Dose Finding Study for QAW039 in Asthma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01437735
First received: September 14, 2011
Last updated: January 27, 2014
Last verified: January 2014
  Purpose

This study aims to demonstrate a clinically significant improvement in Forced Expiratory Volume in one second (FEV1) in moderate to severe allergic asthmatics inadequately controlled by Inhaled Corticosteroid (ICS) therapy. Patients will be treated with QAW039, an active comparator, or placebo. This will be a randomized, placebo-controlled, dose-ranging, multi-centre trial.


Condition Intervention Phase
Asthma
Drug: QAW039
Drug: Comparator leukotriene receptor antagonist (LRTA)
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Placebo-controlled, Dose-ranging, Multi-centre Trial of QAW039 (1-450 mg p.o.), to Investigate the Effect on FEV1 and ACQ in Patients With Moderate-to-severe, Persistent, Allergic Asthma, Inadequately Controlled With ICS Therapy.

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change in trough Forced Expiratory Volume in 1 second (FEV1) from baseline to week 12 [ Time Frame: Baseline and week 12 ] [ Designated as safety issue: No ]
    Forced Expiratory Volume in 1 second (FEV1) (measured in litters), and the trough measurement is taken 24 hours after morning dose on the previous day.


Secondary Outcome Measures:
  • Change in Asthma Control Questionnaire (ACQ) score from baseline to week 12 [ Time Frame: Baseline and week 12 ] [ Designated as safety issue: No ]
    The Asthma Control Questionnaire (ACQ) is a validated questionnaire consisting of 7 items: 5 on symptom assessment, 1 on rescue bronchodilator use and 1 assessing the patients Forced Expiratory Volume in 1 second (FEV1) result against the predicted result for a person of similar age and stature. Each item is graded on a scale of 0-6, and a mean score of 1.5 or greater is considered to demonstrate inadequate asthma control in this trial. The minimal important difference that is considered clinically important is a change of 0.5 in the mean score.

  • Change in Forced Expiratory Volume in 1 second (FEV1) from baseline to weeks 2, 4 and 8. [ Time Frame: Baseline, week 2, week 4 and week 8 ] [ Designated as safety issue: No ]
    Forced Expiratory Volume in 1 second (FEV1) (measured in litters), and the measurement is taken 24 hours after the morning dose on the previous day.

  • Change in the Asthma Control Questionnaire (ACQ) score from baseline to weeks 2, 4 and 8. [ Time Frame: Baseline, week 2, week 4 and week 8 ] [ Designated as safety issue: No ]
    The Asthma Control Questionnaire (ACQ) is a validated questionnaire consisting of 7 items: 5 on symptom assessment, 1 on rescue bronchodilator use and 1 assessing the patients Forced Expiratory Volume in 1 second (FEV1) result against the predicted result for a person of similar age and stature. Each item is graded on a scale of 0-6, and a mean score of 1.5 or greater is considered to demonstrate inadequate asthma control in this trial. The minimal important difference that is considered clinically important is a change of 0.5 in the mean score.

  • Change in the dose response relationship among QAW039 doses with respect to Forced Expiratory Volume in 1 second (FEV1) after 12 weeks treatment. [ Time Frame: Baseline and week 12 ] [ Designated as safety issue: No ]
    Forced Expiratory Volume in 1 second (FEV1) (measured in litters), and the measurement is taken 24 hours after the morning dose on the previous day.

  • Comparison of vital signs, ECG, laboratory tests and adverse events across QAW039 doses and placebo. [ Time Frame: Baseline and week 12 ] [ Designated as safety issue: Yes ]
    Comparisons of vital signs (i.e. systolic and diastolic blood pressure, pulse rate), ECG (e.g. quantitative assessments - heart rate, QTcF, PRS, PR intervals), laboratory tests (haematology, clinical chemistry and urinalysis) and adverse events across QAW039 doses and placebo.

  • Comparison of efficacy of QAW039 with that of active comparator as an add-on therapy to Inhaled Corticosteroids (ICS) [ Time Frame: Baseline and week 12 ] [ Designated as safety issue: No ]
    Forced Expiratory Volume in 1 second (FEV1) measurement taken 24 hours after the morning dose on the previous day. The Asthma Control Questionnaire (ACQ)consisting of 7 items: 5 on system assessment, 1 on rescue bronchodilator use and 1 assessing the patients for FEV1 result against the predicted result for a person of similar age and stature. Each item is graded on a scale of 0-6, and a mean score of 1.5 or greater is considered to demonstrate inadequate asthma control in this trial. The minimal important difference that is considered clinically important is a change of 0.5 in the mean score.

  • Assess the effect of QAW039 on asthma symptoms as measured by asthma control diary. [ Time Frame: Baseline and week 12 ] [ Designated as safety issue: Yes ]
    The asthma control diary mimics the Asthma Control Questionnaire (ACQ), but is recorded daily by the patient, rather than at each visit. As for the ACQ, the ACD consists of 7 questions.


Enrollment: 1040
Study Start Date: August 2011
Study Completion Date: November 2013
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: QAW039 po dose 1 Drug: QAW039
QAW039 po
Experimental: QAW039 po dose 2 Drug: QAW039
QAW039 po
Experimental: QAW039 po dose 3 Drug: QAW039
QAW039 po
Experimental: QAW039 po dose 4 Drug: QAW039
QAW039 po
Experimental: QAW039 po dose 5 Drug: QAW039
QAW039 po
Experimental: QAW039 po dose 6 Drug: QAW039
QAW039 po
Experimental: QAW039 po dose 7 Drug: QAW039
QAW039 po
Experimental: QAW039 po dose 8 Drug: QAW039
QAW039 po
Experimental: QAW039 po dose 9 Drug: QAW039
QAW039 po
Experimental: QAW039 po dose 10 Drug: QAW039
QAW039 po
Experimental: QAW039 po dose 11 Drug: QAW039
QAW039 po
Experimental: QAW039 po dose 12 Drug: QAW039
QAW039 po
Experimental: QAW039 po dose 13 Drug: QAW039
QAW039 po
Active Comparator: leukotriene receptor antagonist (LRTA). Drug: Comparator leukotriene receptor antagonist (LRTA)
leukotriene receptor antagonist (LRTA)
Placebo Comparator: Placebo Drug: Placebo
Placebo

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria: - Physician diagnosis of asthma, as per the Global Initiative for Asthma (GINA) (2009) guidelines, and currently prescribed Inhaled Corticosteroids (ICS) therapy. - Patients with a pre-bronchodilator Forced Expiratory Volume in 1 second (FEV1) value of 40% to 80% of individual predicted value. - Patients should be allergic or atopic, as diagnosed historically or prior to entry into the study. - Patients who are demonstrated to have reversible airway obstruction or airways hyper-reactivity or have shown either of such responses in previous test(s) within the last year. - An Asthma Control Questionnaire (ACQ) score ≥ 1.5 at randomization. Exclusion Criteria: - Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test (> 5 mIU/mL). - Patients with serious co-morbidities including uncontrolled diabetes (HbA1c≥8%), heart failure, cancer, neurodegenerative diseases, rheumatoid arthritis and other autoimmune diseases, other lung diseases including chronic bronchitis, chronic obstructive pulmonary diseases or emphysema or other conditions characterized by eosinophilia and pulmonary symptoms (i.e. Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis, eosinophilic pneumonia, etc.). - Acute illness other than asthma at the start of the study - History of life-threatening asthma, including a history of significant hypercarbia (pCO2>45mmHg), prior intubation, respiratory arrest, or seizures as a result of asthma. - Patients who have had a respiratory tract infection within 4 weeks of the screening visit. Patients who develop a respiratory tract infection between screening and the randomization visit must be screen failed, and may be permitted to re-enroll at a later date. - Current smokers or ex-smokers who stopped smoking within 6 months prior to screening or have a smoking history of ≥ 10 pack years. Other protocol-defined inclusion/exclusion criteria apply.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01437735

  Show 205 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: NCT01437735     History of Changes
Other Study ID Numbers: CQAW039A2206, 2011-001062-18
Study First Received: September 14, 2011
Last Updated: January 27, 2014
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Austria: Bundesamt für Sicherheit im Gesundheitswesen (BASG)
Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Greece: National Organization of Medicines
Guatemala: Ministerio de Salud Pública: Departamento de Regulación y Control de Productos Farmacéuticos y Afines.
Hungary: National Institute for Quality- and Organizational Development in Healthcare and Medicines/National Institute of Pharmacy
India: Drugs Controller General of India
Japan: Pharmaceuticals and Medical Devices Agency
Mexico: Federal Commission for Sanitary Risks Protection
Peru: General Directorate of Pharmaceuticals, Devices, and Drugs
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: Expert Board (FSBI Scientific Center of Medical Application Expertise of Ministry of Health and Social Development of the Russian Federation)
Scotland: Scottish Executive Health Department
South Africa: Medicines Control Council
Turkey: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Venezuela : Ministerio del Poder Popular para la Salud
Venezuela: Instituto Nacional de Higiene Rafael Rangel
Russia: FSI Scientific Center of Expertise of Medical Application

Keywords provided by Novartis:
Asthma
QAW039

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Leukotriene Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014