A phase II, multi-centre, single blind study to evaluate the safety, tolerability and explore the efficacy of 8.0 mg ASM8 inhaled daily for 14 days in adult subjects with moderate to severe asthma - Safety & Tolerability of 8mg ASM8 in moderate to severe asthmatics
- Conditions
- moderate to severe asthmaMedDRA version: 13.1Level: LLTClassification code 10003638Term: Atopic asthmaSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disordersMedDRA version: 13.1Level: LLTClassification code 10001705Term: Allergic asthmaSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
- Registration Number
- EUCTR2011-000126-30-GB
- Lead Sponsor
- Pharmaxis Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 15
The subject must:
1.Be a non-smoker or ex-smoker (who has stopped for at least 6 months and who had less than a 10 pack year history);
2.Be 18 or older and less than 75 years old;
3.Be willing to use adequate and effective contraception as defined in section 5.4 (male and female subjects - female subjects at risk of pregnancy only). Women of childbearing potential must demonstrate a negative test result of serum ß-hCG at screening and must have a negative urine pregnancy at each visit to remain in the study;
4.Be diagnosed with asthma for =3 months and otherwise in good health as assessed by the investigator;
5.Have moderate to severe asthma as defined by ATS criteria [8];
6.Be currently receiving inhaled short-acting bronchodilator and at least a moderate dose inhaled corticosteroid (defined as total daily dose of 500 ug or more of fluticasone or equivalent) with a long acting bronchodilator (LABA) treatment for asthma;
7.Have used inhaled corticosteroids for at least the last 3 consecutive months prior to screening. The dose of inhaled corticosteroids and LABA should be stable over the last 30 days prior to screening;
8.Be on a stable dose if using inhaled anticholinergic agents, antileukotrienes and xanthenes (theophyllines) for the preceding 30 days and the dose will not change during the study;
9.Have an FEV1 % predicted greater than or equal to 50 % (at least 6 hours after last use of salbutamol) and lower or equal to 100%, where the FEV1 recorded is the best of three reproducible values (within a maximum change of 5% on the 2 best values);
10.Have a positive skin-prick test to at least one of common aeroallergens (including cat fur and dander, house dust mite (HDM), mixed grass pollen, etc.) in the previous 12-months. Allergen skin prick tests will be performed to at least 10 common aeroallergens with a positive and negative control. Historical data signed and dated up to 12 months prior to screening date showing at least one positive reaction, can be used in replacement, if the record can be verified by the monitoring CRA. Short-acting antihistamines should not be used within 4 days prior to skin tests and long-acting antihistamines must be avoided at all times during the study.
11.Have a positive response to inhaled mannitol (equal to or less than 200 mg) and be capable of repetitively producing adequate sputum during sputum induction. Adequate sputum is defined as a load of at least 75 mg with a viability factor of not less than 40%; (if sputum contains more than 12 million cells or more than 20 % epithelial cells acceptability will need to be approved by the sponsor); and
12.Be able to understand and provide written informed consent.
For entry into the therapeutic portion of the study (Visit 2), the subject MUST have:
13.A minimum level of daytime symptoms requiring inhaled Beta-agonist on an as-needed-basis with an asthma control questionnaire (ACQ) greater than 1.5 points and less than 5 points,
14.Employed the Aeroneb® Go nebuliser at least 75% of the time within 2 hours of the specified times as reviewed. If this criterion is not fully met, the Run-In phase can be extended for two additional days.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0
The subject must NOT:
1.Have a pulmonary or other health condition (including, but not limited to, cancer, medication dependency or abuse, or psychiatric disease) for which the Investigator considers that participation in this protocol represents a risk for the subject;
2.Have a history of classic chronic obstructive pulmonary disease (COPD, including a 20 pack/year of smoking), vocal cord dysfunction, uncontrolled acid reflux or any chronic active lung disease other than asthma;
3.Have a respiratory tract infection within 4 weeks preceding study entry or an unresolved sinus infection;
4.Have a history of clinically significant hypotensive episodes or symptoms of fainting, dizziness, or light-headedness when performing pulmonary function tests or blood drawing or bronchospasm with inhaled saline solution or mannitol;
5.Have a history or symptoms of cardiovascular disease, particularly coronary artery disease, arrhythmias, hypertension, or congestive heart failure that are judged clinically significant by the investigator;
6.Have a history or symptoms of significant diabetes, renal insufficiency, autoimmune, hematological or neurological disease, including transient ischemic attack (TIA), stroke, seizure disorder, or behavioural disturbances which in the Investigator’s opinion may put the subject at significant risk, may confound results or may interfere significantly with the patient’s participation in the study;
7.Have a history of serious adverse reaction or hypersensitivity to corticosteroids;
8.Have a known coagulopathy;
9.Have an abnormal recent (less than 12 months) chest X-ray or electrocardiogram that is judged clinically significant;
10.Be pregnant or lactating or have positive plasma pregnancy test;
11.Had an exacerbation of asthma in the last 6 weeks;
12.Have used cromones within 2 weeks of screening;
13.Have used omalizumab (xolair) within 5 months of screening;
14.Been receiving more than 20 mg of prednisolone or equivalent, or the dose of oral/systemic corticosteroids modified over the last 6 weeks;
15.Have used tricyclic antidepressants, benzodiazepines, immunosuppressives, anticoagulants (warfarin, heparin, or other long-acting synthetic anticoagulants), for more than one day of the last 60 days of screening;
16.Have used long-acting antihistamine drugs within 2 weeks of screening;
17.Have a history of endotracheal intubation for asthma-related exacerbation within 3 years of screening;
18.Have participated in any other investigational medication treatment protocol within the preceding 30 days, or a longer and more appropriate time as determined by the Investigator (e.g., approximately five half-lives of the previous investigational medication);
19.Have a documented worsening of asthma due to allergies in the period of year where the study will be performed;
20.Have a concomitant disease or lung condition which could interfere with the conduct of the study or for which the treatment might interfere with the conduct of the study;
21.Have a malignancy (other than resected basal and squamous cell carcinoma and in situ cervical cancer) within 5 years of screening visit or if malignancy occurred ? 5 years before, documentation of the absence of recurrence since then;
22.Have had a vaccination within 4 weeks of screening or planned vaccination during the study other than the influenza vaccine;
23.Have a recent (less than 1 year) history of alcohol dependency;
24.Be unable to comply with the study requir
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method