Clinical Trials Register

Summary
EudraCT Number:	2012-005736-29
Sponsor's Protocol Code Number:	178-CL-102
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-12-16
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Czechia - SUKL

A.2

EudraCT number

2012-005736-29

A.3

Full title of the trial

A Randomized, Double-Blind, Parallel-Group, Active-Controlled, Multi-center Study to Evaluate the Long-Term Safety and Efficacy of Combination of Solifenacin Succinate with Mirabegron Compared to Solifenacin Succinate and Mirabegron Monotherapy in Subjects with Overactive Bladder

Randomizované, dvojitě zaslepené multicentrické hodnocení s paralelními skupinami a kontrolou aktivní látkou ke stanovení dlouhodobé bezpečnosti a účinnosti kombinace solifenacin-sukcinátu s přípravkem Mirabegron ve srovnání s monoterapií solifenacin-sukcinátem a přípravkem Mirabegron u osob s hyperaktivním močovým měchýřem

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A study to assess the long-term efficacy and safety of two medicines, solifenacin succinate and mirabegron, taken together or separately, in patients with overactive bladder

A.4.1

Sponsor's protocol code number

178-CL-102

A.5.4

Other Identifiers

Name:

SYNERGY II

Number:

Study Name

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Astellas Pharma Europe B.V.
B.1.3.4	Country	Netherlands
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Astellas Pharma Europe B.V.
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Astellas Pharma Europe B.V.
B.5.2	Functional name of contact point	Service Desk - Gobal Clinical Dev't
B.5.3	Address:
B.5.3.1	Street Address	Sylviusweg 62
B.5.3.2	Town/ city	Leiden
B.5.3.3	Post code	2333 BE
B.5.3.4	Country	Netherlands
B.5.6	E-mail	contact@nl.astellas.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Vesicare
D.2.1.1.2	Name of the Marketing Authorisation holder	Astellas Pharma Europe B.V.
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	solifenacin succinate
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	solifenacin succinate
D.3.9.1	CAS number	242478-38-2
D.3.9.2	Current sponsor code	YM905
D.3.9.3	Other descriptive name	SOLIFENACIN SUCCINATE
D.3.9.4	EV Substance Code	SUB21028
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Betmiga
D.2.1.1.2	Name of the Marketing Authorisation holder	Astellas Pharma Europe B.V.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Mirabegron
D.3.2	Product code	YM178
D.3.4	Pharmaceutical form	Prolonged-release tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	mirabegron
D.3.9.1	CAS number	223673-61-8
D.3.9.3	Other descriptive name	MIRABEGRON
D.3.9.4	EV Substance Code	SUB32690
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Overactive Bladder

E.1.1.1

Medical condition in easily understood language

Overactive Bladder

E.1.1.2

Therapeutic area

Body processes [G] - Physical Phenomena [G01]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.0
E.1.2	Level	LLT
E.1.2	Classification code	10059617
E.1.2	Term	Overactive bladder
E.1.2	System Organ Class	100000004857

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the safety and tolerability of long-term combination treatment of solifenacin (5 mg) with mirabegron (50 mg) compared to solifenacin and mirabegron monotherapy in subjects with overactive bladder (OAB)

E.2.2

Secondary objectives of the trial

To evaluate efficacy of long-term combination treatment with solifenacin and mirabegron

To evaluate Patient Reported Outcomes (PRO) during long-term combination treatment with solifenacin and mirabegron

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Subject is male or female and at least 18 years of age;
• Subject is willing and able to complete the micturition diary and questionnaires correctly and able to measure his/her vital signs at home at stipulated time points, using the device provided by the study personnel, and to adequately record the readings;
• Subject has symptoms of “wet” OAB for at least three months

E.4

Principal exclusion criteria

• Subject has neurological cause for detrusor overactivity (e.g. neurogenic bladder, diabetic neuropathy with autonomic component or bladder involvement, or systemic or central neurological disease such as multiple sclerosis and Parkinson's disease with autonomic component or bladder involvement). An autonomic component can be inferred when autonomic functions are affected, including heart rate, blood pressure, perspiration and digestion.
• Subject has chronic inflammation such as bladder pain syndrome / interstitial cystitis, symptomatic bladder stones or any previous or current radiation cystitis.
• Subject has moderate to severe hepatic impairment
• Subject has severe renal impairment
• Subject has a clinically significant abnormal ECG
• Subject has a concurrent malignancy or history of cancer (except noninvasive skin cancer) within the last 5 years prior to screening.
• Subject has an average QTcF interval > 450 ms for males or > 470 ms for females based on the triplicate ECGs completed at Screening or is at risk of QT prolongation (e.g., family history of long QT syndrome, hypokalaemia).
• Subject has severe hypertension, which is defined as a sitting average systolic blood pressure ≥ 180 mmHg and/or average diastolic blood pressure ≥ 110 mmHg.
• In the opinion of the investigator the subject has clinically significant bladder outflow obstruction at risk of urinary retention;
• Subject has significant PVR volume (> 150 mL);
• Subject has significant stress incontinence or mixed stress/urgency incontinence where stress is the predominant factor as determined by the investigator;
• Subject has an indwelling catheter or practices intermittent self-catheterization;
• Subject has evidence of urinary tract infection (UTI), chronic inflammation such as interstitial cystitis, bladder stones, previous pelvic radiation therapy or previous or current malignant disease of the pelvic organs;
• Subject has had intravesical treatment in the past 12 months with e.g., botulinum toxin, resiniferatoxin, capsaicin;

E.5 End points

E.5.1

Primary end point(s)

• Incidence and severity of treatment emergent adverse events (TEAEs)

Primary Efficacy Variables
• Change from baseline in mean number of incontinence episodes per 24 hours at EoT
• Change from baseline in mean number of micturitions per 24 hours at EoT

E.5.1.1

Timepoint(s) of evaluation of this end point

EoT

E.5.2

Secondary end point(s)

• Vital signs
• Laboratory test
• ECG parameters
• PVR

E.5.2.1

Timepoint(s) of evaluation of this end point

EoT

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

163

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Argentina

Australia

Belgium

Brazil

Bulgaria

Canada

Chile

China

Colombia

Czech Republic

Denmark

Estonia

Finland

Germany

Greece

Hong Kong

Hungary

Italy

Korea, Republic of

Latvia

Lithuania

Malaysia

Mexico

Netherlands

New Zealand

Norway

Peru

Philippines

Poland

Romania

Russian Federation

Singapore

Slovakia

Slovenia

South Africa

Spain

Sweden

Taiwan

Thailand

Turkey

Ukraine

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

1728

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

672

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

151

F.4.2

For a multinational trial

F.4.2.1

In the EEA

600

F.4.2.2

In the whole clinical trial

1800

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2014-01-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-04-03

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-09-08

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