Clinical Trials Register

Summary
EudraCT Number:	2012-005344-15
Sponsor's Protocol Code Number:	BOTC3-OAB-01
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:	2013-01-08
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

2012-005344-15

A.3

Full title of the trial

A Double Blind Study Aiming To Evaluate The Efficacy Of Bladder Instillation With Botulinum Toxin (200U) + TC-3 Gel In Comparison To Instillation With Botulinum Toxin (200U) + TC-3 Gel + DMSO, To DMSO Instillation and To Saline Instillation As Placebo In Overactive Bladder (OAB) Patients.

Klinické hodnocení účinku botulinumtoxinu s gelem TC-3 aplikovaným do močového měchýře u pacientek s hyperaktivním měchýřem.

A.3.1

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

The Effect of Botox Applied in TC-3 Gel in Patients Suffering From Overactive Bladder.

A.4.1

Sponsor's protocol code number

BOTC3-OAB-01

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	Adyton, s.r.o.
B.1.3.4	Country	Czech Republic
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	Adyton, s.r.o.
B.4.2	Country	Czech Republic
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Axon CRO, s.r.o.
B.5.2	Functional name of contact point	Clinical Research Manager
B.5.3	Address:
B.5.3.1	Street Address	Ševce Matouše 26
B.5.3.2	Town/ city	Praha 4
B.5.3.3	Post code	140 00
B.5.3.4	Country	Czech Republic
B.5.4	Telephone number	00420731405460
B.5.5	Fax number	00420241405825
B.5.6	E-mail	richard.vejsada@axon-cro.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	BOTOX botulini toxinum typus A (prášek pro přípravu injekčního roztoku, 100 jednotek v 1 lahvičce - powder for solution for injection, 100 units in 1 vial)
D.2.1.1.2	Name of the Marketing Authorisation holder	Allergan Pharmaceuticals Ireland
D.2.1.2	Country which granted the Marketing Authorisation	Czech Republic
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.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravesical use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Botox
D.3.9.1	CAS number	93384-44-2
D.3.9.3	Other descriptive name	BOTULINUM B TOXIN
D.3.9.4	EV Substance Code	SUB12472MIG
D.3.10	Strength
D.3.10.1	Concentration unit	U unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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	Solution for injection/infusion
D.8.4	Route of administration of the placebo	Intravesical 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 (OAB) syndrome (in women), as defined by the International Continence Society (ICS): severe urgency with or without urge urinary incontinence, usually accompanied with increased daytime frequency and nocturia, in the absence of urinary tract infection or other obvious patology.

Syndrom hyperaktivního měchýře (bez přítomnosti infekce nebo jiné zjevné patologie močového ústrojí), se symptomy imperativního a/nebo častého nucení na močení, případně urgentní inkontinence a nykturie.

E.1.1.1

Medical condition in easily understood language

Overactive bladder syndrome with symptoms of an urgent feeling to go to the toilet, going to the toilet frequently, and sometimes leaking urine before getting to the toilet (urge incontinence).

Hyperaktivní močový měchýř, s projevy náhlé a nutkavé potřeby močit, časté frekvence močení, případně úniku moči kvůli nedostatku času dojít na toaletu a/nebo potřeby močit v noci.

E.1.1.2

Therapeutic area

Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
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

1. To determine whether bladder instillation with BOTOX embedded in TC-3 gel is effective in OAB patients according to objective and subjective parameters.

2. To determine whether bladder instillation with BOTOX embedded in TC-3 gel is superior to placebo in terms of improving subjective and objective parameters.

3. To compare the effect of BOTOX embedded in TC-3 gel to that of BOTOX embedded in TC-3 gel preceded by DMSO instillation.

4. To compare the effect of BOTOX embedded in TC-3 gel to that of DMSO instillation alone.

E.2.2

Secondary objectives of the trial

To assess the safety and tolerability of bladder instillation with BOTOX embedded in TC-3 gel in OAB patients.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

At screening:
1. Female subject ≥ 18 years of age
2. Signed Independent Ethical Committee (IEC) approved informed consent is obtained from the subject (prior to any study-related procedures, including withdrawal of prohibited medication, if applicable).
3. Subject is willing and able to complete the micturition diary and questionnaires correctly.
4. Subject has symptoms of OAB for ≥ 3 months prior to the Screening Visit.

At Randomization:
1. Subject experiences at least 3 episodes of severe urgency (grade 3 or 4) with or without incontinence during the 3-day micturition diary period.
2. Subject experiences frequency of micturition on average ≥ 8 times per 24-hour period during the 3-day micturition diary period.
3. Subject is willing and able to complete the micturition diary and questionnaires correctly.

E.4

Principal exclusion criteria

At Screening:
1. The pregnancy test (HCG in urine) taken at screening visit is positive in women of childbearing positional.
2. Female subject is breastfeeding, pregnant, intends to become pregnant during the study or of childbearing potential and sexually active and not practicing a highly reliable method of birth control.
3. Subject in the opinion of the investigator has clinically significant Bladder Outlet Obstruction (BOO).
4. Subject has post-void residual volume (PVR) >200 mL.
5. Subject has neurogenic bladder.
6. Subject has significant stress incontinence or mixed stress/urgency incontinence where stress is the predominant factor as determined by the investigator (confirmed by a cough provocation test).
7. Subject has an indwelling catheter or practices intermittent self-catheterization.
8. Subject has diabetic neuropathy.
9. Subject has evidence of a symptomatic urinary tract infection (urine Dipstick with nitrites present), chronic inflammation such as interstitial cystitis, bladder stones, previous pelvic radiation therapy or previous or current malignant disease of the pelvic organs.
10. Subject receives non-drug treatment including electro-stimulation therapy (with the exception of a bladder training program or pelvic floor exercises which started more than 30 days prior to screening).
11. Subject has any other clinically significant condition, which in the opinion of the investigator makes the subject unsuitable for the study.
12. Subject did not respond to previous anticholinergic treatment.

At Randomization:¨
1. The pregnancy test (HCG in urine) taken at the Baseline Visit is positive in women of childbearing potential.
2. Female subject is breastfeeding, pregnant, intends to become pregnant during the study or of childbearing potential is sexually active and not practicing a highly reliable method of birth. control.
3. Subject has evidence of a symptomatic urinary tract infection (urine Dipstick with nitrites present)
4. Subject has any other clinically significant condition, which in the opinion of the investigator makes the subject unsuitable for the study.

E.5 End points

E.5.1

Primary end point(s)

1. Change from baseline in the mean number of micturitions per 24 hours
2. Change from Baseline in mean number of incontinence episodes per 24 hours
3. Change from Baseline in mean number of urge incontinence episodes per 24 hours
4. Change from Baseline in mean number of urge episodes (grade 3 or 4) per 24 hours
5. Change from Baseline in mean voided volume per voiding
6. Change from Baseline in mean cystometric capacity
7. Change from Baseline in mean volume to the first involuntary detrusor contraction
8. Change from Baseline in mean maximal detrusor pressure during filling
9. Change from Baseline in mean maximal detrusor pressure during voiding
10. Change from Baseline in mean maximum flow
11. Change from Baseline in mean post-void residual volume (PVR)
12. Change from Baseline in mean projected isovolumetric detrusor pressure.
13. Change from Baseline in total Overactive Bladder Questionnaire (OABq) score
14. Change from Baseline in Patient´s Perception of Bladder Condition (PPBC) scores.

E.5.1.1

Timepoint(s) of evaluation of this end point

The primary time point comparison for all variables is at Visit V2, 4 weeks (±1 week) after the Baseline visit ("Day 0").

E.5.2

Secondary end point(s)

1. Proportion of subjects reporting at least one adverse event during the study
2. Incidence and severity of adverse events.

E.5.2.1

Timepoint(s) of evaluation of this end point

At study visits V2 through V6, i.e. at week 4, week 6, week 8, week 10 and week 12 post-baseline.

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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)

E.8.2.2

Placebo

Yes

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

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

The trial may be considered as completed when 48 subjects have been randomized and passed at least V2 assessments. In total, 6 post-baseline visits are scheduled but subjects may terminate participation before completing the full 12-week post-baseline follow up, as per their perception of the treatment effect on OAB symptoms.
Otherwise the trial may be stopped prematurely for safety reasons at any time. IMP-treated subjects will be followed up and receive standard medical care for the OAB.

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

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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

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)

Any of the currently available OAB treatment options (including resumed pre-study medication).

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2013-03-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-12-18

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-08-13

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