Trial Outcomes & Findings for Drug Use Investigation for Toviaz (NCT NCT01936870)

NCT ID: NCT01936870

Last Updated: 2021-06-11

Results Overview

A treatment-related adverse event was any untoward medical occurrence attributed to fesoterodine fumarate in a participant who received fesoterodine fumarate. Relatedness to fesoterodine fumarate was assessed by the investigator.

• Recruitment status: COMPLETED
• Target enrollment: 2521 participants
• Primary outcome timeframe: 12 Weeks
• Results posted on: 2021-06-11

Participant Flow

Participant milestones

Measure	Fesoterodine Fumarate Participants received fesoterodine fumarate at an oral dose of 4 mg once daily. The dose was increased up to 8 mg once daily according to symptoms.
Overall Study STARTED	2492
Overall Study COMPLETED	2303
Overall Study NOT COMPLETED	189

Reasons for withdrawal

Measure	Fesoterodine Fumarate Participants received fesoterodine fumarate at an oral dose of 4 mg once daily. The dose was increased up to 8 mg once daily according to symptoms.
Overall Study No Visit After Treatment	176
Overall Study Protocol Violation	12
Overall Study No Drug Administration	1

Baseline Characteristics

Drug Use Investigation for Toviaz

Baseline characteristics by cohort

Measure	Fesoterodine Fumarate n=2303 Participants Participants received fesoterodine fumarate at an oral dose of 4 mg once daily. The dose was increased up to 8 mg once daily according to symptoms.
Age, Customized <15 years	1 Participants n=5 Participants
Age, Customized >=15 and <65 years	529 Participants n=5 Participants
Age, Customized ˃=65 years	1773 Participants n=5 Participants
Sex: Female, Male Female	1228 Participants n=5 Participants
Sex: Female, Male Male	1075 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 Weeks

Population: The safety analysis set comprised of participants who had satisfied the inclusion criteria of the study, and who had received fesoterodine fumarate at least once.

A treatment-related adverse event was any untoward medical occurrence attributed to fesoterodine fumarate in a participant who received fesoterodine fumarate. Relatedness to fesoterodine fumarate was assessed by the investigator.

Outcome measures

Measure	Fesoterodine Fumarate n=2303 Participants Participants received fesoterodine fumarate at an oral dose of 4 mg once daily. The dose was increased up to 8 mg once daily according to symptoms.
Number of Participants With Treatment-Related Adverse Events	415 Participants

PRIMARY outcome

Timeframe: 12 Weeks

Population: The effectiveness analysis set comprised of subjects from the safety analysis set who had effectiveness evaluation at least once after treatment with fesoterodine fumarate, excluding those with off-label use.

Clinical efficacy rate, which was defined as the percentage of participants who achieved clinical effectiveness over the total number of assessable effectiveness analysis population, was presented along with the corresponding 2-sided 95% CI. Overall effectiveness of fesoterodine fumarate was determined by the investigator based on clinical symptoms and examinations. Clinical effectiveness was assessed according to the following categories: (1) effective, (2) ineffective, or (3) unassessable at week 12 of the treatment.

Outcome measures

Measure	Fesoterodine Fumarate n=2300 Participants Participants received fesoterodine fumarate at an oral dose of 4 mg once daily. The dose was increased up to 8 mg once daily according to symptoms.
Clinical Efficacy Rate	74.8 Percentage of participants Interval 73.0 to 76.5

SECONDARY outcome

Timeframe: 12 Weeks

Population: The safety analysis set comprised of participants who had satisfied the inclusion criteria of the study, and who had received fesoterodine fumarate at least once.

A treatment-related adverse event was any untoward medical occurrence attributed to fesoterodine fumarate in a participant who received fesoterodine fumarate. A treatment-related serious adverse event was a treatment-related adverse event resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; lifethreatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Relatedness to fesoterodine fumarate was assessed by the investigator.

Outcome measures

Measure	Fesoterodine Fumarate n=2303 Participants Participants received fesoterodine fumarate at an oral dose of 4 mg once daily. The dose was increased up to 8 mg once daily according to symptoms.
Number of Participants With Treatment-Related Serious Adverse Events	8 Participants

SECONDARY outcome

Timeframe: 12 Weeks

Population: The safety analysis set comprised of participants who had satisfied the inclusion criteria of the study, and who had received fesoterodine fumarate at least once.

A treatment-related adverse event was any untoward medical occurrence attributed to fesoterodine fumarate in a participant who received fesoterodine fumarate. Expectedness of the adverse event was determined according to the Japanese package insert. Relatedness to fesoterodine fumarate was assessed by the investigator.

Outcome measures

Measure	Fesoterodine Fumarate n=2303 Participants Participants received fesoterodine fumarate at an oral dose of 4 mg once daily. The dose was increased up to 8 mg once daily according to symptoms.
Number of Participants With Treatment-Related Adverse Events Unexpected From Japanese Package Insert	27 Participants

SECONDARY outcome

Timeframe: 12 Weeks

Population: The safety analysis set comprised of participants who had satisfied the inclusion criteria of the study, and who had received fesoterodine fumarate at least once.

An adverse event was any untoward medical occurrence in a participant who received fesoterodine fumarate without regard to possibility of causal relationship. Adverse events related to cognitive function disorder were identified by broad searches on the Standard MedDRA Queries (SMQ).

Outcome measures

Measure	Fesoterodine Fumarate n=2303 Participants Participants received fesoterodine fumarate at an oral dose of 4 mg once daily. The dose was increased up to 8 mg once daily according to symptoms.
Number of Participants With Adverse Events Related to Cognitive Function Disorder	2 Participants

SECONDARY outcome

Timeframe: Baseline, 12 Weeks

Population: The safety analysis set comprised of participants who had satisfied the inclusion criteria of the study, and who had received fesoterodine fumarate at least once. Participants with observed change in MMSE score were included in table.

Mini-Mental State Examination (MMSE) measured general cognitive functioning: orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two intersecting polygons. Total score derived from sub-scores; total ranged from 0 to 30, higher score indicates better cognitive state. Mean change from baseline in the MMSE score at 12 weeks was presented along with the corresponding standard deviation.

Outcome measures

Measure	Fesoterodine Fumarate n=56 Participants Participants received fesoterodine fumarate at an oral dose of 4 mg once daily. The dose was increased up to 8 mg once daily according to symptoms.
Change From Baseline in the Mini-Mental State Examination (MMSE) Score at 12 Weeks	0.4 Scale Standard Deviation 1.29

SECONDARY outcome

Timeframe: 12 Weeks

Population: The safety analysis set comprised of participants who had satisfied the inclusion criteria of the study, and who had received fesoterodine fumarate at least once. "Number Analyzed" signifies those participants who were evaluable for the specified rows.

Cytochrome P450 3A4 (CYP3A4) inhibitors included atazanavir, clarithromycin, indinavir, itraconazole, nelfinavir, ritonavir, saquinavir, and telithromycin.

Outcome measures

Measure	Fesoterodine Fumarate n=2303 Participants Participants received fesoterodine fumarate at an oral dose of 4 mg once daily. The dose was increased up to 8 mg once daily according to symptoms.
Number of Participants With Treatment-Related Adverse Events Among Whom Received Concomitant CYP3A4 Inhibitors Received Concomitant CYP3A4 Inhibitors	6 Participants
Number of Participants With Treatment-Related Adverse Events Among Whom Received Concomitant CYP3A4 Inhibitors Not Received Concomitant CYP3A4 Inhibitors	409 Participants

SECONDARY outcome

Timeframe: 12 Weeks

Population: The safety analysis set comprised of participants who had satisfied the inclusion criteria of the study, and who had received fesoterodine fumarate at least once. "Number Analyzed" signifies those participants who were evaluable for the specified rows.

Cytochrome P450 2D6 (CYP2D6) inhibitors included quinidine and paroxetine. A treatment-related adverse event was any untoward medical occurrence attributed to fesoterodine fumarate in a participant who received fesoterodine fumarate. Relatedness to fesoterodine fumarate was assessed by the investigator.

Outcome measures

Measure	Fesoterodine Fumarate n=2303 Participants Participants received fesoterodine fumarate at an oral dose of 4 mg once daily. The dose was increased up to 8 mg once daily according to symptoms.
Number of Participants With Treatment-Related Adverse Events Among Whom Received Concomitant CYP2D6 Inhibitors Received Concomitant CYP2D6 Inhibitors	11 Participants
Number of Participants With Treatment-Related Adverse Events Among Whom Received Concomitant CYP2D6 Inhibitors Not Received Concomitant CYP2D6 Inhibitors	404 Participants

SECONDARY outcome

Timeframe: 12 Weeks

Population: The safety analysis set comprised of participants who had satisfied the inclusion criteria of the study, and who had received fesoterodine fumarate at least once. "Number Analyzed" signifies those participants who were evaluable for the specified rows.

A treatment-related adverse event was any untoward medical occurrence attributed to fesoterodine fumarate in a participant who received fesoterodine fumarate. Relatedness to fesoterodine fumarate was assessed by the investigator.

Outcome measures

Measure	Fesoterodine Fumarate n=2303 Participants Participants received fesoterodine fumarate at an oral dose of 4 mg once daily. The dose was increased up to 8 mg once daily according to symptoms.
Number of Participants With Treatment-Related Adverse Events Among Whose Dose Was Increased From 4 mg to 8 mg From 4 mg to 8 mg	53 Participants
Number of Participants With Treatment-Related Adverse Events Among Whose Dose Was Increased From 4 mg to 8 mg 4 mg	330 Participants
Number of Participants With Treatment-Related Adverse Events Among Whose Dose Was Increased From 4 mg to 8 mg 8 mg	32 Participants

SECONDARY outcome

Timeframe: 12 Weeks

Population: The effectiveness analysis set comprised of subjects from the safety analysis set who had effectiveness evaluation at least once after treatment with fesoterodine fumarate, excluding those with off-label use.

Satisfaction rate, which was defined as the percentage of participants who were satisfied by fesoterodine fumarate treatment over the total number of assessable effectiveness analysis population, was presented along with the corresponding 2-sided 95% CI. Satisfaction scale was assessed by the participants according to the following categories: (1) satisfied, (2) unsatisfied, (3) uncertain, or (4) unconfirmed.

Outcome measures

Measure	Fesoterodine Fumarate n=2300 Participants Participants received fesoterodine fumarate at an oral dose of 4 mg once daily. The dose was increased up to 8 mg once daily according to symptoms.
Satisfaction Rate	59.0 Percentage of participants Interval 57.0 to 61.0

SECONDARY outcome

Timeframe: Baseline, 12 Weeks

Population: The effectiveness analysis set comprised of participants from the safety analysis set who had effectiveness evaluation at least once after treatment with fesoterodine fumarate, excluding those with off-label use. Participants with observed change in OABSS were included in table.

Overactive Bladder Symptom Score (OABSS) was defined as the sum score (0 to 15) of the following four OAB symptoms: daytime frequency (2 at maximum), nighttime frequency (3 at maximum), urgency (5 at maximum), and urgency incontinence (5 at maximum). Higher score indicates worse symptoms. Mean change from baseline in the OABSS at 12 weeks was presented along with the corresponding standard deviation.

Outcome measures

Measure	Fesoterodine Fumarate n=1389 Participants Participants received fesoterodine fumarate at an oral dose of 4 mg once daily. The dose was increased up to 8 mg once daily according to symptoms.
Change From Baseline in the Overactive Bladder Symptom Score (OABSS) at 12 Weeks	-3.4 Scale Standard Deviation 3.04

Adverse Events

Fesoterodine Fumarate

Serious events: 12 serious events

Other events: 361 other events

Deaths: 0 deaths

Serious adverse events

Measure	Fesoterodine Fumarate n=2303 participants at risk Participants received fesoterodine fumarate at an oral dose of 4 mg once daily. The dose was increased up to 8 mg once daily according to symptoms.
Infections and infestations Pneumonia	0.04% 1/2303 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Loss of consciousness	0.04% 1/2303 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Cerebral infarction	0.04% 1/2303 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Respiratory arrest	0.04% 1/2303 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.04% 1/2303 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Acute abdomen	0.04% 1/2303 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Constipation	0.04% 1/2303 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Cholecystitis acute	0.04% 1/2303 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Urinary retention	0.13% 3/2303 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Dysuria	0.04% 1/2303 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Condition aggravated	0.04% 1/2303 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Residual urine volume increased	0.04% 1/2303 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Other adverse events

Measure	Fesoterodine Fumarate n=2303 participants at risk Participants received fesoterodine fumarate at an oral dose of 4 mg once daily. The dose was increased up to 8 mg once daily according to symptoms.
Gastrointestinal disorders Dry mouth	1.6% 36/2303 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Constipation	3.1% 72/2303 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Urinary retention	1.0% 24/2303 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Dysuria	2.7% 63/2303 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Thirst	7.2% 166/2303 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Additional Information

Pfizer ClinicalTrials.gov Call Center

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Phone: 1-800-718-1021

Email: ClinicalTrials.gov_Inquiries@pfizer.com

Results disclosure agreements

• Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
• Publication restrictions are in place

Restriction type: OTHER