Pharmacokinetics of Intramuscular Adrenaline in Food--Allergic Teenagers

NCT03366298 | Completed Phase 4 Results

• 3 other identifiers: 17SM41372017-003239-13232931
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Food allergy affects up to 2% of adults and 8% of children in the United Kingdom (UK), and is a major public health issue. It is the commonest cause of life-threatening allergic reactions (anaphylaxis), which can be fatal. Adrenaline (epinephrine) auto-injector (AAI) devices are the first-line treatment for anaphylaxis, yet in a UK survey, over 80% of 245 teenagers experiencing anaphylaxis did not use their AAI. Delays in, or lack of adrenaline (epinephrine) administration during anaphylaxis are risk factors for fatal anaphylaxis. In 2010, a coroner's investigation into the death of a food-allergic teenager in the UK raised several questions around AAI safety and efficacy, since the teenager died despite administering her auto-injector device. This prompted a review by the Medicines and Healthcare products Regulatory Agency (MHRA) in 2014 into the clinical and quality considerations of AAIs. Two recommendations which came from the review was that companies 'should be encouraged to develop a 0.5mg \[dose\] AAI.' In the UK currently only Emerade, one of the three companies selling AAIs, manufactures a 0.5mg (500mcg) version. Emerade also has a longer needle length (23mm) compared to other AAIs (typically 15mm). The investigators plan to formally assess the pharmacokinetics (PK) and pharmacodynamics (PD) of self-injection with intramuscular adrenaline (epinephrine) in teenagers at risk of anaphylaxis due to food allergy, and have been prescribed AAI.

1. 1.The investigators will compare self-injection with 300mcg vs 500mcg in teenagers of body weight \>40kg. In a 40kg person, an adrenaline dose of 300mcg results in an effective UNDER-dosing of 30% by body weight.
2. 2.The investigators will also assess the impact of needle length on injection, by comparing two different devices, both of which deliver 300mcg, but one via a 15mm needle and the other with a 23mm needle.

Conditions

Anaphylaxis

Outcome Measures

Primary Outcomes (3)

• Plasma Catecholamine Levels (Maximum Concentration, Cmax)

  Pharmacokinetics (plasma catecholamine levels: Cmax) following intramuscular self-injection of 300mcg and 500mcg adrenaline using an auto-injector device, in food-allergic teenagers over 40kg.

  3 hours

• Plasma Catecholamine Levels (Time to Maximum Concentration, Tmax)

  Pharmacokinetics (plasma catecholamine levels: Tmax) following intramuscular self-injection of 300mcg and 500mcg adrenaline using an auto-injector device, in food-allergic teenagers over 40kg.

  3 hours

• Plasma Catecholamine Levels (Maximum Concentration, Area-under-curve (AUC))

  Pharmacokinetics (plasma catecholamine levels: AUC) following intramuscular self-injection of 300mcg and 500mcg adrenaline using an auto-injector device, in food-allergic teenagers over 40kg. Baseline corrected.

  At at the following timepoints following injection: 5, 10, 15, 20, 30, 45, 60, 80, 100, 120 and 180 minutes

Secondary Outcomes (11)

• Change in Heart Rate Following Self-injection of Adrenaline (300mcg, 500mcg) on Separate Occasions.

  3 hours

• Change in Blood Pressure Following Self-injection of Adrenaline (300mcg, 500mcg) on Separate Occasions.

  3 hours

• Change in Stroke Volume Following Self-injection of Adrenaline (300mcg, 500mcg) on Separate Occasions.

  3 hours

• Impact of Needle Length on Pharmacokinetics (Plasma Catecholamine Levels: Cmax)

  3 hours

• Impact of Needle Length on Pharmacokinetics (Plasma Catecholamine Levels: Tmax)

  3 hours

Study Arms (4)

1

ACTIVE COMPARATOR

Visit 1: Emerade 300mcg then Epipen 0.3mg Visit 2: Emerade 500mcg

Combination Product: Epipen 0.3mg; Combination Product: Emerade 300mcg; Combination Product: Emerade 500mcg

2

ACTIVE COMPARATOR

Visit 1: Epipen 0.3mg then Emerade 300mcg Visit 2: Emerade 500mcg

Combination Product: Epipen 0.3mg; Combination Product: Emerade 300mcg; Combination Product: Emerade 500mcg

3

ACTIVE COMPARATOR

Visit 1: Emerade 500mcg Visit 2: Emerade 300mcg then Epipen 0.3mg

Combination Product: Epipen 0.3mg; Combination Product: Emerade 300mcg; Combination Product: Emerade 500mcg

4

ACTIVE COMPARATOR

Visit 1: Emerade 500mcg Visit 2: Epipen 0.3mg then Emerade 300mcg

Combination Product: Epipen 0.3mg; Combination Product: Emerade 300mcg; Combination Product: Emerade 500mcg

Interventions

Epipen 0.3mg COMBINATION_PRODUCT

Epipen 0.3mg auto-injector

Also known as: Epinephrine

1; 2; 3; 4

Emerade 300mcg COMBINATION_PRODUCT

Emerade 300mcg auto-injector

Also known as: Epinephrine

1; 2; 3; 4

Emerade 500mcg COMBINATION_PRODUCT

Emerade 500mcg auto-injector

Also known as: Epinephrine

1; 2; 3; 4

Eligibility Criteria

• Age: 13 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age 13 - 18 years inclusive
• Body mass \>40kg
• Prescription of AAI due to physician diagnosis of Immunoglobulin E-mediated food allergy.
• Written informed consent from parent/guardian together with patient assent, for participants under 16 years of age. For young people age 16+ years, consent will be obtained from the participant themselves.

You may not qualify if:

• Known cardiac comorbidity (including hypertension, structural or electrophysiological diagnoses) or prescribed a medicine to control cardiovascular disease/hypertension.
• Known endocrine or renal disease
• Poorly controlled asthma requiring daily rescue treatment with a bronchodilator.
• Pregnancy
• Unwilling or unable to comply with study requirements

Sponsors & Collaborators

• Imperial College London: lead

Study Sites (1)

Imperial College London / Imperial College Healthcare NHS Trust

London, W2 1NY, United Kingdom

Location

Related Publications (1)

• Patel N, Isaacs E, Duca B, Nagaratnam N, Donovan J, Fontanella S, Turner PJ. Optimal dose of adrenaline auto-injector for children and young people at risk of anaphylaxis: A phase IV randomized controlled crossover study. Allergy. 2023 Jul;78(7):1997-2006. doi: 10.1111/all.15675. Epub 2023 Feb 23.

  PMID: 36794963 DERIVED

MeSH Terms

Conditions

Anaphylaxis

Interventions

Epinephrine

Condition Hierarchy (Ancestors)

Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Dr Paul Turner
• Organization: Imperial College London

p.turner@imperial.ac.uk

+44 20 3312 7754

Study Officials

• Paul J Turner, FRACP PhD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MRC Clinician Scientist

Study Record Dates

• First Submitted: November 21, 2017
• First Posted: December 8, 2017
• Study Start: November 24, 2017
• Primary Completion: October 2, 2018
• Study Completion: October 2, 2018
• Last Updated: September 7, 2022
• Results First Posted: April 5, 2021

Record last verified: 2022-08

Locations

GB (1)