Comparative PK/PD of FMXIN002 and EpiPen, in Healthy Adults With Allergic Rhinitis

Fifty participants will receive single and repeat doses of both treatments under normal and nasal congestion conditions induced by nasal allergen challenge. The study will also assess the effect of repeat nasal dosing in the same versus opposite nostrils. PK parameters and hemodynamic responses will be measured, and safety and tolerability will be evaluated.

• FMXIN002 single dose (Drug), also known as NS002: Single dose of FMXIN002 epinephrine microspheres powder for nasal application, 4.0 mg, at normal conditions.
• Epinephrine autoinjector single dose (Drug), also known as EpiPen: Epinephrine IM autoinjector 0.3mg
• FMXIN002 single dose + NAC (Drug), also known as NS002: Single dose of FMXIN002 epinephrine microspheres powder for nasal application, 4.0 mg, after Nasal Allergenic Challenge (NAC)
• Epinephrine autoinjector double dose (Drug), also known as EpiPen: Repeated doses of Epinephrine IM autoinjector 0.3mg, 10 minutes apart
• FMXIN002 double dose (Drug), also known as NS002: Double doses of FMXIN002 epinephrine microspheres powder for nasal application, 4.0 mg, at normal conditions, 10 minutes apart.
• FMXIN002 double dose + NAC (Drug), also known as NS002: Double doses of FMXIN002 epinephrine microspheres powder for nasal application, 4.0 mg, after Nasal Allergenic Challenge, 10 minutes apart.

Primary outcomes

• Epinephrine level in plasma over time [-60 to 240 minutes post administration]: Measurements in 14 timepoints
• Tmax [-60 to 240 minutes post administration]: Time to maximum epinephrine level in plasma
• T100pg/ml [-60 to 240 minutes post administration]: Time to reach epinephrine level of 100pg/ml in plasma
• Cmax [-60 to 240 minutes post administration]: Maximum epinephrine level in plasma
• AUC [0 to 240 minutes post administration]: Total exposure to epinephrine
• Blood pressure [-60 to 120 minutes post administration]: Pharmacodynamic response to epinephrine
• Heart rate [-60 to 120 minutes post administration]: Pharmacodynamic response to epinephrine
• Respiratory rate [-60 to 120 minutes post administration]: Pharmacodynamic response to epinephrine

Secondary outcomes

• Safety and tolerability [Day -29 to day 50]: Adverse events rate at each treatment, and severity.

Sex: All, ages: 18 Years to 55 Years, accepts healthy volunteers

Inclusion Criteria:

1. Non-smoking, male and female participants, from 18 to 55 years of age.
2. Documented positive skin allergy test at screening.
3. History of hay fever, seasonal allergies, or allergic rhinitis during the last year.
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, must be willing to use acceptable effective methods of contraception.
   * 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 and a FSH value consistent with being postmenopausal).
6. Able to tolerate venipuncture.
7. Be informed of the nature of the study and give written consent prior to any study procedure.
8. Willing and able to remain in the clinic for the entire duration of the confinement period.
9. Have good intravenous access on both arms and hands. -

Exclusion Criteria:

* History 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 participant or impact the validity of the study results.
* Have clinically significant findings at screening.
* Females who:

  * Have discontinued or changed the use of implanted, intrauterine, intravaginal, or injected hormonal contraceptives within 6 months prior to the first drug administration;
  * Have discontinued or changed the use of oral or patch hormonal contraceptives within one (1) month prior to the first drug administration;
  * Are pregnant (serum β-hCG consistent with pregnancy); or
  * Are breast-feeding.

• Mark L Freedman, MD, FRCPC, Principal investigator, Pharma Medica Research, Inc.