Acute serious allergic reaction
Conditions
Interventions
Cohort 1:Healthy subjects were randomly assigned to 1 of 6 sequences. During Cycles 1 to 3, the nurse/investigator administered doses,subjects randomly received a single dose of 2.0 mg ARS-1 to the le
Cohort 2:Healthy subjects were randomly assigned to 1 of 2 sequences and receive the following 2 doses:
Two 2.0 mg doses of ARS-1, 10 minutes apart, first to the left nose and then to the right nose
Two doses of 0.5 mg epinephrine intramuscular injection, 10 minutes apart, first the anterolateral left thigh and then the anterolateral right thigh.
Cohort 3:Subjects with allergic rhinitis episodes were randomized to one of 2 sequences and received the following 3 doses, administered by the nurse/investigator:
A single dose of 2.0 mg ARS-1 was ad
Sponsors
Beijing Chao-yang Hospital, Capital Medical University
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Inclusion criteria
Inclusion criteria: 1. Adult male and female subjects aged 18 to 55 years, inclusive, at the time of signing the informed consent form (ICF); 2. Healthy people or subjects with allergic rhinitis episodes: 1)Healthy subjects had a TNSS score of 0 at baseline and pre-dose on Day 1 (Day 1); 2)Subjects with allergic rhinitis episodes need to meet the following conditions: a. History of allergic rhinitis; b. Positive skin prick test or serum-specific IgE within 12 months prior to enrollment; c. TNSS >= 5 points/12 points and nasal congestion score >= 2 points/3 points at baseline and before dosing on Day 1 (Day 1). 3. BMI 19 to 28 kg/m2 (inclusive); total body weight> 50 kg; 4. No history of hypertension or cardiovascular disease in the past 10 years; 5. At screening, vital signs were stable within the following ranges (after 5 minutes of rest): o SBP >= 90 and = 50 and = 50 and = 12 months without other reasons and a recorded serum follicle stimulating hormone (FSH) level>40 mIU/mL or other recorded medical condition (e.g., birth without a uterus)]. 7. If male (with or without vasectomy), agree to use highly effective contraceptive methods between screening and 7 days after the last dose of trial drug; 8. Volunteering to sign the informed consent form, being able to read and complete the questionnaire, understand and comply with the requirements and restrictions listed in the informed consent form and this protocol (including but not limited to scheduled visits, dosing schedules, laboratory tests and other study procedures).
Exclusion criteria
Exclusion criteria: 1. A history of clinically significant gastrointestinal, renal, liver, nervous system, hematology, endocrine, tumor, pulmonary (such as asthma and COPD), immune, psychiatric or cardiovascular disease, or any other condition that, in the opinion of the investigator, would endanger subject safety or affect the validity of study results; 2. Previous or current history of nasal fractures, severe nasal injuries, external nasal deformities or nasal structure abnormalities, sinus/nasal space-occupying lesions, etc. that may interfere with nasal spray administration [e.g., nasal polyps, deviation of the nasal septum (the middle turbinate cannot be seen under nasal endoscopy, which may cause differences in absorption between the nostrils), nasal perforations, and any other nasal passage abnormalities or sleep apnea syndrome requiring treatment], or are not suitable for participation in the study based on the judgment of an otolaryngologist. 3. Patients with drug-induced rhinitis, recurrent epistaxis (>1 epistaxis per month), acute phase or specific inflammation of sinusitis/paranasal sinusitis, nasal symptoms caused by systemic diseases or autoimmune diseases, or patients with mucosal inflammatory diseases that may affect the nasal mucosa (such as pemphigus or Sjogren's syndrome or genetic or congenital diseases such as fungal sinusitis, nasal mucocilia dysfunction); 4. Any clinically significant medical condition or physical examination (PE) results during the screening period deemed by the investigator; 5. History of cardiovascular disease or ECG abnormalities at screening, including any previous history of myocardial infarction or clinically significant abnormalities in electrocardiogram (ECG)[e.g., second-or third-degree heart block, uncontrolled arrhythmia, QTcF (Fridericia's correction) interval>450 ms in male subjects,>470 ms in female subjects]; 6. Severe traumatic injury, major surgery, or open biopsy within 30 days prior to study screening; 7. Subject's abnormalities in blood chemistry, blood routine, coagulation function, and urine routine tests at screening or Day-1 (unless the investigator considers the results out of range to be not clinically significant); 8. Have donated blood (including donated platelets or plasma alone) or acute blood loss (>50mL) within 30 days before trial drug administration, or plan to donate blood or blood components within 30 days after study completion; 9. The test was positive for orthostatic hypotension; 10. Use of tobacco-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco or nicotine patches or chewing gum, etc.) within 2 months prior to dosing with positive nicotine screening; 11. Have a history of drug abuse (defined as the use of any prohibited drug within 12 months prior to screening), or have a positive urine drug screen result for abused drugs or prohibited drugs at screening or upon entry to the study site (baseline); 12. A history of alcohol abuse [defined as drinking more than twice a day (up to 14 times a week)], with one drink defined as 12 ounces of beer (approximately 360 mL), 4 ounces of wine (approximately 120 mL), or 1 ounce of spirits (approximately 30 mL); 13. Eating abnormalities in the first 4 weeks from Day-1 [e.g., strictly restricting certain basic food groups (e.g., ketogenic diet), restricting calories (e.g., fasting), and/or requiring the use of daily supplements to replace foods normally consumed at mealtimes]; 14. Participated in a
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| After a single dose of ARS-1 IN and epinephrine IM administration in healthy adult subjects , compare PK parameters of epinephrine, namely Cmax, Tmax, early partial AUC [AUC(0-10min), AUC(0-15min), AUC (0-20min), AUC(0-45min), AUC(0-60min)] and AUC(0-t) ;After a single dose of ARS-1 IN and epinephrine IM administration in healthy adult subjects, compare PD parameters of epinephrine, namely mean maximum effect (Emax) on systolic blood pressure (SBP) and pulse rate (PR), median maximum effect time (tEmax) on SBP and PR;;After two doses of ARS-1 IN and epinephrine IM administration in healthy adult subjects, compare PK parameters of epinephrine, Cmax, Tmax, early partial AUC [AUC(0-10min), AUC(0-15min), AUC (0-20min), AUC(0-45min), AUC(0-60min)] and AUC(0-t);After two doses of ARS-1 IN and epinephrine IM administration in healthy adult subjects, compare PD parameters of epinephrine, namely Emax of SBP and PR, TtEmax of SBP and PR;;PK parameters after nurse/investigator administration and self-administration of ARS-1, namely Cmax, Tmax, early partial AUC [AUC(0-10min), AUC(0-15min), AUC(0-20min), AUC(0-45min), AUC(0-60min)] and AUC(0-t) ;;PD parameters after nurse/investigator administration and self-administration of ARS-1, namely Emax and tEmax of SBP and PR;;After a single dose of ARS-1 IN and epinephrine IM administration in subjects with allergic rhinitis, compare PK parameters of epinephrine, namely Cmax, Tmax, early partial AUC [AUC(0-10min), AUC(0-15min), AUC (0-20min), AUC(0-45min), AUC(0-60min)] and AUC(0-t) ;After a single dose of ARS-1 IN and epinephrine IM administration in subjects with allergic rhinitis, compare PD parameters of epinephrine, namely Emax of SBP and PR, tEmax of SBP and PR.; | — |
Secondary
| Measure | Time frame |
|---|---|
| Adverse events, vital signs, laboratory tests, nasal irritation assessment, visual analog scale (VAS) for pain;PK parameters, namely Cmax, Tmax, early partial AUC [AUC(0-10min), AUC(0- 15min), AUC (0-20min), AUC (0-45 min), AUC(0-60min)] and AUC(0-t) , as well as PD parameters, namely Emax, tEmax of SBP, PR and diastolic blood pressure (DBP) , and changes from baseline after a single dose of ARS-1 in healthy adult subjects;;PK parameters, namely Cmax, Tmax, early partial AUC [AUC(0-10min), AUC(0- 15min), AUC (0-20min), AUC (0-45 min), AUC(0-60min)] and AUC(0-t) , as well as PD parameters, namely Emax, tEmax of SBP, PR and diastolic blood pressure (DBP) , and changes from baseline after two doses of ARS-1 in healthy adult subjects;;PK parameters, namely Cmax, Tmax, early partial AUC [AUC(0-10min), AUC(0-15min), AUC(0-20min), AUC(0-45min), AUC(0-60min)] and AUC(0-t), and PD parameters, namely Emax, tEmax of SBP, PR and DBP, and changes from baseline after self-administration;;Error rate of key errors after self-administration; PK parameters of subjects with key errors, namely Cmax, Tmax, early partial AUC [AUC(0-10min), AUC(0-15min), AUC(0-20min), AUC(0-45min), AUC(0-60min)] and AUC(0-t) ; and PD parameters of subjects with key errors, namely Emax, tEmax of SBP, PR and DBP, and changes from baseline;;Evaluation of the convenience and hesitation of self-administration subjects;;PK parameters, namely Cmax, Tmax, early partial AUC [AUC(0-10min), AUC(0- 15min), AUC (0-20min), AUC(0-45min), AUC(0-60min)] and AUC(0-t), and PD parameters, namely Emax, tEmax of SBP, PR and DBP, and changes from baseline after ARS-1 administration in subjects with allergic rhinitis.; | — |
Countries
China
Contacts
Public ContactShumin Wang
Beijing Chao-yang Hospital, Capital Medical University
Outcome results
None listed