Clinical trial NCT06205134: Comparative Bioavailability of Intranasal Epinephrine
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Anaphylaxis
Anaphylactic Reaction
Keywords: Anaphylaxis
Epinephrine
Nasal
spray
Pharmacokinetics
Lead sponsor: Nasus Pharma
Sponsor class: INDUSTRY
Collaborators: name: Hadassah Medical Organization
name: Medistat Ltd., Israel
name: Pharma Medica Research, Inc.
First posted: 2024-01-12
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: To evaluate the comparative bioavailability and pharmacodynamic response between:

A. Epinephrine injection, USP auto-injector 0.3 mg for intramuscular (IM) injection B. FMXIN002 epinephrine microspheres powder for nasal application, 3.6 mg and C. FMXIN002 epinephrine microspheres powder for nasal application, 4 mg and after a single-dose administration to healthy adults

Secondary Objective:

To evaluate the safety and tolerability of the study treatments
Primary purpose: TREATMENT

Brief summary: 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

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.)

Eligibility criteria: 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 \&lt;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 \&lt;135 g/L for males or \&lt;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.

Primary outcomes:
measure: Bioavailability of Epinephrine
timeFrame: -1 to 2 hours post dose
measure: Blood pressure
timeFrame: -1 to 4 hours post dose
measure: Heart rate
timeFrame: -1 to 4 hours post dose
measure: Respiratory rate
timeFrame: -1 to 4 hours post dose
Secondary outcomes:
measure: 12-lead electrocardiogram
timeFrame: -2 up to 1 hour post dose
measure: Adverse events
timeFrame: through study completion, an average of 3 weeks
measure: Nasal Mucosa health status
timeFrame: -1 hour until end of each dosing day, an average 3 weeks.
Other outcomes:
Locations:
city: Jerusalem
country: Israel
facility: Clinical Pharmacology Unit, Hadassah Medical Center, Ein Karem
Study officials:
affiliation: Hadassah Medical Organization
name: Yoseph Caraco, Professor
role: PRINCIPAL_INVESTIGATOR
References: