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

NCT03158311 | Completed Phase 3 Results

• 2 other identifiers: CQVM149B23062017-000136-34
• Study Type: interventional
• Target: 1,426
• Locations: 20 countries
• Sites: 163

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.

Conditions

Asthma

Keywords

QVM149; Asthma; Moderate Asthma; Severe Asthma; ICS/LABA/LAMA; ICS/LABA; LAMA; Adult

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Total Score

  The AQLQ is a 32-item asthma specific questionnaire designed to measure functional impairments that are most important to patients with asthma, with a recall time of two weeks and each question to be answered on a 7-point scale, where 1=totally limited/problems all the time and 7= not at all limited/no problems. It consists of 4 domains: symptoms, activity limitation, emotional funtion, and emotional stimuli. The overall score is calculated as the mean of 32 items. Higher AQLQ scores indicate better health-related quality of life.

  Baseline and Week 24

Secondary Outcomes (7)

• Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1)

  Baseline, Week 8, Week 16 and Week 24

• Change From Baseline in Asthma Control Questionnaire (ACQ-7) Total Score

  Baseline, Week 16 and Week 24

• Change From Baseline in AQLQ Total Score

  Baseline and Week 16

• Percentage of Patients Achieving the Minimally Clinically Important Difference (MCID) Decrease From Baseline ACQ-7 ≥ 0.5

  Baseline and Week 24

• Percentage of Patients Achieving the Minimally Clinically Important Difference (MCID) Change From Baseline AQLQ ≥ 0.5

  Baseline and Week 24

Study Arms (3)

QVM149 150/50/80 μg

EXPERIMENTAL

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

Drug: QVM149

QVM149 150/50/160 μg

EXPERIMENTAL

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

Drug: QVM149

Salmeterol/fluticasone 50/500 μg plus tiotropium 5 μg

ACTIVE COMPARATOR

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

Drug: Salmeterol/fluticasone plus tiotropium

Interventions

QVM149 DRUG

Indacaterol acetate / glycopyrronium bromide / mometasone furoate

QVM149 150/50/160 μg; QVM149 150/50/80 μg

Salmeterol/fluticasone plus tiotropium DRUG

Free triple arm of salmeterol / fluticasone plus tiotropium

Salmeterol/fluticasone 50/500 μg plus tiotropium 5 μg

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (163)

Novartis Investigative Site

Berazategui, Buenos Aires, 1888, Argentina

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Novartis Investigative Site

CABA, Buenos Aires, C1122AAK, Argentina

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Caba, Buenos Aires, C1280AEB, Argentina

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CABA, Buenos Aires, C1414AIF, Argentina

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CABA, Buenos Aires, C1424BSF, Argentina

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CABA, Buenos Aires, C1425BEN, Argentina

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Florida, Buenos Aires, B1602DQD, Argentina

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Lanús, Buenos Aires, B8000XAV, Argentina

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Mar del Plata, Buenos Aires, 7600, Argentina

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Nueve de Julio, Buenos Aires, B6500EZL, Argentina

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Ranelagh, Partido de Berazate, Buenos Aires, 1884, Argentina

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Concepción del Uruguay, Entre Ríos Province, 3260, Argentina

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Santa Rosa, La Pampa Province, 6300, Argentina

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Novartis Investigative Site

Buenos Aires, Nueve De Julio, B6500BWQ, Argentina

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Rosario, Santa Fe Province, S2000AII, Argentina

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Rosario, Santa Fe Province, S2000BRH, Argentina

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San Miguel de Tucumán, Tucumán Province, 4000, Argentina

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Bahía Blanca, B8000JRB, Argentina

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Buenos Aires, 1900, Argentina

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Buenos Aires, B1646EBJ, Argentina

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Buenos Aires, C1125ABE, Argentina

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Buenos Aires, C1425FVH, Argentina

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Ciudad Autonoma de Bs As, C1128AAF, Argentina

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Mendoza, 5500, Argentina

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Mendoza, 5501, Argentina

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Mendoza, M5500CBA, Argentina

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Salta, 4400, Argentina

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Santa Fe, S3000FIL, Argentina

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Curicó, Maule Region, 3341643, Chile

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Santiago, Santiago Metropolitan, 7500692, Chile

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Bogota, Cundinamarca, 110911, Colombia

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Bogotá, 110221, Colombia

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Ostrava Poruba, Czech Republic, 708 68, Czechia

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Prague, Czech Republic, 169 00, Czechia

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Teplice, CZE, 415 01, Czechia

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Lovosice, 41002, Czechia

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Miroslav, 67172, Czechia

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Peine, Lower Saxony, 31224, Germany

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Geesthacht, Schleswig-Holstein, 12502, Germany

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Berlin, 10119, Germany

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Berlin, 10625, Germany

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Berlin, 10717, Germany

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Berlin, 10969, Germany

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Berlin, 12157, Germany

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Berlin, 12159, Germany

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Berlin, 12203, Germany

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Berlin, 13086, Germany

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Berlin, 13156, Germany

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Berlin, 13187, Germany

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Berlin, 14050, Germany

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Bonn, 53123, Germany

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Böhlen, 04564, Germany

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Darmstadt, 64283, Germany

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Dortmund, 44263, Germany

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Einbeck, 37574, Germany

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Frankfurt, 60389, Germany

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Frankfurt, 60596, Germany

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Fürstenwalde, 15517, Germany

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Gelsenkirchen, 45879, Germany

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Hamburg, 20354, Germany

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Hamburg, 22335, Germany

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Hanover, 30167, Germany

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Hanover, 30173, Germany

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Leipzig, 04103, Germany

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Leipzig, 04157, Germany

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Leipzig, 04275, Germany

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Leipzig, 04357, Germany

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Ludwigsburg, 71640, Germany

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Lübeck, 23552, Germany

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Marburg, 35037, Germany

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Marburg, D-35037, Germany

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Menden, 58706, Germany

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Mittweida, 09648, Germany

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München, 81241, Germany

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Potsdam, 14467, Germany

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Rüdersdorf, 15562, Germany

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Schleswig, 24837, Germany

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Witten, 58452, Germany

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Athens, GR, 115 27, Greece

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Thessaloniki, GR, 546 03, Greece

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Thessaloniki, GR, 564 29, Greece

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Thessaloniki, GR, 570 10, Greece

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Athens, 12462, Greece

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Püspökladány, HUN, 4150, Hungary

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Balassagyarmat, 2660, Hungary

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Gödöllő, 2100, Hungary

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Komló, 7300, Hungary

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Sellye, 7960, Hungary

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Siófok, 8600, Hungary

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Szarvas, 5540, Hungary

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Szeged, 6722, Hungary

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Vijayawada, Andhra Pradesh, 520008, India

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Kozhikode, Kerala, 673008, India

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Nagpur, Maharashtra, 440019, India

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Pune, Maharashtra, 411014, India

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Mohali, Punjab, 160 062, India

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Coimbatore, Tamil Nadu, 641 045, India

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Vellore, Tamil Nadu, 632004, India

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Hyderabad, Telangana, 500 038, India

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Kolkata, West Bengal, 700 107, India

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Jerusalem, 91031, Israel

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Jerusalem, 91120, Israel

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Ramat Gan, 5266202, Israel

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Rehovot, 76100, Israel

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Guadalajara, Jalisco, 44100, Mexico

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Guadalajara, Jalisco, 44160, Mexico

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Mexico City, Mexico City, 14050, Mexico

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San Martín de Porres, Lima region, 31, Peru

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Santiago de Surco, Lima region, 33, Peru

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Cusco, 84, Peru

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Lima, 1, Peru

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Katowice, 40-648, Poland

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Poznan, 60 823, Poland

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Poznan, 60-214, Poland

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Poznan, 60-693, Poland

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Izhevsk, 426061, Russia

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Kemerovo, 650002, Russia

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Moscow, 105275, Russia

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Moscow, 109544, Russia

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Moscow, 123423, Russia

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Nizhny Novgorod, 603018, Russia

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Novosibirsk, 630102, Russia

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Saint Petersburg, 107022, Russia

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Saint Petersburg, 191186, Russia

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Saint Petersburg, 193312, Russia

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Saint Petersburg, 194354, Russia

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Saint Petersburg, 195271, Russia

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Saint Petersburg, 196143, Russia

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Saint Petersburg, 197022, Russia

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Saratov, 410028, Russia

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Saratov, 410054, Russia

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Ulyanovsk, 432063, Russia

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Yekaterinburg, 620109, Russia

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Belgrade, 11000, Serbia

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Kamenitz, 21204, Serbia

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Kragujevac, 34000, Serbia

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Niš, 18000, Serbia

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Bojnice, Slovak Republic, 972 01, Slovakia

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Humenné, Slovak Republic, 066 01, Slovakia

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Liptovský Hrádok, Slovak Republic, 033 01, Slovakia

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Liptovský Mikuláš, 031 23, Slovakia

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Topoľčany, 95501, Slovakia

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Žilina, 01001, Slovakia

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Berea, Durban, 4001, South Africa

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Cape Town, 7530, South Africa

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Cape Town, 7700, South Africa

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Chatsworth, 4092, South Africa

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Kempton Park, 1619, South Africa

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Pretoria, 0183, South Africa

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Esparraguera, Barcelona, 08292, Spain

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Hostalets de Balenya, Catalonia, 08550, Spain

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Cáceres, Extremadura, 10003, Spain

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Benalmádena, Malaga, 29639, Spain

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Alzira, Valencia, 46600, Spain

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Kaoshiung, Taiwan, 80756, Taiwan

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Taichung, 40447, Taiwan

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Taipei, 10449, Taiwan

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Izmir, 35040, Turkey (Türkiye)

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Mersin, 33343, Turkey (Türkiye)

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Yenisehir/Izmir, 35110, Turkey (Türkiye)

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Novartis Investigative Site

Ho Chi Minh City, VNM, 700000, Vietnam

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Hanoi, 100000, Vietnam

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Novartis Investigative Site

Ho Chi Minh City, 700000, Vietnam

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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; Fluticasone; Tiotropium Bromide

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; Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The free triple combination of salmeterol/fluticasone + tiotropium was open label, for which investigators and patients had full knowledge that the patient had been assigned free triple combination comparator treatment. Within the two QVM149 treatment arms patients, investigator staff, and persons performing the assessments, remained blind to the identity of the actual QVM149 treatment dose but had full knowledge that the patient had been assigned QVM149 as study treatment. The data analysts and sponsor team were blinded to Case Report Forms that reveal the treatment arm. Randomization data and treatment codes were kept strictly confidential until the time of unblinding, and was not accessible by anyone else involved in the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Parallel Assignment

Study Record Dates

• First Submitted: May 16, 2017
• First Posted: May 18, 2017
• Study Start: February 5, 2018
• Primary Completion: July 12, 2019
• Study Completion: July 19, 2019
• Last Updated: October 8, 2021
• Results First Posted: October 14, 2020

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

SL (6); ES (5); HU (8); PE (4); CZ (5); IL (4); CO (2); AR (28); DE (41); ZA (6); SE (4); VN (3); IN (9); RU (18); PL (4); TW (3); TU (3); CL (2); ME (3); GR (5)