Efficacy, Safety and Pharmacokinetics of Indacaterol Acetate in Patients With Persistent Asthma

Asthma Clinical Trial

Official title:

A Multicenter, Randomized, Double-blind, Placebo-controlled, 12-week Treatment, Parallel-group Study to Assess the Efficacy, Safety and Pharmacokinetics of Indacaterol Acetate (75 and 150 µg o.d.) in Patients With Persistent Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01609478
• Other study ID #: CQMF149E2203
• Secondary ID: 2012-000520-18
• Status: Completed
• Phase: Phase 2
• First received: April 23, 2012
• Last updated: January 15, 2015
• Start date: August 2012
• Est. completion date: July 2013

Study information

• Verified date: January 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health CanadaGermany: Federal Institute for Drugs and Medical DevicesJapan: Pharmaceuticals and Medical Devices AgencyLatvia: State Agency of MedicinesNetherlands: Medicines Evaluation Board (MEB)Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsSlovakia: State Institute for Drug ControlBulgaria: Bulgarian Drug AgencyKorea: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

To provide the efficacy, safety and pharmacokinetics of indacaterol acetate in patients with persistent asthma to support dose selection of indacaterol in fixed dose combination QMF149.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 335
• Est. completion date: July 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with persistent asthma, diagnosed according to GINA 2010 guideline and who additionally meet the following criteria:

• Patients who are receiving ICS treatment in a stable regimen for = 4 weeks

• Patients with a pre-bronchodilator FEV1 value of = 40% and = 80% of predicted normal value

• Patients who demonstrate an increase of >= 12% and 200 mL in FEV1

• ACQ-5 score = 1.5

Exclusion Criteria:

• Patients who are current smokers or have a smoking history of greater than 10 pack years (defined as the number of packs of 20 cigarettes smoked per day multiplied by number of years the patient smoked).

• Patients with chronic lung disease, including COPD, pulmonary tuberculosis, bronchiectasis, sarcoidosis, interstitial lung disease and cystic fibrosis.

• Patients with any chronic conditions affecting the respiratory tract (e.g., chronic sinusitis) which in the opinion of the investigator may interfere with the study evaluation or optimal participation in the study.

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, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• indacaterol
indacaterol acetate 75 µg or indacaterol acetate 150 µg delivered via Concept 1 inhaler
• placebo
placebo delivered via Concept 1 inhaler
• mometasone furoate
via Twisthaler inhaler

Locations

Country	Name	City	State
Bulgaria	Novartis Investigative Site	Lovech
Bulgaria	Novartis Investigative Site	Pleven
Bulgaria	Novartis Investigative Site	Plovdiv
Bulgaria	Novartis Investigative Site	Ruse
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Varna
Bulgaria	Novartis Investigative Site	Varna
Bulgaria	Novartis Investigative Site	Veliko Tarnovo
Canada	Novartis Investigative Site	Brampton	Ontario
Canada	Novartis Investigative Site	Downsview	Ontario
Canada	Novartis Investigative Site	Etobicoke	Ontario
Canada	Novartis Investigative Site	Grimsby	Ontario
Canada	Novartis Investigative Site	Hamilton	Ontario
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Newmarket	Ontario
Canada	Novartis Investigative Site	Pointe-Claire	Quebec
Canada	Novartis Investigative Site	St-Romuald	Quebec
Canada	Novartis Investigative Site	Ste-Foy	Quebec
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Woodstock	Ontario
Germany	Novartis Investigative Site	Bad Woerishofen
Germany	Novartis Investigative Site	Bonn
Germany	Novartis Investigative Site	Dortmund
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Lübeck
Germany	Novartis Investigative Site	Mainz
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Wiesbaden
Germany	Novartis Investigative Site	Wiesloch
Japan	Novartis Investigative Site	Ako-shi	Hyogo-Ken
Japan	Novartis Investigative Site	Beppu	Oita
Japan	Novartis Investigative Site	Chuo-ku	Tokyo
Japan	Novartis Investigative Site	Cyuo-ku	Tokyo
Japan	Novartis Investigative Site	Fukuoka
Japan	Novartis Investigative Site	Gifu
Japan	Novartis Investigative Site	Himeji-city	Hyogo
Japan	Novartis Investigative Site	Itabashi-ku	Tokyo
Japan	Novartis Investigative Site	Kishiwada	Osaka
Japan	Novartis Investigative Site	Kiyose-city	Tokyo
Japan	Novartis Investigative Site	Kyoto-shi	Kyoto-Fu
Japan	Novartis Investigative Site	Machida-shi	Tokyo-To
Japan	Novartis Investigative Site	Naka-gun	Ibaraki
Japan	Novartis Investigative Site	Obihiro	Hokkaido
Japan	Novartis Investigative Site	Oita-shi	Oita-Ken
Japan	Novartis Investigative Site	Ota-ku	Tokyo-To
Japan	Novartis Investigative Site	Sakaide	Kagawa
Japan	Novartis Investigative Site	Sapporo-city	Hokkaido
Japan	Novartis Investigative Site	Setagaya-ku	Tokyo
Japan	Novartis Investigative Site	Tsu	Mie
Japan	Novartis Investigative Site	Yanagawa	Fukuoka
Japan	Novartis Investigative Site	Yonezawa	Yamagata
Korea, Republic of	Novartis Investigative Site	Cheongju	Chungbuk
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Wonju	Gangwon-Do
Netherlands	Novartis Investigative Site	Rotterdam
Netherlands	Novartis Investigative Site	Sittard-Geleen
Poland	Novartis Investigative Site	Bialystok
Poland	Novartis Investigative Site	Bienkowka
Poland	Novartis Investigative Site	Bydgoszcz
Poland	Novartis Investigative Site	Gdansk
Poland	Novartis Investigative Site	Krakow
Poland	Novartis Investigative Site	Lodz
Poland	Novartis Investigative Site	Lodz
Poland	Novartis Investigative Site	Lublin
Poland	Novartis Investigative Site	Lublin
Poland	Novartis Investigative Site	Torun
Poland	Novartis Investigative Site	Wroclaw
Poland	Novartis Investigative Site	Znin
Slovakia	Novartis Investigative Site	Banska Bystrica	Slovak Republic
Slovakia	Novartis Investigative Site	Bardejov	Slovak Republic
Slovakia	Novartis Investigative Site	Dunajska Streda
Slovakia	Novartis Investigative Site	Komarno
Slovakia	Novartis Investigative Site	Kosice
Slovakia	Novartis Investigative Site	Levice	Slovak republic
Slovakia	Novartis Investigative Site	Liptovsky Hradok
Slovakia	Novartis Investigative Site	Liptovsky Mikulas
Slovakia	Novartis Investigative Site	Nove Zamky
Slovakia	Novartis Investigative Site	Rimavska Sobota
Slovakia	Novartis Investigative Site	Spisská Nová Ves
Slovakia	Novartis Investigative Site	Topolcany
Slovakia	Novartis Investigative Site	Vysne Hagy
Slovakia	Novartis Investigative Site	Zvolen

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Bulgaria,  Canada,  Germany,  Japan,  Korea, Republic of,  Netherlands,  Poland,  Slovakia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Trough Forced Expiratory Volume in One Second (FEV1) After 12 Weeks (Day 85)	Forced Expiratory Volume in 1 second (FEV1) was measured via 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 after 12 weeks (Day 85)	after 12 weeks (Day 85)	No
Secondary	Asthma Control Questionnaire 5 (ACQ-5) After 12 Weeks (Day 85)	The Asthma Control Questionnaire (ACQ-5) is a validated questionnaire consisting of 5 items for the assessment of asthma symptom which are night symptom, morning symptom, limitation for the activities, shortness of breath, and wheeze. The ACQ-5 score is the mean of the 5 questions and therefore between 0 (totally controlled) and 6 (severely uncontrolled). A negative change in score indicates improvement in symptoms. MIXED model: Change from baseline in ACQ-5 = treatment + gender + baseline ACQ-5 score + age + level of asthma control + region + center (region) + error. Center is included as a random effect nested within region.	aftert 12 weeks (Day 85)	No
Secondary	Trough Forced Expiratory Volume in One Second (FEV1) After 2 Weeks (Day 15), 4 Weeks (Day 29), and 8 Weeks (Day 57) of Treatment.	Forced Expiratory Volume in 1 second (FEV1) was measured via 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 after 2 weeks (Day 15), 4 weeks (Day 29), and 8 weeks (Day 57) of treatment.	Day 15, Day 29 and Day 57	No
Secondary	Forced Vital Capacity (FVC) on Day 1, Day 2, Day 14, Day 15, Day 84, Day 85 at All Time Points	Forced Vital Capacity (FVC) was measured via spirometry conducted according to internationally accepted standards. FVC is measured on Day 1, Day 2, Day 14, Day 15, Day 84, Day 85 at all time points	Day 1, Day 2, Day 14, Day 15, Day 84, Day 85	No
Secondary	Forced Expiratory Volume in One Second (FEV1)/ Forced Vital Capacity (FVC) on Day 1, Day 2, Day 14, Day 15, Day 84, Day 85	Forced Expiratory Volume in 1 second (FEV1)/Forced Vital Capacity (FVC) was measured via spirometry conducted according to internationally accepted standards.	Day 1, Day 2, Day 14, Day 15, Day 84, Day 85	No
Secondary	Forced Expiratory Flow (FEF 25-75% )on Day 1, Day 2, Day 14, Day 15, Day 84, Day 85	Forced Expiratory Flow (FEF 25-75%) was measured via spirometry conducted according to internationally accepted standards.	Day 1, Day 2, Day 14, Day 15, Day 84, Day 85	No
Secondary	Standardized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) at (5 Min - 4 h), (5 Min - 1 h) (1 h - 4 h) Measured on Day 1, 2 Weeks (Day 14)&12 Weeks (Day 84)	Forced Expiratory Volume in 1 second (FEV1)/Area Under the Curve(AUC) was measured via spirometry conducted according to internationally accepted standards.FEV1 AUC(5 min - 4 h), (5 min - 1 h) and (1 h - 4 h) are measured at Day 1, 2 Weeks (Day 14) and 12 Weeks (Day84) and defined as average of FEV1 at specified timepoints above.	Day 1, 2 Weeks, 12 Weeks	No
Secondary	Peak Forced Expiratory Volume in 1 Second (FEV1) at Day 1, 2 Weeks (Day 14), 12 Weeks (Day 84)	Peak Forced Expiratory Volume in 1 second (FEV1) was measured via spirometry conducted according to internationally accepted standards. Peak FEV1 is defined as the maximum FEV1 during the first 4 h post morning dosing at Day 1, 2Weeks and 12 Weeks.	Day 1, 2 weeks (Day 14), 12 weeks (Day 84)	No
Secondary	Asthma Control Questionnaire 5 (ACQ-5) After 4 Weeks (Day 29) and After 8 Weeks (Day 57) of Treatment	The ACQ-5 is a validated questionnaire consisting of 5 items for the assessment of asthma symptom which are night symptom, morning symptom, limitation for the activities, shortness of breath, and wheeze. Each item is graded on a scale of 0-6 and the questions are equally weighted. The ACQ-5 score is the mean of the 5 questions and therefore between 0 (totally controlled) and 6 (severely uncontrolled).	after 4 weeks (Day 29) and after 8 weeks (Day 57)	No
Secondary	Morning and Evening Peak Expiratory Flow Rate (PEFR) Over 12 Weeks of Treatment. This is LS Mean of the Treatment Period.	PEFR is measured with portable spirometer by participants every morning and evening at home.	baseline, 4weeks, 8 weeks and 12 weeks	No
Secondary	The Usage of Rescue Medication (Short Acting ß2-agonist) Over 12 Weeks of Treatment	Participants record the number of puffs of rescue medication taken in the previous 12 hours in the morning and nighttime.	12 weeks	No
Secondary	Asthma Quality of Life Questionnaire (AQLQ(S)) After 4 Weeks (Day 29) and 12 Weeks (Day 85) of Treatment	The AQLQ is a 32-item disease specific questionnaire designed to measure functional impairments in asthma. Patients are asked to score each item on a 7-point scale based on the experience of last 2 weeks. The overall AQLQ score is the mean response to all 32 questions. Therefore, the possible highest score (better) would be 7 and the lowest (worse) would be 1. Changes in scores of 0.5 to 1.0 are considered clinically meaningful; 1.0 to 1.5 as moderate and > 1.5 as marked clinically important differences for any individual domain or for the overall summary score.	4 Weeks, 12 Weeks	No
Secondary	Time to First Asthma Exacerbation (Mild, Moderate, Severe, Moderate or Severe and Any) Over the 12 Week Treatment Period	Duration of treatment until first asthma exacerbation by severity of exacerbation. A severe asthma exacerbation is systemic corticosteroids (SCS) use =3 days and hospitalization or emergency department visit (greater than 24 h) or death due to asthma. A moderate asthma exacerbation is SCS use =3 days either as an outpatient or in emergency department visits (less than or equal to 24 h). Worsening of asthma not requiring more than 3 days of SCS or hospitalization/emergency room will be considered mild asthma exacerbations.	12 weeks	No
Secondary	The Annual Rate of Asthma Exacerbations (Mild, Moderate, Severe, Moderate or Severe and Any) Over the 12 Week Treatment Period	Annual incidence rate of asthma exacerbation by severity of exacerbation. The number of asthma exacerbation is used to calculate annual incidence rate. A severe asthma exacerbation is SCS use =3 days and hospitalization or emergency department visit (greater than 24 h) or death due to asthma. A moderate asthma exacerbation is SCS use =3 days either as an outpatient or in emergency department visits (less than or equal to 24 h). Worsening of asthma not requiring more than 3 days of SCS or hospitalization/emergency room will be considered mild asthma exacerbations. Number of the asthma exacerbation will be analyzed by the negative binomial regression including treatment, history of asthma exacerbation in the 12 months prior to screening and region as factors and FEV1 prior to inhalation and FEV1 30 min post inhalation of salbutamol/albuterol (components of SABA reversibility) as covariates. The estimates are obtained from the model and so we cannot specify a formula.	12 weeks	No
Secondary	Duration of Asthma Exacerbations (Mild, Moderate, Severe, Moderate or Severe and Any) Over the 12 Week Treatment Period	Duration of asthma exacerbations by severity of exacerbation. A severe asthma exacerbation is SCS use =3 days and hospitalization or emergency department visit (greater than 24 h) or death due to asthma. A moderate asthma exacerbation is SCS use =3 days either as an outpatient or in emergency department visits (less than or equal to 24 h). Worsening of asthma not requiring more than 3 days of SCS or hospitalization/emergency room will be considered mild asthma exacerbations.	12 weeks	No
Secondary	The Percentage of Patients With at Least One Asthma Exacerbation (Mild, Moderate, Severe, Moderate or Severe and Any) Over the 12 Week Treatment Period	The percentage of patients with at least one asthma exacerbation by severity of exacerbation. A severe asthma exacerbation is SCS use =3 days and hospitalization or emergency department visit (greater than 24 h) or death due to asthma. A moderate asthma exacerbation is SCS use =3 days either as an outpatient or in emergency department visits (less than or equal to 24 h). Worsening of asthma not requiring more than 3 days of SCS or hospitalization/emergency room will be considered mild asthma exacerbations.	12 weeks	No
Secondary	Time to Permanent Study Discontinuation Due to Asthma Exacerbation Over the 12 Week Treatment Period	Time to permanent study discontinuation due to asthma exacerbation. A severe asthma exacerbation is SCS use =3 days and hospitalization or emergency department visit (greater than 24 h) or death due to asthma. A moderate asthma exacerbation is SCS use =3 days either as an outpatient or in emergency department visits (less than or equal to 24 h). Worsening of asthma not requiring more than 3 days of SCS or hospitalization/emergency room will be considered mild asthma exacerbations.	12 weeks	No
Secondary	The Percentage of Patients Who Permanently Discontinued Study Due to Asthma Exacerbation Over the 12 Week Treatment Period	The percentage of patients who permanently discontinued study due to asthma exacerbation. A severe asthma exacerbation is SCS use =3 days and hospitalization or emergency department visit (greater than 24 h) or death due to asthma. A moderate asthma exacerbation is SCS use =3 days either as an outpatient or in emergency department visits (less than or equal to 24 h). Worsening of asthma not requiring more than 3 days of SCS or hospitalization/emergency room will be considered mild asthma exacerbations.	12 weeks	No
Secondary	Total Amounts (in Doses) of Systemic Corticosteroids Used to Treat Asthma Exacerbations Over the 12 Week Treatment Period	Total amounts (in doses) of systemic corticosteroids (SCS) used to treat asthma exacerbations.SCS includes Intramuscular (IM), Intravenous (IV) and Oral. A severe asthma exacerbation is SCS use =3 days and hospitalization or emergency department visit (greater than 24 h) or death due to asthma. A moderate asthma exacerbation is SCS use =3 days either as an outpatient or in emergency department visits (less than or equal to 24 h). Worsening of asthma not requiring more than 3 days of SCS or hospitalization/emergency room will be considered mild asthma exacerbations.	12 weeks	No
Secondary	Plasma Indacaterol Concentrations at Day 1 and Day 14	Maximum plasma concentration after drug administration (Cmax) was measured for indacaterol acetate 75 µg and indacaterol acetate 150 µg for Pharmacokinetic (PK) Subgroup	Day 1 and Day 14	No