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Efficacy and Safety of QMF149 vs. Salmeterol Xinafoate/Fluticasone Propionate in Patients With Chronic Obstructive Pulmonary Disease (COPD)

This study is currently recruiting participants.
Verified February 2013 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01636076
First received: July 5, 2012
Last updated: February 11, 2013
Last verified: February 2013
History of Changes
  Purpose

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


Condition Intervention Phase
COPD
 Drug: QMF149
Drug: Salmeterol
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:
  • Trough Forced Expiratory Volume in one second (FEV1) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Spirometry is conducted according to the global standard. Trough FEV1 is defined as the average of the 23 hour 10 minute and 23 hour 45 minute post dose FEV1 readings.


Secondary Outcome Measures:
  • Trough FEV1 [ Time Frame: Day 2 (i.e. after first dose of study medication) and Day 29 (i.e. after last dose of study medication) ] [ Designated as safety issue: No ]
    Spirometry is conducted according to the global standard. Trough FEV1 is defined as the average of the 23 hour 10 minute and 23 hour 45 minute post dose FEV1 readings.

  • FEV1 at each timepoint [ Time Frame: Day 1 and Day 28 ] [ Designated as safety issue: No ]
    Spirometry is conducted according to the global standard. FEV1 is measured at pre-dose and post dose up to 1 hours on Day 1 and Day 28; 24 hours post-dose on Day 29 and 85. In a subset of approximately 60 patients, FEV1 is measured up to 20 hours postdose on Day 28 and Day 84.

  • Forced vital capacity (FVC) at each timepoint [ Time Frame: Day 1, Day 2, Day 28, Day , Day 29, Day 84, Day 85 ] [ Designated as safety issue: No ]
    Spirometry is conducted according to the global standard. FVC is measured at pre-dose and post dose up to 4 hour on Day 1, Day 28, and Day 84, at post dose 12 hour, 23 hour 10 minute and 23 hour 45 minutes on Day 2 and Day 29, and at pre-dose 50 min and 15 min on Day 2, Day 28, and Day 84.

  • FEV1/FVC at each timepoint [ Time Frame: Day 1, Day 2, Day 28, Day , Day 29, Day 84, Day 85 ] [ Designated as safety issue: No ]
    Spirometry is conducted according to the global standard. FEV1/FVC is measured at pre-dose and post dose up to 4 hour on Day 1, Day 28, and Day 84, at post dose 12 hour, 23 hour 10 minute and 23 hour 45 minutes on Day 2 and Day 29, and at pre-dose 50 min and 15 min on Day 2, Day 28, and Day 84.

  • FEV1 AUC (5 min-4 h), (5 min-24 h) [ Time Frame: Day 1, Day 28, Day 84 ] [ Designated as safety issue: No ]

    Spirometry is conducted according to the global standard. FEV1 AUC (5 min-4 h), (5 min-24 h) is measured after the first dose on Day 1 and on Day 28 and Day 84 in a subset of approximately 60 patients. Scheduled (not actual) time points are to be used. The interpretation of FEV1 at time 0 is the baseline value at the randomization visit and the latest pre-dose value (-50 min or -15 min) at subsequent visits.

    The standardized AUC(5 min - 4 h) for FEV1 will be summarized by treatment. The same will be repeated for standardized AUC for FEV1 between 5 min and 24 hours post morning dose.


  • The usage of rescue medication (short acting β2-agonist) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Participants record the number of puffs of rescue medication taken in the previous 12 hours each morning and evening throughout the 12 week treatment period.

  • Peak FEV1 [ Time Frame: Day 1, Day 28, Day 84 ] [ Designated as safety issue: No ]
    Spirometry is conducted according to the global standard. Peak FEV1 is measured after the first dose on Day 1 and on Day 28 and Day 84.

  • Patient reported outcome measures: SGRQ (St. George's Respiratory Questionnaire) [ Time Frame: 4 and 12 weeks ] [ Designated as safety issue: No ]
    The proportion of patients who achieve a clinically important improvement of at least 4 units in the total SGRQ will be analyzed.

  • Patient reported outcome measures: TDI (Transitional Dyspnoea Index) [ Time Frame: 4 and 12 weeks ] [ Designated as safety issue: No ]
    A TDI focal score of ≥1 is considered to be a clinically important improvement from baseline. The proportion of patients who achieve this clinically important improvement at visit 203 and 205 will be analyzed.

  • Patient reported outcome measures: COPD Assessment Test [ Time Frame: 4 and 12 weeks ] [ Designated as safety issue: No ]
    It consists of eight items, each presented as a semantic 6-point differential scale, providing a total score out of 40. A higher score indicates a worse health status. Scores of 0 - 10, 11 - 20, 21 - 30 and 31 - 40 represent a mild, moderate, severe or very severe clinical impact of COPD upon the patient.

  • Patient reported outcome measures: Medical Outcome Study (MOS) sleep scale [ Time Frame: 4 and 12 weeks ] [ Designated as safety issue: No ]
    Each patient reported outcome is measured at the start of study treatment and after 4 and 12 weeks of treatment.

  • Exacerbations of Chronic Pulmonary Disease Tool (EXACT) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    The EXACT is a 14-item electronic questionnaire designed to detect the frequency, severity, and duration of exacerbations in patients with COPD.

  • Chronic systemic inflammatory syndrome [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Chronic systemic inflammatory syndrome will be assessed by using inflammatory parameters after 12 weeks of treatment.

  • Number of patients with AEs, SAEs, or death [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.

  • Time to first COPD exacerbation [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Time-to-event variables will be analyzed by the Kaplan-Meier estimates and the stratified Cox proportional hazard model by smoking status and COPD severity. The model will include treatment and country as factors, and FEV1 prior to inhalation and FEV1 15 min post inhalation of salbutamol/albuterol as covariates.

  • Annual rate of COPD exacerbations [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Time-to-event variables will be analyzed by the Kaplan-Meier estimates and the stratified Cox proportional hazard model by smoking status and COPD severity. The model will include treatment and country as factors, and FEV1 prior to inhalation and FEV1 15 min post inhalation of salbutamol/albuterol as covariates.

  • Duration (in days) of COPD exacerbations [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Duration and number of the COPD exacerbation will be analyzed by the negative binomial regression model including treatment, country, smoking status, and COPD severity as factors and FEV1 prior to inhalation and FEV1 15 min post inhalation of salbutamol/albuterol as covariates.

  • Percentage of patients with at least one exacerbation [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Time-to-event variables will be analyzed by the Kaplan-Meier estimates and the stratified Cox proportional hazard model by smoking status and COPD severity. The model will include treatment and country as factors, and FEV1 prior to inhalation and FEV1 15 min post inhalation of salbutamol/albuterol as covariates.

  • Time (in days) to permanent study discontinuation due to COPD exacerbation [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Time-to-event variables will be analyzed by the Kaplan-Meier estimates and the stratified Cox proportional hazard model by smoking status and COPD severity. The model will include treatment and country as factors, and FEV1 prior to inhalation and FEV1 15 min post inhalation of salbutamol/albuterol as covariates.

  • The percentage of patients who permanently discontinued due to COPD exacerbation [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Time-to-event variables will be analyzed by the Kaplan-Meier estimates and the stratified Cox proportional hazard model by smoking status and COPD severity. The model will include treatment and country as factors, and FEV1 prior to inhalation and FEV1 15 min post inhalation of salbutamol/albuterol as covariates.

  • Total amount (in doses) of systemic corticosteroid used to treat COPD exacerbation during the 12 week treatment period [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Total amount (in doses) of systemic corticosteroid used to treat COPD exacerbation will be summarized descriptively by treatment group per each systemic corticosteroid.

  • Plasma cortisol concentrations at each timepoint [ Time Frame: Day 1, Day 2, Day 28, Day 29, Day 84, Day 85 ] [ Designated as safety issue: Yes ]
    Plasma cortisol to be measured in a subset of approximately 60 patients via central laboratory. Blood sample for Plasma cortisol is collected at pre-dose and post dose up to 4 hour on Day 1, up to 12 hours post-dose on Day 28 and Day 84, and 23 hour 35 minute on Day 2, Day 29, and Day 85, and at pre-dose 25 minute on Day 28, and Day 84.

  • Plasma drug concentrations (pharmacokinetics) at each timepoint [ Time Frame: Day 1, 29, 84 ] [ Designated as safety issue: No ]
    Plasma indacaterol and mometasone furoate is to be measured in a subset of approximately 60 patients via central laboratory. Blood samples are collected at pre-dose on Day 1, 29, and 84; and post dose up to 4 hour on Day 1, up to 12 hours on Day 28 and 84. For sparse pharmacokinetic testing, blood samples will be collected at 23h 35 min post-dose following morning dose administration on Day 28 and 84, in all patients participating in this study.

  • Pharmacokinetic parameter: Cmax [ Time Frame: Day 28, 84 ] [ Designated as safety issue: No ]
    Maximum observed plasma concentration after drug administration is to be measured in a subset of approximately 60 patients via central laboratory, and will be determined for indacaterol and MF following morning dosing on Days 28 and 84.

  • Pharmacokinetic parameter--Tmax [ Time Frame: Day 28, 84 ] [ Designated as safety issue: No ]
    Time to reach the maximum plasma concentration after drug administration is to be measured in a subset of approximately 60 patients via central laboratory, and will be determined for indacaterol and MF following morning dosing on Days 28 and 84.

  • Pharmacokinetic parameter--AUC0-t [ Time Frame: Day 28, 84 ] [ Designated as safety issue: No ]
    Area under the plasma concentration time curve from time zero to time "t" post-dose is to be measured in a subset of approximately 60 patients via central laboratory, and will be determined for indacaterol and MF following morning dosing on Days 28 and 84.

  • Pharmacokinetic parameter--AUClast [ Time Frame: Day 28, 84 ] [ Designated as safety issue: No ]
    Area under the plasma concentration time curve from time zero to the time of last quantifiable concentration is to be measured in a subset of approximately 60 patients via central laboratory, and will be determined for indacaterol and MF following morning dosing on Days 28 and 84.


Estimated Enrollment: 576
Study Start Date: November 2012
Estimated Study Completion Date: July 2013
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: QMF149
QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 µg o.d. delivered via Concept1 device
 Drug: QMF149
delivered via Concept1 device
Active Comparator: Salmeterol xinafoate/fluticasone propionate
Salmeterol xinafoate/fluticasone propionate 50/500 µg b.i.d, delivered via Accuhaler®
 Drug: Salmeterol
delivered via Accuhaler®

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01636076

Contacts
Contact: Novartis Pharmaceuticals +41613241111
Contact: Novartis Pharmaceuticals

  Show 157 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01636076     History of Changes
Other Study ID Numbers: CQMF149F2202, 2012-001172-12
Study First Received: July 5, 2012
Last Updated: February 11, 2013
Health Authority: Australia: Therapeutic Goods Administration
Germany: Federal Institute for Drugs and Medical Devices
Greece: National Organization for Medicines
Hungary: National Institute for Quality - and Organizational Development in Healthcare and Medicines/National Institute of Pharmacy
Hong Kong: Medical Device Control Office
India: Drugs Controller General of India
Israel: Ministry of Health
Malaysia: National Pharmaceutical Control Bureau
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
South Africa: Department of Health
Thailand: Food and Drug Administration
Turkey: Ministry of Health
Ukraine: Ministry of Health
Vietnam: Ministry of Health
Spain: Ministry of Health
Romania: Ministry of Public Health

Keywords provided by Novartis:
COPD

Additional relevant MeSH terms:
Lung Diseases
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases
Salmeterol
Albuterol
Fluticasone
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
 Pharmacologic Actions
Physiological Effects of Drugs
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Tocolytic Agents
Reproductive Control Agents
Dermatologic Agents
Anti-Allergic Agents
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on May 19, 2013