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.
The study design is a double-blind, placebo controlled, randomized sequence, three-treatment, three-period, six-sequence, cross-over multiple-dose study to evaluate efficacy, pharmacokinetics, pharmacodynamics, and safety and tolerability of glycopyrronium bromide (bromide) in children from 6 to less than 12 years of age with asthma with forced expiratory volume in one second (FEV1) ≥60% and ≤ 90% of the predicted normal value for the participant. This study will consist of 4 phases: Screening, Run-in, Treatment and Follow-up. After the screening phase, participants will enter the Run-in Phase to further assess eligibility and those participants that meet all eligibility criteria will be randomized. Study treatment will be administered in addition to background asthma LABA+ICS controller therapy (salmeterol xinafoate 50µg/fluticasone propionate 100µg) from entering the run-in period, through to the end of the treatment phase, including the 2 wash-out periods. Participants will be randomized to one of 6 different sequences with an equal (1:1:1:1:1:1) randomization ratio. The Treatment Phase will last 10 weeks, and every sequence is divided in three treatment periods: Glycopyrronium bromide 12.5 µg, Glycopyrronium bromide 25µg or matching placebo dry powder in capsules for inhalation, via Breezhaler. Each treatment period lasts 2 weeks and 2 consecutive treatment periods are separated by a 2-week wash-out period. Participants who discontinue their study treatment prematurely will be required to return to the clinic for an Early Termination Visit. 30 days after last treatment date, a final telephone contact must be conducted for safety follow-up. The total duration of the trial for a participant (from screening to follow up) is approximately 20 weeks including safety follow-up.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
42
25μg Glycopyrronium bromide capsules for oral inhalation via Breezhaler
Placebo to Glycopyrronium bromide capsules for oral inhalation via Breezhaler
12.5ug Glycopyrronium bromide capsules for oral inhalation via Breezhaler
Novartis Investigative Site
Rousse, Bulgaria
RECRUITINGNovartis Investigative Site
Sevlievo, Bulgaria
RECRUITINGNovartis Investigative Site
Sofia, Bulgaria
RECRUITINGNovartis Investigative Site
Ibague, Tolima Department, Colombia
RECRUITINGNovartis Investigative Site
Guatemala City, GTM, Guatemala
WITHDRAWNNovartis Investigative Site
Guatemala City, Guatemala
RECRUITINGNovartis Investigative Site
Debrecen, Hajdu Bihar Megye, Hungary
RECRUITINGNovartis Investigative Site
Budapest, Hungary
RECRUITINGNovartis Investigative Site
Budapest, Hungary
RECRUITINGNovartis Investigative Site
Eger, Hungary
RECRUITING...and 13 more locations
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.
Time frame: At the start and end of each 2 week treatment period (Days 1, 14, 29, 42, 57 and 70)
Steady state pharmacokinetic (PK) parameters C0
Steady state pharmacokinetic (PK) parameters C0 will be provided for plasma glycopyrronium concentrations at pre-dose and post-dose time-points.
Time frame: 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
Systemic exposure following sparse PK sampling will be provided at pre-dose and post-dose time-points for each glycopyrronium dose level
Time frame: 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
Morning and Evening Peak Expiratory Flow Rate (PEF) will be measured. PEF is the peak expiratory flow, the maximum speed of expiration.
Time frame: 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
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.
Time frame: 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
Daily use of rescue medication will be recorded each morning and evening throughout the 2 week treatment by the participant using their electronic diary.
Time frame: At the start and end of each 2 week treatment period (Days 1, 14, 15, 29, 42, 43, 57, 70 and 71)
Adverse events of special interest (AESI) typical of anti-muscarinic side effects
AESIs that are typical of anti-muscarinic agents will be reported.
Time frame: From the start of run-in to 30 days after end of treatment, assessed up to maximum duration of 16 weeks
Novartis Pharmaceuticals
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