Comparison of Long-term Safety of the Combination Product QVA149A Against Placebo and Standard of Care Treatment in Chronic Obstructive Pulmonary Disease Patients With Moderate to Severe Airflow Limitation - Full Text View

Purpose

The study will assess the long-term safety of the fixed combination product QVA149 versus placebo and a standard of care treatment (tiotropium) in Chronic Obstructive Pulmonary Disease (COPD) patients with moderate to severe airflow limitation.

Condition	Intervention	Phase
Chronic Obstructive Pulmonary Disease (COPD)	Drug: QVA149 Drug: Tiotropium Drug: placebo	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	A Placebo and Active Controlled Study to Assess the Long-term Safety of Once Daily QVA149 for 52 Weeks in Chronic Obstructive Pulmonary Disease (COPD) Patients With Moderate to Severe Airflow Limitation

Resource links provided by NLM:

MedlinePlus related topics: COPD (Chronic Obstructive Pulmonary Disease)

Drug Information available for: Tiotropium bromide

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

overall serious adverse event rate [ Time Frame: 56 weeks ] [ Designated as safety issue: Yes ]
The overall rate of serious adverse events reported from initiation through 30 days post last dose will be analyzed.

Secondary Outcome Measures:

Composite endpoint of all-cause mortality and serious cerebro-cardiovascular events [ Time Frame: 56 weeks ] [ Designated as safety issue: Yes ]
A composite endpoint of all-cause mortality and serious cerebro-cardiovascular events will be analyzed.
Electrocardiogram [ Time Frame: weeks 1, 26 and 52 ] [ Designated as safety issue: Yes ]
Data from the electrocardiograms will be summarized by treatment at all times.
Health Status as measured by St. George's Respiratory Questionnaire for COPD patients (SGRQ-C) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
The St. George's Respiratory Questionnaire (SGRQ-C) will be used to provide the health status measurement. The SGRQ-C contains 40 items divided into two parts covering three aspects of health related to Chronic Obstructive Pulmonary Disease. A score will be calculated for each of these three parts and a "Total" score will also be calculated. In each case the lowest possible value is zero and the highest 100. Higher values correspond to greater impairment of health status.
Daily, morning and evening symptom scores [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
Patients will be provided with an electronic diary (eDiary) to record daily clinical symptoms, or rescue medication. The patients will be instructed to routinely complete the patient diary twice daily. There are 9 total symptom questions for a total possible score of 27 at each timepoint. A higher score means the patient is reporting more symptoms related to Chronic Obstructive Pulmonary Disease.
Percentage of nights with 'no nighttime awakenings' [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
A night with 'no nighttime awakenings' is defined from diary data as any night where the patient did not wake up due to symptoms. The percentage of nights with 'no nighttime awakenings' will be analyzed.
Percentage of days with 'no daytime symptoms' [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
A day with 'no daytime symptoms' is defined from the diary data as any day where the patient has recorded in the evening no cough, no wheeze, no production of sputum and no feeling of breathlessness (other than when running) during the past 12 hours (approx 8 am to 8 pm). The percentage of days with 'no daytime symptoms' will be analyzed.
Percentage of 'days able to perform usual daily activities' [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
A 'day able to perform usual daily activities' is defined from diary data as any day where the patient was not prevented from performing their usual daily activities due to respiratory symptoms. The percentage of 'days able to perform usual daily activities' will be analyzed.
Pre-Dose forced expiratory volume over in second (FEV1) [ Time Frame: Weeks 3, 6, 12, 26, 39, and 52 ] [ Designated as safety issue: No ]
The average pre-dose forced expiratory volume in 1 second (FEV1) at visit 4, 5, 6, 7, 8 and 9 will be analyzed.
Pre-Dose forced vital capacity (FVC) [ Time Frame: Weeks 3, 6, 12, 26, 39 and 52 ] [ Designated as safety issue: No ]
The average pre-dose forced vital capacity (FVC) at visit 4, 5, 6, 7, 8 and 9 will be analyzed.
Post dose forced expiratory volume in one second (FEV1) [ Time Frame: Weeks 3, 6, 12, 26, 39, and 52 ] [ Designated as safety issue: No ]
The avg 60 min post dose forced expiratory volume in 1 second (FEV1) at visit 4, 5, 6, 7, 8 and 9 will be analyzed.
Post Dose forced vital capacity (FVC) [ Time Frame: Weeks 3, 6, 12, 26, 39, and 52 ] [ Designated as safety issue: No ]
The avg 60 min post dose forced vital capacity (FVC)at visit 4, 5, 6, 7, 8 and 9 will be analyzed.
Time to discontinuation [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
Time to premature discontinuation will be displayed graphically for each treatment group.
Vital Signs [ Time Frame: Weeks 3, 6, 12, 26, 39, and 52 ] [ Designated as safety issue: Yes ]
Vital signs (blood pressure and radial pulse rate) data will be summarized by treatment at pre-dose and 30 minute post-dose time points at Visits 3-9.
Lab values [ Time Frame: Weeks 6, 12, 26, 39, and 52 ] [ Designated as safety issue: Yes ]
All lab data will be listed with abnormal values flagged. The lab values and the change from baseline for continuous lab parameters will be summarized at each visit. A frequency table of results for categorical lab parameters will be produced by visit. Shift tables relative to normal ranges will be used to summarize the change from baseline to post-baseline by visit.

Estimated Enrollment:	1224
Study Start Date:	October 2012
Estimated Study Completion Date:	July 2014
Estimated Primary Completion Date:	July 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: QVA149	Drug: QVA149 QVA149 110/50 µg will be supplied as capsules in blister packs for once daily inhalation using the Novartis Concept1 SDDPI
Active Comparator: Tiotropium	Drug: Tiotropium Tiotropium 18 µg will be supplied as capsules in blister packs for once daily inhalation using the HandiHaler SDDPI
Placebo Comparator: placebo	Drug: placebo placebo to QVA149A and Tiotropium will be supplied in the appropriate capsule in blister packs for use in either the Novartis Concept1 SDDPI or the HandiHaler SDDPI

Eligibility

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

Criteria

Inclusion Criteria:

Male or female adults aged ≥40 yrs
Smoking history of at least 10 pack years
Diagnosis of Chronic Obstructive Pulmonary Disease (COPD) (moderate to severe airflow limitation as classified by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines, 2011)
Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1)< 80% and ≥ 30% of the predicted normal value and post-bronchodilator FEV1/FVC (forced vital capacity) <70%
Modified Medical Research Council questionnaire grade of 2 or higher

Exclusion Criteria:

Patients who have had a respiratory tract infection within 4 weeks prior to Visit 1
Patients with concomitant pulmonary disease
Patients with a history of asthma
Any patient with lung cancer or a history of lung cancer
Patients with a history of certain cardiovascular co-morbid conditions
Patients with a known history and diagnosis of alpha-1 antitrypsin deficiency
Patients in the active phase of a supervised pulmonary rehabilitation program
Patients contraindicated for inhaled anticholinergic agents and β2 agonists
Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01610037

Contacts

Contact: Novartis Pharmaceuticals, 1862-778-8300

+41 61 324 1111

Show 133 Study Locations

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:

Novartis Pharmaceuticals

More Information

No publications provided

Responsible Party:	Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:	NCT01610037 History of Changes
Other Study ID Numbers:	CQVA149A2339, 2012-002057-38
Study First Received:	May 30, 2012
Last Updated:	January 9, 2013
Health Authority:	Argentina: Administracion Nacional de Alimentos, Medicamentos y Tecnologia Medica (ANMAT) Croatia: Ministry of Health Dominican Republic: Consejo Nacional de Bioetica en Salud (CONABIOS) Estonia: State Agency of Medicine Hungary: Directorate General of National Institute of Pharmacy/ National Institute for Quality and Organisational Development in Healthcare and Medicines India: Drugs Controller General of India Ireland: Irish Medicines Board (IMB) Israel: Israeli Ministry of Health South Korea: Korea Food and Drug Administration (KFDA) Latvia: State Agency of Medicines of Latvia Mexico: Ministry of Health Panama: Comite Nacional de Bioetica de la Investigacion con sede en Instituto Conmemorativo Gorgas de Estudios de la Salud (Ministry of Health) Poland: Ministry of Health Russia: Ministry of Health of the Russian Federation Serbia: Medicines and Medical Devices Agency of Serbia Slovenia: Public Agency of the Republic of Slovenia for Medicinal Products and Medical Devices Turkey: Ministry of Health - Turkish Medicines and Medical Devices Agency United Kingdom: Medicines and Healthcare Products Regulatory Agency Venezuela: Instituto Nacional de Higiene Rafael Rangel

Keywords provided by Novartis:

chronic obstructive pulmonary disease
COPD
QVA149
QAB149

NVA237
Indacaterol maleate
Glycopyronnium bromide

Additional relevant MeSH terms:

Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases
Tiotropium
Parasympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs

Pharmacologic Actions
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Bronchodilator Agents
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on June 18, 2013

Comparison of Long-term Safety of the Combination Product QVA149A Against Placebo and Standard of Care Treatment in Chronic Obstructive Pulmonary Disease Patients With Moderate to Severe Airflow Limitation (GLISTEN)