Efficacy, Safety, and Tolerability of Once Daily Indacaterol in Chronic Obstructive Pulmonary Disease (COPD) Using Formoterol Twice Daily as Active Control

NCT00393458 | Completed Phase 3 Results

• 1 other identifier: CQAB149B2334
• Study Type: interventional
• Target: 1,732
• Locations: 24 countries
• Sites: 172

Brief Summary

This study was designed to assess the efficacy and long-term safety of 300 and 600 µg doses of indacaterol when delivered via a single-dose dry-powder inhaler (SDDPI) in patients with chronic obstructive pulmonary disease (COPD). Patients were randomized to receive either indacaterol 300 µg once daily, indacaterol 600 µg once daily, formoterol 12 µg twice daily, or placebo.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

chronic obstructive pulmonary disease; COPD; indacaterol; long-acting β2 agonist

Outcome Measures

Primary Outcomes (1)

• Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12 + 1 Day, Day 85

  FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 10 minutes and 23 hours 45 minutes post-dose at the end of treatment. The analysis included baseline FEV1, FEV1 pre-dose and 30 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates.

  Week 12 + 1 day, Day 85

Secondary Outcomes (1)

• Percentage of Days of Poor Control During 52 Weeks of Treatment

  Baseline to end of study (Week 52)

Study Arms (4)

Indacaterol 300 μg plus placebo to formoterol

EXPERIMENTAL

Patients inhaled indacaterol 300 μg once daily via a single-dose dry-powder inhaler (SDDPI), placebo to indacaterol once daily via a SDDPI, and placebo to formoterol twice daily via the manufacturer's proprietary inhalation device (Aerolizer®). Indacaterol, placebo to indacaterol, and placebo to formoterol were taken in the morning between 8:00 and 10:00 AM; placebo to formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.

Drug: Indacaterol; Drug: Placebo to formoterol

Indacaterol 600 μg plus placebo to formoterol

EXPERIMENTAL

Patients inhaled indacaterol 600 μg (two 300 μg capsules) once daily via single-dose dry-powder inhalers (SDDPI) plus placebo to formoterol twice daily via the manufacturer's proprietary inhalation device (Aerolizer®). Indacaterol and placebo to formoterol were taken in the morning between 8:00 and 10:00 AM; placebo to formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.

Drug: Indacaterol; Drug: Placebo to formoterol

Formoterol 12 μg plus placebo to indacaterol

ACTIVE COMPARATOR

Patients inhaled formoterol 12 μg twice daily via the manufacturer's proprietary inhalation device (Aerolizer®) plus placebo to indacaterol once daily via a single-dose dry-powder inhaler (SDDPI). Formoterol and placebo to indacaterol were taken in the morning between 8:00 and 10:00 AM; formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.

Drug: Formoterol; Drug: Placebo to indacaterol

Placebo to indacaterol plus placebo to formoterol

PLACEBO COMPARATOR

Patients inhaled placebo to indacaterol once daily via a single-dose dry-powder inhaler (SDDPI) plus placebo to formoterol twice daily via the manufacturer's proprietary inhalation device (Aerolizer®). Placebo to indacaterol and placebo to formoterol were taken in the morning between 8:00 and 10:00 AM; placebo to formoterol was taken again 12 hours later in the evening between 8:00 and 10:00 PM. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.

Drug: Placebo to indacaterol; Drug: Placebo to formoterol

Interventions

Indacaterol DRUG

Indacaterol was supplied in powder-filled capsules with a single-dose dry-powder inhaler (SDDPI).

Indacaterol 300 μg plus placebo to formoterol; Indacaterol 600 μg plus placebo to formoterol

Formoterol DRUG

Formoterol was supplied in powder-filled capsules with the manufacturer's proprietary inhalation device (Aerolizer®).

Formoterol 12 μg plus placebo to indacaterol

Placebo to indacaterol DRUG

Placebo to indacaterol was supplied in powder-filled capsules with a single-dose dry-powder inhaler (SDDPI).

Formoterol 12 μg plus placebo to indacaterol; Placebo to indacaterol plus placebo to formoterol

Placebo to formoterol DRUG

Placebo to formoterol was supplied in powder-filled capsules with the manufacturer's proprietary inhalation device (Aerolizer®).

Indacaterol 300 μg plus placebo to formoterol; Indacaterol 600 μg plus placebo to formoterol; Placebo to indacaterol plus placebo to formoterol

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female adults ≥ 40 years, with a diagnosis of chronic obstructive pulmonary disease (COPD) according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines 2005 and:
• Smoking history of at least 20 pack years
• Post-bronchodilator forced expiratory volume in 1 second (FEV1) \< 80% and ≥ 30% of the predicted normal value
• Post-bronchodilator FEV1/FVC (forced volume capacity) \< 70% (Post refers to within 30 minutes after inhalation of 400 μg of salbutamol)

You may not qualify if:

• Patients who were hospitalized for a COPD exacerbation in the 6 weeks prior to screening.
• Patients who had a respiratory tract infection within 6 weeks prior to screening.
• Patients with concomitant pulmonary disease.
• Patients with a history of asthma.
• Patients with diabetes type I or uncontrolled diabetes type II.
• Any patient with lung cancer or a history of lung cancer.
• Patients with a history of certain cardiovascular co-morbid conditions.

Sponsors & Collaborators

• Novartis: lead

Study Sites (183)

Novartis Investigator Site

Buenos Aires, Argentina

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Buenos Aires, Argentina

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Mendoza, Argentina

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San Miguel, Argentina

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Santa Fe, Argentina

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Rancagua, Chile

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Santiago, Chile

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Viña del Mar, Chile

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Barranquilla, Colombia

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Bogotá, Colombia

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Medellín, Colombia

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Cvikov, Czechia

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Kyjov, Czechia

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Ostrava Poruba, Czechia

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Pardubice, Czechia

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Prague, Czechia

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Tábor, Czechia

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Žatec, Czechia

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Aarhus, Denmark

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Copenhagen, Denmark

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Hellerup, Denmark

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Hvidovre, Denmark

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Molleparkvej, Denmark

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Odense, Denmark

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Guayaquil, Ecuador

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Quito, Ecuador

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Quito, Ecuador

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Alexandria, Egypt

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Asyut, Egypt

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Cairo, Egypt

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Cairo, Egypt

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Tallinn, Estonia

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Tartu, Estonia

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Beuvry, France

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Chamalières, France

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Férolles-Attilly, France

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Grasse, France

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Marseille, France

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Montpellier, France

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Nice, France

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Nîmes, France

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Paris, France

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Perpignan, France

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Pessac, France

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Strasbourg, France

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Augsburg, Germany

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Bad Segeberg, Germany

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Bad Wörishofen, Germany

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Berlin, Germany

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Bielefeld, Germany

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Bochum, Germany

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Bonn, Germany

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Borstel, Germany

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Darmstadt, Germany

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Dortmund, Germany

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Erfurt, Germany

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Forchheim, Germany

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Frankfurt, Germany

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Gauting, Germany

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Geesthacht, Germany

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Gelsenkirchen, Germany

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Großhansdorf, Germany

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Gummersbach, Germany

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Hagen, Germany

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Hamburg, Germany

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Hanover, Germany

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Ilvesheim, Germany

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Kassel, Germany

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Kiel, Germany

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Leipzig, Germany

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Lübeck, Germany

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Lüdenscheid, Germany

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Mainz, Germany

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Marburg, Germany

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München, Germany

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Neumünster, Germany

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Nuremberg, Germany

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Oschersleben, Germany

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Rüdersdorf, Germany

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Schönefeld, Germany

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Strausberg, Germany

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Witten, Germany

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Wuppertal, Germany

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Budapest, Hungary

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Budapest, Hungary

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Deszk, Hungary

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Mátraháza, Hungary

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Mosdós, Hungary

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Sopron, Hungary

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Jerusalem, Israel

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Petah Tikva, Israel

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Rehovot, Israel

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Tel Litwinsky, Israel

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Ancona, Italy

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Catania, Italy

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Ferrara, Italy

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Florence, Italy

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Foggia, Italy

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Genova, Italy

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Milan, Italy

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Milan, Italy

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Pisa, Italy

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Roma, Italy

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Siena, Italy

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Daugavpils, Latvia

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Jēkabpils, Latvia

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Riga, Latvia

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Riga, Latvia

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Alytus, Lithuania

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Kaunas, Lithuania

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Kaunas, Lithuania

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Klaipėda, Lithuania

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Vilnius, Lithuania

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Almelo, Netherlands

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Amersfoort, Netherlands

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Arnhem, Netherlands

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Breda, Netherlands

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Ede, Netherlands

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Eindhoven, Netherlands

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Harderwijk, Netherlands

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Helmond, Netherlands

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Hengelo, Netherlands

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Hoorn, Netherlands

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Leeuwarden, Netherlands

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Rotterdam, Netherlands

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Sneek, Netherlands

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Veldhoven, Netherlands

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Zutphen, Netherlands

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Lima, Peru

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Lima, Peru

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Bucharest, Romania

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Cluj-Napoca, Romania

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Iași, Romania

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Timișoara, Romania

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Kazan', Russia

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Moscow, Russia

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Moscow, Russia

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Saint Petersburg, Russia

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Samara, Russia

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Yekaterinburg, Russia

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Banská Bystrica, Slovakia

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Bratislava, Slovakia

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Bratislava, Slovakia

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Košice, Slovakia

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Partizánske, Slovakia

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Kyunggi, South Korea

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Seoul, South Korea

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Seoul, South Korea

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Suwon, South Korea

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Uijeongbu-si, South Korea

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Alicante, Spain

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Barcelona, Spain

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Barcelona, Spain

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Begonte, Spain

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Cáceres, Spain

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Madrid, Spain

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Mataró, Spain

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Petrel, Spain

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Ponferrada, Spain

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Terrassa, Spain

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Valencia, Spain

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Aarau, Switzerland

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Basel, Switzerland

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Locarno, Switzerland

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Münchenstein, Switzerland

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Zurich, Switzerland

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Ankara, Turkey (Türkiye)

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Bursa, Turkey (Türkiye)

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Istanbul, Turkey (Türkiye)

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Izmir, Turkey (Türkiye)

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Mersin, Turkey (Türkiye)

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Yenişehir, Turkey (Türkiye)

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Belfast, United Kingdom

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Bexhill-on-Sea, United Kingdom

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Blackpool, United Kingdom

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Chertsey, United Kingdom

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Glasgow, United Kingdom

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Leicester, United Kingdom

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London, United Kingdom

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Manchester, United Kingdom

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Newcastle upon Tyne, United Kingdom

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Slough, United Kingdom

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Swansea, United Kingdom

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Related Publications (5)

• Jones PW, Donohue JF, Nedelman J, Pascoe S, Pinault G, Lassen C. Correlating changes in lung function with patient outcomes in chronic obstructive pulmonary disease: a pooled analysis. Respir Res. 2011 Dec 29;12(1):161. doi: 10.1186/1465-9921-12-161.

  PMID: 22206353 DERIVED

• Bleecker ER, Siler T, Owen R, Kramer B. Bronchodilator efficacy and safety of indacaterol 150 mug once daily in patients with COPD: an analysis of pooled data. Int J Chron Obstruct Pulmon Dis. 2011;6:431-8. doi: 10.2147/COPD.S21073. Epub 2011 Aug 18.

  PMID: 22003288 DERIVED

• Jones PW, Mahler DA, Gale R, Owen R, Kramer B. Profiling the effects of indacaterol on dyspnoea and health status in patients with COPD. Respir Med. 2011 Jun;105(6):892-9. doi: 10.1016/j.rmed.2011.02.013. Epub 2011 Mar 11.

  PMID: 21397482 DERIVED

• Worth H, Chung KF, Felser JM, Hu H, Rueegg P. Cardio- and cerebrovascular safety of indacaterol vs formoterol, salmeterol, tiotropium and placebo in COPD. Respir Med. 2011 Apr;105(4):571-9. doi: 10.1016/j.rmed.2010.11.027. Epub 2011 Jan 11.

  PMID: 21227674 DERIVED

• Dahl R, Chung KF, Buhl R, Magnussen H, Nonikov V, Jack D, Bleasdale P, Owen R, Higgins M, Kramer B; INVOLVE (INdacaterol: Value in COPD: Longer Term Validation of Efficacy and Safety) Study Investigators. Efficacy of a new once-daily long-acting inhaled beta2-agonist indacaterol versus twice-daily formoterol in COPD. Thorax. 2010 Jun;65(6):473-9. doi: 10.1136/thx.2009.125435.

  PMID: 20522841 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

indacaterol; Formoterol Fumarate

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862 778-8300

Study Officials

• Novartis Investigator Site

  Novartis

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: October 25, 2006
• First Posted: October 27, 2006
• Study Start: October 1, 2006
• Primary Completion: July 1, 2008
• Study Completion: July 1, 2008
• Last Updated: August 18, 2011
• Results First Posted: August 18, 2011

Record last verified: 2011-07

Locations

LI (5); DE (38); EG (4); RU (6); PE (2); HU (6); CL (3); RO (4); DK (6); KR (5); ES (2); CH (5); TU (6); GB (11); IT (11); AR (5); NL (15); LA (4); FR (12); EC (3); CO (3); IL (4); CZ (7); SL (5)