Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00463567
First received: April 19, 2007
Last updated: July 22, 2011
Last verified: July 2011

April 19, 2007
July 22, 2011
April 2007
August 2008   (final data collection date for primary outcome measure)
Trough Forced Expiratory Volume in 1 Second (FEV1) Assessed by Spirometry 24 Hour Post Dose After 12 Weeks of Treatment [ Time Frame: after 12 weeks of treatment ] [ Designated as safety issue: No ]
FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of the 23 h 10 min and the 23 h 45 min post dose values. Mixed model used baseline FEV1, FEV1 prior to and 30 minutes post inhalation of salbutamol/albuterol, and FEV1 prior to and 1 hour post inhalation of ipratropium as covariates.
To Investigate superiority of at least one dose of indacaterol (selected at study Stage 1 from 75, 150, 300 & 600 µg o.d. via SDDPI) versus placebo with respect to 24 h post dose (trough) FEV1 after 12 weeks of treatment in patients with COPD.
Complete list of historical versions of study NCT00463567 on ClinicalTrials.gov Archive Site
The Percentage of "Days of Poor Control" Reported Over the 26 Week Treatment Period [ Time Frame: up to 26 weeks ] [ Designated as safety issue: No ]
A Chronic Obstructive Pulmonary Disease (COPD) "day of poor control" was defined as any day in the participant's diary with a score ≥2 (moderate or severe) for at least 2 of 5 symptoms (cough, wheeze, production of sputum, color of sputum, breathlessness). Score for each symptom ranges from 0-3; a higher number indicates a more severe symptom. The model contained baseline percentage of "days of poor control" as well as FEV1 reversibility components as covariates.
  • To demonstrate that at least one dose of indacaterol (selected at study Stage 1 from 75, 150, 300 & 600 µg o.d. via SDDPI) is comparable to that of open label tiotropium (18 µg o.d.) with respect to 24 h post dose (trough) FEV1 following 12 weeks of tre
  • To evaluate the effect of two doses of indacaterol (selected at study Stage 1 from 75, 150, 300 & 600 µg o.d. via SDDPI) on the percentage of ‘days of poor control’ reported over the 26 week randomized treatment period, as compared to placebo
  • To compare either or both doses of indacaterol (selected at study Stage 1 from 75, 150, 300 & 600 µg o.d. via SDDPI) versus open label tiotropium (18 µg o.d.) with respect to 24 h post dose (trough) FEV1 following 12 weeks of treatment if non-inferiorit
  • To evaluate the effect of two doses of indacaterol (selected at study Stage 1 from 75, 150, 300 & 600 µg o.d. via SDDPI) on time to first COPD exacerbation during the 26 week randomized treatment period as compared with placebo
  • To evaluate the effect of two doses of indacaterol (selected at study Stage 1 from 75, 150, 300 & 600 µg o.d. via SDDPI) on the total score of the St Georges Respiratory Questionnaire (SGRQ) after 12 weeks treatment as compared with placebo
Not Provided
Not Provided
 
26 Week Efficacy, Safety and Tolerability Study of Indacaterol in Patients With Chronic Obstructive Pulmonary Disease (COPD)
A 26-week Treatment, Multicenter, Randomized, Double Blind, Double Dummy, Placebo-controlled, Adaptive, Seamless, Parallel-group Study to Assess the Efficacy, Safety and Tolerability of Two Doses of Indacaterol (Selected From 75, 150, 300 & 600 µg o.d.) in Patients With Chronic Obstructive Pulmonary Disease Using Blinded Formoterol (12 µg b.i.d.) and Open Label Tiotropium (18 µg o.d.) as Active Controls

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

Not Provided
Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Pulmonary Disease, Chronic Obstructive
  • COPD
  • Lung Diseases, Obstructive
  • Drug: Indacaterol
    In the morning, Indacaterol once daily (o.d.) orally inhaled via a single dose dry powder inhaler (SDDPI).
  • Drug: Formoterol (12 µg b.i.d.)
    Formoterol 12 µg twice daily (b.i.d.) in the morning and in the evening via an aerolizer.
  • Drug: Tiotropium (18 µg o.d.)
    Tiotropium 18 µg once daily (o.d.) dry powder capsules delivered via a SDDPI.
  • Drug: Placebo to Indacaterol
    In the morning, Placebo to Indacaterol once daily (o.d.) orally inhaled via a single dose dry powder inhaler (SDDPI).
  • Drug: Placebo to Formoterol
    In the morning and in the evening, placebo to formoterol delivered via Aerolizer.
  • Experimental: Indacaterol 150 µg (Continued Into Stage 2)

    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.

    Interventions:
    • Drug: Indacaterol
    • Drug: Placebo to Indacaterol
    • Drug: Placebo to Formoterol
  • Experimental: Indacaterol 300 µg (Continued Into Stage 2)

    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.

    Interventions:
    • Drug: Indacaterol
    • Drug: Placebo to Indacaterol
    • Drug: Placebo to Formoterol
  • Active Comparator: Tiotropium 18 µg (Continued Into Stage 2)

    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.

    Intervention: Drug: Tiotropium (18 µg o.d.)
  • Placebo Comparator: Placebo (Continued Into Stage 2)

    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.

    Interventions:
    • Drug: Placebo to Indacaterol
    • Drug: Placebo to Formoterol
  • Experimental: Indacaterol 75 µg (Not Continued into Stage 2)

    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.

    Interventions:
    • Drug: Indacaterol
    • Drug: Placebo to Indacaterol
    • Drug: Placebo to Formoterol
  • Experimental: Indacaterol 600 µg (Not Continued Into Stage 2)

    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.

    Interventions:
    • Drug: Indacaterol
    • Drug: Placebo to Formoterol
  • Active Comparator: Formoterol 12 µg (Not Continued Into Stage 2)

    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.

    Interventions:
    • Drug: Formoterol (12 µg b.i.d.)
    • Drug: Placebo to Indacaterol

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
2059
August 2008
August 2008   (final data collection date for primary outcome measure)

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

Both
40 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Canada,   Germany,   India,   Italy,   Korea, Republic of,   Puerto Rico,   Spain,   Sweden,   Taiwan,   Turkey
 
NCT00463567
CQAB149B2335S
Not Provided
external affairs, Novartis
Novartis
Not Provided
Study Chair: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
July 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP