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

Chronic Obstructive Pulmonary Disease Clinical Trial

— INSTEAD  

Official title:

A Randomized, Double-blind, Parallel-group, 26-week Study Comparing the Efficacy and Safety of Indacaterol (Onbrez® Breezhaler® 150 mcg o.d.) With Salmeterol/Fluticasone Propionate (Seretide® Accuhaler® 50 mcg/500 mcg b.i.d.) in Patients With Moderate Chronic Obstructive Pulmonary Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01555138
• Other study ID #: CQAB149B2401
• Secondary ID: 2011-003732-31
• Status: Completed
• Phase: Phase 4
• First received: March 13, 2012
• Last updated: April 8, 2015
• Start date: February 2012
• Est. completion date: February 2014

Study information

• Verified date: April 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationSwitzerland: Swiss Agency for Therapeutic ProductsColumbia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y AlimentosArgentina: 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 AgencyMalaysia: National Pharmaceutical Control BureauItalian Medicines Agency - AIFANetherlands: Centrale Commissie Mensgebonden Onderzoek -The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 581
• Est. completion date: February 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Indacaterol
Indacaterol is delivered via a SDDPI.
• Salmeterol
Salmeterol/fluticasone is delivered via a MDDPI

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Buenos aires
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	C A B A	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba
Argentina	Novartis Investigative Site	Concepción del Uruguay	Entre Ríos
Argentina	Novartis Investigative Site	Cordoba
Argentina	Novartis Investigative Site	La Plata	Buenos Aires
Argentina	Novartis Investigative Site	Mar del Plata	Buenos Aires
Argentina	Novartis Investigative Site	Mar del Plata	Buenos Aires
Argentina	Novartis Investigative Site	Mendoza
Argentina	Novartis Investigative Site	Mendoza
Argentina	Novartis Investigative Site	Quilmes	Buenos Aires
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	Salta
Argentina	Novartis Investigative Site	San Miguel de Tucuman	Tucuman
Argentina	Novartis Investigative Site	San Miguel de Tucuman	Tucuman
Argentina	Novartis Investigative Site	Santa Fe	Rosario
Argentina	Novartis Investigative Site	Santa Fe
Argentina	Novartis Investigative Site	Villa María	Córdoba
Colombia	Novartis Investigative Site	Barranquilla
Colombia	Novartis Investigative Site	Bogota	Cundinamarca
Colombia	Novartis Investigative Site	Bogotá
Italy	Novartis Investigative Site	Acquaviva delle Fonti	BA
Italy	Novartis Investigative Site	Bologna	BO
Italy	Novartis Investigative Site	Caserta	CE
Italy	Novartis Investigative Site	Cassano delle Murge	BA
Italy	Novartis Investigative Site	Cassino	FR
Italy	Novartis Investigative Site	Cittadella	PD
Italy	Novartis Investigative Site	Cona	FE
Italy	Novartis Investigative Site	Cuasso al Monte	VA
Italy	Novartis Investigative Site	Foggia	FG
Italy	Novartis Investigative Site	Forlì	FC
Italy	Novartis Investigative Site	Genova	GE
Italy	Novartis Investigative Site	Messina	ME
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Negrar	VR
Italy	Novartis Investigative Site	Parma	PR
Italy	Novartis Investigative Site	Pavia	PV
Italy	Novartis Investigative Site	Pisa	PI
Italy	Novartis Investigative Site	Pordenone	PN
Italy	Novartis Investigative Site	Salerno	SA
Italy	Novartis Investigative Site	Sesto San Giovanni	Mi
Italy	Novartis Investigative Site	Tradate	VA
Italy	Novartis Investigative Site	Treviglio	BG
Italy	Novartis Investigative Site	Verona	VR
Malaysia	Novartis Investigative Site	Kuching	Sarawak
Malaysia	Novartis Investigative Site	Pulau Pinang
Malaysia	Novartis Investigative Site	Wilayah Persekutuan	Kuala Lumpur
Mexico	Novartis Investigative Site	Ciudad De Mexico	Distrito Federal
Mexico	Novartis Investigative Site	Guadalajara	Jalisco
Mexico	Novartis Investigative Site	Mexico	Distrito Federal
Mexico	Novartis Investigative Site	Monterrey	Nuevo León
Mexico	Novartis Investigative Site	Querétaro
Mexico	Novartis Investigative Site	San Luis Potosi
Netherlands	Novartis Investigative Site	Breda
Netherlands	Novartis Investigative Site	Helmond
Netherlands	Novartis Investigative Site	Rotterdam
Spain	Novartis Investigative Site	Barcelona	Cataluña
Spain	Novartis Investigative Site	Canet de Mar	Cataluña
Spain	Novartis Investigative Site	Corbera de Llobregat	Cataluña
Spain	Novartis Investigative Site	Lerida	Cataluña
Spain	Novartis Investigative Site	Loja	Andalucia
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Pozuelo de Alarcón	Madrid
Spain	Novartis Investigative Site	Sanlúcar de Barrameda	Andalucia
Spain	Novartis Investigative Site	Valladolid	Castilla y Leon
Switzerland	Novartis Investigative Site	Basel
Switzerland	Novartis Investigative Site	Biel
Switzerland	Novartis Investigative Site	Gossau
Switzerland	Novartis Investigative Site	Muenchenstein
United Kingdom	Novartis Investigative Site	Bradford
United Kingdom	Novartis Investigative Site	Chester
United Kingdom	Novartis Investigative Site	Dundee	Perthshire
United Kingdom	Novartis Investigative Site	East Yorkshire
United Kingdom	Novartis Investigative Site	Hants	Southampton
United Kingdom	Novartis Investigative Site	Kettering
United Kingdom	Novartis Investigative Site	Lancaster
United Kingdom	Novartis Investigative Site	Newcastle-upon-Tyne
United Kingdom	Novartis Investigative Site	Surrey

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Argentina,  Colombia,  Italy,  Malaysia,  Mexico,  Netherlands,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Trough Forced Expiratory Volume in One Second (FEV1) at 12 Weeks (Imputed With LOCF): Treatment Comparisons	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.	12 weeks	No
Secondary	Trough FEV1 (L) at Week 26 (Imputed With LOCF): Treatment Comparisons	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.	26 weeks	No
Secondary	FEV1 (L) at Individual Time Points After 12 Weeks Treatment: Treatment Comparisons	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.	12 weeks	No
Secondary	FEV1 (L) at Individual Time Points After 26 Weeks Treatment: Treatment Comparisons	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 .	26 weeks	No
Secondary	FVC Over 26 Weeks of Treatment	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.	12 and 26 weeks	No
Secondary	Analysis of AUC (5 Min - 4 h) for FEV1 (L) at Week 12 and Week 26: Treatment Comparison	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.	12 and 26 weeks	No
Secondary	TDI Focal Score at Week 12 and Week 26: Treatment Comparisons	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.Total score ranging - 9 to + 9. The lower the score, the more deterioration in severity of dyspnea. One additional option in each category, which does not contribute to the score, allows for circumstances in which impairment is due to reasons other than dyspnea.	12 and 26 weeks	No
Secondary	Number of COPD Exacerbations Per Patient Over 26 Weeks: Treatment Comparisons (Without Imputation; Full Analysis Set)	The number of exacerbations during the 26 week treatment period will be analyzed using a generalized linear model assuming a negative binomial distribution.	26 weeks	No
Secondary	Mean Daily Number of Puffs of Rescue Medication Used Over 26 Weeks of Treatment	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.	12 and 26 weeks	No
Secondary	Rescue Medication Use Over 26 Weeks: Percentage of 'Days With no Rescue Use'	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'.	26 weeks	No
Secondary	St Georges Respiratory Questionnaire for COPD	A Total and three component scores are calculated: Symptoms; Activity; Impacts. Each component of the questionnaire is scored separately:The score for each component is calculated separately by dividing the summed weights by the maximum possible weight for that component and expressing the result as a percentage: Score = 100 x Summed weights from all positive items in that component divided by Sum of weights for all items in that component The Total score is calculated in similar way: Score = 100 x Summed weights from all positive items in the questionnaire divided by Sum of weights for all items in the questionnaire Sum of maximum possible weights for each component and Total: Symptoms 566.2 Activity 982.9 Impacts 1652.8 Total (sum of maximum for all three components) 3201.9 The proportion of patients who achieve a clinically important improvement of at least 4 units in the total SGRQ will be analyzed. The higher the score the more symptoms of disease are present.	12 and 26 weeks	No