Bioavailability of Nasal Epinephrine

Anaphylaxis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04696822
• Other study ID #: NP-002
• Status: Completed
• Phase: Phase 1
• Start date: November 1, 2020
• Est. completion date: September 28, 2021

Study information

• Verified date: October 2021
• Source: Nasus Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: September 28, 2021
• Est. primary completion date: September 28, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

The following inclusion criteria will be assessed at screening (within 28 days prior to the

first drug administration):

1. Non-smoking, male and female subjects from 18 to 55 years of age.

2. Documented Positive skin allergy test during the last year.

3. History of hay fever, seasonal allergies, or rhinitis.

4. BMI =18 and <=30 kg/m2.

5. 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.

6. Willing to use acceptable, effective methods of contraception.

7. Able to tolerate venipuncture.

8. Be informed of the nature of the study and give written consent prior to any study procedure.

9. Willing and being able to remain in the clinic for the entire duration of the confinement period.

10. 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.

Related Conditions & MeSH terms

• Anaphylaxis

Intervention

Drug:
• Epinephrine Nasal Product, 1.6 mg
Single dose Nasal powder spray without allergen challenge
• Epinephrine nasal product, 1.6 mg + allergen
Single dose Nasal powder spray with allergen challenge
• Epinephrine Injection 0.3 mg
Intramuscular injection
• Epinephrine Nasal Product, 3.2 mg
Twice dose Nasal powder spray without allergen challenge
• Epinephrine Nasal Product, 3.2 mg + allergen
Twice dose Nasal powder spray with allergen challenge

Locations

Country	Name	City	State
Israel	Hadassah Medical Center, Ein Kerem	Jerusalem

Sponsors (1)

Lead Sponsor	Collaborator
Nasus Pharma

Country where clinical trial is conducted

Israel, 

References & Publications (1)

Tal Y, Ribak Y, Rubin L, Talmon A, Shamriz O, Hershko AY, Blotnick S, Bouhajib M, Krayz GT, Abrutzky C, Megiddo D, Lapidot T, Caraco Y. Fast Acting, Dry Powder, Needle-Free, Intranasal Epinephrine Spray: A Promising Future Treatment for Anaphylaxis. J All — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Epinephrine in blood - Cmax	pharmacokinetic analysis	-1 hour to 8 hours post-dose
Primary	Epinephrine in blood- Tmax	pharmacokinetic analysis	-1 hour to 8 hours post-dose
Primary	Epinephrine in blood- AUC	pharmacokinetic analysis	-1 hour to 8 hours post-dose
Primary	Epinephrine in blood- T half	pharmacokinetic analysis	-1 hour to 8 hours post-dose
Secondary	body temperature	Safety Monitoring	morning
Secondary	Hemoglobin level in blood	Safety Monitoring, blood test	at check-in morning
Secondary	blood hematocrit	Safety Monitoring: the ratio of the volume of red blood cells to the total volume of blood	check-in morning
Secondary	Blood pressure	Vital signs	Prior to drug administration
Secondary	Pulse	Vital signs	Prior to drug administration
Secondary	Blood pressure	Vital signs	15 minutes
Secondary	Pulse	Vital signs	15 minutes
Secondary	Blood pressure	Vital signs	30 minutes
Secondary	Pulse	Vital signs	30 minutes
Secondary	Blood pressure	Vital signs	45 minutes
Secondary	Pulse	Vital signs	45 minutes
Secondary	Blood pressure	Vital signs	1 hour
Secondary	Pulse	Vital signs	1 hour
Secondary	Blood pressure	Vital signs	2 hours
Secondary	Pulse	Vital signs	2 hours
Secondary	Blood pressure	Vital signs	4 hours post-dose
Secondary	Pulse	Vital signs	4 hours post-dose
Secondary	electrocardiogram	Safety Monitoring	3 hours prior to drug administration
Secondary	electrocardiogram	Safety Monitoring	45 minutes

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