Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Glycopyrronium (Bromide) in Children (6 to Less Than 12 Years) With Asthma

NCT05222529 | Recruiting Phase 2 DMC

• 2 other identifiers: CQVM149C22012021-004972-32
• Study Type: interventional
• Target: 42
• Locations: 8 countries
• Sites: 23

Brief Summary

The purpose of this study is to characterize the bronchodilator effect, systemic exposure and safety/tolerability of two different doses of inhaled glycopyrronium, when compared to placebo. Outcome of this study will be used to determine the dose of inhaled glycopyrronium for the development of fixed dose combination indacaterol/mometasone/glycopyrronium (QVM149) for children aged 6 to less than 12 years old with moderate to severe asthma.

Conditions

Asthma

Keywords

Glycopyrronium, pediatric, asthma, Breezhaler, PK

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in trough FEV1

  Forced Expiratory Volume in 1 second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured by spirometry.

  At the start and end of each 2 week treatment period (Days 1, 14, 29, 42, 57 and 70)

Secondary Outcomes (6)

• Steady state pharmacokinetic (PK) parameters C0

  At the start and end of each 2 week treatment period (Days 1, 14, 15, 29, 42, 43, 57, 70 and 71)

• Systemic exposure following sparse PK sampling

  At the start and end of each 2 week treatment period (Days 1, 14, 15, 29, 42, 43, 57, 70 and 71)

• Change from Baseline in PEF rate

  At the start and end of each 2 week treatment period (Days 1, 14, 15, 29, 42, 43, 57, 70 and 71)

• Change from Baseline in FEV1

  At the start and end of each 2 week treatment period (Days 1, 14, 15, 29, 42, 43, 57, 70 and 71)

• Change from baseline in rescue medication use

  At the start and end of each 2 week treatment period (Days 1, 14, 15, 29, 42, 43, 57, 70 and 71)

Study Arms (3)

Glycopyrronium 25μg

EXPERIMENTAL

Glycopyrronium 25μg for two weeks

Drug: Glycopyrronium bromide 25ug; Drug: Placebo; Drug: Glycopyrronium bromide 12.5ug

Glycopyrronium 12.5μg

EXPERIMENTAL

Glycopyrronium 12.5μg for two weeks

Drug: Glycopyrronium bromide 25ug; Drug: Placebo; Drug: Glycopyrronium bromide 12.5ug

Placebo

PLACEBO COMPARATOR

Placebo for two weeks

Drug: Glycopyrronium bromide 25ug; Drug: Placebo; Drug: Glycopyrronium bromide 12.5ug

Interventions

Glycopyrronium bromide 25ug DRUG

25μg Glycopyrronium bromide capsules for oral inhalation via Breezhaler

Also known as: NVA237

Glycopyrronium 12.5μg; Glycopyrronium 25μg; Placebo

Placebo DRUG

Placebo to Glycopyrronium bromide capsules for oral inhalation via Breezhaler

Glycopyrronium 12.5μg; Glycopyrronium 25μg; Placebo

Glycopyrronium bromide 12.5ug DRUG

12.5ug Glycopyrronium bromide capsules for oral inhalation via Breezhaler

Also known as: NVA237

Glycopyrronium 12.5μg; Glycopyrronium 25μg; Placebo

Eligibility Criteria

• Age: 6 Years - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Confirmed diagnosis of asthma for at least 6 months
• Signed informed consent by parent(s)/legal guardian(s) and assent by the pediatric participant (depending on local requirements)
• Participant on stable dose of inhaled low-to-medium dose ICS with one additional controller for at least 4 weeks prior to run-in
• Pre-Bronchodilator FEV1 ≥60% to ≤90% of predicted normal at beginning of Run-in and randomization. If FEV1 eligibility criteria are not met at -45min pre-dose of the End of Run-in (Visit 30), the visit can be rescheduled once within 5 days from the previous attempt.
• 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 participants must perform a reversibility test at start of Run-in. If reversibility is not demonstrated at Run-in, it may be attempted at up to two ad hoc, unscheduled separate visits within 5 days from previous attempt. If reversibility is still not demonstrated after repeated assessment participants must be screen failed
• Demonstrated acceptable inhaler use technique for Diskus/Accuhaler (prior to run-in) and Breezhaler (prior to randomization) and able to complete spirometry procedures prior to randomization.
• A parent/legal guardian must be designated to complete all e-Diary entries and attend all clinic visits with the participant.
• 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 participant diary
• Female participants 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.

You may not qualify if:

• Systemic corticosteroid use for any reason within 3 months of Run-in
• Participants on low to medium mono ICS alone
• Participants 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
• Participants 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
• Participants 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)
• Participants 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 (Visit 1)
• History of Type I diabetes or uncontrolled Type II diabetes
• Participants who are sexually active at screening
• Hemoglobin levels outside normal ranges at Run-in (Visit 20)

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (23)

Novartis Investigative Site

Rousse, 7002, Bulgaria

RECRUITING

Novartis Investigative Site

Sevlievo, 5400, Bulgaria

RECRUITING

Novartis Investigative Site

Sofia, 1510, Bulgaria

RECRUITING

Novartis Investigative Site

Ibagué, Tolima Department, 730006, Colombia

RECRUITING

Novartis Investigative Site

Guatemala City, GTM, 01010, Guatemala

WITHDRAWN

Novartis Investigative Site

Guatemala City, 01015, Guatemala

RECRUITING

Novartis Investigative Site

Debrecen, Hajdu Bihar Megye, 4032, Hungary

RECRUITING

Novartis Investigative Site

Budapest, 1033, Hungary

RECRUITING

Novartis Investigative Site

Budapest, H-1083, Hungary

RECRUITING

Novartis Investigative Site

Eger, 3300, Hungary

RECRUITING

Novartis Investigative Site

Kaposvár, 7400, Hungary

WITHDRAWN

Novartis Investigative Site

Nagykanizsa, 8800, Hungary

WITHDRAWN

Novartis Investigative Site

Szigetvár, 7900, Hungary

RECRUITING

Novartis Investigative Site

Tarnów, 33-100, Poland

RECRUITING

Novartis Investigative Site

Lodz, Łódź Voivodeship, 90-329, Poland

RECRUITING

Novartis Investigative Site

George, Western Cape, 6529, South Africa

RECRUITING

Novartis Investigative Site

Cape Town, 7531, South Africa

RECRUITING

Novartis Investigative Site

Esplugues, Barcelona, 08950, Spain

RECRUITING

Novartis Investigative Site

Sabadell, Barcelona, 08208, Spain

RECRUITING

Novartis Investigative Site

Mérida, Extremadura, 06800, Spain

WITHDRAWN

Novartis Investigative Site

Barcelona, 08035, Spain

RECRUITING

Novartis Investigative Site

London, SE5 9RS, United Kingdom

RECRUITING

Novartis Investigative Site

Stoke-on-Trent, ST4 6QG, United Kingdom

RECRUITING

MeSH Terms

Conditions

Asthma

Interventions

Glycopyrrolate

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Novartis Pharmaceuticals

CONTACT

+41613241111; novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants, investigator staff, persons performing the assessments, data analysts and the Sponsor Clinical Trial Team (CTT) will remain blind to the identity of the treatment from the time of randomization until database lock.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2022
• First Posted: February 3, 2022
• Study Start: August 29, 2022
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): August 30, 2027
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

ZA (2); ES (4); CO (1); GU (2); HU (7); GB (2); PL (2); BU (3)