Study to Compare QVM149 and Free Triple Combination of Salmeterol/Fluticasone + Tiotropium

NCT ID: NCT03158311

Last Updated: 2021-10-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1426 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-05
• Study Completion Date: 2019-07-19

Brief Summary

The purpose of this trial was to demonstrate that the efficacy of two treatment arms of the fixed-dose combination product QVM149 was non-inferior to the efficacy of the free combination arm of salmeterol/ fluticasone+ tiotropium in uncontrolled moderate to severe asthmatic patients.

The planned duration of treatment in this study was 24 weeks, followed up by a 7-day follow-up period.

Detailed Description

This study used a randomized, partially-blinded, 24-week, parallel-group, non-inferiority, open-label active controlled design. The study was partially open-label. Investigators and patients had knowledge of treatment allocation between QVM149 and/or comparator, however the QVM149 strength allocation was masked. The global sponsor team responsible for data review and analysis was blinded to all treatment allocations The study consisted of a screening period of up to 1-week, run-in period of 2-weeks, randomized treatment period of 24-weeks, and a follow-up period of 1-week.

At the screening visit, informed consent was obtained, and current and prohibited medications were reviewed. Rescue medication was provided to all patients who met the eligibility criteria and was to be used on an "as needed" basis throughout the study.

At the run-in visit, inclusion and exclusion criteria were reviewed and the patients were supplied with open-label long acting β2-adrenergic agonist/inhaled corticosteroids (LABA/ICS) salmeterol/fluticasone 50/250 μg b.i.d or 50/500 μg b.i.d to match their ICS background medication dose to be stopped at randomization visit.

All patients who met the eligibility criteria were randomized to 1 of 3 treatment arms with a randomization ratio of 1:1:1. The patients were stratified at randomization according to the ICS dose component of background ICS/LABA (medium or high dose) and region.

Treatment period visits were scheduled every 8 weeks. The study used two doses of QVM149 (high dose [150/50/160 μg] and a medium dose [150/50/80 μg] o.d. delivered via Concept1 inhaler) and a comparator treatment (salmeterol/fluticasone 50/500 μg b.i.d. delivered via Accuhaler® plus tiotropium 5 μg o.d delivered via Respimat®).

All randomized patients were contacted (by telephone) 7 days following the last dose of study medication or last visit, whichever was later, for Safety Follow-up visit.

Conditions

Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

QVM149 150/50/80 μg

QVM149 150/50/80 μg o.d. delivered via Concept1

Group Type: EXPERIMENTAL

QVM149

Intervention Type: DRUG

Indacaterol acetate / glycopyrronium bromide / mometasone furoate

QVM149 150/50/160 μg

QVM149 150/50/160 μg o.d. delivered via Concept1

Group Type: EXPERIMENTAL

QVM149

Intervention Type: DRUG

Indacaterol acetate / glycopyrronium bromide / mometasone furoate

Salmeterol/fluticasone 50/500 μg plus tiotropium 5 μg

Salmeterol/fluticasone 50/500 μg b.i.d. delivered via Accuhaler® plus tiotropium 5 μg o.d. delivered via Respimat®

Group Type: ACTIVE_COMPARATOR

Salmeterol/fluticasone plus tiotropium

Intervention Type: DRUG

Free triple arm of salmeterol / fluticasone plus tiotropium

Interventions

QVM149

Indacaterol acetate / glycopyrronium bromide / mometasone furoate

Intervention Type: DRUG

Salmeterol/fluticasone plus tiotropium

Free triple arm of salmeterol / fluticasone plus tiotropium

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients with a diagnosis of asthma for a period of at least 6 months prior to Visit 1 with current asthma severity ≥ step 4 (GINA 2017).
• Patients who had used ICS/LABA combinations for asthma for at least 3 months and at stable medium or high dose of ICS/LABA for at least 1 month prior to Visit 1.
• Patients were required to be symptomatic at screening despite treatment with medium or high stable doses of ICS/LABA as defined by ACQ-7 score ≥ 1.5 at visits 101 and 201 (randomization visit).
• Patients with history of at least one severe asthma exacerbation which required medical care from a physician, emergency room visit (or local equivalent structure) or hospitalization in the 12 months prior to Visit 1 and required systemic corticosteroid treatment for at least 3 days including physician guided self-management treatment with oral corticosteroids as part of written asthma action plan.
• Pre-bronchodilator FEV1 of < 85 % of the predicted normal value for the patient after withholding bronchodilators prior to spirometry at both Visit 101 and Visit 201.
• Patients who demonstrated an increase in FEV1 of ≥ 12% and 200 ml.

Exclusion Criteria

• Patients who had a smoking history of greater than 20 pack years.
• Patients diagnosed with Chronic Obstructive Pulmonary Disease (COPD).
• Patients who had an asthma attack/exacerbation requiring systemic steroids or hospitalization or emergency room visit within 6 weeks of Visit 1 (Screening).
• Patients treated with a LAMA for asthma within 3 months prior to Visit 1.
• Patients who had a respiratory tract infection or clinical significant asthma worsening as defined by Investigator within 4 weeks prior to Visit 1 or between Visit 1 and Visit 201.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Alzira, Valencia, Spain

Novartis Investigative Site

Kaoshiung, Taiwan, Taiwan

Novartis Investigative Site

Taichung, , Taiwan

Novartis Investigative Site

Taipei, , Taiwan

Novartis Investigative Site

Izmir, , Turkey (Türkiye)

Novartis Investigative Site

Mersin, , Turkey (Türkiye)

Novartis Investigative Site

Yenisehir/Izmir, , Turkey (Türkiye)

Novartis Investigative Site

Berazategui, Buenos Aires, Argentina

Novartis Investigative Site

CABA, Buenos Aires, Argentina

Novartis Investigative Site

Caba, Buenos Aires, Argentina

Novartis Investigative Site

CABA, Buenos Aires, Argentina

Novartis Investigative Site

CABA, Buenos Aires, Argentina

Novartis Investigative Site

CABA, Buenos Aires, Argentina

Novartis Investigative Site

Florida, Buenos Aires, Argentina

Novartis Investigative Site

Lanús, Buenos Aires, Argentina

Novartis Investigative Site

Mar del Plata, Buenos Aires, Argentina

Novartis Investigative Site

Nueve de Julio, Buenos Aires, Argentina

Novartis Investigative Site

Ranelagh, Partido de Berazate, Buenos Aires, Argentina

Novartis Investigative Site

Concepción del Uruguay, Entre Ríos Province, Argentina

Novartis Investigative Site

Santa Rosa, La Pampa Province, Argentina

Novartis Investigative Site

Buenos Aires, Nueve De Julio, Argentina

Novartis Investigative Site

Rosario, Santa Fe Province, Argentina

Novartis Investigative Site

Rosario, Santa Fe Province, Argentina

Novartis Investigative Site

San Miguel de Tucumán, Tucumán Province, Argentina

Novartis Investigative Site

Bahía Blanca, , Argentina

Novartis Investigative Site

Buenos Aires, , Argentina

Novartis Investigative Site

Buenos Aires, , Argentina

Novartis Investigative Site

Buenos Aires, , Argentina

Novartis Investigative Site

Buenos Aires, , Argentina

Novartis Investigative Site

Ciudad Autonoma de Bs As, , Argentina

Novartis Investigative Site

Mendoza, , Argentina

Novartis Investigative Site

Mendoza, , Argentina

Novartis Investigative Site

Mendoza, , Argentina

Novartis Investigative Site

Salta, , Argentina

Novartis Investigative Site

Santa Fe, , Argentina

Novartis Investigative Site

Curicó, Maule Region, Chile

Novartis Investigative Site

Santiago, Santiago Metropolitan, Chile

Novartis Investigative Site

Bogota, Cundinamarca, Colombia

Novartis Investigative Site

Bogotá, , Colombia

Novartis Investigative Site

Ostrava Poruba, Czech Republic, Czechia

Novartis Investigative Site

Prague, Czech Republic, Czechia

Novartis Investigative Site

Teplice, CZE, Czechia

Novartis Investigative Site

Lovosice, , Czechia

Novartis Investigative Site

Miroslav, , Czechia

Novartis Investigative Site

Peine, Lower Saxony, Germany

Novartis Investigative Site

Geesthacht, Schleswig-Holstein, Germany

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Berlin, , Germany

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Berlin, , Germany

Novartis Investigative Site

Berlin, , Germany

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Berlin, , Germany

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Berlin, , Germany

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Berlin, , Germany

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Bonn, , Germany

Novartis Investigative Site

Böhlen, , Germany

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Darmstadt, , Germany

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Dortmund, , Germany

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Einbeck, , Germany

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Frankfurt, , Germany

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Frankfurt, , Germany

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Fürstenwalde, , Germany

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Gelsenkirchen, , Germany

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Hamburg, , Germany

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Hamburg, , Germany

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Hanover, , Germany

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Hanover, , Germany

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Leipzig, , Germany

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Leipzig, , Germany

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Leipzig, , Germany

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Leipzig, , Germany

Novartis Investigative Site

Ludwigsburg, , Germany

Novartis Investigative Site

Lübeck, , Germany

Novartis Investigative Site

Marburg, , Germany

Novartis Investigative Site

Marburg, , Germany

Novartis Investigative Site

Menden, , Germany

Novartis Investigative Site

Mittweida, , Germany

Novartis Investigative Site

München, , Germany

Novartis Investigative Site

Potsdam, , Germany

Novartis Investigative Site

Rudersdorf, , Germany

Novartis Investigative Site

Schleswig, , Germany

Novartis Investigative Site

Witten, , Germany

Novartis Investigative Site

Athens, GR, Greece

Novartis Investigative Site

Thessaloniki, GR, Greece

Novartis Investigative Site

Thessaloniki, GR, Greece

Novartis Investigative Site

Thessaloniki, GR, Greece

Novartis Investigative Site

Athens, , Greece

Novartis Investigative Site

Püspökladány, HUN, Hungary

Novartis Investigative Site

Balassagyarmat, , Hungary

Novartis Investigative Site

Gödöllő, , Hungary

Novartis Investigative Site

Komló, , Hungary

Novartis Investigative Site

Sellye, , Hungary

Novartis Investigative Site

Siófok, , Hungary

Novartis Investigative Site

Szarvas, , Hungary

Novartis Investigative Site

Szeged, , Hungary

Novartis Investigative Site

Vijayawada, Andhra Pradesh, India

Novartis Investigative Site

Kozhikode, Kerala, India

Novartis Investigative Site

Nagpur, Maharashtra, India

Novartis Investigative Site

Pune, Maharashtra, India

Novartis Investigative Site

Mohali, Punjab, India

Novartis Investigative Site

Coimbatore, Tamil Nadu, India

Novartis Investigative Site

Vellore, Tamil Nadu, India

Novartis Investigative Site

Hyderabad, Telangana, India

Novartis Investigative Site

Kolkata, West Bengal, India

Novartis Investigative Site

Jerusalem, , Israel

Novartis Investigative Site

Jerusalem, , Israel

Novartis Investigative Site

Ramat Gan, , Israel

Novartis Investigative Site

Rehovot, , Israel

Novartis Investigative Site

Guadalajara, Jalisco, Mexico

Novartis Investigative Site

Guadalajara, Jalisco, Mexico

Novartis Investigative Site

Mexico City, Mexico City, Mexico

Novartis Investigative Site

San Martín de Porres, Lima region, Peru

Novartis Investigative Site

Santiago de Surco, Lima region, Peru

Novartis Investigative Site

Cusco, , Peru

Novartis Investigative Site

Lima, , Peru

Novartis Investigative Site

Katowice, , Poland

Novartis Investigative Site

Poznan, , Poland

Novartis Investigative Site

Poznan, , Poland

Novartis Investigative Site

Poznan, , Poland

Novartis Investigative Site

Izhevsk, , Russia

Novartis Investigative Site

Kemerovo, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

Novartis Investigative Site

Nizhny Novgorod, , Russia

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Novosibirsk, , Russia

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Saint Petersburg, , Russia

Novartis Investigative Site

Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

Novartis Investigative Site

Saratov, , Russia

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Saratov, , Russia

Novartis Investigative Site

Ulyanovsk, , Russia

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Yekaterinburg, , Russia

Novartis Investigative Site

Belgrade, , Serbia

Novartis Investigative Site

Kamenitz, , Serbia

Novartis Investigative Site

Kragujevac, , Serbia

Novartis Investigative Site

Niš, , Serbia

Novartis Investigative Site

Bojnice, Slovak Republic, Slovakia

Novartis Investigative Site

Humenné, Slovak Republic, Slovakia

Novartis Investigative Site

Liptovský Hrádok, Slovak Republic, Slovakia

Novartis Investigative Site

Liptovský Mikuláš, , Slovakia

Novartis Investigative Site

Topoľčany, , Slovakia

Novartis Investigative Site

Žilina, , Slovakia

Novartis Investigative Site

Berea, Durban, South Africa

Novartis Investigative Site

Cape Town, , South Africa

Novartis Investigative Site

Cape Town, , South Africa

Novartis Investigative Site

Chatsworth, , South Africa

Novartis Investigative Site

Kempton Park, , South Africa

Novartis Investigative Site

Pretoria, , South Africa

Novartis Investigative Site

Esparraguera, Barcelona, Spain

Novartis Investigative Site

Hostalets de Balenya, Catalonia, Spain

Novartis Investigative Site

Cáceres, Extremadura, Spain

Novartis Investigative Site

Benalmádena, Malaga, Spain

Novartis Investigative Site

Ho Chi Minh City, VNM, Vietnam

Novartis Investigative Site

Hanoi, , Vietnam

Novartis Investigative Site

Ho Chi Minh City, , Vietnam

Countries

Argentina; Chile; Colombia; Czechia; Germany; Greece; Hungary; India; Israel; Mexico; Peru; Poland; Russia; Serbia; Slovakia; South Africa; Spain; Taiwan; Turkey (Türkiye); Vietnam

References

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.

Reference Type: DERIVED

PMID: 36472162 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=657

A Plain Language Trial Summary is available on novartisclinicaltrials.com

Other Identifiers

2017-000136-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CQVM149B2306

Identifier Type: -

Identifier Source: org_study_id