Bioavailability of Nasal Epinephrine

Study Overview
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Brief Summary
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A Study to Compare the Bioavailability of Epinephrine following a Single Nasal Dose of FMXIN002 Microspheres Powder with Epinephrine 0.3 mg Intramuscular Injection in Adult Subjects with Seasonal Allergic Rhinitis with and without Nasal Allergen Challenge

Detailed Description
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Study Design: Open-label, single-dose, two-period, three-treatment, fixed-sequence, comparative bioavailability study Study Population: Non-smoking, male and female subjects, from 18 to 55 years of age with known history of hay fever, seasonal allergies, or rhinitis during the last year.

Official Title
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Bioavailability Comparison of Epinephrine Following a Single Nasal Dose of Microspheres Powder With Epinephrine Intramuscular Injection in Adults With Seasonal Allergic Rhinitis With and Without Nasal Allergen Challenge

Conditions
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Anaphylaxis

Intervention / Treatment
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* Drug: Epinephrine Nasal Product, 1.6 mg
* Drug: Epinephrine nasal product, 1.6 mg + allergen
* Drug: Epinephrine Injection 0.3 mg
* Drug: Epinephrine Nasal Product, 3.2 mg
* Drug: Epinephrine Nasal Product, 3.2 mg + allergen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The following inclusion criteria will be assessed at screening (within 28 days prior to the first drug administration): Non-smoking, male and female subjects from 18 to 55 years of age. Documented Positive skin allergy test during the last year. History of hay fever, seasonal allergies, or rhinitis. BMI ≥18 and <=30 kg/m2. Females may be of childbearing or non-childbearing potential: Childbearing potential: o Physically capable of becoming pregnant Non-childbearing potential: Surgically sterile (i.e., both ovaries removed, uterus removed, or bilateral tubal ligation); and/or Postmenopausal (no menstrual period for at least 12 consecutive months without any other medical cause. Willing to use acceptable, effective methods of contraception. Able to tolerate venipuncture. Be informed of the nature of the study and give written consent prior to any study procedure. Willing and being able to remain in the clinic for the entire duration of the confinement period. Have good intravenous access on both arms and hands. - Exclusion Criteria: Known history or presence of clinically significant neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, genitourinary, psychiatric, or cardiovascular disease or any other condition which, in the opinion of the Investigator, would jeopardize the safety of the subject or impact the validity of the study results. Known or suspected carcinoma. Known history or presence of hypersensitivity or idiosyncratic reaction to epinephrine, sulfite, other excipients of epinephrine auto-injector, or any other drug substances with similar activity. Known history or presence of clinically significant lactose, galactose, or fructose intolerance. Known history or presence of cardiac arrythmias, coronary artery disease or organic heart disease. Known history or presence of hyperthyroidism. Known history or presence of diabetes. Known history or presence of Parkinson's disease. Known history or presence of any food allergy. Presence of hepatic or renal dysfunction. Presence of nostril or septum piercing. Presence of abnormal nasal anatomy (e.g., polyps, unilateral or bilateral abnormalities of the nares, nasal turbinates, or septum including deviated septum). History of nasal surgery. Presence of a medical condition requiring regular medication (prescription and/or over-the-counter) with systemic absorption. History of drug or alcohol addiction requiring treatment or positive alcohol breath test at check-in. Any acute illness (e.g. cold, acute infection) which is considered significant by the Investigator and that has not resolved within 7 days before the first drug administration. Positive test result for HIV, Hepatitis B surface antigen, or Hepatitis C antibody. Positive test result for urine drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, opiates, phencyclidine, and tricyclic antidepressants) or urine cotinine. Difficulty fasting or consuming standard meals. Inability to communicate well with the Investigators and staff (e.g., language problem, poor mental development or impaired cerebral function). Non-cooperative or unwilling to sign consent form or unwilling to attend scheduled clinic visits and/or comply with the study protocol. Use of tobacco or nicotine-containing products within 6 months prior to drug administration. Females who: Have discontinued or changed the use of implanted, intrauterine, intravaginal, or injected hormonal contraceptives within 6 months prior to drug administration; Have discontinued or changed the use of oral or patch hormonal contraceptives within 1 month prior to drug administration; Are pregnant (serum hCG consistent with pregnancy); or Are lactating. Donation or loss of whole blood (including clinical trials): ≥50 mL and <500 mL within 30 days prior to drug administration; ≥500 mL within 56 days prior to drug administration. Participation in a clinical trial that involved administration of an investigational medicinal product within 30 days prior to drug administration, or recent participation in a clinical investigation that, in the opinion of the Investigator, would jeopardize subject safety or the integrity of the study results. On a special diet within 30 days prior to drug administration (e.g., liquid, protein, raw food diet). Have had a tattoo or body piercing within 30 days prior to drug administration. Have clinically significant findings in vital signs measurements at screening. Systolic blood pressure increase or decrease in value by more than 20 mmHg and/or diastolic blood pressure decrease in value by more than 10 mmHg, from supine or sitting to standing position during orthostatic blood pressure measurement taken at screening. Have clinically significant findings in a 12-lead ECG. Have clinically significant abnormal laboratory values and hemoglobin <135 g/L for males or <120 g/L for females at screening. Have significant diseases at the screening. Have clinically significant findings from a physical examination. Use of the following drugs within 14 days prior to drug administration: Alpha-adrenergic blocking drugs (e.g., phentolamine); Anti-arrhythmics; Beta-adrenergic blocking drugs (e.g., propranolol); Cardiac glycosides; Diuretics; Drugs having an effect on cytochrome P450 (CYP450); Enzyme-altering drugs (e.g., barbiturates, phenothiazines, cimetidine, carbamazepine, etc.); Enzyme-modifying drugs known to induce/inhibit hepatic drug metabolism; Ergot alkaloids; Levothyroxine sodium; Monoamine oxidase inhibitors; Oral or topical corticosteroids; Phenylephrine; Reserpine-type or clonidine-type antihypertensives; Sodium cromoglycate; or Tricyclic antidepressants. Use of the following drugs within 7 days prior to drug administration: Nasal decongestants; Nonsteroidal anti-inflammatory drugs (NSAIDs); or Oral or topical antihistamines.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional Model Description: Open-label, single-dose, two-period, three-treatment, fixed-sequence, comparative bioavailability study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adults with seasonal allergic rhinitis<br>Single administration of 1.6mg or 3.2 mg Epinephrine powder nasal spray, with or without allergenic challenge, and single IM 0.3 mg Epinephrine without allergenic challenge. | Drug: Epinephrine Nasal Product, 1.6 mg<br>* Single dose Nasal powder spray without allergen challenge<br>* Other names: FMXIN002 Microspheres Powder;Drug: Epinephrine nasal product, 1.6 mg + allergen<br>* Single dose Nasal powder spray with allergen challenge<br>* Other names: FMXIN002 Microspheres Powder;Drug: Epinephrine Injection 0.3 mg<br>* Intramuscular injection<br>* Other names: EpiPen;Drug: Epinephrine Nasal Product, 3.2 mg<br>* Twice dose Nasal powder spray without allergen challenge<br>* Other names: FMXIN002 Microspheres Powder, double dose;Drug: Epinephrine Nasal Product, 3.2 mg + allergen<br>* Twice dose Nasal powder spray with allergen challenge<br>* Other names: FMXIN002 Microspheres Powder, double dose;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Epinephrine in blood - Cmax | pharmacokinetic analysis | -1 hour to 8 hours post-dose | 
| Epinephrine in blood- Tmax | pharmacokinetic analysis | -1 hour to 8 hours post-dose | 
| Epinephrine in blood- AUC | pharmacokinetic analysis | -1 hour to 8 hours post-dose | 
| Epinephrine in blood- T half | pharmacokinetic analysis | -1 hour to 8 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| body temperature | Safety Monitoring | morning | 
| Hemoglobin level in blood | Safety Monitoring, blood test | at check-in morning | 
| blood hematocrit | Safety Monitoring: the ratio of the volume of red blood cells to the total volume of blood | check-in morning | 
| Blood pressure | Vital signs | Prior to drug administration | 
| Pulse | Vital signs | Prior to drug administration | 
| Blood pressure | Vital signs | 15 minutes | 
| Pulse | Vital signs | 15 minutes | 
| Blood pressure | Vital signs | 30 minutes | 
| Pulse | Vital signs | 30 minutes | 
| Blood pressure | Vital signs | 45 minutes | 
| Pulse | Vital signs | 45 minutes | 
| Blood pressure | Vital signs | 1 hour | 
| Pulse | Vital signs | 1 hour | 
| Blood pressure | Vital signs | 2 hours | 
| Pulse | Vital signs | 2 hours | 
| Blood pressure | Vital signs | 4 hours post-dose | 
| Pulse | Vital signs | 4 hours post-dose | 
| electrocardiogram | Safety Monitoring | 3 hours prior to drug administration | 
| electrocardiogram | Safety Monitoring | 45 minutes |