A double-blind, placebo controlled, randomised, parallel group phase IIa study to investigate the efficacy, tolerability, and safety of different dosing regimens of AZD8848 administered intranasally to seasonal allergic rhinitis patients out of pollen season in a nasal allergen challenge model
- Conditions
- Allergic RhinitisMedDRA version: 12.1Level: LLTClassification code 10001723Term: Allergic rhinitis
- Registration Number
- EUCTR2010-020747-13-SE
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- Not specified
For inclusion in the study patients should fulfil the following criteria:
1. Provision of signed and dated informed consent prior to any study specific procedures
2. Female and/or male patients, aged 18 to 55 years inclusive. Females must be of non-childbearing potential or must have been stable on highly effective contraceptive method for at least 3 months prior to Visit 1 and be willing to continue on the chosen method, with additional use of a condom by male partner, until 3 months after the last dose
3. Females must have a negative pregnancy test and a date of last menstruation consistent with non-pregnancy at Visit 1
4. Have a body mass index (BMI) between 19 and 30 kg/m2 and a weight between 50 and 100 kg
5. Seasonal allergic rhinitis patients out of pollen season
6. Have a history of birch and/or timothy grass pollen induced seasonal allergic rhinitis for at least the previous 2 years
7. Have presence of allergic sensitivity to birch and/or timothy grass pollen verified by a positive skin prick test documented within the previous 24 months or at Visit 1
8. Have a need of treatment for their nasal symptoms during the pollen season
9. Have reaction to an individually titrated dose of nasal allergen resulting in at least 5 sneezes and/or recorded score of 2 or more on a scale from 0 to 3 in either of the symptoms nasal blockage or runny nose
10. Be able to metabolise AZD8848 (an in vitro screening assay will determine BChE activity in a blood sample taken at Visit 1 using a pre-defined limit)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
Patients should not enter the study if any of the following exclusion criteria are fulfilled:
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
2. Any clinically relevant abnormal findings in physical examination, clinical chemistry, hematology, 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
3. QTcF > 450 ms (confirmed with repeated measurements) at Visit 1
4. Rhythm, conduction (e.g. intermittent or constant Bundle branch block; Intraventricular conduction disturbance with repolarization changes; intermittent or constant AV block [including 1st degree AV block with PR interval > 220 msec, 2nd or 3rd degree AV block]); or morphologic changes affecting repolarization (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
5. History of additional risk factors for Torsade de pointes (eg, heart failure, hypokalemia, family history of Long QT syndrome, or sudden death)
6. Medical history suggesting or confirming abnormal immune function, apart from allergic rhinitis
7. Family history (parent or sibling) of autoimmune disease including, but not limited to, Wegeners granulomatosis, systemic lupus erythematosus, rheumatoid arthritis, Sjögren´s syndrome, multiple sclerosis, autoimmune thrombocytopenia, primary biliary cirrhosis, Mb Crohn, ulcerative colitis, type 1 diabetes or other autoimmune disease considered relevant by the Investigator
8. History of asthma
9. Symptomatic perennial allergic or non-allergic rhinitis, except for cat and dog sensitivity under the condition that these patients will not be exposed to cats and dogs during the study up until Visit 16, as judged by the Investigator
10. History of or ongoing immunotherapy, including but not limited to specific immunotherapy (SIT)
11. Topical or inhaled glucocorticosteroid treatment within 1 month prior to Visit 1
12. Systemic glucocorticosteroid therapy for any reason during 6 weeks prior to Visit 1
13. Antihistamine treatment within 1 week prior to Visit 1
14. Use of any medication (including vaccinations, over-the-counter drugs, herbal medicines and nutritional supplements,) or therapy within 2 weeks prior to Visit 2 (or longer if the medication has a half-life long enough to 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 occasional intake of paracetamol
15. Suspicion of Gilbert’s syndrome
16. A suspected/manifested infection according to World Health Organisation (WHO) risk groups 2, 3, or 4
17. Positive results on screening tests for serum Hepatitis B surface antigen, Hepatitis C antibodies, and/or HIV
18. Any upper respiratory tract infection (bacterial, viral or fungal infections of the airways) or any other clinically significant illness within 2 weeks prior to Visit 2 being symptomatic enough to affect study conduct or the wellbeing of the patient as judged by the Investigator
19. Structural abnormalities of the nose or nasal disorder symptomatic enough to cause significant nasal obstruction as judged b
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