To investigate the potential influence of time of dosing (morning or evening)on the bronchodilator effect of once daily orally inhaled QVM149 compared toplacebo.
ID
Source
Brief title
Condition
- Bronchial disorders (excl neoplasms)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To investigate the potential influence of time of dosing (morning or evening)
on the bronchodilator effect of once daily orally inhaled QVM149 compared to
placebo.
Secondary outcome
* To investigate the potential influence of time of dosing (morning or
evening) on trough FEV1 of once daily orally inhaled QVM149 compared
to placebo.
* To investigate the potential influence of time of dosing (morning or
evening), on peak expiratory flow rate (PEF) of once daily orally inhaled
QVM149 compared to placebo.
* To evaluate safety and tolerability of QVM149 when dosed in the
morning or in the evening in patients with asthma after during two weeks
of treatment in each treatment period.
Background summary
Asthma is a chronic inflammatory disorder of the airways associated with airway
hyperresponsiveness that leads to recurrent episodes of wheezing,
breathlessness, chest
tightness, and coughing, particularly at night or in the early morning. These
episodes are
usually associated with widespread but variable bronchial airflow obstruction
that is often
reversible either spontaneously or with treatment. Airflow limitation occurs as
a result of
obstruction or narrowing of the airways, when exposed to precipitating factors
(GINA 2016).
Despite existing therapies there is still significant unmet medical need in
asthma, with an
estimated 300 million people affected worldwide. The Global Burden of Asthma
Report
estimates that 15 million disability*adjusted life years (DALYs) are lost
annually due to
asthma, representing 1% of the total global burden. Annual worldwide deaths
have been
estimated at 250,000 (Beasley 2004).
Recently, tiotropium (long-acting muscarinic antagonist; LAMA) has been
approved in
the EU as an add-on maintenance bronchodilator treatment in adult patients ( *
18 years)
with asthma who are currently treated with the maintenance combination of
inhaled
corticosteroids (ICS; * 800*g budesonide/day or equivalent) and long-acting
beta2-agonists (LABA), and who experienced one or more severe exacerbations in
the
previous year. This is reflected in the GINA 2016 guideline by recommending
tiotropium as
an add-on option in patients requiring asthma therapy step 4 and 5 according to
the GINA
treatment algorithm.
There is mounting evidence that in patients who are poorly controlled on mid
and high dose
ICS/LABA a triple combination of LABA, LAMA and ICS can provide additional
benefit
in terms of lung function, symptom control and a reduction in exacerbations.
QVM149 is a fixed-dose combination of indacaterol acetate (LABA), glycopyrronium
bromide (LAMA), and mometasone furoate (MF; ICS) in development for once-daily
maintenance treatment of asthma GINA step * 4. QVM149 is formulated as
lactose-blended inhalation powder delivered via the Concept1 inhalation device
(Breezhaler®), a single dose dry powder inhaler (SDDPI). The three
mono-components of
QVM149, indacaterol, glycopyrronium bromide and MF have previously been
developed as
individual drugs or dual combinations (indacaterol acetate/MF called QMF149;
indacaterol
maleate/glycopyrronium bromide called QVA149) for treatment of either COPD or
asthma
as detailed below, thereby supporting the efficacy and safety of individual
components and
the selection of doses for their combination in QVM149.
Study objective
To investigate the potential influence of time of dosing (morning or evening)
on the bronchodilator effect of once daily orally inhaled QVM149 compared to
placebo.
Study design
This is a randomized, placebo-controlled, double-blind, six-sequence,
three-period cross-over study in asthma patients.
Intervention
The study will consist of a
14-day screening period, followed by a 14-day run-in period, and a treatment
epoch which consists of three treatment periods, with a minimum duration of
14 days each followed (for the 2 first treatment periods) by a wash-out period.
The duration of each treatment period may be extended up to aduration of 18
days if needed for operational reasons. The third treatment period will be
followed by a Study Completion evaluation at 1-7 days following the last
dose. The treatment periods will be separated by wash-out periods of 14 to
21 days duration.
The total duration of the study is approximately 13 weeks (minimum) to
19 weeks (maximum) for each patient.
Study burden and risks
N.A.
Lichtstrasse 35 4056
Basel 4056
CH
Lichtstrasse 35 4056
Basel 4056
CH
Listed location countries
Age
Inclusion criteria
Patients with a documented physician diagnosis of asthma and who
additionally meet the following criteria:
* patients receiving daily treatment with an inhaled corticosteroid
at a low or medium daily dose
* on a stable regimen for at least 4 weeks prior to screening.
* Pre-bronchodilator FEV1 * 60 % and < 100% of the predicted normal
value for the patient during screening.
* Patients who demonstrate an increase in FEV1 of * 12 % and * 200 mL
after administration of 400 *g salbutamol/360 *g albuterol (or
equivalent dose) at Screening. All patients must perform a reversibility
test at Screening.
* At screening, and baseline (day 1 pre-dose time) of the first treatment
period, vital signs (systolic and diastolic blood pressure and pulse rate)
will be assessed in the sitting position and again in the standing position
as outlined in the SOM. Sitting and standing vital signs should be within
the following ranges:
* oral body temperature between 35.0-37.5 °C
* systolic blood pressure, 90-159 mmHg
* diastolic blood pressure, 50-99 mmHg
* pulse rate, 40-90 bpm
* Hypertensive patients must have been on stable antihypertensive therapy
for at least 4 weeks prior to screening to be included in the trial.
* Patients must weigh at least 50 kg at screening to participate in the
study, and must have a body mass index (BMI) within the range of 18 to
40 kg/m2.
Exclusion criteria
* Contraindicated for treatment with, or having a history of reactions/
hypersensitivity to any of the drugs of a similar class
* Patients who have had an asthma attack/exacerbation requiring systemic
steroids or hospitalization or emergency room visit within 1 year of
Screening.
* Patients who have had previous intubation for a severe asthma
attack/exacerbation.
* Patients with a history of clinically relevant bronchoconstriction upon
repeated forced expiratory maneuvers.
* History of paradoxical bronchospasm in response to inhaled medicines.
* Patients who during the run-in period prior to randomization require the
use of *12 puffs / 24 hours of rescue medication for 48 hours (over two
consecutive days) or who have a decline in PEF from the reference PEF
of * 30% for 6 consecutive scheduled PEF readings
* Patients who do not maintain regular day/night, waking/sleeping cycles
(e.g., night shift workers).
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-000644-17-NL |
| ClinicalTrials.gov | NCT03108027 |
| CCMO | NL61785.056.17 |