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Bioavailability of Nasal Epinephrine

Primary Purpose

Anaphylaxis

Status
Completed
Phase
Phase 1
Locations
Israel
Study Type
Interventional
Intervention
Epinephrine Nasal Product, 1.6 mg
Epinephrine nasal product, 1.6 mg + allergen
Epinephrine Injection 0.3 mg
Epinephrine Nasal Product, 3.2 mg
Epinephrine Nasal Product, 3.2 mg + allergen
Sponsored by
Nasus Pharma
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anaphylaxis

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Hadassah Medical Center, Ein Kerem

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Adults with seasonal allergic rhinitis

Arm Description

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.

Outcomes

Primary Outcome Measures

Epinephrine in blood - Cmax
pharmacokinetic analysis
Epinephrine in blood- Tmax
pharmacokinetic analysis
Epinephrine in blood- AUC
pharmacokinetic analysis
Epinephrine in blood- T half
pharmacokinetic analysis

Secondary Outcome Measures

body temperature
Safety Monitoring
Hemoglobin level in blood
Safety Monitoring, blood test
blood hematocrit
Safety Monitoring: the ratio of the volume of red blood cells to the total volume of blood
Blood pressure
Vital signs
Pulse
Vital signs
Blood pressure
Vital signs
Pulse
Vital signs
Blood pressure
Vital signs
Pulse
Vital signs
Blood pressure
Vital signs
Pulse
Vital signs
Blood pressure
Vital signs
Pulse
Vital signs
Blood pressure
Vital signs
Pulse
Vital signs
Blood pressure
Vital signs
Pulse
Vital signs
electrocardiogram
Safety Monitoring
electrocardiogram
Safety Monitoring

Full Information

First Posted
December 1, 2020
Last Updated
October 12, 2021
Sponsor
Nasus Pharma
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1. Study Identification

Unique Protocol Identification Number
NCT04696822
Brief Title
Bioavailability of Nasal Epinephrine
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
November 1, 2020 (Actual)
Primary Completion Date
September 28, 2021 (Actual)
Study Completion Date
September 28, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nasus Pharma

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief 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
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anaphylaxis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
Open-label, single-dose, two-period, three-treatment, fixed-sequence, comparative bioavailability study
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Adults with seasonal allergic rhinitis
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Epinephrine Nasal Product, 1.6 mg
Other Intervention Name(s)
FMXIN002 Microspheres Powder
Intervention Description
Single dose Nasal powder spray without allergen challenge
Intervention Type
Drug
Intervention Name(s)
Epinephrine nasal product, 1.6 mg + allergen
Other Intervention Name(s)
FMXIN002 Microspheres Powder
Intervention Description
Single dose Nasal powder spray with allergen challenge
Intervention Type
Drug
Intervention Name(s)
Epinephrine Injection 0.3 mg
Other Intervention Name(s)
EpiPen
Intervention Description
Intramuscular injection
Intervention Type
Drug
Intervention Name(s)
Epinephrine Nasal Product, 3.2 mg
Other Intervention Name(s)
FMXIN002 Microspheres Powder, double dose
Intervention Description
Twice dose Nasal powder spray without allergen challenge
Intervention Type
Drug
Intervention Name(s)
Epinephrine Nasal Product, 3.2 mg + allergen
Other Intervention Name(s)
FMXIN002 Microspheres Powder, double dose
Intervention Description
Twice dose Nasal powder spray with allergen challenge
Primary Outcome Measure Information:
Title
Epinephrine in blood - Cmax
Description
pharmacokinetic analysis
Time Frame
-1 hour to 8 hours post-dose
Title
Epinephrine in blood- Tmax
Description
pharmacokinetic analysis
Time Frame
-1 hour to 8 hours post-dose
Title
Epinephrine in blood- AUC
Description
pharmacokinetic analysis
Time Frame
-1 hour to 8 hours post-dose
Title
Epinephrine in blood- T half
Description
pharmacokinetic analysis
Time Frame
-1 hour to 8 hours post-dose
Secondary Outcome Measure Information:
Title
body temperature
Description
Safety Monitoring
Time Frame
morning
Title
Hemoglobin level in blood
Description
Safety Monitoring, blood test
Time Frame
at check-in morning
Title
blood hematocrit
Description
Safety Monitoring: the ratio of the volume of red blood cells to the total volume of blood
Time Frame
check-in morning
Title
Blood pressure
Description
Vital signs
Time Frame
Prior to drug administration
Title
Pulse
Description
Vital signs
Time Frame
Prior to drug administration
Title
Blood pressure
Description
Vital signs
Time Frame
15 minutes
Title
Pulse
Description
Vital signs
Time Frame
15 minutes
Title
Blood pressure
Description
Vital signs
Time Frame
30 minutes
Title
Pulse
Description
Vital signs
Time Frame
30 minutes
Title
Blood pressure
Description
Vital signs
Time Frame
45 minutes
Title
Pulse
Description
Vital signs
Time Frame
45 minutes
Title
Blood pressure
Description
Vital signs
Time Frame
1 hour
Title
Pulse
Description
Vital signs
Time Frame
1 hour
Title
Blood pressure
Description
Vital signs
Time Frame
2 hours
Title
Pulse
Description
Vital signs
Time Frame
2 hours
Title
Blood pressure
Description
Vital signs
Time Frame
4 hours post-dose
Title
Pulse
Description
Vital signs
Time Frame
4 hours post-dose
Title
electrocardiogram
Description
Safety Monitoring
Time Frame
3 hours prior to drug administration
Title
electrocardiogram
Description
Safety Monitoring
Time Frame
45 minutes

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yoseph Caraco, Prof.
Organizational Affiliation
Hadassah Medical Organization
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hadassah Medical Center, Ein Kerem
City
Jerusalem
Country
Israel

12. IPD Sharing Statement

Plan to Share IPD
No

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Bioavailability of Nasal Epinephrine

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