medicines you take. Keep a list of them with you to show your healthcare provider and pharmacist each time you get a new medicine.
How should I take TOVIAZ? • Take TOVIAZ exactly as your healthcare provider tells you to take it. • Your healthcare provider may lower your dose of TOVIAZ if you are an adult with severe kidney problems. • Your healthcare provider may lower or stop your dose of TOVIAZ if you are a child 6 years of age and older with a body weight greater than 77 pounds (35 kg) and have severe kidney problems or are taking certain medicines. • Take TOVIAZ with liquid and swallow the tablet whole. Do not chew, divide, or crush the tablet. • Take TOVIAZ with or without food. • If you miss a dose of TOVIAZ, begin taking TOVIAZ again the next day. Do not take 2 doses of TOVIAZ in the same day. • If you take too much TOVIAZ, call your healthcare provider or go to an emergency department right away.
What should I avoid while taking TOVIAZ? • TOVIAZ can cause blurred vision, dizziness, and drowsiness. Do not drive, operate machinery, or do other dangerous activities until you know how TOVIAZ affects you. • Use caution in hot environments. Decreased sweating and severe heat illness can happen when medicines such as TOVIAZ are used in a hot environment. • Drinking alcohol while taking medicines such as TOVIAZ may cause increased drowsiness.
What are the possible side effects of TOVIAZ? TOVIAZ may cause serious side effects, including: • serious allergic reactions. Symptoms of a serious allergic reaction may include swelling of the face, lips, throat, or tongue. If you have any of these symptoms, you should stop taking TOVIAZ and get emergency medical help right away. • inability to empty bladder (urinary retention). TOVIAZ may increase your chances of not being able to empty your bladder if you have bladder outlet obstruction. Tell your healthcare provider right away if you are unable to empty your bladder. • central nervous system (CNS) effects. Talk to your healthcare provider right away if you get any of these side effects: headache, dizziness, and drowsiness. • worsening of Myasthenia Gravis symptoms. The most common side effects of TOVIAZ in adults include: • dry mouth • constipation The most common side effects of TOVIAZ in children 6 years of age and older include:
• diarrhea • urinary tract infection	• dry mouth • constipation	• stomach pain • nausea	• weight gain • headache
Talk to your healthcare provider about any side effect that bothers you or that does not go away. These are not all the possible side effects of TOVIAZ. Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store TOVIAZ? • Store TOVIAZ at room temperature between 68° to 77°F (20° to 25°C). • Protect the medicine from moisture by keeping the bottle closed tightly. • Keep TOVIAZ and all medicines out of the reach of children.
General information about the safe and effective use of TOVIAZ. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use TOVIAZ for a condition for which it was not prescribed. Do not give TOVIAZ to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information about TOVIAZ that is written for health professionals.
What are the ingredients in TOVIAZ? Active ingredient: fesoterodine fumarate. Inactive ingredients: glyceryl behenate, hypromellose, indigo carmine aluminum lake, lactose monohydrate, soya lecithin, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, talc, titanium dioxide, and xylitol. This product's labeling may have been updated. For the most recent prescribing information, please visit www.pfizer.com. LAB-0382-14.0 For more information, go to www.TOVIAZ.com or call 1-877-9-TOVIAZ (1-877)-986-8429.
This Patient Information has been approved by the U.S. Food and Drug Administration.				Revised: 2/2024

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