Safety and Efficacy of Indacaterol Once Daily Versus Salmeterol Twice Daily in Chronic Obstructive Pulmonary Disease (COPD) (INSIST)

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00821093
First received: January 9, 2009
Last updated: July 22, 2011
Last verified: July 2011
  Purpose

This study compared the safety and efficacy of indacaterol 150 µg taken once daily (o.d.) versus salmeterol 50 µg taken twice daily (b.i.d) in patients 40 years old or older with chronic obstructive pulmonary disease.


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease (COPD)
Drug: Indacaterol 150 µg
Drug: Salmeterol 50 µg
Drug: Placebo to indacaterol
Drug: Placebo to salmeterol
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 12 Week Treatment, Multi-center, Randomized, Parallel Group, Double Blind, Double Dummy Study to Assess the Superiority of Indacaterol (150 µg o.d.) Via a SDDPI in Patients With Moderate to Severe COPD, Using Salmeterol (50 µg b.i.d.) as an Active Comparator Delivered Via a DISKUS Inhaler

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Time) Area Under the Curve (AUC) From 5 Minutes to 11 Hours 45 Minutes Post-dose at the End of the Study (Week 12, Day 84) [ Time Frame: From 5 minutes to 11 hours 45 minutes post-dose at the end of the study (Week 12, Day 84) ] [ Designated as safety issue: No ]
    FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5 and 30 minutes; 1, 2, 3, 4, and 8 hours; 11 hours 10 minutes and 11 hours 45 minutes post-dose at the end of the study (Week 12, Day 84). Standardized FEV1 AUC was calculated by the trapezoidal rule. The analysis included baseline FEV1 and FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening as covariates.


Secondary Outcome Measures:
  • Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of the Study (Week 12 + 1 Day, Day 85) [ Time Frame: 24 hours post-dose at the end of the study (Week 12 + 1 day, Day 85) ] [ Designated as safety issue: No ]
    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 and FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening as covariates.


Enrollment: 1123
Study Start Date: January 2009
Study Completion Date: October 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Indacaterol 150 µg
Patients inhaled indacaterol 150 μg once daily in the morning between 8:00 and 11:00 AM via a single-dose dry-powder inhaler (SDDPI) for 12 weeks. Patients also inhaled placebo to salmeterol twice daily, once in the morning between 8:00 and 11:00 AM and once in the evening between 8:00 and 11:00 PM via the manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI, [DISKUS]) for 12 weeks. 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 150 µg
Indacaterol 150 μg was provided in powder-filled capsules with a single-dose dry-powder inhaler (SDDPI).
Drug: Placebo to salmeterol
Placebo to salmeterol was provided in the manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI, [DISKUS]).
Active Comparator: Salmeterol 50 µg
Patients inhaled salmeterol 50 μg twice daily, once in the morning between 8:00 and 11:00 AM and once in the evening between 8:00 and 11:00 PM via the manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI, [DISKUS]) for 12 weeks. Patients also inhaled placebo to indacaterol once daily in the morning between 8:00 and 11:00 AM via a single-dose dry-powder inhaler (SDDPI) for 12 weeks. 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: Salmeterol 50 µg
Salmeterol 50 μg was provided in the manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI, [DISKUS]).
Drug: Placebo to indacaterol
Placebo to indacaterol was provided in powder-filled capsules with a single-dose dry-powder inhaler (SDDPI).

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adults aged ≥ 40 years
  • Diagnosis of chronic obstructive pulmonary disease (COPD) (moderate to severe as classified by the GOLD Guidelines, 2007) and:

    • Smoking history of at least 10 pack years
    • Post-bronchodilator forced expiratory volume in 1 second (FEV1) < 80% and ≥ 30% of the predicted normal value at screening
    • Post-bronchodilator FEV1/FVC (forced vital capacity) < 70% at screening

Exclusion Criteria:

  • Patients who have received systemic corticosteroids for a COPD exacerbation in the 6 weeks prior to screening or during the run-in period
  • Patients requiring long-term oxygen therapy (> 15 h a day) for chronic hypoxemia
  • Patients who have 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
  • 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 (Fridericia's) measured at screening is prolonged
  • Patients who have been vaccinated with live attenuated vaccines within 30 days prior to screening or during the run-in period
  • Patients unable to successfully use a dry powder inhaler device or perform spirometry measurements

Other protocol-defined inclusion/exclusion criteria applied to the study.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00821093

  Show 144 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceticals Novartis Pharmaceuticals
  More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: External Affairs, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00821093     History of Changes
Other Study ID Numbers: CQAB149B2349, 2008-005146-23
Study First Received: January 9, 2009
Results First Received: July 22, 2011
Last Updated: July 22, 2011
Health Authority: United States: Food and Drug Administration
Turkey: Ministry of Health
India: Drugs Controller General of India
Germany: Ethics Commission
Spain: Spanish Agency of Medicines
Slovakia: State Institute for Drug Control
Hungary: National Institute of Pharmacy
Czech Republic: State Institute for Drug Control
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Novartis:
respiratory
dyspnea
breathlessness
COPD
indacaterol
long-acting β2-agonist

Additional relevant MeSH terms:
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases
Salmeterol
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 19, 2013