Dose Finding Study for QAW039 in Asthma
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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. |
- 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.
- 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.
| Estimated Enrollment: | 950 |
| Study Start Date: | August 2011 |
| Estimated Study Completion Date: | August 2013 |
| Estimated Primary Completion Date: | August 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 |
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| Contact: Novartis Pharmaceuticals | 1-888-669-6682 | |
| Contact: Novartis Pharmaceuticals |
Show 238 Study Locations| 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: | March 26, 2013 |
| 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 May 22, 2013