Assess Bronchodilator Effect and Safety of Two Doses of QVM149 Compared to a Fixed Dose Combination of Salmeterol/Fluticasone in Patients With Asthma.

Novartis

Status and phase: Completed; Phase 2

Conditions: Asthma

Treatments: Drug: salmeterol/fluticasone FDC 50/500 μg b.i.d.; Drug: QVM149 150/50/160 μg o.d.; Drug: QVM149 150/50/80 μg o.d.

Study type: Interventional

Funder types: Industry

Identifiers

NCT03063086

CQVM149B2208

Details and patient eligibility

About

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.

Enrollment: 116 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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116 participants in 6 patient groups

Sequence 1

Active Comparator group

Description:

A-B-C

Treatment:

Drug: salmeterol/fluticasone FDC 50/500 μg b.i.d.

Drug: QVM149 150/50/160 μg o.d.

Drug: QVM149 150/50/80 μg o.d.

Sequence 2

Active Comparator group

Description:

A-C-B

Treatment:

Drug: salmeterol/fluticasone FDC 50/500 μg b.i.d.

Drug: QVM149 150/50/160 μg o.d.

Drug: QVM149 150/50/80 μg o.d.

Sequence 3

Active Comparator group

Description:

B-C-A

Treatment:

Drug: salmeterol/fluticasone FDC 50/500 μg b.i.d.

Drug: QVM149 150/50/160 μg o.d.

Drug: QVM149 150/50/80 μg o.d.

Sequence 4

Active Comparator group

Description:

B-A-C

Treatment:

Drug: salmeterol/fluticasone FDC 50/500 μg b.i.d.

Drug: QVM149 150/50/160 μg o.d.

Drug: QVM149 150/50/80 μg o.d.

Sequence 5

Active Comparator group

Description:

C-A-B

Treatment:

Drug: salmeterol/fluticasone FDC 50/500 μg b.i.d.

Drug: QVM149 150/50/160 μg o.d.

Drug: QVM149 150/50/80 μg o.d.

Sequence 6

Active Comparator group

Description:

C-B-A

Treatment:

Drug: salmeterol/fluticasone FDC 50/500 μg b.i.d.

Drug: QVM149 150/50/160 μg o.d.

Drug: QVM149 150/50/80 μg o.d.