Safety and Efficacy of Mometasone Furoate Delivered Via Concept1 Device or Twisthaler® Device in Adult and Adolescent Patients With Persistent Asthma

Asthma Clinical Trial

Official title:

A Randomized, Double-blind, Double-dummy, 4-week Treatment, Parallel-group Study to Evaluate the Efficacy and Safety of Two Doses of Mometasone Furoate Delivered Via Concept1 or Twisthaler® in Adult and Adolescent Patients With Persistent Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01555151
• Other study ID #: CQMF149E2201
• Secondary ID: 2011-005100-14
• Status: Completed
• Phase: Phase 2
• First received: March 13, 2012
• Last updated: April 10, 2015
• Start date: July 2012
• Est. completion date: July 2013

Study information

• Verified date: April 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health ProductsCanada: Health CanadaEstonia: The State Agency of MedicineGermany: Federal Institute for Drugs and Medical DevicesHungary: National Institute for Quality - and Organizational Development in Healthcare and Medicines/National Institute of PharmacyIndia: Drugs Controller General of IndiaJapan: Pharmaceuticals and Medical Devices AgencyLatvia: State Agency of MedicinesLithuania: State Medicine Control Agency - Ministry of HealthNetherlands: Medicines Evaluation Board (MEB)Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsRussia: Expert Board (FSBI Scientific Center of Medical Application Expertise of Ministry of Health and Social Development of the Russian Federation)Slovakia: State Institute for Drug ConThailand: Food and Drug AdministrationTurkey: Ministry of HealthUkraine: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare the efficacy, safety and pharmacokinetics of Mometasone furoate delivered via Concept1 device or Twisthaler® device in adult and adolescent patients with persistent asthma.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 739
• Est. completion date: July 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• Males or females who were = 12 years old at the time informed consent was obtained

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

• Patients who were receiving ICS treatment up to the maximum dose per day as indicated in the corresponding package leaflet and also a stable ICS regimen for at least 4 weeks prior to screening (Visit 2).

• Patients whose level of asthma control according to GINA 2010 guideline was "Partly Controlled" or "Uncontrolled" at screening (Visit 2).

• Patients with a pre-bronchodilator FEV1 value of = 80% of predicted normal value at screening (Visit 2).

• Patients who demonstrated an increase of = 12% and 200 mL in FEV1 over prebronchodilator value within 30 minutes after inhalation of 400 µg of salbutamol (360 µg of albuterol) at Visit 2 or between Visit 2 and Visit 5.

• Patients who were confirmed as "ICS sensitive" by ACQ-5 and FEV1 at Visit 5.

Key exclusion criteria included:

• Patients diagnosed with COPD as defined by the Global Initiative for Chronic Obstructive Lung Disease, updated 2010.

• Patients with concomitant pulmonary disease, pulmonary tuberculosis (unless confirmed by chest X-ray to be no longer active), or clinically significant bronchiectasis.

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

• Patients with seasonal allergy which is likely to deteriorate his/her asthma condition during the study period judged by the investigator.

• Patients who have had a severe asthma attack/exacerbation requiring hospitalization in the 6 months prior to Visit 1 or any time between Visit 1 and Visit 5 must discontinue from the trial (screening failure).

• Patients who have had an emergency room visit for an asthma attack/exacerbation within 4 weeks prior to Visit 1 or any time between Visit 1 and Visit 5 must discontinue from the trial (screening failure).

• Patients who have ever required intubation for a severe asthma attack/exacerbation.

• Patients who have had a respiratory tract infection within 6 weeks prior to Visit 1, or any time between Visit 1 and Visit 5 must discontinue from the trial (screening failure).

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:
• Mometasone furoate
Mometasone furoate (MF) 80 µg once daily delivered via Concept1 device; MF 200 µg once daily delivered via Concept1 device; MF 320µg once daily delivered via Twisthaler® device or 800 µg once daily delivered via Twisthaler® device

Device:
• Concept 1
A single dose dry powder inhaler (SDDPI)
• Twisthaler
A single dose dry powder inhaler (SDDPI)

Locations

Country	Name	City	State
Belgium	Novartis Investigative Site	Kortrijk
Belgium	Novartis Investigative Site	Liège
Canada	Novartis Investigative Site	Mirabel	Quebec
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Niagara Falls	Ontario
Canada	Novartis Investigative Site	Quebec
Canada	Novartis Investigative Site	Trois-Rivières	Quebec
Canada	Novartis Investigative Site	Windsor	Ontario
Estonia	Novartis Investigative Site	Kohtla-Järve
Estonia	Novartis Investigative Site	Tallinn
Estonia	Novartis Investigative Site	Tartu
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Goch
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Luebeck
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Reinfeld
Germany	Novartis Investigative Site	Schwerin
Hungary	Novartis Investigative Site	Baja
Hungary	Novartis Investigative Site	Balassagyarmat
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Cegled
Hungary	Novartis Investigative Site	Debrecen
Hungary	Novartis Investigative Site	Godollo
Hungary	Novartis Investigative Site	Gyor
Hungary	Novartis Investigative Site	Gyula
Hungary	Novartis Investigative Site	Kistelek
Hungary	Novartis Investigative Site	Komarom
Hungary	Novartis Investigative Site	Makó
Hungary	Novartis Investigative Site	Mohacs
Hungary	Novartis Investigative Site	Monor
Hungary	Novartis Investigative Site	Mosonmagyarovar
Hungary	Novartis Investigative Site	Nagykanizsa
Hungary	Novartis Investigative Site	Nyiregyhaza
Hungary	Novartis Investigative Site	Százhalombatta
Hungary	Novartis Investigative Site	Szeged
Hungary	Novartis Investigative Site	Szikszo
Hungary	Novartis Investigative Site	Szombathely
Hungary	Novartis Investigative Site	Torokbalint
India	Novartis Investigative Site	Bangalore	Karnataka
India	Novartis Investigative Site	Bangalore	Karnataka
India	Novartis Investigative Site	Bangalore	Karnataka
India	Novartis Investigative Site	Coimbatore	Tamil Nadu
India	Novartis Investigative Site	Jaipur
India	Novartis Investigative Site	Karamsad
India	Novartis Investigative Site	Ludhiana
India	Novartis Investigative Site	Mysore	Karnataka
India	Novartis Investigative Site	Nagpur
India	Novartis Investigative Site	Pune	Maharashtra
India	Novartis Investigative Site	Thrissur
India	Novartis Investigative Site	Vellore	Tamil Nadu
Japan	Novartis Investigative Site	Chiyoda-ku	Tokyo
Japan	Novartis Investigative Site	Chuo-ku	Tokyo
Japan	Novartis Investigative Site	Chuo-ku	Tokyo
Japan	Novartis Investigative Site	Fukuyama-shi	Hiroshima
Japan	Novartis Investigative Site	Hachioji-city	Tokyo
Japan	Novartis Investigative Site	Kawasaki-shi	Kanagawa
Japan	Novartis Investigative Site	Kitahiroshima-shi	Hokkaido
Japan	Novartis Investigative Site	Kobe-shi	Hyogo
Japan	Novartis Investigative Site	Kurashiki-city	Okayama
Japan	Novartis Investigative Site	Kurashiki-shi	Okayama
Japan	Novartis Investigative Site	Mizunami-city	Gifu
Japan	Novartis Investigative Site	Obihiro-shi	Hokkaido
Japan	Novartis Investigative Site	Obihiro-shi	Hokkaido
Japan	Novartis Investigative Site	Osaka-city	Osaka
Japan	Novartis Investigative Site	Sakai-city	Osaka
Japan	Novartis Investigative Site	Sapporo-shi	Hokkaido
Japan	Novartis Investigative Site	Sapporo-shi	Hokkaido
Japan	Novartis Investigative Site	Shinagawa-ku	Tokyo
Japan	Novartis Investigative Site	Suita	Osaka
Japan	Novartis Investigative Site	Tachikawa	Tokyo
Japan	Novartis Investigative Site	Tomakomai	Hokkaido
Japan	Novartis Investigative Site	Toon-shi	Ehime
Japan	Novartis Investigative Site	Toshima-ku	Tokyo
Japan	Novartis Investigative Site	Toyonaka-city	Osaka
Latvia	Novartis Investigative Site	Rezekne	LV
Latvia	Novartis Investigative Site	Riga	LV
Latvia	Novartis Investigative Site	Riga
Latvia	Novartis Investigative Site	Riga
Latvia	Novartis Investigative Site	Riga
Latvia	Novartis Investigative Site	Talsi	LV
Lithuania	Novartis Investigative Site	Kaunas	LT
Lithuania	Novartis Investigative Site	Kaunas
Lithuania	Novartis Investigative Site	Klaipeda
Lithuania	Novartis Investigative Site	Klaipeda	LT
Lithuania	Novartis Investigative Site	Vilnius
Malaysia	Novartis Investigative Site	Kota Kinabalu
Malaysia	Novartis Investigative Site	Kuala Lumpur
Malaysia	Novartis Investigative Site	Kuching	Sarawak
Netherlands	Novartis Investigative Site	Almere	The Netherlands
Netherlands	Novartis Investigative Site	Eindhoven	The Netherlands
Netherlands	Novartis Investigative Site	Geleen
Netherlands	Novartis Investigative Site	Hoofddorp
Netherlands	Novartis Investigative Site	Leiderdorp	The Netherlands
Netherlands	Novartis Investigative Site	Rotterdam	The Netherlands
Netherlands	Novartis Investigative Site	Zoetermeer	The Netherlands
Poland	Novartis Investigative Site	Bialystok
Poland	Novartis Investigative Site	Gdansk
Poland	Novartis Investigative Site	Katowice
Poland	Novartis Investigative Site	Krakow
Poland	Novartis Investigative Site	Krakow
Poland	Novartis Investigative Site	Lodz
Poland	Novartis Investigative Site	Poznan
Poland	Novartis Investigative Site	Skierniewice
Poland	Novartis Investigative Site	Warszawa
Poland	Novartis Investigative Site	Wroclaw
Russian Federation	Novartis Investigative Site	Ekaterinburg	Russia
Russian Federation	Novartis Investigative Site	Kazan	Russia
Russian Federation	Novartis Investigative Site	Moscow	Russia
Russian Federation	Novartis Investigative Site	Sankt-Peterburg	Russia
Russian Federation	Novartis Investigative Site	St. Petersburg	Russia
Russian Federation	Novartis Investigative Site	St. Petersburg	Nizhny Novgorod
Russian Federation	Novartis Investigative Site	Yaroslavl
Slovakia	Novartis Investigative Site	Bojnice	Slovak Republic
Slovakia	Novartis Investigative Site	Bratislava	Slovak Republic
Slovakia	Novartis Investigative Site	Bratislava	Slovak Republic
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Kosice	Slovak Republic
Slovakia	Novartis Investigative Site	Levice	Slovak republic
Slovakia	Novartis Investigative Site	Liptovsky Hradok	Slovak Republic
Slovakia	Novartis Investigative Site	Martin
Slovakia	Novartis Investigative Site	Nitra	Slovak Republic
Slovakia	Novartis Investigative Site	Poprad
Slovakia	Novartis Investigative Site	Roznava	Slovak Republic
Slovakia	Novartis Investigative Site	Ruzomberok
Slovakia	Novartis Investigative Site	Surany	Slovak Republic
Slovakia	Novartis Investigative Site	Trencin	Slovak Republic
Thailand	Novartis Investigative Site	Muang
Thailand	Novartis Investigative Site	Muang
Thailand	Novartis Investigative Site	Rajathevee
Thailand	Novartis Investigative Site	Ratchathewi
Turkey	Novartis Investigative Site	Adana
Turkey	Novartis Investigative Site	Bursa
Turkey	Novartis Investigative Site	Gaziantep
Turkey	Novartis Investigative Site	Istanbul
Turkey	Novartis Investigative Site	Izmir
Turkey	Novartis Investigative Site	Izmir
Turkey	Novartis Investigative Site	Talas / Kayseri
Ukraine	Novartis Investigative Site	Dnipropetrovsk
Ukraine	Novartis Investigative Site	Dnipropetrovsk
Ukraine	Novartis Investigative Site	Donetsk
Ukraine	Novartis Investigative Site	Kharkiv
Ukraine	Novartis Investigative Site	Kharkiv
Ukraine	Novartis Investigative Site	Kharkiv
Ukraine	Novartis Investigative Site	Kyiv
Ukraine	Novartis Investigative Site	Kyiv
Ukraine	Novartis Investigative Site	Kyiv
Ukraine	Novartis Investigative Site	Kyiv
Ukraine	Novartis Investigative Site	Vinnytsia
Ukraine	Novartis Investigative Site	Vinnytsia

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Belgium,  Canada,  Estonia,  Germany,  Hungary,  India,  Japan,  Latvia,  Lithuania,  Malaysia,  Netherlands,  Poland,  Russian Federation,  Slovakia,  Thailand,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Trough Forced Expiratory Volume in 1 Second (FEV1)	Forced Expiratory Volume in 1 second (FEV1) was measured via spirometry conducted according to internationally accepted standards. Measurements were taken on day 29 after treatment.	Day 29	No
Secondary	Trough Forced Expiratory Volume in 1 Second (FEV1) After Days 8, 15 and 22 of Treatment	Forced Expiratory Volume in 1 second (FEV1) was measured via spirometry conducted according to internationally accepted standards. Measurements were taken on days 8, 15 and 22 after treatment. Data within 6 hr of rescue medication use is excluded from this analysis.	Days 8, 15 and 22	No
Secondary	Forced Vital Capacity (FVC) at All Time Points	Forced Vital Capacity (FVC) is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Data within 6 hr of rescue medication use is excluded from this analysis. Mixed model: FVC = treatment + gender+ baseline FVC + age + level of asthma control + region + center (region) + error. Center is included as a random effect nested within region.	Days 1, 8, 15, 22, 28 and 29 at all time points	No
Secondary	Forced Expiratory Flow Between 25% and 75% (FEF25-75%) at All Time Points	The Forced Expiratory Flow (FEF) 25%-75% measurement describes the amount of air expelled from the lungs during the middle half (25% - 75%) of the forced vital capacity test and is measured using spirometry.	Days 1, 8, 15, 22, 28 and 29 at all time points	No
Secondary	Forced Expiratory Volume in 1 Second Forced Vital Capacity (FEV1/FVC) Percent at All Time Points	Forced Expiratory Volume in 1 second (FEV1)/Forced Vital Capacity (FVC) was measured via spirometry conducted according to internationally accepted standards. Data within 6 hr of rescue medication use is excluded from this analysis.	Days 1, 8, 15, 22, 28 and 29 at all time points	No
Secondary	Change From Baseline in Mean Morning and Evening Peak Expiratory Flow Rate (PEFR) Over 4 Weeks of Treatment	Peak expiratory flow rate (PEFR) was measured via electronice Peak flow meter by patient at home. Mixed model used: change from baseline in the mean evening PEFR = treatment + age + gender + baseline evening PEFR + level of asthma control + region + center (region)+ error. Center is included as a random effect nested within region.	Baseline and week 4	No
Secondary	Change From Baseline in Asthma Control Questionnaire (ACQ-5) by Visit	Asthma symptoms were evaluated by the Asthma Control Questionnaire (ACQ). The ACQ-5 has five questions of the asthma symptoms to be answered by the patient. The overall score is the average of the 5 questions; a minimum overall score of 0 = good control of asthma whereas a maximum overall score of 6 = poor control of asthma. 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. - Baseline ACQ-5 is defined as the questionnaire completed on Day 1 (randomization).	Baseline, days 8,15,22 and 29	No
Secondary	Change From Baseline in Mean Daily Number of Puffs of Rescue Medication Over 4 Weeks of Treatment	Rescue medication data recorded during the 14 day run-in period is used to calculate the baseline. - Total number of puffs of rescue medication per day over the full 4 weeks is calculated and divided by the total number of days with non-missing rescue medication data to derive the mean daily number of puffs of rescue medication taken for the subject. - MIXED model: Change = treatment + gender + baseline mean daily number of puffs + age + level of asthma control + region + center (region) + error. Center is included as a random effect nested within region.	Baseline and 4 weeks	No
Secondary	Percentage of Days With no Rescue Medication Use Over 4 Weeks of Treatment	Mixed model used: percentage of days with no rescue medication use = treatment + age + gender + baseline percentage of days with no rescue use + level of asthma control + region + center (region) + error. Center is included as a random effect nested within region.; A day with no rescue use is defined from diary data as any day where the subject does not use any puffs of rescue medication.; The total number of days with no rescue use over the 4 week treatment period is divided by the total number of evaluable days in order to derive the percentage of days with no rescue use.	4 weeks	No
Secondary	Fractional Exhaled Nitric Oxide (FeNO)	FeNO is widely accepted as a non-invasive marker for airway inflammation such as asthma and conducted according to published guideline. FeNO was measured on days 15 and 29 after treatment.	Days 15 and 29	No
Secondary	Plasma Cortisol Concentrations	Blood samples were taken from each subject participating in the study post dose at day 1 and week 4. Cortisol concentrations were evaluated. Results are presented as nmol/L	Baseline, days 1 and 28	Yes