Study to Evaluate Efficacy/Safety of Combination Budesoni... | NCT02055352

NCT02055352

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Budesonide/indacaterol	Experimental	Participants will receive a fixed combination of fluticasone and salmeterol during 4 weeks followed by a free combination of budesonide and indacaterol for the remainig of study.	Drug: Budesonide Drug: Fluticasone Drug: Indacaterol Drug: Salmeterol
Fluticasone / salmeterol	Active Comparator	Fixed combination of fluticasone and salmeterol	Drug: Fluticasone Drug: Salmeterol

Name	Type	Description	Arm Group Labels	Other Names
Budesonide	Drug	Budesonide 400 mcg twice a day via Breezhaler® device	Budesonide/indacaterol

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Trough Forced Expiratory Volume in 1 Second (Non-inferiority Analysis).	Forced Expiratory Volume in 1 second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation.	Baseline and week 12

Secondary Outcomes

Measure	Description	Time Frame
Change in Health Status - mMRC	Modified Medical Research Council scale (mMRC) questionnaire will be completed by participants. 0 Not troubled with breathlessness except with strenuous exercise; 1 Troubled by shortness of breath when hurrying on the level or walking up a slight hill; 2 Walks slower than people of the same age on the level because of breathlessness or has to stop for breath when walking at own pace on the level; 3 Stops for breath after walking about 100 yards or after a few minutes on the level; 4 Too breathless to leave the house or breathless when dressing or undressing

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Written informed consent must be obtained before any assessment is performed
Outpatients with stable COPD groups C and D according to the 2011 GOLD Guidelines.
Current or ex-smokers who have a smoking history of at least 10 pack years
Patients with a history of at least one exacerbation.
Patients able to read and complete

Exclusion Criteria:

Use of other investigational drugs within 30 days
Patients with a history of hypersensitivity to any of the study drugs
History or current diagnosis of ECG abnormalities
Patients with diabetes Type I or uncontrolled diabetes Type II including patients with a history of blood glucose levels consistently outside the normal range
Patients who have not achieved an acceptable spirometry result at Visit 1
Patients with a body mass index (BMI) of more than 40 kg/m2
Patients with lung cancer or a history of lung cancer
Patients with a history of malignancy of any organ system
Pregnant or nursing (lactating) women
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment
Patients who do not maintain regular day/night, waking/sleeping cycles (e.g., night shift workers)
Patients that are uncontrolled or unstable on permitted therapy, who in the opinion of the investigator, have clinically significant renal, cardiovascular, neurological, endocrine, immunological, psychiatric, gastrointestinal, hepatic, or haematological abnormalities which could interfere with the assessment of the efficacy and safety of the study treatment
Patients requiring oxygen therapy for chronic hypoxemia
Patients who have had a respiratory tract infection within 6 weeks prior to Visit 1
Patients with concomitant pulmonary disease, e.g. pulmonary tuberculosis, bronchiectasis, sarcoidosis, interstitial lung disorder or pulmonary hypertension
Patients with a known diagnosis of Alpha-1 Antitrypsin deficiency.
Patients with history of lung surgery
Patients who are participating in the active phase of a supervised pulmonary rehabilitation program.
Patients with a history of asthma Other protocol-defined inclusion/exclusion criteria may apply

Contacts/Locations Module

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigative Site		Buenos Aires	Buenos Aires	C1125ABE	Argentina
Novartis Investigative Site

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Budesonide/Indacaterol	Participants will receive a fixed combination of fluticasone and salmeterol during 4 weeks followed by a free combination of budesonide and indacaterol for the remainig of study.
FG001	Fluticasone / Salmeterol

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Budesonide/Indacaterol	Participants will receive a fixed combination of fluticasone and salmeterol during 4 weeks followed by a free combination of budesonide and indacaterol for the remainig of study.
BG001	Fluticasone / Salmeterol	Fixed combination of fluticasone and salmeterol
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	OG0000.080± 0.027 OG0010.019± 0.028

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Mixed effects General linear model		0.004														Non-Inferiority or Equivalence	A change of 5-10% from baseline values is considered to be clinically important. The estimated adjusted treatment difference for budesonide 400 μg twice a day/ indacaterol 150 μg once daily minus fixed combination of fluticasone/ salmeterol 250/ 50 μg twice daily was displayed along with the associated one-sided 97.5% confidence interval. If the lower limit of this confidence interval was to the right (i.e. above) - 10 mL, then non-inferiority could be claimed.

Secondary

Change in Health Status - mMRC

Modified Medical Research Council scale (mMRC) questionnaire will be completed by participants. 0 Not troubled with breathlessness except with strenuous exercise; 1 Troubled by shortness of breath when hurrying on the level or walking up a slight hill; 2 Walks slower than people of the same age on the level because of breathlessness or has to stop for breath when walking at own pace on the level; 3 Stops for breath after walking about 100 yards or after a few minutes on the level; 4 Too breathless to leave the house or breathless when dressing or undressing

Posted

Least Squares Mean

Standard Error

Score on a scale

Baseline, week 12 and week 24

ID	Title	Description
OG000	Budesonide/Indacaterol	Participants will receive a fixed combination of fluticasone and salmeterol during 4 weeks followed by a free combination of budesonide and indacaterol for the remainig of study.
OG001	Fluticasone / Salmeterol	Fixed combination of fluticasone and salmeterol

Secondary

Change From Baseline in Mean Daily Number of Puffs of Rescue Medication Used Over the 24 Week Treatment

A day with no rescue medication use is defined from the diary data as any day where the patient recorded no rescue medicine use during the previous 12 hours.

Per-protocol set (PPS) included all patients in the FAS without any major protocol deviations. Major protocol deviations were defined in the validation analysis plan prior to database lock and the unblinding of the study. Patients that were not discontinued before Visit 3 (day 28±3).

Posted

Mean

Standard Deviation

Puffs

24 weeks

ID	Title	Description
OG000	Budesonide/Indacaterol	Participants will receive a fixed combination of fluticasone and salmeterol during 4 weeks followed by a free combination of budesonide and indacaterol for the remainig of study.
OG001	Fluticasone / Salmeterol	Fixed combination of fluticasone and salmeterol

Units	Counts
Participants

Secondary

Change From Baseline in Trough Forced Expiratory Volume in 1 Second at Week 24 (Analysis of Superiority)

Forced Expiratory Volume in 1 second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing.

Posted

Least Squares Mean

Standard Error

Liters

Baseline and week 24

ID	Title	Description
OG000	Budesonide/Indacaterol	Participants will receive a fixed combination of fluticasone and salmeterol during 4 weeks followed by a free combination of budesonide and indacaterol for the remainig of study.
OG001	Fluticasone / Salmeterol	Fixed combination of fluticasone and salmeterol

Units	Counts
Participants

Secondary

Change in Health Status - SGRQ-C

St George's Respiratory Questionnaire short version questionnaire will be completed by participants. The SGRQ ranges from 0 (no impairment of quality of life) to 100 (highest impairment of quality of life)

Posted

Least Squares Mean

Standard Error

Score on a scale

Baseline, week 12 and week 24

ID	Title	Description
OG000	Budesonide/Indacaterol	Participants will receive a fixed combination of fluticasone and salmeterol during 4 weeks followed by a free combination of budesonide and indacaterol for the remainig of study.
OG001	Fluticasone / Salmeterol	Fixed combination of fluticasone and salmeterol

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Budesonide / Indacaterol (A)	Budesonide / Indacaterol (A)			10	109	24	109
EG001	Fluticasone / Salmeterol (B)	Fluticasone / Salmeterol (B)			9	113	39	113

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute myocardial infarction	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected109 at risk EG0011 affected113 at risk
Bradycardia	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected109 at risk EG0011 affected113 at risk
Cor pulmonale	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected109 at risk EG0011 affected113 at risk
Nodal arrhythmia	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected109 at risk EG0011 affected113 at risk
Cellulitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected109 at risk EG0011 affected113 at risk
Pneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0003 affected109 at risk EG0011 affected113 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected109 at risk EG0011 affected113 at risk
Bronchial carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected109 at risk EG0010 affected113 at risk
Hepatocellular carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected109 at risk EG0011 affected113 at risk
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected109 at risk EG0011 affected113 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0006 affected109 at risk EG0012 affected113 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected109 at risk EG0010 affected113 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected109 at risk EG0010 affected113 at risk
Peripheral arterial occlusive disease	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected109 at risk EG0011 affected113 at risk
Vascular insufficiency	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected109 at risk EG0011 affected113 at risk
Venous thrombosis limb	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected109 at risk EG0011 affected113 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Influenza	Infections and infestations	MedDRA	Systematic Assessment	EG0006 affected109 at risk EG00110 affected113 at risk
Nasopharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG00011 affected109 at risk EG00110 affected113 at risk
Urinary tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0003 affected109 at risk EG0017 affected113 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected109 at risk EG0017 affected113 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected109 at risk EG0016 affected113 at risk
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected109 at risk EG0019 affected113 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0003 affected109 at risk EG0018 affected113 at risk

ID	Term
D029424	Pulmonary Disease, Chronic Obstructive

Ancestor Terms

ID	Term
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D019819	Budesonide
D000068298	Fluticasone
C510790	indacaterol
D000068299	Salmeterol Xinafoate

Ancestor Terms

ID	Term
D011282	Pregnenediones
D011283	Pregnenes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D000730	Androstadienes
D000736	Androstenes
D000731	Androstanes
D000420	Albuterol
D004983	Ethanolamines
D000605	Amino Alcohols
D000438	Alcohols
D009930	Organic Chemicals
D000588	Amines
D010627	Phenethylamines
D005021	Ethylamines

Units	Counts
Participants	OG000108 OG001111