A multicenter, randomized, double-blind, double dummy, placebo controlled crossover study, to investigate the 24 hour FEV1 profile of a single dose of QMF Twisthaler® (500/400 µg o.d.) delivered in the evening in adult patients with persistent asthma using fluticasone propionate/salmeterol (250/50 µg b.i.d.) as an active control.

• Register: EUCTR
• Last refreshed on: 27 October 2014
• Main ID: EUCTR2007-003192-39-BE
• Date of registration: 30/08/2007
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A multicenter, randomized, double-blind, double dummy, placebo controlled crossover study, to investigate the 24 hour FEV1 profile of a single dose of QMF Twisthaler® (500/400 µg o.d.) delivered in the evening in adult patients with persistent asthma using fluticasone propionate/salmeterol (250/50 µg b.i.d.) as an active control.
• Scientific title: A multicenter, randomized, double-blind, double dummy, placebo controlled crossover study, to investigate the 24 hour FEV1 profile of a single dose of QMF Twisthaler® (500/400 µg o.d.) delivered in the evening in adult patients with persistent asthma using fluticasone propionate/salmeterol (250/50 µg b.i.d.) as an active control.
• Date of first enrolment: 16/10/2007
• Target sample size: 39
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-003192-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: yes Other trial design description: double dummy If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: yes Other specify the comparator: fluticasone propionate/salmeterol (250/50 µg b.i.d.) as an active control.

Countries of recruitment

Belgium

Key inclusion & exclusion criteria

Inclusion criteria:
• Male and female adult patients aged 18-75 years (inclusive), who have signed an Informed Consent Form prior to initiation of any study-related procedure, including any adjustments to asthma medication prior to Visit 1.
• Patients with persistent asthma, diagnosed according to GINA guidelines and who additionally meet the following criteria:
Patients receiving daily treatment with inhaled corticosteroid up to the maximum dose per day indicated in the product label, and on a stable regimen for the month prior to Visit 1.
Patients with an FEV1 at Visit 1 of =50% of the predicted normal value. This criterion for FEV1 will have to be demonstrated after a washout period of at least 6 hours during which no short acting ß2-agonist has been inhaled, and a minimum of 48 hours for a long acting ß2-agonist.
Patients who demonstrate an increase of =12% and =200 mL in FEV1 over their prebronchodilator value within 30 minutes after inhaling a total of 200/180 µg of salbutamol/albuterol MDI (or equivalent dose of DPI) (the reversibility test).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• Pregnant women, nursing mothers, or females of childbearing potential, regardless of whether or not sexually active, if they are not using a reliable form of contraception.
• Patients who have used tobacco products within the 6 months period prior to Visit 1, or who 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 diagnosed with COPD as defined by the GOLD guidelines [Global Initiative for Chronic Obstructive Lung Disease 2006].
• Patients with seasonal allergy whose asthma is likely to deteriorate during the study period.
• Patients who have had an acute asthma attack/exacerbation requiring hospitalization in the 6 months prior to Visit 1.
• Patients who have had an acute asthma attack / exacerbation requiring an emergency room visit within 6 weeks prior to Visit 1 or at any time between Visit 1 and Visit 2.
• Patients who have had a respiratory tract infection within 4 weeks prior to Visit 1 or at any time between Visit 1 and Visit 2.
• Patients with a history of long QT syndrome or whose QTc interval (Bazett’s) measured at Visit 1 or Visit 2 is prolonged: > 450 ms (males) or > 470 ms (females).
• Other clinically significant conditions which may interfere with the study conduct or patient safety as specified in the protocol.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients with persistent asthma, diagnosed according to GINA guidelines [National Institute of Health., National Heart, Lung and Blood Institute, 2006]
MedDRA version: 9.1 Level: LLT Classification code 10003553 Term: Asthma

Intervention(s)

Product Name: Indacaterol maleate / mometasone furoate
Product Code: QMF149
Pharmaceutical Form: Inhalation powder
INN or Proposed INN: Indacaterol maleate
Current Sponsor code: QAB149
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 250-
INN or Proposed INN: mometasone furoate
CAS Number: 83919-23-7
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Inhalation powder
Route of administration of the placebo: Inhalation use

Trade Name: Seretide Diskus® 250/50 mcg
Product Name: Seretide Diskus 250/50 mcg
Pharmaceutical Form: Inhalation powder
INN or Proposed INN: Fluticasone propionate
CAS Number: 80474-14-2
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 250-
INN or Proposed INN: Salmeterol
CAS Number: 89365-50-4
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Inhalation powder
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Primary end point(s): Primary efficacy assessment:
•change from period baseline FEV1 to 24 hr post-dose trough FEV1
Secondary efficacy assessment:
•Time to peak FEV1
•FEV1 and FVC at time-points: 5, 30 min, 1, 2, 3, 4 hrs post-dosing on Day 1 and 11 hr 10 min, 11 hr 45 min, 12 hr 30 min, 14 hr, 16 hr, 18 hr, 20 hr, 22 hr, 23 hr 10 min, 23 hr 45 min post-dosing on Day 2.
Safety assessments:
•Monitoring for adverse events, laboratory evaluations (including serum potassium and blood glucose), vital signs (blood pressure and pulse rate) and ECGs.
Pharmacokinetic evaluations:
•Blood samples will be collected for determination of indacaterol maleate and mometasone furoate in serum at - 25 min prior to evening dose and 20 min, 1 h, 2 h, 4 h post-dosing on Day 1 then at 11 h 35 min and 23 hr 35 min post-dosing on Day 2

Secondary Objective: 1-To assess the bronchodilator effect of QMF Twisthaler® 500/400 µg o.d. (2 x 250/200 µg) administered in the evening in patients with persistent asthma compared to placebo as measured by:
-Time to peak FEV1
-FEV1 and FVC at each time point post-dose
- Standardized FEV1 AUC between baseline (pre-dose) and 4 hr post-dose
- Standardized FEV1 AUC between 11 hr 10 min - 23 hr 45 min post-dose
- Standardized FEV1 AUC between baseline (pre-dose) and 23 hr 45 min post-dose
2- To assess the effects of treatment between fluticasone propionate/salmeterol (250/50 µg b.i.d.) vs placebo for all of the efficacy variables above.

Main Objective: To evaluate bronchodilator effects of QMF Twisthaler® 500/400 µg o.d. (2x 250/200 µg) administered in the evening compared with placebo in terms of change from (period) baseline FEV1 to 24 hr post-dose trough FEV1 in patients with persistent asthma (The period baseline FEV1 is defined as the average of two FEV1 assessments taken at 50 min and 15 min before bthe study drug administration in that treatment period. 24 hr post-dose trough FEV1 is defined as the average of 2 FEV1 measurements at 23 hr 10 min and 23 hr 45 min post-dose).

Secondary ID(s)

CQMF149A2202