Efficacy and Safety Study of Indacaterol Maleate/Glycopyr... | NCT02487498

Label	Type	Description	Intervention Names
QVA149	Experimental	QVA149 capsules for inhalation, delivered via QVA149 SDDPI	Drug: QVA149 Drug: Placebo (umeclidinium/vilanterol )
Umeclidinium/vilanterol	Experimental	Umeclidinium/vilanterol for inhalation, delivered via ELLIPTA® inhaler	Drug: Umeclidinium/vilanterol Drug: Placebo (QVA149)

Name	Type	Description	Arm Group Labels	Other Names
QVA149	Drug	QVA149 capsules for inhalation, delivered via QVA149 SDDPI	QVA149

Measure	Description	Time Frame
Change From Baseline in Forced Expiratory Volume (FEV1) Area Under the Curve (AUC) 0-24h	FEV1 was measured with spirometry conducted according to internationally accepted standards. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time over an entire day (AUC 0-24h). A positive change from baseline indicates improvement.	baseline, 0 to 24 hours post-dose at week 12

Measure	Description	Time Frame
Change From Baseline in Forced Expiratory Volume (FEV1) Area Under the Curve (AUC) 0-24h	FEV1 was measured with spirometry conducted according to internationally accepted standards. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time over an entire day (AUC 0-24h). A positive change from baseline indicates improvement.	baseline, 0 to 24 hours post-dose at week 12

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigative Site		Anaheim	California	92801	United States
Novartis Investigative Site

PubMed Identifier	Type	Citation	Retractions
28993871	Derived	Kerwin E, Ferguson GT, Sanjar S, Goodin T, Yadao A, Fogel R, Maitra S, Sen B, Ayers T, Banerji D. Dual Bronchodilation with Indacaterol Maleate/Glycopyrronium Bromide Compared with Umeclidinium Bromide/Vilanterol in Patients with Moderate-to-Severe COPD: Results from Two Randomized, Controlled, Cross-over Studies. Lung. 2017 Dec;195(6):739-747. doi: 10.1007/s00408-017-0055-9. Epub 2017 Oct 9.

ID	Title	Description
FG000	First QVA149, Then Umeclidinium/Vilanterol	Participants received QVA149 27.5/12.5 ug via inhalation twice daily (b.i.d.) for 12 weeks. Then after 3 weeks washout, participants received Umeclidinium/vilanterol 62.5/25 ug via inhalation once daily for 12 weeks.
FG001	First Umeclidinium/Vilanterol, Then QVA149

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in Forced Expiratory Volume (FEV1) Area Under the Curve (AUC) 0-24h

FEV1 was measured with spirometry conducted according to internationally accepted standards. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time over an entire day (AUC 0-24h). A positive change from baseline indicates improvement.

The full analysis, which included all randomized patients who received at least one dose of double-blind treatment, was considered for the analysis. Only participants with a value at both baseline and the post-baseline time point were included in the analysis.

Posted

Least Squares Mean

Standard Error

Liters

baseline, 0 to 24 hours post-dose at week 12

ID	Title	Description
OG000	First QVA149, Then Umeclidinium/Vilanterol	Participants received QVA149 27.5/12.5 ug via inhalation twice daily (b.i.d.) for 12 weeks. Then after 3 weeks washout, participants received Umeclidinium/vilanterol 62.5/25 ug via inhalation once daily for 12 weeks.
OG001	First Umeclidinium/Vilanterol, Then QVA149	Participants received Umeclidinium/vilanterol 62.5/25 ug via inhalation once daily for 12 weeks. Then after 3 weeks washout, participants received QVA149 27.5/12.5 ug via inhalation twice daily (b.i.d.) for 12 weeks.

Units	Counts
Participants	OG000319 OG001326

Title

Denominators

Categories

Title	Measurements
	OG0000.1846± 0.01193 OG0010.2028± 0.01188

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	Ho: QVA149 27.5/12.5 μg b.i.d. is inferior to umeclidinium/vilanterol 62.5/25 μg q.d; Ha: QVA149 27.5/12.5 μg b.i.d. is non-inferior to umeclidinium/vilanterol 62.5/25 μg q.d.	Linear Mixed Model		0.415		Mean Difference (Net)	-0.0182	Standard Error of the Mean	0.00813	2-Sided	95	-0.0342	-0.0023					Non-Inferiority or Equivalence	Non-inferiority was demonstrated if the lower limit (LL) of the 97.5% one -sided confidence interval (CI) > -20 mL

Secondary

Change From Baseline in Forced Expiratory Volume (FEV1) Area Under the Curve (AUC) 0-24h

The full analysis, which included all randomized patients who received at least one dose of double-blind treatment, was considered for the analysis. Only participants with a value at both baseline and post-baseline time point were included in the analysis

Posted

Least Squares Mean

Standard Error

Liters

baseline, 0 to 24 hours post-dose at week 12

ID	Title	Description
OG000	First QVA149, Then Umeclidinium/Vilanterol	Participants received QVA149 27.5/12.5 ug via inhalation twice daily (b.i.d.) for 12 weeks. Then after 3 weeks washout, participants received Umeclidinium/vilanterol 62.5/25 ug via inhalation once daily for 12 weeks.
OG001	First Umeclidinium/Vilanterol, Then QVA149	Participants received Umeclidinium/vilanterol 62.5/25 ug via inhalation once daily for 12 weeks. Then after 3 weeks washout, participants received QVA149 27.5/12.5 ug via inhalation twice daily (b.i.d.) for 12 weeks.

Secondary

Superiority of QVA149 Compared to Umeclidinium/Vilanterol in Terms of Change From Baseline in Trough FEV1 (Mean of 23h 15 Minutes and 23 h 45 Minutes Post Previous Morning Dose)

FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 15 minutes and 23 hours 45 minutes post-dose for each treatment.

Posted

Least Squares Mean

Standard Error

Liters

baseline, 23 hours 15 minutes and 23 hours 45 minutes post previous morning dose at week 12

ID	Title	Description
OG000	First QVA149, Then Umeclidinium/Vilanterol	Participants received QVA149 27.5/12.5 ug via inhalation twice daily (b.i.d.) for 12 weeks. Then after 3 weeks washout, participants received Umeclidinium/vilanterol 62.5/25 ug via inhalation once daily for 12 weeks.
OG001	First Umeclidinium/Vilanterol, Then QVA149	Participants received Umeclidinium/vilanterol 62.5/25 ug via inhalation once daily for 12 weeks. Then after 3 weeks washout, participants received QVA149 27.5/12.5 ug via inhalation twice daily (b.i.d.) for 12 weeks.

Secondary

Change From Baseline in FEV1 AUC 12-24h

Posted

Least Squares Mean

Standard Error

Liters

baseline, 12 hours to 24 hours post-dose at week 12

ID	Title	Description
OG000	First QVA149, Then Umeclidinium/Vilanterol	Participants received QVA149 27.5/12.5 ug via inhalation twice daily (b.i.d.) for 12 weeks. Then after 3 weeks washout, participants received Umeclidinium/vilanterol 62.5/25 ug via inhalation once daily for 12 weeks.
OG001	First Umeclidinium/Vilanterol, Then QVA149	Participants received Umeclidinium/vilanterol 62.5/25 ug via inhalation once daily for 12 weeks. Then after 3 weeks washout, participants received QVA149 27.5/12.5 ug via inhalation twice daily (b.i.d.) for 12 weeks.

Units

Secondary

Change From Baseline in FEV1 AUC 0-12h

Posted

Least Squares Mean

Standard Error

Liters

baseline, 0 to 12 hours post-dose at week 12

ID	Title	Description
OG000	First QVA149, Then Umeclidinium/Vilanterol	Participants received QVA149 27.5/12.5 ug via inhalation twice daily (b.i.d.) for 12 weeks. Then after 3 weeks washout, participants received Umeclidinium/vilanterol 62.5/25 ug via inhalation once daily for 12 weeks.
OG001	First Umeclidinium/Vilanterol, Then QVA149	Participants received Umeclidinium/vilanterol 62.5/25 ug via inhalation once daily for 12 weeks. Then after 3 weeks washout, participants received QVA149 27.5/12.5 ug via inhalation twice daily (b.i.d.) for 12 weeks.

Units	Counts

Secondary

Change From Baseline in FEV1 AUC 0-4h, AUC 4-8h, AUC 8-12h, AUC 12-16h, AUC 16-20h and AUC 20-24h

FEV1 was measured with spirometry conducted according to internationally accepted standards. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time over 4 hour intervals FEV1 AUC 0-4h, AUC 4-8h, AUC 8-12h, AUC 12-16h, AUC 16-20h and AUC 20-24h.

Posted

Least Squares Mean

Standard Error

Liter

baseline, 12 weeks

ID	Title	Description
OG000	First QVA149, Then Umeclidinium/Vilanterol	Participants received QVA149 27.5/12.5 ug via inhalation twice daily (b.i.d.) for 12 weeks. Then after 3 weeks washout, participants received Umeclidinium/vilanterol 62.5/25 ug via inhalation once daily for 12 weeks.
OG001	First Umeclidinium/Vilanterol, Then QVA149	Participants received Umeclidinium/vilanterol 62.5/25 ug via inhalation once daily for 12 weeks. Then after 3 weeks washout, participants received QVA149 27.5/12.5 ug via inhalation twice daily (b.i.d.) for 12 weeks.

Secondary

QVA149 Compared to Umeclidinium/Vilanterol in Terms of Change From Baseline in Pre-dose Trough FEV1 (Mean of 15 Minutes and 45 Minutes Pre Morning Dose)

FEV1 was measured with spirometry conducted according to internationally accepted standards. Pre-dose trough FEV1 was defined as the average of measurements made 15 minutes and 45 minutes pre morning dose for each treatment.

Posted

Least Squares Mean

Standard Error

Liters

baseline, 12 weeks

ID	Title	Description
OG000	First QVA149, Then Umeclidinium/Vilanterol	Participants received QVA149 27.5/12.5 ug via inhalation twice daily (b.i.d.) for 12 weeks. Then after 3 weeks washout, participants received Umeclidinium/vilanterol 62.5/25 ug via inhalation once daily for 12 weeks.
OG001	First Umeclidinium/Vilanterol, Then QVA149	Participants received Umeclidinium/vilanterol 62.5/25 ug via inhalation once daily for 12 weeks. Then after 3 weeks washout, participants received QVA149 27.5/12.5 ug via inhalation twice daily (b.i.d.) for 12 weeks.

Secondary

QVA149 Compared to Umeclidinium/Vilanterol in Terms of Change From Baseline in FEV1 at Any Time Point

FEV1 was measured with spirometry conducted according to internationally accepted standards.

Posted

Least Squares Mean

Standard Error

Liters

Day 1 (5min, 15min, 30min, hours 1, 2, 4, 8, 11h 55min, 23h 15min, 23h 45min); week 6 (-45min, -15min); week 12 (-45min, -15min, 5min, 15min, 30min, hours 1, 2, 4, 8, 11h 55min, 12h 5min, 12h 15min, 12h 30min, 13, 14, 16, 20, 23h 15min, 23h 45min)

ID	Title	Description
OG000	First QVA149, Then Umeclidinium/Vilanterol	Participants received QVA149 27.5/12.5 ug via inhalation twice daily (b.i.d.) for 12 weeks. Then after 3 weeks washout, participants received Umeclidinium/vilanterol 62.5/25 ug via inhalation once daily for 12 weeks.
OG001	First Umeclidinium/Vilanterol, Then QVA149	Participants received Umeclidinium/vilanterol 62.5/25 ug via inhalation once daily for 12 weeks. Then after 3 weeks washout, participants received QVA149 27.5/12.5 ug via inhalation twice daily (b.i.d.) for 12 weeks.

Secondary

QVA149 Compared to Umeclidinium/Vilanterol in Terms of Change From Baseline in Forced Vital Capacity (FVC) at Any Time Point

FEV1 was measured with spirometry conducted according to internationally accepted standards.

Posted

Least Squares Mean

Standard Error

Liters

Day 1 (5min, 15min, 30 min, hours 1, 2, 4, 8, 11h 55min, 23h 15min, 23h 45min); week 6 (-45min, -15min); week 12 (-45min, -15min, 5min, 15min, 30min, hours 1, 2, 4, 8, 11h 55min, 12h 5min, 12h 15min, 12h 30min, 13, 14, 16, 20, 23h 15min, 23h 45min)

ID	Title	Description
OG000	First QVA149, Then Umeclidinium/Vilanterol	Participants received QVA149 27.5/12.5 ug via inhalation twice daily (b.i.d.) for 12 weeks. Then after 3 weeks washout, participants received Umeclidinium/vilanterol 62.5/25 ug via inhalation once daily for 12 weeks.
OG001	First Umeclidinium/Vilanterol, Then QVA149	Participants received Umeclidinium/vilanterol 62.5/25 ug via inhalation once daily for 12 weeks. Then after 3 weeks washout, participants received QVA149 27.5/12.5 ug via inhalation twice daily (b.i.d.) for 12 weeks.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute coronary syndrome	Cardiac disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected337 at risk EG0010 affected347 at risk EG0021 affected355 at risk
Coronary artery disease	Cardiac disorders	MedDRA (19.0)	Systematic Assessment	EG0002 affected337 at risk EG0010 affected347 at risk EG0022 affected355 at risk
Myocardial infarction	Cardiac disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected337 at risk EG0011 affected347 at risk EG0022 affected355 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected337 at risk EG0010 affected347 at risk EG0021 affected355 at risk
Bronchitis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 affected337 at risk EG0011 affected347 at risk EG0021 affected355 at risk
Clostridium difficile infection	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 affected337 at risk EG0011 affected347 at risk EG0021 affected355 at risk
Escherichia urinary tract infection	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0001 affected337 at risk EG0010 affected347 at risk EG0021 affected355 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 affected337 at risk EG0011 affected347 at risk EG0021 affected355 at risk
Pneumonia	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0001 affected337 at risk EG0012 affected347 at risk EG0023 affected355 at risk
Pneumonia staphylococcal	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0001 affected337 at risk EG0010 affected347 at risk EG0021 affected355 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected337 at risk EG0011 affected347 at risk EG0021 affected355 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected337 at risk EG0010 affected347 at risk EG0021 affected355 at risk
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected337 at risk EG0010 affected347 at risk EG0021 affected355 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (19.0)	Systematic Assessment	EG0000 affected337 at risk EG0011 affected347 at risk EG0021 affected355 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (19.0)	Systematic Assessment	EG0000 affected337 at risk EG0011 affected347 at risk EG0021 affected355 at risk
Cervix carcinoma stage iii	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (19.0)	Systematic Assessment	EG0000 affected337 at risk EG0011 affected347 at risk EG0021 affected355 at risk
Papillary thyroid cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (19.0)	Systematic Assessment	EG0001 affected337 at risk EG0010 affected347 at risk EG0021 affected355 at risk
Squamous cell carcinoma of lung	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (19.0)	Systematic Assessment	EG0001 affected337 at risk EG0010 affected347 at risk EG0021 affected355 at risk
Squamous cell carcinoma of the oral cavity	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (19.0)	Systematic Assessment	EG0001 affected337 at risk EG0010 affected347 at risk EG0021 affected355 at risk
Tonsil cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (19.0)	Systematic Assessment	EG0000 affected337 at risk EG0011 affected347 at risk EG0021 affected355 at risk
Encephalopathy	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected337 at risk EG0010 affected347 at risk EG0021 affected355 at risk
Seizure	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected337 at risk EG0011 affected347 at risk EG0021 affected355 at risk
Ureterolithiasis	Renal and urinary disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected337 at risk EG0010 affected347 at risk EG0021 affected355 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected337 at risk EG0010 affected347 at risk EG0021 affected355 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0008 affected337 at risk EG0012 affected347 at risk EG00210 affected355 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected337 at risk EG0010 affected347 at risk EG0021 affected355 at risk
Arteriosclerosis	Vascular disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected337 at risk EG0010 affected347 at risk EG0021 affected355 at risk
Peripheral artery occlusion	Vascular disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected337 at risk EG0010 affected347 at risk EG0021 affected355 at risk
Thrombosis	Vascular disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected337 at risk EG0010 affected347 at risk EG0021 affected355 at risk
Vascular insufficiency	Vascular disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected337 at risk EG0010 affected347 at risk EG0021 affected355 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute sinusitis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0003 affected337 at risk EG0011 affected347 at risk EG0024 affected355 at risk
Bronchitis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG00011 affected337 at risk EG0016 affected347 at risk EG00216 affected355 at risk
Gastroenteritis viral	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0003 affected337 at risk EG0011 affected347 at risk EG0024 affected355 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0004 affected337 at risk EG0013 affected347 at risk EG0027 affected355 at risk
Nasopharyngitis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0003 affected337 at risk EG0014 affected347 at risk EG0027 affected355 at risk
Oral candidiasis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0004 affected337 at risk EG0012 affected347 at risk EG0026 affected355 at risk
Sinusitis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0006 affected337 at risk EG0015 affected347 at risk EG00211 affected355 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0005 affected337 at risk EG0018 affected347 at risk EG00213 affected355 at risk
Upper respiratory tract infection bacterial	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0004 affected337 at risk EG0017 affected347 at risk EG0029 affected355 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0003 affected337 at risk EG0018 affected347 at risk EG00211 affected355 at risk
Laceration	Injury, poisoning and procedural complications	MedDRA (19.0)	Systematic Assessment	EG0002 affected337 at risk EG0012 affected347 at risk EG0024 affected355 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0003 affected337 at risk EG0012 affected347 at risk EG0025 affected355 at risk
Headache	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0002 affected337 at risk EG0013 affected347 at risk EG0024 affected355 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG00050 affected337 at risk EG00151 affected347 at risk EG00289 affected355 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected337 at risk EG0017 affected347 at risk EG0028 affected355 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0003 affected337 at risk EG0014 affected347 at risk EG0026 affected355 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected337 at risk EG0014 affected347 at risk EG0025 affected355 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0003 affected337 at risk EG0012 affected347 at risk EG0024 affected355 at risk

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
C554862	indacaterol-glycopyrronium combination
C573971	GSK573719
C550468	vilanterol

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	QVA 27.5/12.5 Bid	QVA149 capsules for inhalation, delivered via QVA149 SDDPI	17	337	78	337
EG001	U/V 62.5/25 od	Umeclidinium/vilanterol for inhalation, delivered via ELLIPTA® inhaler	10	347	89	347
EG002	All Patients	All Patients	26	355	140	355