Clinical trial NCT03063086: Assess Bronchodilator Effect and Safety of Two Doses of QVM149 Compared to a Fixed Dose Combination of Salmeterol/Fluticasone in Patients With Asthma.
Official title: A Randomized, Double-blind, Double-dummy, Active-controlled, 3-period Complete Cross-over Study to Assess the Bronchodilator Effect and Safety of Two Doses of QVM149 Compared to a Fixed Dose Combination of Salmeterol/Fluticasone in Patients With Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2017-02-24
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess peak FEV1 of two doses of QVM149 compared to a fixed-dose combination of salmeterol/fluticasone (50/500μg b.i.d.) and to characterize the respective 24 hour bronchodilator effect profiles in patients with asthma. Data from this study will complement lung function data obtained in the pivotal QVM149 phase 3 program by assessing the bronchodilatory effect of QVM149 at multiple time-points over an entire dosing interval of 24 hours.


Eligibility criteria: Key Inclusion criteria

* Male and female adult patients ≥ 18 years old and ≤ 75 years.
* Patients with a documented physician diagnosis of asthma for a period of at least 12 months prior to Visit 1 (Screening).
* Patients who have used ICS and LABA combinations for asthma for at least 3 month and at a stable medium or high dose of ICS for at least 1 month prior to Visit 1 (Screening).
* Pre-bronchodilator FEV1 of \< 80 % of the predicted normal value at screening Visit 1 (spirometry will not be repeated at baseline prior to randomization).
* Patients who demonstrate an increase in FEV1 of ≥ 12 % and 200 mL after administration of 400 µg salbutamol/360 µg albuterol (or equivalent do se) at Visit 1 (Screening). All patients must perform a reversibility test at Visit 1 (Screening). If reversibility is not demonstrated at Visit 1 (Screening), then, reversibility testing may be repeated once during the screening period.
* If reversibility is not demonstrated at Visit 1 (retesting allowed once), patients must be screen failed. Spacer devices are not permitted during reversibility testing Key Exclusion criteria
* Patients who have smoked or inhaled tobacco products within the 6 month period prior to Visit 1
* Patients who have had an asthma attack/exacerbation requiring systemic steroids or hospitalization or emergency room visit within 6 weeks of Visit 1
* Patients with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia (BPH) or bladder-neck obstruction or severe renal impairment or urinary retention
* Patients who have had a respiratory tract infection or asthma worsening within 4 weeks prior to Visit 1
* Patients with any chronic conditions affecting the upper respiratory tract
* Patients with a history of chronic lung diseases other than asthma, including (but not limited to) COPD, sarcoidosis, interstitial lung disease, cystic fibrosis, clinically significant bronchiectasis and active tuberculosis.
* Patients with Type I diabetes or uncontrolled Type II diabetes (HbA1c \>9% at screening).
* Patients who have a clinically significant ECG abnormality at Visit 1
* Patients with a history of hypersensitivity or intolerance to any of the study drugs (including excipients)
* Patients with narcolepsy and/or insomnia.
* Patients on Maintenance Immunotherapy (desensitization) for allergies for less than 3 months prior to Visit 2 or patients on Maintenance Immunotherapy for more than 3 months prior to Visit 2 but expected to change throughout the course of the study.
* Pregnant or nursing (lactating) women
* Women of child-bearing potential must use Highly effective contraception methods
* Patients who have discontinued LAMA therapy in the past for any safety, tolerability or perceived lack of efficacy reason.
* History of paradoxical bronchospasm in response to inhaled medicines.
* Patients with a history of clinically relevant bronchoconstriction upon repeated forced expiratory maneuvers.
* Patient with a serum potassium level below the laboratory limit of normal at screening.

Primary outcomes:
measure: Peak FEV1 (L) Defined as the Highest Bronchodilatory Effect on FEV1 During a Period of 5 Min to 4 h After the Last Evening Dose of Each Treatment Period
timeFrame: 3 weeks
Secondary outcomes:
measure: FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose
timeFrame: -45 min, -15 min, 5 min, 15 min, 30 min, 1 h, 2 h, 3h, 4 h, 8 h, 10 h, 11 h 55 min, 14 h, 18 h, 21 h, 23 h 15 min, 23 h 45 min at 3 weeks
measure: FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose
timeFrame: -45 min, -15 min, 5 min, 15 min, 30 min, 1 h, 2 h, 3h, 4 h, 8 h, 10 h, 11 h 55 min, 14 h, 18 h, 21 h, 23 h 15 min, 23 h 45 min at 3 weeks
measure: FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose
timeFrame: -45 min, -15 min, 5 min, 15 min, 30 min, 1 h, 2 h, 3h, 4 h, 8 h, 10 h, 11 h 55 min, 14 h, 18 h, 21 h, 23 h 15 min, 23 h 45 min at 3 weeks
measure: FEV1 AUC 5 Min - 1 h (Day 21) FEV1 AUC 5 Min - 4 h (Day 21) and FEV1 AUC 5 Min - 23 h 45 Min (Day 21)
timeFrame: 3 weeks
measure: Trough FEV1 After 21 Days of Treatment
timeFrame: 3 weeks
Other outcomes:
Locations:
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Chang Chun
country: China
facility: Novartis Investigative Site
state: Jilin
city: Tianjin
country: China
facility: Novartis Investigative Site
state: Tianjin
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Grosshansdorf
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Wiesbaden
country: Germany
facility: Novartis Investigative Site
city: Groningen
country: Netherlands
facility: Novartis Investigative Site
state: GZ
city: Bucharest
country: Romania
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
References: