Clinical Trials Register

Summary
EudraCT Number:	2014-001631-36
Sponsor's Protocol Code Number:	CPL061-01
National Competent Authority:	Slovakia - SIDC (Slovak)
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2014-09-18
Trial 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

Slovakia - SIDC (Slovak)

A.2

EudraCT number

2014-001631-36

A.3

Full title of the trial

A Double-blind, Randomised, Placebo Controlled Study of the Efficacy of Glycopyrronium bromide 1mg /5ml in the Treatment of Non-drug Induced Hypersalivation with an Open Single-arm Extension to Investigate Longer Term Efficacy and Safety of Glycopyrronium bromide

Dvojito slepá, randomizovaná, placebom kontrolovaná štúdia účinnosti glykopyrónium bromidu 1mg/5ml v liečbe hypersalivácie nespôsobenej liekmi s nadväzujúcim jednoramenným otvoreným podávaním glykopyrónium bromidu za účelom skúmania jeho dlhodobejšej účinnosti a bezpečnosti.

A.3.1

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

Study to Assess the Efficacy and Safety of the Glycopyrronium bromide in the Treatment of Non-drug Induced Hypersalivation

Štúdia zisťujúca účinnosť a bezpečnosť Glycopyrronium bromidu v liečbe hypersalivácie nespôsobené liečivami

A.4.1

Sponsor's protocol code number

CPL061-01

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	Colonis Pharma Limited
B.1.3.4	Country	United Kingdom
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	Colonis Pharma Limited
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Accord Research, s.r.o.
B.5.2	Functional name of contact point	Clinical Trials Information
B.5.3	Address:
B.5.3.1	Street Address	Evropská 2690/17
B.5.3.2	Town/ city	Praha 6
B.5.3.3	Post code	160 00
B.5.3.4	Country	Czech Republic
B.5.4	Telephone number	+420602335548
B.5.5	Fax number	+420224174573
B.5.6	E-mail	marietta.tesarova@accordresearch.eu

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	No
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	Glycopyrronium bromide 1mg/5ml
D.3.4	Pharmaceutical form	Oral solution
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	GLYCOPYRRONIUM BROMIDE
D.3.9.1	CAS number	596-51-0
D.3.9.4	EV Substance Code	SUB07951MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200
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	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	Oral solution
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

Neurodevelopmental disability associated with hypersalivation

vývojové poruchy nervovej sústavy spojené s hypersaliváciou

E.1.1.1

Medical condition in easily understood language

Neurodevelopmental disability associated with drooling

vývojové poruchy nervovej sústavy spojené s nadmernou tvorbou slín

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.1
E.1.2	Level	PT
E.1.2	Classification code	10064062
E.1.2	Term	Neurodevelopmental disorder
E.1.2	System Organ Class	10037175 - Psychiatric disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.1
E.1.2	Level	LLT
E.1.2	Classification code	10020746
E.1.2	Term	Hypersalivation
E.1.2	System Organ Class	100000004856

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 efficacy and safety of glycopyrronium bromide in non-drug induced
hypersalivation associated with neurodevelopemental disability

hodnotenie účinnosti a bezpečnosti glycopyrronium bromidu v liečbe hypersalivácie nespôsobené liečivami spojené poruchami vývoja nervového systému

E.2.2

Secondary objectives of the trial

not applicable

nerelevantné

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Children (male and female) ≥ 3 and < 18 years of age
2. Neurodevelopmental disability associated with hypersalivation; defined as drooling in the absence of treatment so that clothing became damp on most days (approximately five to seven days per week) by confirming the Modified Teacher's Drooling Scale score ≥ 5
3. Weight ≥ 13 kg
4. Female subjects of childbearing potential must have a negative pregnancy test at screening
5. Female subjects of childbearing potential must be practicing one of the following methods of birth control and must agree to continue with the regimen throughout the study: hormonal methods such as oral, implantable, injectable, or transdermal contraceptives for a minimum of 90 days before IMP administration; total abstinence from sexual intercourse; intrauterine device (IUD); double-barrier method (condoms, sponge, diaphragm, or vaginal ring with spermicidal jellies or cream). Male subjects must also agree to use acceptable methods of birth control with their female partners, and this may include use of a male condom plus
spermicide.
6. Informed consent signed by both parents or legally acceptable representative and children ≥ 7 years (if the child is able to understand and sign the document)
7. Ability and willingness of children and their parents/caregivers to comply with study requirements, including the visit requirements, study procedures, concomitant medication restrictions and diary completion

1. Deti (mužského a ženského pohlavia) vo veku ≥ 3 a < 18 rokov
2. Vývojové poruchy nervového systému spojené s hypersaliváciou, definované ako množstvo slín, keď bez liečenia dochádza k prevlhnutiu oblečenia vo väčšine dní (približne 5 - 7 x týždenne), potvrdenej Modifikovaným skóre tvorby slín podľa Teachera ≥ 5
3. Hmotnosť ≥ 13 kg
4. Ženy v reprodukčnom veku musia mať negatívny tehotenský test počas skríningu
Ženy v reprodukčnom veku musia používať jednu z nasledujúcich antikoncepčných metód a musia súhlasiť s týmto režimom v priebehu celej štúdie: transdermálna antikoncepcia minimálne 90 dní pred podaním skúšaného lieku; úplná sexuálna abstinencia, vnútromaternicové teliesko (IUD), dvojitá bariérová metóda (kondómy, vaginálna špongia, vaginálna diafragma alebo vaginálny krúžok so spermicidným želé alebo krémom). Muži musia tiež súhlasiť s prijateľnou metódou antikoncepcie, ako je kondóm so spermicidom
6. Informovaný súhlas podpísaný obidvomi rodičmi alebo zákonným zástupcom a dieťaťom vo veku ≥ 7 rokov (ak dieťa dokáže porozumieť dokumentu a podpísať sa)
7. Schopnosť a ochota detí a ich rodičov/opatrovateľov dodržovať požiadavky štúdie vrátane návštev, procedúr v štúdii, obmedzenie súbežnej medikácie a vyplňovanie denníkov

E.4

Principal exclusion criteria

1. Use of any medication known to cause hypersalivation
2. Use of glycopyrronium bromide within 24 hours prior to baseline
3. Cholinergic or anticholinergic medications within three plasma half-lives of the medication
prior to baseline
4. Intrasalivary gland botulinum toxin within 10 months prior to baseline
5. Intraoral devices or prosthetics for treatment of drooling within 1 week
6. Acupuncture for treatment of drooling within 3 months
7. History of any significant cardiovascular, hepatic, or renal disease
8. Acute illness at the time of either the pre-study medical evaluation or dosing
9. Abnormal and clinically significant laboratory test results
10. Allergy or hypersensitivity to glycopyrronium bromide or other related products
11. History of difficulties in swallowing, or any gastrointestinal disease which could affect the drug absorption
12. Medical conditions contraindicating anticholinergic therapy
13. Any other clinically significant abnormality, that in the Investigator’s opinion would put the subject at increased risk of illness or injury, would interfere with study participation, or would interfere with the evaluation or quality of the data
14. Previous enrollment or randomization in this study
15. Participation in another clinical trial with investigational drugs within the last 1 month before screening
16. Pregnant or breastfeeding subjects

1. Užívanie akejkoľvek medikácie spôsobujúcej hypersaliváciu
2. Užitie glykopyrónium bromidu v priebehu 24 hodín pred zaradením do
štúdie
3. Cholinergné a anticholinergné lieky s plazmatickým polčasom kratším než je trojnásobok plazmatického polčasu medikácie
4. Intraglandulárna aplikácia botulotoxínu do slinných žliaz pred menej ako 10 mesiacmi
5.Intraorálne prístroje a protetické pomôcky na zníženie tvorby slín v poslednom týždni
6. Akupunktúra za účelom terapie nadmernej tvorby slín v posledných 3 mesiacoch
7. Významné kardiovaskulárne, pečeňové alebo obličkové ochorenie v anamnéze
8. Akútne ochorenie v screeningovom období alebo po zaradení do štúdie
9. Patologické a klinicky významné výsledky laboratórnych testov
10. Alergia alebo hypersenzitivita na glykopyrónium bromid alebo iné príbuzné produkty
11. Ťažkosti s prehĺtaním alebo iná gastrointestinálna choroba v anamnéze, ktoré by mohla ovplyvniť vstrebávanie
12. Kontraindikácie anticholinergnej terapie
13. Akékoľvek iné klinicky významné abnormality, ktoré by mohli podľa názoru skúšajúceho znamenať zvýšenie rizika ochorenia alebo zranenia, ovplyvnili by účasť na štúdii alebo mohli ovplyvniť kvalitu dát
14. Zaradenie alebo randomizácia do tejto štúdie v minulosti
15. Účasť na inej klinickej štúdii so skúšanými liekmi v poslednom mesiaci pred screeningom
16. Tehotenstvo a dojčenie

E.5 End points

E.5.1

Primary end point(s)

Rate of patients showing response from baseline to week 8. Response is defined as a decrease in modified 9-point Teacher’s Drooling Scale (mTDS) by 3 units.

Proporcia pacientov, u ktorých došlo k odpovedi od zaradenia do 8. týždňa. Odpoveď je definovaná ako pokles hodnoty modifikovaného skóre tvorby slín podľa Teacher o 3 jednotky

E.5.1.1

Timepoint(s) of evaluation of this end point

8th week

8 .týždeň

E.5.2

Secondary end point(s)

1. Longer-term response to glycopyrronium bromide within 24 weeks of administration
2. mTDS at individual time points
3. Global assessment of treatment completed by parent/caregiver and investigator at week 8 and study end·
4. VAS assessment of extent of drooling by parent/caregiver and investigator at each visit

1. Dlhodobejšia odpoveď na glycopyrronium bromide pri podávaní po dobu 24 týždňov
2. mTDS v jednotlivých časových úsekoch
3. celkové hodnotenie liečby rodičom / opatrovateľom a skúšajúcim v 8. týždni a pri ukončeniu štúdie
4: VAS hodnotenie rozsahu tvorby slín rodičom / opatrovateľom a skúšajúcim počas každej návštevy

E.5.2.1

Timepoint(s) of evaluation of this end point

Ad1) 24 th week
Ad2) 3times/day during 3 days prior to baseline, then on one day weekly - 3 times/d.
Ad 3) Week 8 and week 24 or at withdrawal
Ad4) Baseline, week 2, 4, 6, 8, 10,12, 16, 20, 24 or at withdrawal

Ad1) 24. týždeň
Ad2) 3x denne v priebehu 3 dní pred zaradením, potom raz za týždeň
AD3) Týždeň 8 a týždeň 24 alebo vyradenie
Ad4) Zaradenie, týždeň 2, 4, 6, 8, 10, 12, 16, 20, 24 alebo vyradenie

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

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

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

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

Czech Republic

Georgia

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

Yes

F.1.1

Number of subjects for this age range:

100

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)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

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

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

children with neurodevelopmental disability

deti s poruchou vývoja nervového systému

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

100

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

žiadna

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

2014-11-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-10-22

P. End of Trial
P.	End of Trial Status	Ongoing

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