Comparison of Indacaterol 150 μg Once Daily (o.d.) With Salmeterol/Fluticasone Propionate 50 μg/500 μg Twice Daily (b.i.d.) (INSTEAD)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01555138
First received: March 13, 2012
Last updated: December 2, 2013
Last verified: December 2013
  Purpose

The purpose of this study is to compare the effectiveness and safety of indacaterol with salmeterol /fluticasone propionate treatment in patients with moderate chronic obstructive pulmonary disease who, on entry to the study are being treated with salmeterol /fluticasone propionate.


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease
Drug: Indacaterol
Drug: Salmeterol
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Parallel-group, 26-week Study Comparing the Efficacy and Safety of Indacaterol (Onbrez® Breezhaler® 150 μg o.d.) With Salmeterol/Fluticasone Propionate (Seretide® Accuhaler® 50 μg/500 μg b.i.d.) in Patients With Moderate Chronic Obstructive Pulmonary Disease

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Trough forced expiratory volume in one second (FEV1) at 12 weeks [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Spirometry conducted to internationally accepted standards. Trough FEV1 defined as the mean of the FEV1 measurements at 23 h 10 min and 23 h 45 min post the Day 84 morning dose. The primary variable (imputed with last observation carried forward) will be analysed using a mixed model for the Per Protocol Set (PPS). The model will contain treatment as a fixed effect with the baseline FEV1 measurement, FEV1 prior to inhalation and FEV1 10-15 min post inhalation of salbutamol (components of reversibility at Visit 1) as covariates.


Secondary Outcome Measures:
  • Trough FEV1 [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    Trough FEV1 is defined as the average of the 23 h 10 min and the 23 h 45 min values taken in the clinic at Visit 11. At Visits 4, 5, 6 and 10 trough FEV1 is defined as the average of the 50 min and the 15 min pre-dose values taken in the clinic.

  • FEV1 [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    FEV1 at each time point, for each visit, will be analyzed using the same mixed model as specified for the primary analysis. Least squares means will be displayed by treatment group along with the estimated treatment differences and the associated 95% confidence intervals and 2-sided p-values.

  • FVC [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    FVC at each time point, for each visit, will be analyzed using the same mixed model as specified for the primary analysis. Least squares means will be displayed by treatment group along with the estimated treatment differences and the associated 95% confidence intervals and 2-sided p-values.The standardized (with respect to the length of time) AUC for FEV1 will be calculated between 5 min and 4 h post morning dose as the sum of trapezoids divided by the length of time at Day 84 (Visit 6) and Day 182 (Visit 10).

  • Standardized AUC (5min-4h) for FEV1 [ Time Frame: 12 and 26 weeks ] [ Designated as safety issue: No ]
    The standardized (with respect to the length of time) AUC for FEV1 will be calculated between 5 min and 4 h post morning dose as the sum of trapezoids divided by the length of time at Day 84 (Visit 6) and Day 182 (Visit 10). Scheduled (not actual) time points are to be used. FEV1 measurements taken within 6 h of rescue use will be set to missing before the standardized AUC is calculated.

  • Transition Dyspnea Index [ Time Frame: 12 and 26 weeks ] [ Designated as safety issue: No ]
    The Transition Dyspnea Index (TDI) total score after 12 and 26 weeks of treatment will be analyzed using the same mixed model as specified for the primary analysis with the Baseline Dyspnea Index (BDI) total score as the baseline.

  • COPD Exacerbations [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    The number of exacerbations during the 26 week treatment period will be analyzed using a generalized linear model assuming a negative binomial distribution.

  • Mean daily rescue medication use [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    The mean daily number of puffs of rescue medication taken by the patient will be derived. If the number of puffs is missing for part of the day (either morning or evening) then a half day will be used in the denominator. Rescue medication data recorded during the 14 day run-in period will be used to calculate the baseline. The mean change from baseline in the daily number of puffs of rescue medication will be analyzed using the same mixed model as specified for the primary analysis, with the baseline FEV1 replaced with the baseline daily rescue use.

  • Percentage of days with no rescue medication use [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    A 'day with no rescue use' is defined from diary data as any day where the patient has taken no puffs of rescue medication. The percentage of 'days with no rescue use' will be derived and analyzed as for the percentage of 'nights with no nighttime awakenings'.

  • St Georges Respiratory Questionnaire for COPD [ Time Frame: 12 and 26 weeks ] [ Designated as safety issue: No ]

    The total score of SGRQ-C and handling of missing data will be conducted in accordance with the user guide.

    The SGRQ total score at Weeks 12 and 26 will be summarized by treatment and analyzed using a mixed model for the FAS. The same model as specified for the primary analysis was used, however, with baseline SGRQ total score instead of baseline FEV1 as covariate.


  • Adverse event data [ Time Frame: 26 weeks ] [ Designated as safety issue: Yes ]
    All study emergent adverse events will be summarized and listed. Adverse events starting on or after the time of the first treatment of study drug but not later than 7 days (30 days in the case of a serious adverse event) after the last treatment will be classified as a treatment emergent adverse event.

  • ECG [ Time Frame: 26 weeks ] [ Designated as safety issue: Yes ]
    Data from the electrocardiogram will be summarized by treatment. The maximum post first dosing (i.e. post baseline) value will also be summarized. Changes from baseline will also be summarized by treatment.

  • Vital signs [ Time Frame: 26 weeks ] [ Designated as safety issue: Yes ]

    Vital signs data will be summarized by treatment. All data will be included in the analysis regardless of rescue medication usage.

    The number (%) of patients with notable values for vital signs and notable changes from baseline will be summarized.


  • Biochemistry, haematology, urinalysis data [ Time Frame: 26 weeks ] [ Designated as safety issue: Yes ]
    All laboratory data will be summarized by treatment. Shift tables relative to the normal reference ranges will be used to summarize the change from baseline to post-dose values at each scheduled time point.


Estimated Enrollment: 600
Study Start Date: February 2012
Estimated Study Completion Date: February 2014
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Indacaterol
Indacaterol 150 μg once daily (o.d.) delivered via the Novartis single dose dry power inhaler (SDDPI) (Onbrez® Breezhaler®)
Drug: Indacaterol
Indacaterol is delivered via a SDDPI.
Active Comparator: Salmeterol/fluticasone propionate
Salmeterol 50 μg /fluticasone propionate 500 μg for inhalation delivered via a proprietary multi dose dry powder inhaler (MDDPI) device (Seretide® Accuhaler®) twice daily (b.i.d.)
Drug: Salmeterol
Salmeterol/fluticasone is delivered via a MDDPI

  Eligibility

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

Inclusion Criteria:

  • Patients with moderate COPD (Stage II)
  • Able to perform spirometry assessments
  • Current or ex-smokers
  • On treatment with the fixed-dose combination of salmeterol 50 µg/fluticasone propionate 500 µg MDDPI b.i.d. for the treatment of COPD for ≥ 3 months directly preceding Visit 1.

Exclusion Criteria:

  • Having had a COPD exacerbation that required treatment with antibiotics and/or oral corticosteroids and/or hospitalization in the past year.
  • Having a history of, or current ECG abnormality
  • Asthma

Other protocol-defined inclusion/exclusion criteria may apply.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01555138

Contacts
Contact: Novartis Pharmaceuticals +41613241111
Contact: Novartis Pharmaceuticals

  Show 122 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01555138     History of Changes
Other Study ID Numbers: CQAB149B2401, 2011-003732-31
Study First Received: March 13, 2012
Last Updated: December 2, 2013
Health Authority: United States: Food and Drug Administration
Switzerland: Swiss Agency for Therapeutic Products
Columbia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Argentina: National Administration of Drugs, Foods and Medical Technology - Administración Nacional de Medicamentos, Alimentos y Tecnología Médica (ANMAT)
Mexico: COFEPRIS - Comisión Federal para la Protección contra Riesgos Sanitarios.Spain: Agencia Española de Medicamentos y Productos Sanitarios (AEMPS)
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Malaysia: National Pharmaceutical Control BureauItalian Medicines Agency - AIFANetherlands: Centrale Commissie Mensgebonden Onderzoek -The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Novartis:
Chronic Obstructive Pulmonary Disease
Indacaterol
Salmeterol/fluticasone propionate

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

ClinicalTrials.gov processed this record on September 16, 2014