- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03366298
Pharmacokinetics of Intramuscular Adrenaline in Food--Allergic Teenagers (PIMAT)
Pharmacokinetics of Intramuscular Adrenaline in Food--Allergic Teenagers: Does Dose Matter?
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.
- 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.
- 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.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
-
London, United Kingdom, W2 1NY
- Imperial College London / Imperial College Healthcare NHS Trust
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: 1
Visit 1: Emerade 300mcg then Epipen 0.3mg Visit 2: Emerade 500mcg
|
Epipen 0.3mg auto-injector
Other Names:
Emerade 300mcg auto-injector
Other Names:
Emerade 500mcg auto-injector
Other Names:
|
Active Comparator: 2
Visit 1: Epipen 0.3mg then Emerade 300mcg Visit 2: Emerade 500mcg
|
Epipen 0.3mg auto-injector
Other Names:
Emerade 300mcg auto-injector
Other Names:
Emerade 500mcg auto-injector
Other Names:
|
Active Comparator: 3
Visit 1: Emerade 500mcg Visit 2: Emerade 300mcg then Epipen 0.3mg
|
Epipen 0.3mg auto-injector
Other Names:
Emerade 300mcg auto-injector
Other Names:
Emerade 500mcg auto-injector
Other Names:
|
Active Comparator: 4
Visit 1: Emerade 500mcg Visit 2: Epipen 0.3mg then Emerade 300mcg
|
Epipen 0.3mg auto-injector
Other Names:
Emerade 300mcg auto-injector
Other Names:
Emerade 500mcg auto-injector
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Plasma Catecholamine Levels (Maximum Concentration, Cmax)
Time Frame: 3 hours
|
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)
Time Frame: 3 hours
|
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))
Time Frame: At at the following timepoints following injection: 5, 10, 15, 20, 30, 45, 60, 80, 100, 120 and 180 minutes
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Heart Rate Following Self-injection of Adrenaline (300mcg, 500mcg) on Separate Occasions.
Time Frame: 3 hours
|
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
|
Change in Blood Pressure Following Self-injection of Adrenaline (300mcg, 500mcg) on Separate Occasions.
Time Frame: 3 hours
|
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
|
Change in Stroke Volume Following Self-injection of Adrenaline (300mcg, 500mcg) on Separate Occasions.
Time Frame: 3 hours
|
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
|
Impact of Needle Length on Pharmacokinetics (Plasma Catecholamine Levels: Cmax)
Time Frame: 3 hours
|
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
|
Impact of Needle Length on Pharmacokinetics (Plasma Catecholamine Levels: Tmax)
Time Frame: 3 hours
|
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
|
Impact of Needle Length on Pharmacokinetics (Plasma Catecholamine Levels: AUC)
Time Frame: 3 hours
|
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
|
Impact of Needle Length on Pharmacodynamics (Cardiovascular Parameters: Heart Rate)
Time Frame: 3 hours
|
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
|
Impact of Needle Length on Pharmacodynamics (Cardiovascular Parameters: Blood Pressure)
Time Frame: 3 hours
|
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
|
Impact of Needle Length on Pharmacodynamics (Cardiovascular Parameters: Stroke Volume)
Time Frame: 3 hours
|
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
|
Adverse Events Following Self-administration of Adrenaline Via Autoinjector Device
Time Frame: 1 day
|
Adverse events following self-administration of adrenaline via autoinjector device defined as in protocol
|
1 day
|
Change in Health-related Quality of Life (HRQL) as Measured Using FAQLQ
Time Frame: 1 month
|
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
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Paul J Turner, FRACP PhD, Imperial College London
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Hypersensitivity, Immediate
- Hypersensitivity
- Anaphylaxis
- Physiological Effects of Drugs
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Adrenergic alpha-Agonists
- Adrenergic Agonists
- Bronchodilator Agents
- Anti-Asthmatic Agents
- Respiratory System Agents
- Adrenergic beta-Agonists
- Sympathomimetics
- Vasoconstrictor Agents
- Mydriatics
- Epinephrine
- Racepinephrine
- Epinephryl borate
Other Study ID Numbers
- 17SM4137
- 2017-003239-13 (EudraCT Number)
- 232931 (Other Identifier: HRA)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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