A 52-WEEK, DOUBLE-BLIND, RANDOMISED, MULTI-CENTRE, PHASE III, PARALLEL-GROUP STUDY IN PATIENTS 12 YEARS AND OLDER WITH ASTHMA, EVALUATING THE EFFICACY AND SAFETY OF SYMBICORT (BUDESONIDE/FORMOTEROL) TURBUHALER 160/4.5 μG ‘AS NEEDED’ COMPARED WITH PULMICORT (BUDESONIDE) TURBUHALER 200 μG TWICE DAILY PLUS TERBUTALINE TURBUHALER 0.4 MG ‘AS NEEDED’

• Register: RPEC
• Last refreshed on: 4 September 2023
• Main ID: PER-059-14
• Date of registration: 24/12/2014
• Prospective Registration: Yes
• Primary sponsor: ASTRAZENECA - PERU,
• Public title: A 52-WEEK, DOUBLE-BLIND, RANDOMISED, MULTI-CENTRE, PHASE III, PARALLEL-GROUP STUDY IN PATIENTS 12 YEARS AND OLDER WITH ASTHMA, EVALUATING THE EFFICACY AND SAFETY OF SYMBICORT (BUDESONIDE/FORMOTEROL) TURBUHALER 160/4.5 μG ‘AS NEEDED’ COMPARED WITH PULMICORT (BUDESONIDE) TURBUHALER 200 μG TWICE DAILY PLUS TERBUTALINE TURBUHALER 0.4 MG ‘AS NEEDED’
• Scientific title: A 52-WEEK, DOUBLE-BLIND, RANDOMISED, MULTI-CENTRE, PHASE III, PARALLEL-GROUP STUDY IN PATIENTS 12 YEARS AND OLDER WITH ASTHMA, EVALUATING THE EFFICACY AND SAFETY OF SYMBICORT (BUDESONIDE/FORMOTEROL) TURBUHALER 160/4.5 μG ‘AS NEEDED’ COMPARED WITH PULMICORT (BUDESONIDE) TURBUHALER 200 μG TWICE DAILY PLUS TERBUTALINE TURBUHALER 0.4 MG ‘AS NEEDED’
• Date of first enrolment: 02/01/2015
• Target sample size: 250
• Recruitment status: Complete
• URL: https://www.ins.gob.pe/ensayosclinicos/rpec/recuperarECPBNuevoEN.asp?numec=059-14
• Study type: Interventional
• Study design: This is a 52-week, double-blind, randomised, multi-centre, parallel-group, phase III study in patients 12 years and older with asthma, evaluating the efficacy and safety of Symbicort (budesonide/formoterol) Turbuhaler 160/4.5 μg ‘as needed’ compared with Pulmicort (budesonide) Turbuhaler 200 μg twice daily plus terbutaline Turbuhaler 0.4 mg ‘as needed’.
• Phase: III

Countries of recruitment

Argentina, Australia, Brazil, Bulgaria, Chile, Colombia, Congo, Czech Republic, France, Germany, Hungary, Italy, Korea South, New Zealand, Romania, Russian Federation, Slovakia, South Africa, Spain, Sweden, Ukraine, Vietnam

Contacts

• Name: Ursula Chavez Rodriguez-Frias
• Affiliation: ASTRAZENECA PERU S.A.

• Name: Ursula Chavez Rodriguez-Frias
• Affiliation: ASTRAZENECA PERU S.A.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Provision of informed consent prior to any study specific procedures. For patients under-age, signed informed consent from both the patient and the patient’s parent/legal guardian is required
2. Outpatients of either gender aged ≥12 years at Visit 1
3. Diagnosis of asthma according to GINA criteria with a documented history of at least 6 months prior to Visit 1
4. Patients who are in need of GINA (2012) step 2 treatment:
- uncontrolled on SABA ‘as needed’ as judged by the investigator for the last 30 days before Visit 2, or
- controlled on mono-maintenance therapy with low stable dose ICS (≤ 400 μg budesonide per day or corresponding dose of other ICS) (see Appendix E for conversion) or LTRA as judged by the investigator for the last 30 days prior to Visit 2
5. Based on lung function tests (see Section 5.1.2) at Visit 2, patients pre-treated with
- a SABA only should have pre-bronchodilator FEV1 ≥ 60 % of predicted normal (PN) and post-bronchodilator FEV1 ≥ 80 % of PN according to the European Respiratory Society (ERS) guidelines (Quanjer et al 2012)
- low dose ICS or LTRA medication should have pre-bronchodilator FEV1 ≥80 % PN according to the ERS guidelines
6. Reversible airway obstruction according to a reversibility test (see Section 5.1.2.2) performed at Visit 2 defined as an increase in FEV1 ≥12% and ≥200 ml relative to baseline, after inhalation of 1 mg Bricanyl Turbuhaler. The test can be repeated at Visit 3 in case the patients fail at Visit 2. If patients on low dose ICS or LTRA fail at both occasions, they can still be included if they have a documented historical reversibility test within the last 12 months prior to Visit 3, with an increase in FEV1 ≥12% and ≥200 ml relative to baseline after administration of a rapid acting β2-agonist.

Exclusion criteria:
1.Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
2.Previous enrolment in the present study
3.Participation in another clinical study with a non-biologic investigational product or new formulation of a marketed non-biologic drug during the last 30 days prior to Visit 1
4.Participation in another clinical trial with any marketed or investigational biologic drug within 4 months or 5 half-lives whichever is longer, prior to Visit 1
5.Any asthma worsening requiring change in asthma treatment other than SABA within 30 days prior to Visit 1
6.Use of oral, rectal or parenteral GCS within 30 days and/or depot parenteral GCS within 12 weeks prior to Visit 1
7.Use of any β-blocking agent including eye-drops
8.Known or suspected hypersensitivity to study drugs or excipient
9.Smoker (current or previous) with a smoking history of ≥ 10 pack years
10.Medical history of life-threatening asthma including intubation and intensive care unit admission
11.Any significant disease or disorder (e.g., cardiovascular, pulmonary other than asthma, gastrointestinal, hepatic, renal, neurological, musculoskeletal, endocrine, metabolic, malignant, psychiatric, major physical impairment) which, in the opinion of the investigator, may either put the patient at risk because of participation in the study, or may influence the results of the study, or the patient’s ability to participate in the study
12.Any clinically relevant abnormal findings in physical examination and/or vital signs at Visit 2, which, in the opinion of the investigator, may put the patient at risk if participating in the study
13.Pregnancy, breast-feeding or planned pregnancy during the study. Fertile women not using acceptable contraceptive measures, as judged by the investigator
14.Planned hospitalisation during the study
15.Suspected poor capability, as judged by the investigator, of following instructions of the study.
For randomisation at Visit 3, patients should not fulfil any of the following criteria:
16.Use of ≥ 6 Bricanyl Turbuhaler ‘as needed’ inhalations per day, for a certain number of days depending on the actual length of run-in: for ≥ 2 days out of 14 days; for ≥ 3 days out of 15-21 days; for ≥ 4 days out of 22 or more days of run-in
17.Any asthma worsening requiring change in treatment other than SABA from Visit 1 until randomisation.


Age minimum: 12
Age maximum: 100
Gender: --

Health Condition(s) or Problem(s) studied

J45

-J45

Intervention(s)

This study starts with an enrolment visit (Visit 1) where informed consent is obtained and inclusion and exclusion criteria are reviewed. At Visit 2 patients will enter a 2-4 week run-in period during which all of them will be treated with a short acting β2 agonist (Bricanyl) ‘as needed’. Eligible patients will be randomised at Visit 3 and enter a 52-week double-blind treatment period. Two weeks after the completion of study treatment a follow-up telephone contact will be performed. The total expected duration of the study for a patient will be 56-59 weeks.
Investigational product, dosage and mode of administration
Symbicort Turbuhaler 160/4.5 µg (budesonide 160 μg and formoterol fumarate dihydrate 4.5 μg per inhalation, powder for inhalation in a dry powder inhaler) used ‘as needed’ (to relieve asthma symptoms) in addition to Placebo for budesonide (powder for inhalation in a dry powder inhaler matching the Pulmicort Turbuhaler) administered two times daily.
Comparators, dosage and mode of administration
Terbutaline Turbuhaler 0.4 mg (terbutaline sulphate 0.4 mg per inhalation, powder for inhalation in a dry powder inhaler) used ‘as needed’ (to relieve asthma symptoms) in addition to Pulmicort Turbuhaler 200 µg (budesonide 200 µg per inhalation, powder for inhalation in a dry powder inhaler) administered two times daily.
Non-investigational medicinal product, dosage and mode of administration
Bricanyl Turbuhaler 0.5 mg (terbutaline sulphate 0.5 mg per inhalation, powder for inhalation in a dry powder inhaler) used ‘as needed’ during the run-in period and as a bronchodilator for the lung function measurements.

Source(s) of Monetary Support

AstraZeneca Peru S.A.

Ethics review

Status: Approved
Approval date: 15/09/2014
Contact:

[e-mail] - [e-mail]

Universidad San Martin de Porres

999098514

[e-mail] - [e-mail]

Status: Approved
Approval date: 15/12/2014
Contact:

[e-mail] - [e-mail]

Universidad San Martin de Porres

999098514

[e-mail] - [e-mail]

Status: Approved
Approval date: 05/02/2015
Contact:

[e-mail]

Hospital Nacional Arzobispo Loayza

88339014 - 3301677

[e-mail]

Status: Approved
Approval date: 18/05/2015
Contact:

[e-mail] - [e-mail]

Universidad San Martin de Porres

999098514

[e-mail] - [e-mail]

Status: Approved
Approval date: 22/06/2015
Contact:

[e-mail] - [e-mail]

Universidad San Martin de Porres

999098514

[e-mail] - [e-mail]

Status: Approved
Approval date: 12/08/2015
Contact:

[e-mail]

Hospital Nacional Guillermo Almenara Irigoyen - EsSalud

999436950

[e-mail]

Status: Approved
Approval date: 28/01/2016
Contact:

[e-mail]

Comite Institucional de Etica en Investigacion de la Asociacion Benefica Prisma

616-5500 Anx. 246

[e-mail]

Status: Approved
Approval date: 16/02/2016
Contact:

[e-mail] - [e-mail]

Universidad San Martin de Porres

999098514

[e-mail] - [e-mail]