Study of QMF149 (150/80 µg) Compared With MF Twisthaler® (200 µg) in Patients With Asthma

Mild Asthma Clinical Trial

Official title:

A Multi-center, Randomized, 12-week Treatment, Doubleblind Study to Assess the Efficacy and Safety of QMF149 (150/80 Microgram) Compared With MF Twisthaler® (200 Microgram) in Adult and Adolescent Patients With Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02892344
• Other study ID #: CQVM149B2303
• Secondary ID: 2016-000472-22
• Status: Completed
• Phase: Phase 3
• Start date: January 16, 2017
• Est. completion date: November 30, 2018

Study information

• Verified date: October 2021
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the trial was to evaluate efficacy and safety of QMF149 150/80 microgram o.d. delivered via Concept1 compared to MF 200 microgram o.d., delivered via Twisthaler® in terms of lung function and symptom control in poorly (ie inadequately) controlled asthma patients. This study was to assess contribution of LABA as an add-on therapy to low dose ICS monotherapy.

Description:

The primary objective of this study was to demonstrate the superiority of QMF149 150/80 microgram o.d. (in the evening) delivered via Concept1 compared with MF 200 microgram o.d. (in the evening) delivered via Twisthaler® in terms of trough FEV1 after 12 weeks of treatment in adults and adolescents. The key secondary objective of this study was to demonstrate the superiority of QMF149 150/80 microgram to MF 200 microgram o.d. in terms of ACQ-7 after 12 weeks of treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 802
• Est. completion date: November 30, 2018
• Est. primary completion date: November 5, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 75 Years

Eligibility

Inclusion Criteria:

• Patients with a documented diagnosis of asthma for a period of at least 3 months prior to Screening Visit
• Patients who have used low dose ICS , with or without controller (ie, LABA, Leukotriene Receptor Antagonist ) at stable dose for at least 1 month prior to Screening Visit
• Adult patients who are symptomatic at screening despite treatment with existing therapy. Patients with ACQ-7 score = 1.5 at Visit 101 and at Visit 102 (inadequately controlled).
• Adolescent patients :
• If taking only ICS (without LABA) and are symptomatic at screening despite treatment with low doses of ICS. These patients must have ACQ-7 score = 1.5 at Visit 101 and at Visit 102 .
• If taking ICS (low dose)/ LABA, and have ACQ-7 score =1 and <1.5 at Visit 101: they must have ACQ-7 score=1.5 at Visit 102 ( prior to randomization).
• Pre-bronchodilator FEV1= 60 % and < 90 % of the predicted normal value for the patient after withholding bronchodilators at both Visits 101 and 102
• Patients who demonstrate an increase in FEV1 of 12% and = 200 mL within 30 minutes after administration of 400 microgram salbutamol/360 microgram albuterol (or equivalent dose) at Visit 101.

Exclusion Criteria:

• Patients who have smoked or inhaled tobacco products (including electronic cigarettes) within the 6 month period prior to Visit 1, or who have a smoking history of greater than or equal to 10 pack year.
• Patients who have had an asthma attack/exacerbation requiring systemic steroids or

hospitalization (> 24 hours) or emergency room visit (= 24 hours) as follows:

• For adults: within 6 weeks of Screening Visit. If patients experience an asthma attack/exacerbation requiring systemic steroids or emergency room visit between Visit 1 and Visit 102 they may be re-screened 6 weeks after recovery from the exacerbation
• For adolescents: Severe asthma attack/exacerbation requiring systemic corticosteroids in the last 6 months, OR hospitalization (> 24 hours) due to severe asthma attack/exacerbation requiring systemic corticosteroids in the last 6 months, OR emergency room visit (= 24 hours) due to severe asthma attack/exacerbation requiring systemic corticosteroids within the last 6 months.
• Patients who ever required intubation for a severe asthma attack/exacerbation
• Patients with a clinical condition (eg. glaucoma, cataract and fragility fractures) which may be worsened by ICS administration (according to investigator's medical judgment )
• Patients who have had a respiratory tract infection or asthma worsening within 4 weeks prior to Screening Visit or between Visit 1and Visit 102. Patients may be re-screened 4 weeks after recovery from their respiratory tract infection or asthma worsening.
• Patients with any chronic conditions affecting the upper respiratory tract (eg. chronic sinusitis) which in the opinion of the investigator may interfere with the study.
• Patients with a history of chronic lung diseases other than asthma, including (but not limited to) COPD, sarcoidosis, interstitial lung disease, cystic fibrosis, clinically significant bronchiectasis and active tuberculosis.
• Patients with Type I diabetes or uncontrolled Type II diabetes.
• Patients with narcolepsy and/or insomnia.
• Patients on Maintenance Immunotherapy (desensitization) for allergies or less than 3 months prior to Visit 101 or patients on Maintenance Immunotherapy for more than 3 months prior to Visit 101 but expected to change throughout the course of the study.
• Patients with diagnosed rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption or with known intolerance to lactose or milk products.
• Patients who use a long acting muscarinic antagonist (LAMA) within 3 months prior to Visit 1.

Related Conditions & MeSH terms

• Asthma
• Mild Asthma

Intervention

Drug:
• QMF149 150/80 µg
QMF149 150/80 µg o.d via Concept1
• MF 200 µg
MF 200 µg o.d. via Twisthaler®

Locations

Country	Name	City	State
Bulgaria	Novartis Investigative Site	Bulgaria
Bulgaria	Novartis Investigative Site	Pleven
Bulgaria	Novartis Investigative Site	Stara Zagora
Chile	Novartis Investigative Site	Santiago	Region Metropolitana
Chile	Novartis Investigative Site	Santiago
Chile	Novartis Investigative Site	Santiago
Chile	Novartis Investigative Site	Vina del Mar
Colombia	Novartis Investigative Site	Bogota	Cundinamarca
Colombia	Novartis Investigative Site	Bogota
Colombia	Novartis Investigative Site	Bucaramanga
Colombia	Novartis Investigative Site	Medellin
Colombia	Novartis Investigative Site	Medellin	Antioquia
Estonia	Novartis Investigative Site	Kohtla-Jarve
Estonia	Novartis Investigative Site	Tallinn
Estonia	Novartis Investigative Site	Tartu
Germany	Novartis Investigative Site	Bad Woerishofen
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Bochum
Germany	Novartis Investigative Site	Darmstadt
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Gauting
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Landsberg
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Lubeck
Germany	Novartis Investigative Site	Mainz
Germany	Novartis Investigative Site	Marburg
Hungary	Novartis Investigative Site	Cegled
Hungary	Novartis Investigative Site	Godollo
Hungary	Novartis Investigative Site	Gyor	HUN
Hungary	Novartis Investigative Site	Szarvas
Hungary	Novartis Investigative Site	Szazhalombatta	HUN
Hungary	Novartis Investigative Site	Szeged
Hungary	Novartis Investigative Site	Torokbalint	Pest
India	Novartis Investigative Site	Ahmedabad	Gujarat
India	Novartis Investigative Site	Bangalore	Karnataka
India	Novartis Investigative Site	Bikaner	Rajasthan
India	Novartis Investigative Site	Cherthala	Kerala
India	Novartis Investigative Site	Coimbatore	Tamil Nadu
India	Novartis Investigative Site	Hubli	Karnataka
India	Novartis Investigative Site	Hyderabad	Telangana
India	Novartis Investigative Site	Mumbai	Maharashtra
India	Novartis Investigative Site	Mysore	Karnataka
India	Novartis Investigative Site	Nagpur	Maharashtra
India	Novartis Investigative Site	Vadodara	Gujarat
India	Novartis Investigative Site	Varanasi	Uttar Pradesh
Italy	Novartis Investigative Site	Cassano delle Murge	BA
Italy	Novartis Investigative Site	Firenze	FI
Italy	Novartis Investigative Site	Fiumicino	RM
Italy	Novartis Investigative Site	Genova
Italy	Novartis Investigative Site	Roma
Japan	Novartis Investigative Site	Chuo ku	Tokyo
Japan	Novartis Investigative Site	Chuo-ku	Tokyo
Japan	Novartis Investigative Site	Setagaya-ku	Tokyo
Japan	Novartis Investigative Site	Shinjuku-ku	Tokyo
Japan	Novartis Investigative Site	Toshima-ku	Tokyo
Korea, Republic of	Novartis Investigative Site	Anyang si	Gyeonggi Do
Korea, Republic of	Novartis Investigative Site	Bucheon-Si	Gyeonggi-Do
Korea, Republic of	Novartis Investigative Site	Busan
Korea, Republic of	Novartis Investigative Site	Hwaseong si	Gyeonggi Do
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Seocho Gu
Korea, Republic of	Novartis Investigative Site	Suwon si	Gyeonggi Do
Latvia	Novartis Investigative Site	Daugavpils
Latvia	Novartis Investigative Site	Jurmala	LVA
Latvia	Novartis Investigative Site	Riga	LV
Latvia	Novartis Investigative Site	Riga
Latvia	Novartis Investigative Site	Riga
Latvia	Novartis Investigative Site	Riga
Lithuania	Novartis Investigative Site	Vilnius
Lithuania	Novartis Investigative Site	Vilnius
Malaysia	Novartis Investigative Site	Alor Setar	Kedah
Malaysia	Novartis Investigative Site	Kuala Terengganu	Terengganu
Malaysia	Novartis Investigative Site	Putrajaya
Malaysia	Novartis Investigative Site	Taiping	Perak
Peru	Novartis Investigative Site	Cusco
Peru	Novartis Investigative Site	Lima
Peru	Novartis Investigative Site	Lima
Peru	Novartis Investigative Site	Piura
Peru	Novartis Investigative Site	Santiago de Surco	Lima
Philippines	Novartis Investigative Site	Iloilo city	Iloilo
Philippines	Novartis Investigative Site	Manila
Philippines	Novartis Investigative Site	Quezon City
Poland	Novartis Investigative Site	Bialystok
Poland	Novartis Investigative Site	Biaystok
Poland	Novartis Investigative Site	Grudziadz
Poland	Novartis Investigative Site	Katowice
Russian Federation	Novartis Investigative Site	Ekaterinburg
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Rostov-on-Don
Russian Federation	Novartis Investigative Site	Saint-Petersburg
Russian Federation	Novartis Investigative Site	St Petersburg
Russian Federation	Novartis Investigative Site	St.Petersburg
Slovakia	Novartis Investigative Site	Banska Bystrica	SVK
Slovakia	Novartis Investigative Site	Bardejov	Slovak Republic
Slovakia	Novartis Investigative Site	Bojnice	Slovak Republic
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Cadca
Slovakia	Novartis Investigative Site	Humenne	Slovak Republic
Slovakia	Novartis Investigative Site	Liptovsky Hradok	Slovak Republic
Slovakia	Novartis Investigative Site	Poprad	SVK
Slovakia	Novartis Investigative Site	Presov
Slovakia	Novartis Investigative Site	Sabinov
Slovakia	Novartis Investigative Site	Spisska Nova Ves	Slovak Republic
Slovakia	Novartis Investigative Site	Stropkov	Slovak Republic
Slovakia	Novartis Investigative Site	Zvolen
South Africa	Novartis Investigative Site	Belleville
South Africa	Novartis Investigative Site	Brandfort	Free State
South Africa	Novartis Investigative Site	Cape Town
South Africa	Novartis Investigative Site	Cape Town	ZAF
South Africa	Novartis Investigative Site	Middelburg	Mpumalanga
South Africa	Novartis Investigative Site	Panorama
Sweden	Novartis Investigative Site	Linkoping	Ostergotlands Lan
Sweden	Novartis Investigative Site	Stockholm
Sweden	Novartis Investigative Site	Uppsala
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Chiang Mai
Thailand	Novartis Investigative Site	Khon Kaen	THA
Vietnam	Novartis Investigative Site	Hai Phong
Vietnam	Novartis Investigative Site	Ho Chi Minh	VNM

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Bulgaria,  Chile,  Colombia,  Estonia,  Germany,  Hungary,  India,  Italy,  Japan,  Korea, Republic of,  Latvia,  Lithuania,  Malaysia,  Peru,  Philippines,  Poland,  Russian Federation,  Slovakia,  South Africa,  Sweden,  Thailand,  Vietnam, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Trough FEV1	demonstrate the superiority of QMF149 150/80 microgram o.d. (in the evening) delivered via Concept1 compared with MF 200 microgram o.d. (in the evening) delivered via Twisthaler® in terms of trough FEV1 after 12 weeks of treatment in adults and adolescents. 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 by spirometry.	week 12
Secondary	ACQ-7	ACQ-7 is an asthma control questionnaire (scoring 5 symptoms, FEV1 entered by the investigator and daily rescue bronchodilator use entered by the patient) validated to evaluate different levels of asthma control. the ACQ-7 was used to assess improvements in asthma symptom control. The ACQ-7, a seven-item disease-specific instrument developed and validated to assess asthma control in patients in clinical trials as well as in individuals in clinical practice, was provided to the site. All seven items were then scored on a 7-point Likert scale, with 0 indicating total control and 6 indicating no control. The questions were equally weighted and the total score was the mean of the seven items. The first 6 questions of the ACQ-7 were completed by the patient while the last question (question 7) was completed by the study investigator using spirometry data generated by the spirometry equipment.	week 12
Secondary	Trough FEV1 at Day 2	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	Day 2
Secondary	Pre-dose FEV1 at Week 4	Pre-dose FEV1 is defined as the mean of -45 min and -15 min FEV1 values pre-evening dose	week 4
Secondary	FVC Over 12 Weeks	FVC is the total amount of air exhaled during the FEV test. Forced Vital Capacity (FVC) and Forced Expiratory Flow between 25% and 75% of FVC (FEF25-75) will be measured	week 12
Secondary	PEF Over 4 and 12 Weeks	Morning and Evening Peak Expiratory Flow Rate (PEF) will be measured. PEF is the peak expiratory flow, the maximum speed of expiration	week 12
Secondary	Percentage of Patients With ACQ-7 MID at Week 12	MID is Minimum Important Difference. ACQ-7 is an asthma control questionnaire (scoring 5 symptoms, FEV1 entered by the investigator and daily rescue bronchodilator use entered by the patient) validated to evaluate different levels of asthma control. Percent of patients achieving the minimal important difference (MID) in ACQ-7 (i.e. at least 0.5 decrease from baseline) will be measured.	week 12
Secondary	Daily E-diary Over 12 Weeks	Percentage of asthma symptoms free days, the percentage of nights without nighttime awakenings, and the percentage of mornings without symptoms on awakening as recorded by daily electronic Diary (e-Diary) over 12 weeks of treatment	week 12
Secondary	ACQ-7 at Week 4	ACQ-7 is an asthma control questionnaire (scoring 5 symptoms, FEV1 entered by the investigator and daily rescue bronchodilator use entered by the patient) validated to evaluate different levels of asthma control	week 4
Secondary	Rescue Medication Use Over 12 Weeks	Rescue salbutamol/albuterol usage (mean daily, nighttime and daytime use) from e-Diary recordings over 12 weeks of treatment	week 12
Secondary	Percentage of Rescue Medication Free Days Over 12 Weeks	Percentage of rescue medication free days over 12 weeks of treatment period	week 12
Secondary	Quality of Life Assessed by Asthma Quality of Life Questionnaire AQLQ-S 12	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.	week 12
Secondary	Number of Patients With Asthma Exacerbation Over 12 Weeks	The exacerbation categories are: mild, moderate, severe and the combination of moderate or severe. Time to first asthma exacerbation by exacerbation category. Annual rate of asthma exacerbations by exacerbation category.	Week 12
Secondary	The Number of Asthma Exacerbations (Moderate or Severe) 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 (Systemic Corticosteroids) 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	Week 12
Secondary	Number of Patients With First Asthma Exacerbations (Moderate or Severe) Over the 12 Week Treatment Period	The annual rate of asthma exacerbations were analyzed using a generalized linear model.	Week 12

External Links

•   A Plain Language Trial Summary is available on novartisclinicaltrials.com