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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 6 November 2018
Main ID:  EUCTR2015-000353-20-HU
Date of registration: 13/07/2015
Prospective Registration: Yes
Primary sponsor: Vectura Limited
Public title: Clinical study to evaluate the the efficacy and safety of two doses of nebulised budesonide delivered by the VR475 Inhalation System, in comparison to conventionally nebulised budesonide, in patients with uncontrolled asthma
Scientific title: A randomised, double-blind, placebo-controlled, parallel group study to evaluate the efficacy and safety of two doses of nebulised budesonide delivered by the VR475 Inhalation System, with an open-label comparison to conventionally nebulised budesonide, in patients with uncontrolled asthma despite treatment with high dose inhaled corticosteroid and at least a second controller (GINA Step 4) and those receiving oral corticosteroid (GINA Step 5)
Date of first enrolment: 15/09/2015
Target sample size: 600
Recruitment status: Not Recruiting
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-000353-20
Study type:  Interventional clinical trial of medicinal product
Study design:  Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: yes Other specify the comparator: Budesonide nebuliser suspension 1 mg/2 ml (open-label) delivered by the PARI BOY® Inhalation System Number of treatment arms in the trial: 4  
Phase:  Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no
Countries of recruitment
Bulgaria Germany Greece Hungary Philippines Poland Romania Russian Federation
Serbia Ukraine United Kingdom
Contacts
Name: Clinical Trials Information   
Address:  1 Prospect west SN14 6FH Chippenham, Wiltshire United Kingdom
Telephone: +441249667700
Email: clinical.enquiries@vectura.com
Affiliation:  Vectura Limited
Name: Clinical Trials Information   
Address:  1 Prospect west SN14 6FH Chippenham, Wiltshire United Kingdom
Telephone: +441249667700
Email: clinical.enquiries@vectura.com
Affiliation:  Vectura Limited
Key inclusion & exclusion criteria
Inclusion criteria:
1.Adolescents aged 12 to 17 years (inclusive) and adults aged 18 to 74 years (inclusive). For those countries where local regulations permit enrolment of adults only, subject recruitment will be restricted to those who are = 18 years of age;
2.FEV1 reversibility (increase of at least 12% in absolute FEV1 and 200 ml from pre-bronchodilator value within 15-30 minutes after the use of inhaled bronchodilator) at the Screening or Randomisation Visits or during past 24 months;
A positive airways hyper-responsiveness test (fall in FEV1 from baseline of = 20% with standard doses of methacholine or histamine, or =15% with standardised hyperventilation, hypertonic saline or mannitol
challenge) during the past 24 months is also acceptable;
3. High dose inhaled glucocorticosteroid at a total daily dose of = 500 µg of fluticasone proprionate DPI or equivalent) for at least 3 months prior to the Screening Visit;
4. Treatment with at least a second asthma controller medication (i.e. not a short acting ß-agonist [SABA]) for at least 3 months prior to the Screening Visit;
5. FEV1 <80% of predicted value at the Screening and Randomisation Visits;
6. ACQ-5 score (symptom-only version) of 1.5 or higher at the Screening and Randomisation Visits;
7. Subjects with a previously confirmed history of at least two clinically significant asthma exacerbations defined as those requiring treatment or increased treatment with oral/systemic corticosteroids for at least 3 days and/or requiring hospitalisation and/or visit to an emergency department for an exacerbation in the 12 months prior to the Screening Visit, despite the use of high-dose ICS and at least one additional controller medication (or Symbicort SMART) at the time the exacerbation occurred;
8. Written informed consent obtained from the subject or subject’s parents/legal representatives (according to local regulations) and written or verbal assent by the subject (when appropriate), prior to participation in the study;
9. A negative pregnancy test must be available for any women of childbearing potential at the Screening and Randomisation Visits (prior to randomisation to one of the treatment groups);
10. Subjects able to read, comprehend and write at a level sufficient to complete study-related materials.
Are the trial subjects under 18? yes
Number of subjects for this age range: 60
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 490
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion criteria:
1. Asthma exacerbation or significant change in asthma treatment within the 4 weeks prior to the Screening Visit or during the Screening Period;
2. Abnormal lab values for biochemistry tests during the Screening Period that may indicate impaired ability to metabolise and/or excrete budesonide (aspartate transaminase [AST], alanine transaminase [ALT] > 3 times upper limit of normal range, serum creatinine > 1.5 times upper limit of normal range).
3.Current smokers or subjects with a recent smoking history (less than 6 months before randomisation) of =10 pack years (number of pack years = number of cigarettes per day / 20 x number of years smoked);
4.Presence of a clinically important lung condition other than asthma. This includes, but is not limited to, current infection, bronchiectasis, pulmonary fibrosis, bronchopulmonary aspergillosis or diagnoses of emphysema or chronic bronchitis (chronic obstructive pulmonary disease other than asthma) or a history of lung cancer;
5.Subjects with a diagnosis of active malignancy or in the process of investigation for a suspected malignancy. Subjects with a past medical history of malignancy can be allowed in the trial if in remission and provided anyone with a diagnosis of a recurrent malignant tumour or having received treatment for a malignancy within 12 months prior to the Screening Visit are excluded;
6.Subjects with a known immunodeficiency (e.g. human immunodeficiency virus),) or receiving immunosuppressant and/or immune modulating therapy (e.g. rheumatoid arthritis) other than that explained by the use of corticosteroids taken as therapy for asthma;
7. Subjects who have clinically significant cardiovascular, endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, haematological or any other system abnormalities that were uncontrolled with standard treatment and which in the investigator’s opinion places the subject at undue risk by participating in the study;
8. History of substance abuse that may impair or risk the subject’s full participation in the study, in the judgment of the investigator;
9. Treatment with other investigational treatment within 4 weeks prior to the Screening Visit;
10. Regular oral/systemic corticosteroids for the treatment of conditions other than asthma in the 3 months prior to the Screening Visit;
11. History of allergy or adverse experience with budesonide or any of the excipients of budesonide nebuliser suspension (see VR475 Investigator’s Brochure 2016);
12. Use of a monoclonal antibody for the treatment of asthma within the 6 months prior to the Screening Visit;
13.Pregnant or lactating females. or females who are planning to become pregnant during the study.
14. Subjects with features suggestive of Cushing's syndrome;
15. Subjects who have failed screening twice before in this study or who have completed this study;
16. Treatment with the following medications during the Screening Period: benzodiazepines, barbiturates and opiates (except at prescription doses for analgesia and/or insomnia), new or nonmaintenance
immunotherapy, methotrexate, oral gold, dapsone or i.v. ? globulin, monoclonal antibodies, anti-IgE treatment, ß-blockers, macrolides (either as a chronic therapy or as an antimicrobial treatment for infection) and any investigational treatment other than the study medication.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Therapeutic area: Body processes [G] - Circulatory and Respiratory Physiological Phenomena [G09]
Uncontrolled Asthma
MedDRA version: 19.0 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Intervention(s)

Product Name: Budesonide nebuliser suspension delivered via the VR475 Inhalation System
Product Code: VR475
Pharmaceutical Form: Nebuliser suspension
INN or Proposed INN: BUDESONIDE
CAS Number: 51333-22-3
Current Sponsor code: VR475/3/001
Other descriptive name: VR475
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Nebuliser suspension
Route of administration of the placebo: Inhalation use

Product Name: Budesonide nebuliser suspension delivered via the VR475 Inhalation System
Product Code: VR475
Pharmaceutical Form: Nebuliser suspension
INN or Proposed INN: BUDESONIDE
CAS Number: 51333-22-3
Current Sponsor code: VR475/3/001
Other descriptive name: VR475
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 0.5-
Pharmaceutical form of the placebo: Nebuliser suspension
Route of administration of the placebo: Inhalation use

Product Name: Budesonide nebuliser suspension delivered by PARI BOY® Inhalation System
Pharmaceutical Form: Nebuliser suspension
INN or Proposed INN: BUDESONIDE
CAS Number: 51333-22-3
Current Sponsor code: VR475/3/001
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1-

Primary Outcome(s)
Main Objective: To evaluate the clinical efficacy, safety and tolerability of VR475 1 mg/2 ml twice daily given for 52 weeks compared to placebo.
Primary end point(s): The annualised rate of clinically significant exacerbations during the Treatment Period.
Secondary Objective: -To evaluate the clinical efficacy, safety and tolerability of VR475 1 mg/2 ml compared to conventionally nebulised budesonide 1 mg/2 ml twice daily;
-To investigate the dose-response relationship of VR475;
-To evaluate pre and post-dose blood levels of budesonide;
-To evaluate any change from Baseline to End-of-Treatment in OCS dose in those subjects receiving OCS at Baseline
Timepoint(s) of evaluation of this end point: During Treatment Period.
Secondary Outcome(s)
Timepoint(s) of evaluation of this end point: Baseline to End-of-Treatment/Week 52
Secondary end point(s): -Change in in-clinic pre bronchodilator FEV1 from baseline during the Treatment Period;
- Change in in-clinic forced expiratory flow between 25% and 75% of FVC [FEF25-75]) from baseline during the Treatment Period;
- Time to first clinically significant exacerbation;
- Change in ACQ-5 scores from baseline during the Treatment Period
Secondary ID(s)
VR475/3/001
2015-000353-20-DE
Source(s) of Monetary Support
Vectura Limited
Secondary Sponsor(s)
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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