Clinical trial NCT01636076: Efficacy and Safety of QMF149 vs. Salmeterol Xinafoate/Fluticasone Propionate in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Official title: A Randomized, Double-blind, 12-week Treatment, Parallel-group Study to Evaluate the Efficacy and Safety of QMF149 (150 µg/160 µg o.d.) Compared With Salmeterol Xinafoate/Fluticasone Propionate (50 µg/500 µg b.i.d.) in Patients With Chronic Obstructive Pulmonary Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: COPD
Keywords: COPD
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-07-10
Enrollment: 629
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To compare the efficacy, safety and pharmacokinetics of QMF149 delivered via Concept1 to salmeterol xinafoate/fluticasone propionate delivered via Accuhaler in adult patients with COPD


Eligibility criteria: Inclusion Criteria:

* Patients with moderate to very severe COPD (GOLD 2 to GOLD 4) according to the 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines
* Patients with a post-bronchodilator FEV1 \< 70% of the predicted normal, and a post-bronchodilator FEV1/FVC \< 0.70 at run-in (Visit 101).
* Current or ex-smokers who have a smoking history of at least 10 pack years (defined as the number of packs of 20 cigarettes smoked per day multiplied by number of years the patient smoked. e.g.10 pack years = 1 pack /day x 10 yrs, or ½ pack/day x 20 yrs). An ex-smoker may be defined as a subject who has not smoked for ≥ 6 months at screening.

Exclusion Criteria:

* Patients who have had a COPD exacerbation that required treatment with antibiotics and/or oral corticosteroids and/or hospitalization in the 6 weeks prior to screening (Visit 1).
* Patients who develop a COPD exacerbation 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.
* Patients who have had a respiratory tract infection within 4 weeks prior to screening Visit 1.
* Patients who develop a respiratory tract infection between screening (Visit 1) and treatment (Visit 201) will not be eligible, but will be permitted to be re-screened 4 weeks after the resolution of the respiratory tract infection.
* Patients requiring long term oxygen therapy prescribed for \>12 hours per day.
* Patients with, a) any history of asthma or, b) onset of respiratory symptoms prior to age 40 years.

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for Trough FEV1 (L) on Day 85
timeFrame: 12 weeks
Secondary outcomes:
measure: Trough FEV1 After First Dose and After 4 Weeks of Treatment
timeFrame: Day 1 and Day 85
measure: Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint
timeFrame: Day 1 through day 85
measure: Forced Vital Capacity (FVC) at Each Timepoint
timeFrame: Day 1, Day 2, Day 28, Day , Day 29, Day 84, Day 85
measure: FEV1/FVC at Each Timepoint
timeFrame: Day 1, Day 2, Day 28, Day , Day 29, Day 84, Day 85
measure: FEV1 (L) on Day 1 Between-treatment Comparisons of AUC (5min - 4h)
timeFrame: Day 1
measure: FEV1 AUC (5 Min-4 h),
timeFrame: Day 1(Baseline), Day 28, Day 84
measure: Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for AUC (5 Min - 23 h 45 Min) for FEV1 (L) on Day 28 and Day 84 (Full Analysis Set, 24-h Profiling Subgroup)
timeFrame: Day 28, Day 84
measure: The Usage of Rescue Medication (Short Acting β2-agonist)
timeFrame: 12 weeks
measure: The Overall Change in Usage of Rescue Medication (Short Acting β2-agonist) .
timeFrame: Baseline to 12 weeks
measure: Patient Reported Outcome Measures: SGRQ (St. George's Respiratory Questionnaire)
timeFrame: 4 and 12 weeks
measure: Analysis of the Proportion of Subjects With a Clinically Important Improvement of >=1 Point in the TDI (Transitional Dyspnoea Index)Focal Score by Visit
timeFrame: 4 and 12 weeks
measure: Patient Reported Outcome Measures: COPD Assessment Test
timeFrame: Baseline, 4 and 12 weeks
measure: Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale
timeFrame: Baseline, 4 and 12 weeks
measure: Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Sleep Quantity Subscale
timeFrame: Baseline, 4 and 12 weeks
measure: Summary Statistics of COPD Exacerbations over12 Weeks as Defined by Chronic Pulmonary Disease Tool (EXACT)
timeFrame: 12 weeks
measure: Time to First COPD Exacerbation
timeFrame: 12 weeks
measure: Annual Rate of COPD Exacerbations
timeFrame: 12 weeks
measure: Duration (in Days) of COPD Exacerbations
timeFrame: 12 weeks
measure: Percentage of Patients With at Least One Exacerbation up to Week 12
timeFrame: 12 weeks
measure: Time (in Days) to Permanent Study Discontinuation Due to COPD Exacerbation
timeFrame: 12 weeks
measure: The Percentage of Patients Who Permanently Discontinued Due to COPD Exacerbation
timeFrame: 12 weeks
measure: Total Amount (in Doses) of Systemic Corticosteroid Used to Treat COPD Exacerbation During the 12 Week Treatment Period
timeFrame: 12 weeks
measure: Plasma Cortisol Concentrations at Each Timepoint
timeFrame: Day 1, Day 28, Day 84
measure: Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint
timeFrame: Day 1, 29, 84
measure: Pharmacokinetic Parameter: Cmax
timeFrame: Day 28, 84
measure: Pharmacokinetic Parameter--Tmax
timeFrame: Day 28, 84
measure: Pharmacokinetic Parameter--AUC0-t
timeFrame: Day 28, 84
Other outcomes:
Locations:
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facility: Novartis Investigative Site
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city: Wroclaw
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state: Jud. Constanta
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country: Romania
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city: Cluj Napoca
country: Romania
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state: Gauteng
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country: South Africa
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city: Cape Town
country: South Africa
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city: Cape Town
country: South Africa
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city: Cape Town
country: South Africa
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city: Cape Town
country: South Africa
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city: Durban
country: South Africa
facility: Novartis Investigative Site
city: Umkomaas
country: South Africa
facility: Novartis Investigative Site
city: Barcelona
country: Spain
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state: Cataluña
city: Barcelona
country: Spain
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state: Cataluña
city: Valencia
country: Spain
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state: Comunidad Valenciana
city: Palma De Mallorca
country: Spain
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state: Islas Baleares
city: Göteborg
country: Sweden
facility: Novartis Investigative Site
city: Göteborg
country: Sweden
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city: Lund
country: Sweden
facility: Novartis Investigative Site
city: Malmö
country: Sweden
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city: Vällingby
country: Sweden
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country: Thailand
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state: Nonthaburi
city: Bangkok
country: Thailand
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city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Muang
country: Thailand
facility: Novartis Investigative Site
city: Nakhon Naiyok
country: Thailand
facility: Novartis Investigative Site
city: Songkla
country: Thailand
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: