26 Week Efficacy, Safety and Tolerability Study of Indacaterol in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Novartis

Status and phase: Completed; Phase 3; Phase 2

Conditions: Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; COPD

Treatments: Drug: Tiotropium (18 µg o.d.); Drug: Placebo to Indacaterol; Drug: Indacaterol; Drug: Placebo to Formoterol; Drug: Formoterol (12 µg b.i.d.)

Study type: Interventional

Funder types: Industry

Identifiers

NCT00463567

CQAB149B2335S

Details and patient eligibility

About

Stage 1 of the study is designed to provide data about the risk-benefit of 4 dose regimens of indacaterol (75, 150, 300 & 600 µg o.d.) in order to select two doses to carry forward into study Stage 2. Study Stage 2 will provide pivotal confirmation of efficacy, safety, and tolerability of the selected indacaterol doses in patients with COPD

Enrollment: 2,059 patients

Sex: All

Ages: 40+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male and female adults aged ≥ 40 years, who have signed an Informed Consent Form prior to initiation of any study-related procedure

• Co-operative outpatients with a diagnosis of COPD (moderate to severe as classified by the Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) Guidelines, 2005) and:

  • Smoking history of at least 20 pack years
  • Post-bronchodilator FEV1 < 80% and ≥ 30% of the predicted normal value.
  • Post-bronchodilator FEV1/FVC < 70% (Post refers to within 30 min of inhalation of 400 µg of salbutamol)

Exclusion criteria

• Pregnant or lactating females
• Patients who have been hospitalized for a COPD exacerbation in the 6 weeks prior to Visit 1 or during the run-in period
• Patients requiring long term oxygen therapy (> 15 h a day)
• Patients who have had a respiratory tract infection 6 weeks prior to V1 (with further criteria)
• Patients with concomitant pulmonary disease, pulmonary tuberculosis, or clinically significant bronchiectasis
• Patients with a history of asthma (with further criteria)
• Patients with Type I or uncontrolled Type II diabetes
• Patients with contraindications for tiotropium
• Patients who have clinically relevant laboratory abnormalities or a clinically significant abnormality
• Any patient with active cancer or a history of cancer with less than 5 years disease free survival time
• Patients with a history of long QT syndrome or whose QTc interval is prolonged
• Patients with a hypersensitivity to any of the study drugs or drugs with similar chemical structures
• Patients who have had treatment with the investigational drug (with further criteria)
• Patients who have had live attenuated vaccinations within 30 days prior to visit 1, or during run-in period
• Patients with known history of non compliance to medication
• Patients unable to satisfactorily use a dry powder inhaler device or perform spirometry measurements

Other protocol-defined inclusion/exclusion criteria may apply

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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2,059 participants in 7 patient groups, including a placebo group

Indacaterol 150 µg (Continued Into Stage 2)

Experimental group

Description:

In the morning, Indacaterol 150 µg once daily orally inhaled via a single dose dry powder inhaler (SDDPI) + Placebo to Indacaterol delivered via SDDPI + Placebo to Formoterol delivered via Aerolizer. In the evening, Placebo to Formoterol delivered via Aerolizer. Participated in the 2 week Stage 1 and continued treatment up to 26 weeks in Stage 2. Placebo to Formoterol inhalation in the morning and in the evening was discontinued after Stage 1. Daily Inhaled Corticosteroid (ICS) monotherapy (if applicable) was to remain stable and Salbutamol/albuterol was available for rescue use throughout study.

Treatment:

Drug: Placebo to Indacaterol

Drug: Indacaterol

Drug: Placebo to Formoterol

Indacaterol 300 µg (Continued Into Stage 2)

Experimental group

Description:

In the morning, Indacaterol 300 µg once daily orally inhaled via a SDDPI + Placebo to Indacaterol delivered via SDDPI + Placebo to Formoterol delivered via Aerolizer. In evening, Placebo to Formoterol delivered via Aerolizer. Participated in the 2 week Stage 1 and continued treatment up to 26 weeks in Stage 2. Placebo to Formoterol inhalation in the morning and in the evening was discontinued after Stage 1. Daily ICS monotherapy (if applicable) was to remain stable and Salbutamol/albuterol was available for rescue use throughout study.

Treatment:

Drug: Placebo to Indacaterol

Drug: Indacaterol

Drug: Placebo to Formoterol

Tiotropium 18 µg (Continued Into Stage 2)

Active Comparator group

Description:

Tiotropium 18 µg dry powder capsules delivered (open label) via manufacturer's proprietary SDDPI, (Handihaler®). Participated in the 2 week Stage 1 and continued treatment up to 26 weeks in Stage 2. Daily ICS monotherapy (if applicable) was to remain stable and Salbutamol/albuterol was available for rescue use throughout study.

Treatment:

Drug: Tiotropium (18 µg o.d.)

Placebo (Continued Into Stage 2)

Placebo Comparator group

Description:

In the morning, Placebo to Indacaterol delivered via two SDDPI devices + Placebo to Formoterol delivered via Aerolizer. In the evening, Placebo to Formoterol delivered via Aerolizer. Participated in the 2 week Stage 1 and continued treatment up to 26 weeks in Stage 2. Placebo to Formoterol inhalation in the morning and in the evening was discontinued after Stage 1. Daily ICS monotherapy (if applicable) was to remain stable and Salbutamol/albuterol was available for rescue use throughout study.

Treatment:

Drug: Placebo to Indacaterol

Drug: Placebo to Formoterol

Indacaterol 75 µg (Not Continued into Stage 2)

Experimental group

Description:

In the morning, Indacaterol 75 µg once daily orally inhaled via a SDDPI + Placebo to Indacaterol delivered via SDDPI + Placebo to Formoterol delivered via Aerolizer. In the evening, Placebo to Formoterol delivered via Aerolizer. Participated in the 2 week Stage 1 but did not continue to Stage 2. Daily ICS monotherapy (if applicable) was to remain stable and Salbutamol/albuterol was available for rescue use throughout study.

Treatment:

Drug: Placebo to Indacaterol

Drug: Indacaterol

Drug: Placebo to Formoterol

Indacaterol 600 µg (Not Continued Into Stage 2)

Experimental group

Description:

In the morning, 2 capsules of Indacaterol 300 µg once daily orally inhaled via two SDDPI devices + Placebo to Formoterol delivered via Aerolizer. In the evening, Placebo to Formoterol delivered via Aerolizer. Participated in the 2 week Stage 1 but did not continue to Stage 2. Daily ICS monotherapy (if applicable) was to remain stable and Salbutamol/albuterol was available for rescue use throughout study.

Treatment:

Drug: Indacaterol

Drug: Placebo to Formoterol

Formoterol 12 µg (Not Continued Into Stage 2)

Active Comparator group

Description:

In the morning, Placebo to Indacaterol delivered via two SDDPI devices + Formoterol 12 µg delivered via Aerolizer. In evening, Formoterol 12 µg delivered via Aerolizer. Participated in the 2 week Stage 1 but did not continue to Stage 2. Daily ICS monotherapy (if applicable) was to remain stable and Salbutamol/albuterol was available for rescue use throughout study.

Treatment:

Drug: Placebo to Indacaterol

Drug: Formoterol (12 µg b.i.d.)