AnaphylaxisPhase 4PIMATNCT03366298

Pharmacokinetics of Intramuscular Adrenaline in Food--Allergic Teenagers

A Phase 4 study testing Epipen 0.3mg, Emerade 300mcg and Emerade 500mcg in people with Anaphylaxis, run by Imperial College London at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 13 to 18 years
Conditions the study is for: Anaphylaxis
What is being tested?: Epipen 0.3mg, Emerade 300mcg and Emerade 500mcg
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 12 participants
Where: 1 siteUnited Kingdom
Study dates: 24 Nov 2017to 2 Oct 2018
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 13 to 18 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

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.

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

Imperial College London / Imperial College Healthcare NHS Trust
London, W2 1NY

Other trials in United Kingdom

About this study

Official title: 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.

Conditions: Anaphylaxis
Being tested: Epipen 0.3mg, Emerade 300mcg, Emerade 500mcg
Medical subject headings: Anaphylaxis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Epipen 0.3mgCombination product
Also called Epinephrine
Epipen 0.3mg auto-injector
Emerade 300mcgCombination product
Also called Epinephrine
Emerade 300mcg auto-injector
Emerade 500mcgCombination product
Also called Epinephrine
Emerade 500mcg auto-injector

Study groups in NCT03366298
Study group	Role	What they receive
1	Active comparator	Visit 1: Emerade 300mcg then Epipen 0.3mg Visit 2: Emerade 500mcg Receives: 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 Receives: 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 Receives: 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 Receives: Combination Product: Epipen 0.3mg; Combination Product: Emerade 300mcg; Combination Product: Emerade 500mcg

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Pharmacodynamics (heart rate) following intramuscular self-injection of 300mcg and 500mcg adrenaline using an auto-injector device, in food-allergic teenagers over 40kg.
Measured: 3 hours
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.
Measured: 3 hours
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.
Measured: 3 hours
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.
Measured: 3 hours
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.
Measured: 3 hours
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.
Measured: 3 hours
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.
Measured: 3 hours
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.
Measured: 3 hours
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.
Measured: 3 hours
Adverse Events Following Self-administration of Adrenaline Via Autoinjector Device
Adverse events following self-administration of adrenaline via autoinjector device defined as in protocol
Measured: 1 day
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.
Measured: 1 month

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

24 Nov 20172 Oct 2018

First posted8 Dec 2017
Study start24 Nov 2017
Primary completion2 Oct 2018
Study completion2 Oct 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for AnaphylaxisStudies of the same condition, open and under way.
More trials run by Imperial College LondonThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 12 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03366298
Sponsor's protocol ID: 17SM4137
Other IDs: 2017-003239-13, 232931, 2017
Acronym: PIMAT
Status last verified: Aug 2022
First submitted: 21 Nov 2017
Last updated: 7 Sep 2022
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: No
FDA-regulated device: No

Publications

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.
PubMed 36794963

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Anaphylaxis trials

Study at a glance

From the registry record, last updated by the sponsor on 7 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Pharmacokinetics of Intramuscular Adrenaline in Food--Allergic Teenagers: Does Dose Matter?
ClinicalTrials.gov ID: NCT03366298
Acronym / sponsor ID: PIMAT / 17SM4137
Conditions: Anaphylaxis
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 12 participants (actual)
Lead sponsor: Imperial College LondonUniversity, hospital or other
Study start: 24 Nov 2017 (actual)
Primary completion: 2 Oct 2018 (actual)
Study completion: 2 Oct 2018 (actual)
First posted: 8 Dec 2017 (actual)
Results: Posted 5 Apr 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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 design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
1	Active comparator	Combination Product: Epipen 0.3mg, Combination Product: Emerade 300mcg, Combination Product: Emerade 500mcgVisit 1: Emerade 300mcg then Epipen 0.3mg Visit 2: Emerade 500mcg
2	Active comparator	Combination Product: Epipen 0.3mg, Combination Product: Emerade 300mcg, Combination Product: Emerade 500mcgVisit 1: Epipen 0.3mg then Emerade 300mcg Visit 2: Emerade 500mcg
3	Active comparator	Combination Product: Epipen 0.3mg, Combination Product: Emerade 300mcg, Combination Product: Emerade 500mcgVisit 1: Emerade 500mcg Visit 2: Emerade 300mcg then Epipen 0.3mg
4	Active comparator	Combination Product: Epipen 0.3mg, Combination Product: Emerade 300mcg, Combination Product: Emerade 500mcgVisit 1: Emerade 500mcg Visit 2: Epipen 0.3mg then Emerade 300mcg

Who may qualify

Ages: 13 to 18 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (5 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Epipen 0.3mgAlso: EpinephrineEpipen 0.3mg auto-injector	Combination product	1, 2, 3, 4
Emerade 300mcgAlso: EpinephrineEmerade 300mcg auto-injector	Combination product	1, 2, 3, 4
Emerade 500mcgAlso: EpinephrineEmerade 500mcg auto-injector	Combination product	1, 2, 3, 4

Primary outcome

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.
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.
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.

11 secondary outcomes

Change in Heart Rate Following Self-injection of Adrenaline (300mcg, 500mcg) on Separate Occasions.
Time frame: 3 hours
Change in Blood Pressure Following Self-injection of Adrenaline (300mcg, 500mcg) on Separate Occasions.
Time frame: 3 hours
Change in Stroke Volume Following Self-injection of Adrenaline (300mcg, 500mcg) on Separate Occasions.
Time frame: 3 hours
Impact of Needle Length on Pharmacokinetics (Plasma Catecholamine Levels: Cmax)
Time frame: 3 hours
Impact of Needle Length on Pharmacokinetics (Plasma Catecholamine Levels: Tmax)
Time frame: 3 hours
Impact of Needle Length on Pharmacokinetics (Plasma Catecholamine Levels: AUC)
Time frame: 3 hours
Impact of Needle Length on Pharmacodynamics (Cardiovascular Parameters: Heart Rate)
Time frame: 3 hours
Impact of Needle Length on Pharmacodynamics (Cardiovascular Parameters: Blood Pressure)
Time frame: 3 hours
Impact of Needle Length on Pharmacodynamics (Cardiovascular Parameters: Stroke Volume)
Time frame: 3 hours
Adverse Events Following Self-administration of Adrenaline Via Autoinjector Device
Time frame: 1 day
Change in Health-related Quality of Life (HRQL) as Measured Using FAQLQ
Time frame: 1 month

Results and safety

Results posted to the registry on 5 Apr 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Emerade 300 / Epipen 0.3mg / Emerade 500	3	3
Epipen 0.3mg / Emerade 300 / Emerade 500	3	3
Emerade 500 / Emerade 300 / Epipen 0.3mg	3	3
Emerade 500 / Epipen 0.3mg / Emerade 300	3	3

Primary outcome: Plasma Catecholamine Levels (Maximum Concentration, Cmax)

Time frame: 3 hours. Mean (95% Confidence Interval). Unit: pg/ml

Measure	Emerade 300mcg Injection n = 12	Emerade 500mcg Injection n = 12	Epipen 0.3mg n = 12
Value	218 (132 to 359)	394 (310 to 500)	290 (200 to 421)

Primary outcome: Plasma Catecholamine Levels (Time to Maximum Concentration, Tmax)

Time frame: 3 hours. Mean (95% Confidence Interval). Unit: minutes

Measure	Emerade 300mcg Injection n = 12	Emerade 500mcg Injection n = 12	Epipen 0.3mg n = 12
Value	9.6 (5.3 to 17.4)	8.5 (6.1 to 11.8)	5.9 (4.9 to 7.3)

Primary outcome: 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. Mean (95% Confidence Interval). Unit: hr*pg/ml

Measure	Emerade 300mcg Injection n = 12	Emerade 500mcg Injection n = 12	Epipen 0.3mg n = 12
Value	174 (86 to 354)	387 (263 to 570)	203 (142 to 292)

11 secondary outcomes are reported in the full results.

Adverse events

Time frame: Within 24h of injection only. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Emerade 300mcg Injection	0 of 12 (0%)	4 of 12 (33.3%)	0 of 12
Emerade 500mcg Injection	0 of 12 (0%)	9 of 12 (75%)	0 of 12
Epipen 0.3mg	0 of 12 (0%)	8 of 12 (66.7%)	0 of 12

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Sep 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 36794963Patel 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.

Related trials for Anaphylaxis

Active, not recruitingPhase 2
A Safety and Efficacy Study of PVX108 in Children and Adolescents With Peanut Allergy
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RecruitingObservational study
Maximum Lysis on Thromboelastography as a Marker of Systemic Severity in Acute Allergic Reactions
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Paul J Turner, FRACP PhD principal investigator

Imperial College London

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Epipen 0.3mg, Emerade 300mcg and Emerade 500mcg in people with Anaphylaxis, run by Imperial College London at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Plasma Catecholamine Levels (Maximum Concentration, Cmax) (time frame: 3 hours). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03366298, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Sep 2022.