Allergic Asthma MedDRA version: 12.0 Level: LLT Classification code 10001705 Term: Allergic asthma
Conditions
Interventions
Product Name: AZD8848
Product Code: AZD8848
Pharmaceutical Form: Nasal spray, solution
CAS Number: 866269-28-5
Current Sponsor code: AZD
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of informed consent prior to any study specific procedures 2. Male or female patients aged 18 to 55 years (inclusive). Females must be of non-childbearing potential or must have been stable on a highly effective contraceptive method for at least 3 months prior to Visit 1 and be willing to continue on the chosen contraceptive method, with additional use of a condom, until Visit 19. Women must be non-lactating and must have a date of menstruation consistent with non-pregnancy (see section 4.1.2 for more details) 3. A minimum of 6 months documented history of asthma defined according to the GINA guidelines (Global Initiative for Asthma 2008) prior to Visit 1 4. The presence of allergic sensitivity (grass, house dust mite, cat) verified by a positive skin prick test documented within the previous 24 months or at Visit 1 5. FEV1 (forced expiratory volume in 1 second) >70% of predicted normal value, prebronchodilator 6. The presence of an Early Asthmatic Response corresponding to = 20% FEV1 decrease within 2 hours post-allergen challenge as verified and documented within the previous 12 months or at screening. The inhaled allergen will be one of those giving a positive response in the skin prick test (see section 6.2.1). 7. Methacholine PC20 (the provocative concentration of methacholine causing a 20% fall in FEV1) =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Any clinically relevant disease and/or abnormality (past or present), which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, or influence the results of the study, or the patient’s ability to participate in the study. Includes pregnant or lactating females. 2. Symptomatic allergic rhinitis (those with a history of allergic rhinitis may participate if asymptomatic at screening and if, in the opinion of the Investigator, it is unlikely that disease exacerbation will occur during the course of the study) 3. Any clinical relevant abnormal findings in physical examination, clinical chemistry, haematology, urinalysis, vital signs, or ECG at baseline which, in the opinion of the investigator, may put the patient at risk because of participation in the study 4. QTcF >450ms, confirmed with repeated measurements at Visit 1 5. Rhythm, conduction (eg intermittent or constant Bundle branch block; Intraventricular conduction disturbance with repolarisation changes: intermittent or constant AV block (including 1st degree AV block with PR interval >220msec, 2nd or 3rd degree AV block)); or morphologic changes affecting repolirization (eg, flat, biphasic or inverted T waves in primary lead V2), that may limit ability to measure QTc and assess changes in QTc intervals or QTc morphology 6. History of additional risk factors for Torsade de pointes (eg heart failure, hypokaelamia, family history of Long QT syndrome, or sudden death) 7. Medical history suggesting or confirming abnormal immune function, except for asthma 8. Family history (parent or sibling) of autoimmune disease including but not limited to Wegener’s granulomatosis, system lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome, multiple sclerosis, autoimmune thrombocytopenia, primary biliary cirrhosis or any other autoimmune disease considered clinically relevant by the investigator 9. Any detection of anti-PR3 autoantibodies in the blood 10. History of or ongoing immunotherapy 11. Topical or inhaled glucocorticosteroid +/- Long-Acting ß-Agonists (LABAs) treatment within 4 weeks prior to Visit 1 12. Systemic glucocorticosteroid therapy for any reason within 6 weeks prior to Visit 1 13. Antihistamine treatment within 1 week prior to Visit 1. This period should be extended for antihistamines with a long half-life (see exclusion criteria 14) 14. Use of any medication (including vaccinations, over the counter drugs and herbal medicines such as St John's Wort) or therapy within 2 weeks prior to Visit 1 which may potentially expose the patient to any significant systemic exposure that may interfere with the objectives of the study or the safety of the patients as judged by the investigator, except for inhaled short-acting ß2 agonists for treatment of asthma symptoms and occasional intake of paracetamol 15. An exacerbation of asthm
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of AZD8848 on the Late Asthmatic Response (LAR) compared with placebo after 8 doses of once weekly intranasal administration in mild to moderate asthma patients challenged with inhaled allergen (Main Part only). ; Secondary Objective: • To evaluate the efficacy of AZD8848 compared with placebo after 8 doses of once weekly intranasal administration in mild to moderate asthma patients challenged with inhaled allergen as measured by the Early Asthmatic Response (EAR), Bronchial Hyperreactivity (BHR) and Sputum Biomarkers (Main Part only). • To investigate tolerability and safety of AZD8848 after 8 doses of once weekly intranasal administration in asthma patients (Pilot and Main Parts). • To investigate plasma concentrations of the acid metabolite around Cmax after the first and last dose of AZD8848 administered intranasally (concentrations represent the sum of AZD8848 and acid metabolite) (Main Part only). • To investigate the influence of butyrylcholinesterase genotype on pharmacokinetic and pharmacodynamic responses (Main Part only). ; Primary end point(s): • Efficacy - FEV1 (Late Asthmatic Response) - Primary Variable - FEV1 (Early Asthmatic Response) - PC20 (Methacholine challenge) - Sputum Cellularity and Cytokines • Safety and Tolerability - Vital signs, ECG, clinical chemistry, haematology, urinalysis, physical examination, clinical inspection of the nose, spirometry (FEV1), autoantibodies, adverse events • Pharmacokinetics and Pharmacogenetics - Concentration of acid metabolite in plasma (representing the sum of the | — |
Countries
United Kingdom
Outcome results
None listed