Evaluation of the efficacy and safety of QVA149 (110/50 µg o.d.) vs tiotropium (18 µg o.d.) + salmeterol/fluticasone propionate FDC (50/500 µg b.i.d.) in patients with moderate to severe COPD

• Register: EUCTR
• Last refreshed on: 16 October 2017
• Main ID: EUCTR2015-000114-22-SK
• Date of registration: 22/09/2015
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: Evaluation of the efficacy and safety of QVA149 (110/50 µg o.d.) vs tiotropium (18 µg o.d.) + salmeterol/fluticasone propionate FDC (50/500 µg b.i.d.) in patients with moderate to severe COPD
• Scientific title: A 26-week, randomized, double blind, parallel-group multicenter study to assess the efficacy and safety of QVA149 (110/50 µg o.d.) vs tiotropium (18 µg o.d.) + salmeterol/fluticasone propionate FDC (50/500 µg b.i.d.) in patients with moderate to severe COPD
• Date of first enrolment: 27/10/2015
• Target sample size: 1000
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-000114-22
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Argentina, Austria, Belgium, Bulgaria, Canada, Colombia, Croatia, Czech Republic, Denmark, Estonia, France, Germany, Greece, Guatemala, Hungary, Italy, Latvia, Lithuania, Mexico, Netherlands, Poland, Romania, Serbia, Slovakia, Spain, United Kingdom

Contacts

• Name: DRA dept.
• Affiliation: Novartis Slovakia s.r.o.

• Name: DRA dept.
• Affiliation: Novartis Slovakia s.r.o.

Key inclusion & exclusion criteria

Inclusion criteria:
- Patients who have signed Informed Consent Form prior to initiation of any study-related procedure.
- Male and female adults aged = 40 years.
- Patients with moderate to severe airflow obstruction with stable COPD (Stage 2 or Stage 3)according to the 2014 GOLD Guidelines.
- Patients with a post-bronchodilator FEV1 =40 and < 80% of the predicted normal value, and post-bronchodilator FEV1/FVC <0.70 at run-in Visit 101. (Post refers to 15 min after inhalation of 400 µg of salbutamol).
- Current or ex-smokers who have a smoking history of at least 10 pack years (e.g. 10 pack years = 1 pack /day x 10 years, or ½ pack/day x 20 years). An ex-smoker is defined as a patient who has not smoked for = 6 months at screening.
- Patients who are on triple treatment at least for the last 6 months (LAMA +LABA/ICS).
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 300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 700

Exclusion criteria:
- Patients who have not achieved acceptable spirometry results at Visit 101 in accordance with ATS (American Thoracic Society)/ERS (European Respiratory Society) criteria for acceptability (one retest may be performed for patients that don’t meet the acceptability
criteria)
- Patients who have had more than one COPD exacerbation that required treatment with antibiotics and/or oral corticosteroids and/or hospitalization in the last year prior to Visit 1.
- Patients who developed a COPD exacerbation of any severity either 6 weeks before the
screening (Visit 1) or between screening (Visit 1) and treatment (Visit 201) will not be eligible but will be permitted to be re-screened after a minimum of 6 weeks after the resolution of the COPD exacerbation.


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

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Chronic Obstructive Pulmonary Disease (COPD)
MedDRA version: 18.0 Level: LLT Classification code 10010952 Term: COPD System Organ Class: 100000004855

Intervention(s)

Trade Name: Ultibro Breezhaler
Product Name: indacaterol maleate/glycopyrronium bromide
Product Code: QVA149
Pharmaceutical Form: Inhalation powder, hard capsule
INN or Proposed INN: INDACATEROL MALEATE
CAS Number: 753498-25-8
Current Sponsor code: QAB149
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 110-
INN or Proposed INN: GLYCOPYRRONIUM BROMIDE
CAS Number: 596-51-0
Current Sponsor code: NVA237
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Inhalation powder, hard capsule
Route of administration of the placebo: Inhalation use

Trade Name: Seretide
Product Name: salmeterol/fluticasone
Pharmaceutical Form: Inhalation powder
INN or Proposed INN: SALMETEROL
CAS Number: 89365-50-4
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 50-
INN or Proposed INN: FLUTICASONE
CAS Number: 90566-53-3
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 500-
Pharmaceutical form of the placebo: Inhalation powder, pre-dispensed
Route of administration of the placebo: Inhalation use

Trade Name: Spiriva
Product Name: tiotropium
Pharmaceutical Form: Inhalation powder, hard capsule
INN or Proposed INN: TIOTROPIUM BROMIDE
CAS Number: 411207-31-3
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 18-
Pharmaceutical form of the placebo: Inhalation powder, hard capsule
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: week 26

Secondary Objective: - To evaluate the effect of QVA149 (110/50 µg o.d.) compared with tiotropium (18 µg o.d.) + salmeterol/fluticasone propionate FDC (50/500 µg b.i.d.) over 26 weeks of treatment in terms of Rate of moderate or severe COPD exacerbations.
- To evaluate the effect of QVA149 compared with tiotropium + salmeterol/fluticasone propionate FDC on:
- Trough FEV1 and FVC over 26 weeks
- Total score of the SGRQ-C after 12 and 26 weeks
- Total score of the TDI after 12 and 26 weeks
- Mean use of rescue therapy (number of puffs/day) and the percentage of days without rescue therapy over 26 weeks.
- To assess the safety of QVA149 vs. tiotropium + salmeterol/fluticasone propionate FDC over 26 weeks (particularly with regard to ECG, laboratory tests, vital signs and adverse events) and tolerability (discontinuation due to adverse events).

Main Objective: To demonstrate the non-inferiority of QVA149 (110/50 µg o.d.) on trough FEV1 vs. tiotropium (18 µg o.d.) + salmeterol/fluticasone propionate FDC (50/500 µg b.i.d.) after 26 weeks of treatment in moderate-to-severe COPD patients.

Primary end point(s): Mean change from baseline in post-dose trough FEV1

Secondary Outcome(s)

Secondary end point(s): - Rate of moderate to severe COPD exacerbations requiring treatment with systemic glucocorticosteroids and/or antibiotics at 26 weeks
- Rate of moderate to severe COPD exacerbations requiring hospitalisation at 26 weeks
- Trough FEV1 and FVC at 26 weeks
- Total St. George's Respiratory Questionnaire score at 12 weeks and 26 weeks
- Total Transitional Dyspnea Index score at 12 weeks and 26 weeks
- Number of puffs of rescue medication at 26 weeks
- HPA axis function at 26 weeks
- Safety and tolerability at 26 weeks

Timepoint(s) of evaluation of this end point: week 12 and week 26

Secondary ID(s)

2015-000114-22-BE

CQVA149A2316

Source(s) of Monetary Support

Novartis Pharma Services AG