Pharmacokinetics of Intramuscular Adrenaline in Food--Allergic Teenagers

Anaphylaxis Clinical Trial

— PIMAT  

Official title:

Pharmacokinetics of Intramuscular Adrenaline in Food--Allergic Teenagers: Does Dose Matter?

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03366298
• Other study ID #: 17SM4137
• Secondary ID: 2017-003239-1323
• Status: Completed
• Phase: Phase 4
• Start date: November 24, 2017
• Est. completion date: October 2, 2018

Study information

• Verified date: August 2022
• Source: Imperial College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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. 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. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: October 2, 2018
• Est. primary completion date: October 2, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years to 18 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Anaphylaxis

Intervention

Combination Product:
• Epipen 0.3mg
Epipen 0.3mg auto-injector
• Emerade 300mcg
Emerade 300mcg auto-injector
• Emerade 500mcg
Emerade 500mcg auto-injector

Locations

Country	Name	City	State
United Kingdom	Imperial College London / Imperial College Healthcare NHS Trust	London

Sponsors (1)

Lead Sponsor	Collaborator
Imperial College London

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	Change in Heart Rate Following Self-injection of Adrenaline (300mcg, 500mcg) on Separate Occasions.	Pharmacodynamics (heart rate) following intramuscular self-injection of 300mcg and 500mcg adrenaline using an auto-injector device, in food-allergic teenagers over 40kg.	3 hours
Secondary	Change in Blood Pressure Following Self-injection of Adrenaline (300mcg, 500mcg) on Separate Occasions.	Pharmacodynamics (blood pressure) following intramuscular self-injection of 300mcg and 500mcg adrenaline using an auto-injector device, in food-allergic teenagers over 40kg.	3 hours
Secondary	Change in Stroke Volume Following Self-injection of Adrenaline (300mcg, 500mcg) on Separate Occasions.	Pharmacodynamics (stroke volume) following intramuscular self-injection of 300mcg and 500mcg adrenaline using an auto-injector device, in food-allergic teenagers over 40kg.	3 hours
Secondary	Impact of Needle Length on Pharmacokinetics (Plasma Catecholamine Levels: Cmax)	Pharmacokinetics (plasma catecholamine levels: Cmax) following intramuscular self-injection of 300mcg adrenaline using two auto-injector devices with different needle lengths (15mm vs 23mm), in food-allergic teenagers over 40kg.	3 hours
Secondary	Impact of Needle Length on Pharmacokinetics (Plasma Catecholamine Levels: Tmax)	Pharmacokinetics (plasma catecholamine levels: Tmax) following intramuscular self-injection of 300mcg adrenaline using two auto-injector devices with different needle lengths (15mm vs 23mm), in food-allergic teenagers over 40kg.	3 hours
Secondary	Impact of Needle Length on Pharmacokinetics (Plasma Catecholamine Levels: AUC)	Pharmacokinetics (plasma catecholamine levels: AUC) following intramuscular self-injection of 300mcg adrenaline using two auto-injector devices with different needle lengths (15mm vs 23mm), in food-allergic teenagers over 40kg.	3 hours
Secondary	Impact of Needle Length on Pharmacodynamics (Cardiovascular Parameters: Heart Rate)	The pharmacodynamics (cardiovascular parameters: heart rate) following intramuscular self-injection of 300mcg adrenaline using two auto-injector devices with different needle lengths (15mm vs 23mm), in food-allergic teenagers over 40kg.	3 hours
Secondary	Impact of Needle Length on Pharmacodynamics (Cardiovascular Parameters: Blood Pressure)	The pharmacodynamics (cardiovascular parameters: blood pressure) following intramuscular self-injection of 300mcg adrenaline using two auto-injector devices with different needle lengths (15mm vs 23mm), in food-allergic teenagers over 40kg.	3 hours
Secondary	Impact of Needle Length on Pharmacodynamics (Cardiovascular Parameters: Stroke Volume)	The pharmacodynamics (cardiovascular parameters: stroke volume) following intramuscular self-injection of 300mcg adrenaline using two auto-injector devices with different needle lengths (15mm vs 23mm), in food-allergic teenagers over 40kg.	3 hours
Secondary	Adverse Events Following Self-administration of Adrenaline Via Autoinjector Device	Adverse events following self-administration of adrenaline via autoinjector device defined as in protocol	1 day
Secondary	Change in Health-related Quality of Life (HRQL) as Measured Using FAQLQ	The impact of self-administration of adrenaline autoinjectors (in a non-reaction setting) on health-related quality of life (HRQL) measures in food-allergic teenagers and their parents.	1 month