Comparative Bioavailability of Intranasal Epinephrine

A Study to Compare the Bioavailability of Epinephrine Following a Single Nasal Dose of FMXIN002 Microspheres Powder 3.6mg, and 4mg With EpiPen 0.3mg Intramuscular Injection in Healthy Adults

A Study to Compare the Bioavailability of Epinephrine following a Single Nasal Dose of FMXIN002 Microspheres Powder 3.6 mg, and 4mg with EpiPen 0.3mg Intramuscular Injection in Healthy Adults

Study Overview

• Status: Completed
• Conditions: Anaphylaxis; Anaphylactic Reaction
• Intervention / Treatment: Drug: A: Epinephrine injection; Drug: B: FMXIN002 3.6mg; Drug: C: FMXIN002 4.0mg

Detailed Description

An open-label trial in 12 healthy adults. FMXIN002 (3.6 mg and 4.0 mg) will be administered intranasally to healthy adults and compared to IM (0.3mg, EpiPen) by Epinephrine pharmacokinetics, pharmacodynamic response and clinical safety.

(https://my.health.gov.il/CliniTrials/Pages/MOH_2023-07-01_012776.aspx.)

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Israel
  • Jerusalem, Israel, 91120
    • Clinical Pharmacology Unit, Hadassah Medical Center, Ein Karem

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 1) Non-smoking, male and female subjects from 18 to 55 years of age. 2) BMI ≥18 < 30 kg/m2. 3) Females may be of childbearing or non-childbearing potential:

  • Childbearing potential:

    o Physically capable of becoming pregnant, must be willing to use acceptable effective methods of contraception

  • Non-childbearing potential:

    • Surgically sterile

    • Postmenopausal (no menstrual period for at least 12 consecutive months without any other medical cause).

      4) Able to tolerate venipuncture. 5) Be informed of the nature of the study and give written consent prior to any study procedure.

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

      7) Have good intravenous access on both arms and hands.

Exclusion Criteria:

• 1) Known history or presence of clinically significant neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, genitourinary, psychiatric, ischemic heart disease or Arteriosclerosis or cardiovascular disease, autoimmune disease, or Raynaud Phenomenon and 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.

  1. 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.
  2. Known history or presence of clinically significant lactose, galactose, or fructose allergy
  3. Known history or presence of any food allergy.
  4. Presence of nostril or septum piercing.
  5. Presence of abnormal nasal anatomy (e.g., polyps, unilateral or bilateral abnormalities of the nares, nasal turbinates, or septum including deviated septum).
  6. History of nasal surgery.
  7. Presence of a medical condition requiring regular medication (prescription and/or over-the-counter) with systemic absorption other than oral contraceptives.
  8. History of drug or alcohol addiction requiring treatment or positive alcohol breath test at check-in.
  9. 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.
  10. Positive test result for HIV, Hepatitis B surface antigen, or Hepatitis C antibody.
  11. Positive test result for urine drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, opiates, phencyclidine, and tricyclic antidepressants) or urine cotinine.
  12. Inability to communicate well with the Investigators and staff
  13. Non-cooperative or unwilling to sign consent form or unwilling to attend scheduled clinic visits and/or comply with the study protocol.
  14. Use of tobacco or nicotine-containing products within 6 months prior to drug administration.

  15. 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 (Urine hCG consistent with pregnancy); or
      • Are lactating.

  16. 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.
  17. 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.
  18. On a special diet within 30 days prior to drug administration (e.g., liquid, protein, raw food diet).
  19. Have had a tattoo or body piercing within 30 days prior to drug administration.
  20. Have clinically significant findings in vital signs measurements at screening.
  21. 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.
  22. Have clinically significant findings in a 12-lead ECG.
  23. Have clinically significant abnormal laboratory values and hemoglobin <135 g/L for males or <120 g/L for females at screening.
  24. Have significant diseases at screening.
  25. Have clinically significant findings from a physical examination.

  26. 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 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.

  27. Use of the following drugs within 7 days prior to drug administration:

      • Nasal decongestants;
      • Nonsteroidal anti-inflammatory drugs (NSAIDs); or
      • Oral or topical antihistamines.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 6 Healthy volunteers, sequence ABC; Three drug administrations to each subject, each administration on a separate day. treatment order: A B C	Drug: A: Epinephrine injection; Autoinjector for intramuscular, single-use, 0.3mg; Other Names: EpiPen; Drug: B: FMXIN002 3.6mg; Nasus Pharma nasal powder spray 3.6 mg, single use in one nostril; Other Names: Epinephrine Nasal Product; Drug: C: FMXIN002 4.0mg; Nasus Pharma nasal powder spray 4.0 mg, single use in one nostril; Other Names: Epinephrine Nasal Product
Experimental: 6 Healthy volunteers, sequence BAC; Three drug administrations to each subject, each administration on a separate day. treatment order: B A C	Drug: A: Epinephrine injection; Autoinjector for intramuscular, single-use, 0.3mg; Other Names: EpiPen; Drug: B: FMXIN002 3.6mg; Nasus Pharma nasal powder spray 3.6 mg, single use in one nostril; Other Names: Epinephrine Nasal Product; Drug: C: FMXIN002 4.0mg; Nasus Pharma nasal powder spray 4.0 mg, single use in one nostril; Other Names: Epinephrine Nasal Product

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bioavailability of Epinephrine	Plasma level of Epinephrine	-1 to 2 hours post dose
Blood pressure	Pharmacodynamic response	-1 to 4 hours post dose
Heart rate	Pharmacodynamic response	-1 to 4 hours post dose
Respiratory rate	Pharmacodynamic response	-1 to 4 hours post dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
12-lead electrocardiogram	Safety	-2 up to 1 hour post dose
Adverse events	Safety	through study completion, an average of 3 weeks
Nasal Mucosa health status	Nasal cavity examination by physician, recorded on a severity scale; Nasal and Non-Nasal Questionnaire of symptomes, completed by the subjects, using a severity scale.	-1 hour until end of each dosing day, an average 3 weeks.

Collaborators and Investigators

• Sponsor: Nasus Pharma
• Collaborators: Hadassah Medical Organization; Pharma Medica Research, Inc.; Medistat Ltd., Israel
• Investigators: Principal Investigator: Yoseph Caraco, Professor, Hadassah Medical Organization

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2023
• Primary Completion (Actual): February 2, 2024
• Study Completion (Actual): February 5, 2024

Study Registration Dates

• First Submitted: December 18, 2023
• First Submitted That Met QC Criteria: January 3, 2024
• First Posted (Actual): January 12, 2024

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Epinephrine; Anaphylaxis; Nasal; spray
• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Anaphylaxis; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-Agonists; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Epinephrine; Racepinephrine; Epinephryl borate
• Other Study ID Numbers: NP-006-Epinephrine

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes