An Extension Study to Examine the Safety and Tolerability... | NCT03583372

ID	Type	Description	Link
2017-003294-33	EudraCT Number

Status Module

Label	Type	Description	Intervention Names
Vibegron + Placebo to match Tolterodine	Experimental		Drug: Vibegron Drug: placebos
Tolterodine + Placebo to match vibegron	Active Comparator		Drug: placebos Drug: Tolterodine Tartrate ER

Name	Type	Description	Arm Group Labels	Other Names
Vibegron	Drug	single daily dose 75 mg	Vibegron + Placebo to match Tolterodine

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With the Indicated Type of Treatment-emergent Adverse Event	Adverse events were collected in participants with overactive bladder (OAB) who previously completed treatment in Study RVT-901-3003. The treatment-emergent period was defined as the period of time from the first dose date of the active double-blind study treatment, whether in Study RVT-901-3003 or Study RVT-901-3004, through 28 days after the last dose of study treatment, or the date of initiation of another investigational agent or surgical intervention, whichever occurred first.	up to 56 weeks

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline (CFB) at Week 52 in the Average Number of Micturitions Per 24 Hours in All Overactive Bladder (OAB) Participants	A micturition/void is defined as "Urinated in Toilet" as indicated on the Patient Voiding Diary (PVD). The number of micturitions is defined as the number of times a participant voided in the toilet as indicated in the PVD. The average daily number of micturitions was calculated using the daily entries in the PVD (which was to be completed prior to each study visit) as the total number of micturitions that occurred on a Complete Diary Day (CDD) divided by the number of CDDs in the PVD. CFB was calculated as the post-BL value minus the BL value. "Per 24 hours" corresponds to one Diary Day (i.e., time between when the participant got up for the day each morning and time the participant got up for the day the next morning as recorded in the PVD). Covariates included in the mixed model for repeated measures (MMRM) were study visit, treatment, treatment by study visit interaction, Baseline, and the statistically significant terms in Study RVT-901-3003: OAB type (Wet versus Dry) and sex.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Has completed participation in study RVT-901-3003.
Has demonstrated ≥ 80% compliance with self-administration of Study Treatment in study RVT-901-3003.

Exclusion Criteria:

Has a change in history or current evidence of any clinically significant condition, therapy, lab abnormality, or other circumstance that might, in the opinion of the Investigator, confound the results of the study, interfere with the participant's ability to comply with study procedures, or make participation in the study not in the participant's best interest.
Has coronary or neurovascular interventions planned during the duration of the study.
Has uncontrolled hyperglycemia (defined as fasting blood glucose >150 mg/dL or 8.33 mmol/L and/or non-fasting blood glucose >200 mg/dL or 11.1 mmol/L) based on most recent available lab results in study RVT-901-3003 or, if in the opinion of the Investigator, is uncontrolled.
Has uncontrolled hypertension (systolic blood pressure of ≥ 180 mm Hg and/or diastolic blood pressure of ≥ 100 mm Hg) or has a resting heart rate (by pulse) > 100 beats per minute.
Has clinically significant ECG abnormality which, in the opinion of the Investigator, exposes the participant to risk by participating in the study
Has alanine aminotransferase or aspartate aminotransferase > 2.0 times the upper limit of normal (ULN), or bilirubin (total bilirubin) > 1.5 x ULN (or > 2.0 x ULN if secondary to Gilbert syndrome or pattern consistent with Gilbert syndrome) based on most recent available lab results in study RVT-901-3003.
Has an estimated glomerular filtration rate (eGFR) < 30mL/min/1.73 m2 based on most recent available lab results in study RVT-901-3003.
Use of any prohibited medications as detailed in Section 7.7.3.
Plans to initiate or change the dosing of any medications listed in Section 7.7.5 during the study that in the opinion of the investigator is assessed to be clinical significant.
Has an allergy, intolerance, or a history of a significant clinical or laboratory adverse experience associated with any of the active or inactive components of the vibegron formulation or tolterodine formulation.
Is currently participating or has participated in a study with an investigational compound or device within 28 days of signing informed consent, not including participation in study RVT-901-3003.
Has a history of significant drug or alcohol abuse/dependence within a year of informed consent, as assessed by the investigator.
Has a varying sleep schedule anticipated during times when the voiding diaries are to be completed.

Facility	Status	City	State	ZIP	Country	Contacts
Coastal Clinical Research Inc.		Mobile	Alabama	36608	United States
Clinical Research Consortium

PubMed Identifier	Type	Citation	Retractions
33356445	Derived	Staskin D, Frankel J, Varano S, Shortino D, Jankowich R, Mudd PN Jr. Once-Daily Vibegron 75 mg for Overactive Bladder: Long-Term Safety and Efficacy from a Double-Blind Extension Study of the International Phase 3 Trial (EMPOWUR). J Urol. 2021 May;205(5):1421-1429. doi: 10.1097/JU.0000000000001574. Epub 2020 Dec 28.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	40 Weeks Vibegron 75 mg	Participants who had been randomized to the placebo group in Study RVT-901-3003 were randomized to receive blinded study treatment of vibegron 75 mg once daily for 40 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Apr 12, 2019	Jan 11, 2021

Arm/Group Information

ID	Title	Description
BG000	40 Weeks Vibegron 75 mg	Participants who had been randomized to the placebo group in Study RVT-901-3003 were randomized to receive blinded study treatment of vibegron 75 mg once daily for 40 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
BG001	52 Weeks Vibegron 75 mg	Participants who had been randomized in Study RVT-901-3003 to receive vibegron 75 milligrams (mg) were to continue their same treatment once daily in a blinded fashion for 40 weeks. Thus, through participation in both Study RVT-901-3003 and this extension study, participants originally randomized to vibegron 75 mg were to receive 52 weeks total of vibegron. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
BG002	40 Weeks Tolterodine ER 4 mg	Participants who had been randomized to the placebo group in Study RVT-901-3003 were randomized to receive blinded study treatment of tolterodine extended release (ER) 4 mg once daily for 40 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
BG003	52 Weeks Tolterodine ER 4 mg	Participants who had been randomized in Study RVT-901-3003 to receive tolterodine ER 4 mg were to continue their same treatment once daily in a blinded fashion for 40 weeks. Thus, through participation in both Study RVT-901-3003 and this extension study, participants originally randomized to tolterodine ER 4 mg were to receive 52 weeks total of tolterodine ER. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
BG004	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00058.8± 13.69 BG00162.1± 12.39 BG00262.1± 12.14 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00073 BG001140 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

American Indian or Alaska Native

Title	Measurements
	BG0002 BG0010 BG002

Overactive Bladder (OAB) Type

Urgency incontinence is the involuntary loss of urine accompanied by urgency (referred to as OAB Wet). In the absence of incontinence, OAB is referred to as OAB Dry.

Count of Participants

Participants

Title

Denominators

Categories

Wet

Title	Measurements
	BG00071 BG001146

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With the Indicated Type of Treatment-emergent Adverse Event

Adverse events were collected in participants with overactive bladder (OAB) who previously completed treatment in Study RVT-901-3003. The treatment-emergent period was defined as the period of time from the first dose date of the active double-blind study treatment, whether in Study RVT-901-3003 or Study RVT-901-3004, through 28 days after the last dose of study treatment, or the date of initiation of another investigational agent or surgical intervention, whichever occurred first.

Safety Extension Set (SAF-Ext) Population: all participants who received at least 1 dose of double-blind study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received. Adverse event datasets for Study RVT-901-3003 and Study RVT-901-3004 were combined for the safety analyses.

Posted

Number

participants

up to 56 weeks

ID	Title	Description
OG000	Overall Vibegron 75 mg	Participants who received 40 weeks and 52 weeks vibegron 75 milligrams (mg). Participants who had been randomized to the placebo group in Study RVT-901-3003 were randomized to receive blinded study treatment of vibegron 75 mg once daily for 40 weeks in RVT-901-3004. Participants who received 52 weeks vibegron 75 mg were randomized to receive vibegron 75 mg in both studies. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
OG001	Overall Tolterodine ER 4 mg	Participants who received 40 weeks and 52 weeks tolterodine ER 4 mg. Participants who had been randomized to the placebo group in RVT-901-3003 were randomized to receive blinded study treatment of tolterodine ER 4 mg once daily for 40 weeks in Study RVT-901-3004. Participants who received 52 weeks tolterodine ER 4 mg were randomized to receive tolterodine ER 4 mg in both studies. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.

Units	Counts
Participants	OG000273 OG001232

Title

Denominators

Categories

Any TEAE

Title	Measurements
	OG000171 OG001126

Any study drug-related TEAE

Title	Measurements
	OG000

Secondary

Change From Baseline (CFB) at Week 52 in the Average Number of Micturitions Per 24 Hours in All Overactive Bladder (OAB) Participants

A micturition/void is defined as "Urinated in Toilet" as indicated on the Patient Voiding Diary (PVD). The number of micturitions is defined as the number of times a participant voided in the toilet as indicated in the PVD. The average daily number of micturitions was calculated using the daily entries in the PVD (which was to be completed prior to each study visit) as the total number of micturitions that occurred on a Complete Diary Day (CDD) divided by the number of CDDs in the PVD. CFB was calculated as the post-BL value minus the BL value. "Per 24 hours" corresponds to one Diary Day (i.e., time between when the participant got up for the day each morning and time the participant got up for the day the next morning as recorded in the PVD). Covariates included in the mixed model for repeated measures (MMRM) were study visit, treatment, treatment by study visit interaction, Baseline, and the statistically significant terms in Study RVT-901-3003: OAB type (Wet versus Dry) and sex.

Full Analysis Set Extension (FAS-Ext) Population: all randomized OAB participants who took at least 1 dose of double-blind study treatment during this extension study and had at least 1 subsequent evaluable CFB micturition measurement in this extension study. Only participants with evaluable data were analyzed.

Posted

Least Squares Mean

Standard Error

micturitions per 24 hours

Baseline; Week 52

ID	Title	Description
OG000	52 Weeks Vibegron 75 mg	Participants who had been randomized in Study RVT-901-3003 to receive vibegron 75 milligrams (mg) were to continue their same treatment once daily in a blinded fashion for 40 weeks. Thus, through participation in both Study RVT-901-3003 and this extension study, participants originally randomized to vibegron 75 mg were to receive 52 weeks total of vibegron. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.

Secondary

CFB at Week 52 in the Average Number of Urge Urinary Incontinence (UUI) Episodes Per 24 Hours in OAB Wet Participants

The number of UUI episodes is defined as the number of times a participant had checked "urge" as the main reason for the leakage in the PVD, regardless of whether more than one reason for leakage in addition to "urge" was checked. The average daily number of UUI episodes was calculated using the daily entries in the PVD (which was to be completed prior to each study visit) as the total number of UUI episodes that occurred on a CDD divided by the number of CDDs in the PVD. CFB was calculated as the post-BL value minus the BL value. "Per 24 hours" corresponds to one Diary Day (i.e., time between when participant got up for the day each morning and time participant got up for the day the next morning as recorded in the PVD). Covariates included in the MMRM were study visit, treatment, treatment by study visit interaction, Baseline, and the statistically significant terms in Study RVT-901-3003: sex. Only participants with evaluable data were analyzed.

Full Analysis Set Extension for Incontinence (FAS-Ext-I) Population: all randomized OAB Wet participants who were included in the FAS-I population in Study RVT-901-3003, who took at least 1 dose of double-blind study treatment in this extension study and had at least 1 subsequent evaluable CFB UUI measurement.

Posted

Least Squares Mean

Standard Error

UUI episodes per 24 hours

Baseline; Week 52

ID	Title	Description
OG000	52 Weeks Vibegron 75 mg	Participants who met the definition of OAB Wet at study entry (based on the PVD and had been randomized in Study RVT-901-3003 to receive vibegron 75 milligrams (mg) were to continue their same treatment once daily in a blinded fashion for 40 weeks. Thus, through participation in both Study RVT-901-3003 and this extension study, participants originally randomized to vibegron 75 mg were to receive 52 weeks total of vibegron. OAB Wet participants were those participants with an average of ≥8.0 micturitions per Diary Day (DD); with an average of ≥1.0 UUI episodes per DD; and, if stress urinary incontinence (SUI) was present, with a total number of UUI episodes greater than the total number of SUI episodes from the previous visit diary. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.

Secondary

CFB at Week 52 in the Average Number of Urgency Episodes (Need to Urinate Immediately) Over 24 Hours in All OAB Participants

The number of urgency episodes is defined as the number of times a participant had checked "need to urinate immediately" on a CDD divided by the number of CDDs in the PVD. CFB is calculated as the post-BL value minus the BL value. "Over 24 hours" corresponds to one Diary Day (i.e., time between when the participant got up for the day each morning and time the participant got up for the day the next morning as recorded in the PVD). Covariates included in the MMRM were study visit, treatment, treatment by study visit interaction, Baseline, and the statistically significant terms in Study RVT-901-3003: OAB type (Wet versus Dry) and sex.

FAS-Ext Population. Only participants with evaluable data were analyzed.

Posted

Least Squares Mean

Standard Error

urgency episodes over 24 hours

Baseline; Week 52

ID	Title	Description
OG000	52 Weeks Vibegron 75 mg	Participants who had been randomized in Study RVT-901-3003 to receive vibegron 75 milligrams (mg) were to continue their same treatment once daily in a blinded fashion for 40 weeks. Thus, through participation in both Study RVT-901-3003 and this extension study, participants originally randomized to vibegron 75 mg were to receive 52 weeks total of vibegron. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
OG001	52 Weeks Tolterodine ER 4 mg

Secondary

CFB at Week 52 in the Average Number of Total Urinary Incontinence Episodes Over 24 Hours in OAB Wet Participants

The number of total incontinence episodes is defined as the number of times a participant had checked the accidental urine leakage box in the PVD, including for reasons of "urge," "stress," or "other." CFB was calculated as the post-BL value minus the BL value. "Over 24 hours" corresponds to one Diary Day (i.e., time between when the participant got up for the day each morning and time the participant got up for the day the next morning as recorded in the PVD). Covariates included in the MMRM were study visit, treatment, treatment by study visit interaction, Baseline, and the statistically significant terms in Study RVT-901-3003: sex. hr = hour.

FAS-Ext-I Population. Only participants with evaluable data were analyzed.

Posted

Least Squares Mean

Standard Error

Urinary incontinence episodes over 24 hr

Baseline; Week 52

ID	Title	Description
OG000	52 Weeks Vibegron 75 mg	Participants who met the definition of OAB Wet at study entry (based on the PVD and had been randomized in Study RVT-901-3003 to receive vibegron 75 milligrams (mg) were to continue their same treatment once daily in a blinded fashion for 40 weeks. Thus, through participation in both Study RVT-901-3003 and this extension study, participants originally randomized to vibegron 75 mg were to receive 52 weeks total of vibegron. OAB Wet participants were those participants with an average of ≥8.0 micturitions per Diary Day (DD); with an average of ≥1.0 UUI episodes per DD; and, if stress urinary incontinence (SUI) was present, with a total number of UUI episodes greater than the total number of SUI episodes from the previous visit diary. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Overall Vibegron 75 mg	Participants who received 40 weeks and 52 weeks vibegron 75 milligrams (mg). Participants who had been randomized to the placebo group in Study RVT-901-3003 were randomized to receive blinded study treatment of vibegron 75 mg once daily for 40 weeks in RVT-901-3004. Participants who received 52 weeks vibegron 75 mg were randomized to receive vibegron 75 mg in both studies. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.	1	273	9	273	65	273
EG001	Overall Tolterodine ER 4 mg	Participants who received 40 weeks and 52 weeks tolterodine ER 4 mg. Participants who had been randomized to the placebo group in RVT-901-3003 were randomized to receive blinded study treatment of tolterodine ER 4 mg once daily for 40 weeks in Study RVT-901-3004. Participants who received 52 weeks tolterodine ER 4 mg were randomized to receive tolterodine ER 4 mg in both studies. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.	0	232	10	232	56	232

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Colitis	Gastrointestinal disorders	MedDra 20.1	Systematic Assessment	EG0001 affected273 at risk EG0010 affected232 at risk
Colitis microscopic	Gastrointestinal disorders	MedDra 20.1	Systematic Assessment	EG0001 affected273 at risk EG0010 affected232 at risk
Gastric ulcer haemorrhage	Gastrointestinal disorders	MedDra 20.1	Systematic Assessment	EG0000 affected273 at risk EG0011 affected232 at risk
Appendicitis	Infections and infestations	MedDra 20.1	Systematic Assessment	EG0001 affected273 at risk EG0011 affected232 at risk
Urosepsis	Infections and infestations	MedDra 20.1	Systematic Assessment	EG0001 affected273 at risk EG0010 affected232 at risk
Angina unstable	Cardiac disorders	MedDra 20.1	Systematic Assessment	EG0001 affected273 at risk EG0010 affected232 at risk
Cardiac failure	Cardiac disorders	MedDra 20.1	Systematic Assessment	EG0000 affected273 at risk EG0011 affected232 at risk
Cardiomyopathy	Cardiac disorders	MedDra 20.1	Systematic Assessment	EG0000 affected273 at risk EG0011 affected232 at risk
Chest pain	General disorders	MedDra 20.1	Systematic Assessment	EG0001 affected273 at risk EG0011 affected232 at risk
Aortic stenosis	Vascular disorders	MedDra 20.1	Systematic Assessment	EG0000 affected273 at risk EG0011 affected232 at risk
Arteriosclerosis	Vascular disorders	MedDra 20.1	Systematic Assessment	EG0001 affected273 at risk EG0010 affected232 at risk
Vertigo positional	Ear and labyrinth disorders	MedDra 20.1	Systematic Assessment	EG0000 affected273 at risk EG0011 affected232 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDra 20.1	Systematic Assessment	EG0000 affected273 at risk EG0011 affected232 at risk
Pelvic fracture	Injury, poisoning and procedural complications	MedDra 20.1	Systematic Assessment	EG0001 affected273 at risk EG0010 affected232 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDra 20.1	Systematic Assessment	EG0001 affected273 at risk EG0010 affected232 at risk
Syncope	Nervous system disorders	MedDra 20.1	Systematic Assessment	EG0000 affected273 at risk EG0011 affected232 at risk
Depression	Psychiatric disorders	MedDra 20.1	Systematic Assessment	EG0000 affected273 at risk EG0011 affected232 at risk
Ureterolithiasis	Renal and urinary disorders	MedDra 20.1	Systematic Assessment	EG0000 affected273 at risk EG0011 affected232 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDra 20.1	Systematic Assessment	EG0000 affected273 at risk EG0011 affected232 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Dry mouth	Gastrointestinal disorders	MedDra 20.1	Systematic Assessment	EG0005 affected273 at risk EG00112 affected232 at risk
Nasopharyngitis	Infections and infestations	MedDra 20.1	Systematic Assessment	EG00013 affected273 at risk EG00112 affected232 at risk
Urinary tract infection	Infections and infestations	MedDra 20.1	Systematic Assessment	EG00018 affected273 at risk EG00117 affected232 at risk
Headache	Nervous system disorders	MedDra 20.1	Systematic Assessment	EG00015 affected273 at risk EG0019 affected232 at risk
Hypertension	Vascular disorders	MedDra 20.1	Systematic Assessment	EG00024 affected273 at risk EG00120 affected232 at risk

ID	Term
D053201	Urinary Bladder, Overactive
D053202	Urinary Incontinence, Urge
D014570	Urologic Diseases
D059411	Lower Urinary Tract Symptoms

ID	Term
D001745	Urinary Bladder Diseases
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D052801	Male Urogenital Diseases
D020924	Urological Manifestations
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms
D014549	Urinary Incontinence
D014555	Urination Disorders

ID	Term
D010665	Phenylpropanolamine
D011412	Propanolamines
D000605	Amino Alcohols
D000438	Alcohols
D009930	Organic Chemicals
D020005	Propanols
D000588	Amines
D001559	Benzhydryl Compounds
D001555	Benzene Derivatives
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D003408	Cresols
D010636	Phenols

ID	Term
C000608232	N-(4-((5-(hydroxy(phenyl)methyl)pyrrolidin-2-yl)methyl)phenyl)-4-oxo-4,6,7,8-tetrahydropyrrolo(1,2-a)pyrimidine-6-carboxamide
D000068737	Tolterodine Tartrate