Clinical Trials Register

Summary
EudraCT Number:	2021-004972-32
Sponsor's Protocol Code Number:	CQVM149C2201
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2022-05-31
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

Poland - Office for Medicinal Products

A.2

EudraCT number

2021-004972-32

A.3

Full title of the trial

A Phase II, double-blind, randomized, multiple dose, cross over, three-treatment, three-period, six sequence placebo controlled trial to evaluate efficacy, pharmacokinetics (PK), pharmacodynamics (PD) and safety and tolerability of glycopyrronium (bromide) in children from 6 to less than 12 years of age with asthma

Randomizowane, kontrolowane placebo badanie fazy II prowadzone metodą podwójnie ślepej próby w układzie naprzemiennym, dotyczące wielokrotnego podawania trzech leków w trzech okresach w sześciu sekwencjach, mające na celu ocenę skuteczności, farmakokinetyki (PK), farmakodynamiki (PD) oraz bezpieczeństwa i tolerancji glikopironium (bromku) u chorych na astmę dzieci w wieku od 6 do < 12 lat

A.3.1

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

Pharmacokinetics, pharmacodynamics, safety and tolerability of glycopyrronium (bromide) in children (6 to less than 12 years) with asthma.

A.3.2

Name or abbreviated title of the trial where available

Pharmacokinetics, pharmacodynamics, safety and tolerability of glycopyrronium (bromide) in children

A.4.1

Sponsor's protocol code number

CQVM149C2201

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/362/2021

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Novartis Pharma AG
B.1.3.4	Country	Switzerland
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	Novartis Pharma AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Pharma Services AG
B.5.2	Functional name of contact point	Punkt informacyjny badania kliniczn
B.5.3	Address:
B.5.3.1	Street Address	Forum 1, Novartis Campus / Lichtstrasse 35
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4056
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	+41 61 3241 111
B.5.5	Fax number	+41 61 3248 001
B.5.6	E-mail	clinicaltrial.enquiries@novartis.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	Seebri Breezhaler
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
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	Glycopyrronium bromide 25 μg of active moiety in the capsule
D.3.2	Product code	NVA237
D.3.4	Pharmaceutical form	Inhalation powder, hard capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation 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.3.9.2	Current sponsor code	NVA237
D.3.9.4	EV Substance Code	SUB07951MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
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.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	Seebri Breezhaler
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
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	Glycopyrronium bromide 12.5 μg of active moiety in the capsule
D.3.2	Product code	NVA237
D.3.4	Pharmaceutical form	Inhalation powder, hard capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation 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.3.9.2	Current sponsor code	NVA237
D.3.9.4	EV Substance Code	SUB07951MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	12.5
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	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	Inhalation powder, hard capsule
D.8.4	Route of administration of the placebo	Inhalation use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Asthma

E.1.1.1

Medical condition in easily understood language

Asthma

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10003553
E.1.2	Term	Asthma
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Evaluate the change from Baseline in trough forced expiratory volume in one second (FEV1) at week 2 of each treatment period

E.2.2

Secondary objectives of the trial

● To characterize systemic exposure following 2 doses of glycopyrronium (GLY)
● To evaluate the change from Baseline in peak expiratory flow (PEF) rate at week 2 of each treatment period
● To evaluate the change from Baseline in FEV1 at 30 min and 1 hour post dose at week 2 of each treatment period
● To evaluate the change from Baseline in rescue medication use over each treatment period
● To evaluate the safety and tolerability of each treatment, including in laboratory parameters including blood glucose and serum potassium
● To assess typical anti-muscarinic side effects (including dry mouth, fatigue, constipation and urinary retention)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Confirmed diagnosis of asthma for at least 6 months
- Signed informed consent by parent(s)/legal guardian(s) and assent by the pediatric patient (depending on local requirements)
- Patient on stable dose of inhaled low-to-medium dose ICS with one additional controller for at least 4 weeks prior to randomization
- Pre-Bronchodilator FEV1 ≥60% to ≤90% of predicted normal at beginning of Run-in and randomization
- FEV1 reversibility, done using up to 4 puffs of SABA (up to 400μg salbutamol or 360μg albuterol) at Run-in visit (Visit 20): increase >
and/or = 12% (performed according to American Thoracic Society (ATS)/European Respiratory Society (ERS) 2019 guidelines). All patients
must perform a reversibility test at start of Run-in. If reversibility is not demonstrated at Run-in, it may be repeated once on the same day. If
reversibility is still not demonstrated after repeated assessment patients must be screen failed
- Demonstrated acceptable inhaler use technique for Breezhaler and Diskus/Accuhaler prior to randomization, and able to complete spirometry
procedures prior to randomization
- A parent/legal guardian must be designated to complete all e-Diaryentries and attend all clinic visits with the patient
- Parents/legal guardian must be willing and able to assist the child with the procedures outlined in the protocol, e.g. compliance with study
medication, completion of electronic patient diary
- Female patients of child-bearing potential, who might become sexually active, must be informed of the need to prevent pregnancy during the study
using effective contraceptive methods. The decision on the contraceptive method should be reviewed at least every 3 months to evaluate the
individual need and compatibility of the method chosen.

E.4

Principal exclusion criteria

- Systemic corticosteroid use for any reason within 3 months of Run-in
- Patients on low to medium mono ICS alone-Patients requiring six or more puffs of rescue medication per day on more than two consecutive days in
the four weeks prior to Screening (Visit 1) and/or in the four weeks prior to the Run-in visit-Patients who have had an asthma attack/exacerbation
requiring a) systemic corticosteroids (SCS) or b) hospitalization or c) emergency room visit, within 3 months prior to Screening (Visit 1), or more than
3 separate exacerbations in the 12 months preceding the Screening visit-Patients with a known narrow-angle glaucoma, bladder dysfunction, bladder
outlet obstruction or any other conditions where anticholinergic treatment is contraindicated prior to Screening (Visit 1)-Patients with a history of
long QT syndrome or whose corrected QT interval (QTc) measured at start of Run-in and confirmed at Baseline (prior to randomization) (Fridericia
method) is prolonged (> 450 msec for boys and girls) and confirmed by a central assessor (these patients should not be rescreened)
- Suspected or documented active infections (bacterial, viral, fungal, mycobacterial or other, including active SARS-CoV-2, tuberculosis or atypical
mycobacterial disease) of the upper or lower respiratory tract, sinus or middle ear that is not resolved within 6 weeks of Screening (Visit1)
- History of Type I diabetes or uncontrolled Type II diabetes
- Patients who are sexually active at screening
- Hemoglobin levels outside normal ranges at Run-in (Visit 20)
- Female patients of childbearing potential (e.g., are menstruating) who do not agree to abstinence or, if they become sexually active during study
participation, do not agree to the use of contraception as defined in the inclusion criteria.

E.5 End points

E.5.1

Primary end point(s)

Change from Baseline in trough FEV1 at week 2 of each treatment period.

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 2

E.5.2

Secondary end point(s)

• Steady state PK parameters C0 will be provided for plasma glycopyrronium concentrations at pre-dose and post-dose time-points at the start and end of each 2 week treatment period. Systemic exposure following sparse PK sampling will be provided at pre-dose and post-dose time-points for each glycopyrronium dose level at the start and end of each 2 week treatment period.
• Change from baseline in Morning and Evening PEF will be measured at the start and end of each 2 week treatment period.
• Change from baseline in FEV1 will be measured at the start and end of each 2 week treatment period.
• Change from baseline in rescue medication use will be recorded each morning and evening throughout the 2 week treatment by the participant using their electronic diary.
• AESIs that are typical of anti-muscarinic agents will be assessed from the start of run-in to 30 days after end of treatment, up to maximum duration of 16 weeks.

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 2

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

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

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

Yes

E.6.13.1

Other scope of the trial description

Tolerability

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

Yes

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

Colombia

Guatemala

Russian Federation

South Africa

United Kingdom

Bulgaria

Hungary

Poland

Spain

E.8.7

Trial has a data monitoring committee

Yes

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

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:

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)

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

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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)

Once the participant has completed the end of study visit or early termination study, the participant will stop taking the background and investigational treatment. The investigator will assign the patient to the best available asthma maintenance treatment

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

2022-09-14

Ethics Committee Opinion of the trial application

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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