Comparing the Efficacy of Symbicort® pMDI and Formoterol Turbuhaler in Reducing Exacerbations in Patients With Cronic Obstructive Pulmonary Disease (RISE)

AstraZeneca

Status and phase: Completed; Phase 3

Conditions: COPD Patients

Treatments: Other: Placebo for Symbicort pMDI; Drug: Formoterol turbohaler; Other: Placebo for Formoterol Turbohaler; Drug: Symbicort

Study type: Interventional

Funder types: Industry

Identifiers

NCT02157935

D589UC00001

Details and patient eligibility

About

Comparing the efficacy of Symbicort® pMDI and Formoterol Turbuhaler in reducing exacerbations in patients with Chronic Obstructive Pulmonary Disease (COPD).

Full description

A Phase IIIB, 6-Month, Double-blind, Double-dummy, Randomized, Parallel-group, Multicenter Exacerbation Study of Symbicort® pMDI 160/4.5 μg x 2 Actuations Twice-daily Compared to Formoterol Turbuhaler 4.5 μg x 2 Inhalations Twice-daily in COPD Patients.

Enrollment: 2,026 patients

Sex: All

Ages: 40 to 95 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

3. A current clinical diagnosis of COPD with COPD symptoms for more than 1 year, according to the GOLD guidelines.

4. Current or previous smoker with a smoking history equivalent to 10 or more pack years (1 pack year = 20 cigarettes smoked per day for 1 year).

5. Post-bronchodilator FEV1/forced vital capacity (FVC) <0.7 (70%) and FEV1 ≤70% of predicted normal (PN) value.

6. Documented use of a short-acting inhaled bronchodilator (β2-agonists or anticholinergics) as rescue medication within 6 months prior to study start.

7. A score of ≥2 on the modified medical research council (MMRC) dyspnea scale. 8. Documented history of ≥1 moderate or severe COPD exacerbation(s) that required treatment with systemic (oral, IM, IV) corticosteroids (a minimum 3 day course of an oral corticosteroid treatment or single depot corticosteroid injection), or hospitalization (defined as an inpatient stay or >24 hour stay in an observation area in the emergency department or other equivalent facility depending on the country and healthcare system) within 2-52 weeks before Visit 1 (i.e., not within the 14 days prior to Visit 1). A history of an exacerbation treated exclusively with antibiotics will not be considered adequate.

Exclusion criteria

1. A history of asthma at or after 18 years of age.
2. Subjects with significant or unstable ischemic heart disease, arrhythmia, cardiomyopathy, heart failure (including significant cor pulmonale), uncontrolled hypertension as defined by the Investigator, or any other relevant cardiovascular disorder as judged by the Investigator.
3. Known homozygous alpha-1 antitrypsin deficiency.
4. Any significant disease or disorder (e.g., gastrointestinal, liver, renal, neurological, musculoskeletal, endocrine, metabolic, malignant, psychiatric, major physical impairment) which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results of the study, or the subject's ability to participate in the study.
5. A history of malignancy (except basal cell carcinoma) within the past 5 years.
6. Active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, primary pulmonary hypertension, interstitial lung disease, or other active pulmonary diseases.
7. Subjects who have needed additions or alterations to their usual maintenance or change in formulation of rescue therapy for COPD due to worsening symptoms within the 14 days prior to Visit 1 and up to Visit 3.
8. CXR (frontal and lateral) with suspicion of pneumonia or other condition/abnormality that will require additional investigation/treatment, or put the subject at risk because of participation in the study.
9. Risk factors for pneumonia: immune suppression (HIV, lupus) or other risk for pneumonia (e.g. neurological disorders affecting control of the upper airway, such as Parkinson's disease, myasthenia gravis, etc.).
10. Pneumonia not resolved within 14 days of Visit 1.
11. Moderate or severe COPD exacerbation that has not resolved within 14 days prior to Visit 1 or a moderate or severe COPD exacerbation that occurs between Visit 1 and Visit 2.
12. Long-term oxygen therapy (LTOT) or nocturnal oxygen therapy required for greater than 12 hours a day.
13. Subjects who are currently in the intensive rehabilitation phase or scheduled to begin new participation (intensive rehabilitation phase) in a pulmonary rehabilitation program during the study or have started a new pulmonary rehabilitation program within 60 days of Visit 1. Subjects in the maintenance phase of pulmonary rehabilitation program are not excluded.
14. Treatment with oral, parenteral, or intra-articular corticosteroids within 4 weeks prior to Visit 1.
15. Omalizumab or any other monoclonal or polyclonal antibody therapy taken for any reason within 6 months prior to Visit 1.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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2,026 participants in 2 patient groups

Symbicort pMDI

Active Comparator group

Description:

Symbicort pMDI, budesonide/formoterol, 160/4.5 μg x 2 actuations BID, for oral inhalation

Treatment:

Drug: Symbicort

Other: Placebo for Symbicort pMDI

Formoterol Turbuhaler

Active Comparator group

Description:

Formoterol Turbuhaler, 4.5 μg x 2 actuations BID, for oral inhalation

Treatment:

Drug: Formoterol turbohaler

Other: Placebo for Formoterol Turbohaler