Pharmacokinetics and Safety of a Single Dose of Epinephrine Nasal Spray in Paediatric Allergy Patients

• Male and female children and adolescents aged between 2 and 17 years (inclusive) at the time of Screening.
• Diagnosed with type I allergy with food or venom allergy, which is prone to anaphylactic reactions and requires the prescription of epinephrine products.
• Body weight ≥15 kg (33 lbs) measured in light clothing and without shoes.
• Have a BMI within the 5-95% percentile, considering the regional, sex and age-specific growth charts.
• Signed informed consent form (ICF) by the parent/legally authorised representative (LAR).
• Signed assent form by the child/adolescent.
• Willingness to comply with the requirements and restrictions listed in the ICF and this Clinical Study Protocol.
• Females of childbearing potential must agree to use highly effective methods of contraception from the beginning of Screening until the last visit.

Note: acceptable highly effective methods of contraception include methods that can achieve a failure rate of less than 1% per year when used consistently and correctly: the intrauterine device; intrauterine system; bilateral tubal occlusion (must be documented); oral, intravaginal, transdermal, injectable, and implantable methods of hormonal contraception associated with inhibition of ovulation (combined estrogen and progesterone containing; or progesterone-only hormonal contraception); vasectomised partner (must be documented); or sexual abstinence (only when it is the usual and preferred lifestyle of the participant).

Note 1: Hormonal contraception may be susceptible to interaction with the study drug, which may reduce the efficacy of the contraception method.

Note 2: Vasectomized partner is a highly effective birth control method provided that partner is the sole sexual partner of the WOCBP study participant and that the vasectomized partner has received medical assessment of the surgical success.

Note 3: In the context of this guidance sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the study participant

• If the participant is a fertile male, the participant must use a condom, or his female partner of childbearing potential must use a highly effective form of contraception described in the note above, or the participant can practice abstinence (only when it is the usual and preferred lifestyle of the participant) from the beginning of Screening until the last visit.

Exclusion Criteria:

• Prior nasal fractures, severe nasal injuries or surgeries, nostril or septum piercings, as well as presence of nasal obstruction, that could interfere with nasal spray administration.
• Known cardiac comorbidity (including hypertension, cardiac arrhythmias, tachycardia [PR >140/min in participants ≤10 years old or >100/min in participants >10 years], coronary artery disease, or any other structural or electrophysiological diagnosis).

Note: To account for stress-related elevations, if BP and/or PR are elevated on Day 1 pre-dose, the Investigator may consider repeating the measurement prior to participant exclusion. If BP and/or PR are elevated on repeated measurements, the participant should be excluded.

• Known increased risk of cerebrovascular haemorrhage (i.e., arteriovenous malformations, aneurysms, recent head traumas, or history of brain tumours).
• Diagnosis of hyperthyroidism, diabetes, hepatic or renal dysfunction.
• Presence of acute illness, such as common cold, flu or other acute infection, within 7 days prior to Day 1.
• 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 jeopardise the safety of the participant or impact the validity of the study results.
• Clinically significant findings at Screening in vital signs measurements, ECG findings, physical and nasal cavity examination.
• Positive urine screen for alcohol, drugs of abuse and cotinine for participants ≥12 years of age.
• Use of the following substances within 72 hours prior to Day 1: any intranasal or sinus medication (including corticosteroids, decongestants, saline washes).
• Use of the following substances within 14 days prior to Day 1: beta-adrenergic blockers, tricyclic antidepressants, monoamine oxidase inhibitors.
• Use of the following substances within 24 hours prior to Day 1: other catecholamines (e.g., norepinephrine, dopamine) or vasopressors.
• Use of the following substances within 7 days prior to Day 1: ergot alkaloids; levothyroxine (if not on a stable, replacement dose); strong inhibitors or inducers of CYP3A4, CYP2D6, CYP2C9, and CYP1A2 enzymes; catechol-O-methyltransferase (COMT) inhibitors (e.g., entacapone); antiarrhythmics, other alpha-adrenergic blockers, reserpine, and clonidine-type antihypertensives.
• Participant not willing to avoid using methylxanthine-containing products (e.g., chocolate, cocoa, or cola) within 24 hours before dosing on Day 1.
• Known reaction or sensitivity to epinephrine or any of the ingredients of the product, including sodium bisulfite.
• Females who are pregnant or breastfeeding.
• Lifetime use of tobacco, vape or nicotine-containing products.
• Participation in another clinical study with any investigational medicinal product within 90 days before dosing.