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

NCT03063086 | Completed Phase 2 Results

• 1 other identifier: CQVM149B2208
• Study Type: interventional
• Target: 116
• Locations: 6 countries
• Sites: 12

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.

Conditions

Asthma

Outcome Measures

Primary Outcomes (1)

• 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

  The highest bronchodilator effect on FEV1 during a period of 5 min to 4 h after the last evening dose of each treatment period . To demonstrate superiority in peak bronchodilator effect of QVM149 at a dose of 150/50/160 μg o.d. and 150/50/80 μg o.d. compared to a FDC of salmeterol/fluticasone at a dose of 50/500 μg b.i.d. after 3 weeks of treatment in patients with asthma

  3 weeks

Secondary Outcomes (5)

• FEV1 Over 24 h After 21 Days of Treatment in Relation to Evening Dose

  -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

• FVC Over 24 h After 21 Days of Treatment in Relation to Evening Dose

  -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

• FEV1/FVC Ratio Over 24 h After 21 Days of Treatment in Relation to Evening Dose

  -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

• 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)

  3 weeks

• Trough FEV1 After 21 Days of Treatment

  3 weeks

Study Arms (6)

Sequence 1

ACTIVE COMPARATOR

A-B-C

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

Sequence 2

ACTIVE COMPARATOR

A-C-B

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

Sequence 3

ACTIVE COMPARATOR

B-C-A

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

Sequence 4

ACTIVE COMPARATOR

B-A-C

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

Sequence 5

ACTIVE COMPARATOR

C-A-B

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

Sequence 6

ACTIVE COMPARATOR

C-B-A

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

Interventions

QVM149 150/50/80 μg o.d. DRUG

A

Sequence 1; Sequence 2; Sequence 3; Sequence 4; Sequence 5; Sequence 6

QVM149 150/50/160 μg o.d. DRUG

B

Sequence 1; Sequence 2; Sequence 3; Sequence 4; Sequence 5; Sequence 6

salmeterol/fluticasone FDC 50/500 μg b.i.d. DRUG

C

Sequence 1; Sequence 2; Sequence 3; Sequence 4; Sequence 5; Sequence 6

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (12)

Novartis Investigative Site

Sofia, 1612, Bulgaria

Location

Novartis Investigative Site

Changchun, Jilin, 130021, China

Location

Novartis Investigative Site

Tianjin, Tianjin Municipality, 300192, China

Location

Novartis Investigative Site

Shanghai, 200433, China

Location

Novartis Investigative Site

Berlin, 10117, Germany

Location

Novartis Investigative Site

Frankfurt, 60596, Germany

Location

Novartis Investigative Site

Großhansdorf, 22947, Germany

Location

Novartis Investigative Site

Hanover, 30625, Germany

Location

Novartis Investigative Site

Wiesbaden, 65187, Germany

Location

Novartis Investigative Site

Groningen, GZ, 9713, Netherlands

Location

Novartis Investigative Site

Bucharest, Romania

Location

Novartis Investigative Site

Manchester, M23 9QZ, United Kingdom

Location

Related Publications (1)

• Oba Y, Anwer S, Maduke T, Patel T, Dias S. Effectiveness and tolerability of dual and triple combination inhaler therapies compared with each other and varying doses of inhaled corticosteroids in adolescents and adults with asthma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2022 Dec 6;12(12):CD013799. doi: 10.1002/14651858.CD013799.pub2.

  PMID: 36472162 DERIVED

Related Links

• A Plain Language Trial Summary is available on novartisclinicaltrials.com

MeSH Terms

Conditions

Asthma

Interventions

Salmeterol Xinafoate

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

862-778-8300

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2017
• First Posted: February 24, 2017
• Study Start: January 21, 2017
• Primary Completion: August 2, 2018
• Study Completion: August 2, 2018
• Last Updated: October 4, 2021
• Results First Posted: December 13, 2019

Record last verified: 2021-09

Locations

RO (1); BU (1); DE (5); NL (1); CN (3); GB (1)