A 2-part BA study to compare PK in 3 formulations of adrenaline
Research type
Research Study
Full title
A single-centre, open-label, randomised, 2-part, crossover, comparative bioavailability study to assess adrenaline plasma concentrations in healthy volunteers following administrations of KL-01401 (test product) and an adrenaline injection (reference product)
IRAS ID
305647
Contact name
Helen Philpott
Contact email
Sponsor organisation
Klaria AB
Eudract number
2021-003701-21
Duration of Study in the UK
0 years, 4 months, 25 days
Research summary
The purpose of this study is to investigate the study drug adrenaline.\n\nThe objectives are:\n- To determine the safety and tolerability (degree to which side effects of a drug can be tolerated) of adrenaline when it is administered as single doses in 3 different formulations i.e., as an oral mucosal film (a film which sticks to the inside of the cheek – KL-01401), an EpiPen® Auto Injector (administering the drug directly into a muscle) and as a subcutaneous injection (injection into the tissue layer between the skin and muscle).\n\n- To investigate the concentration of adrenaline in the blood, determining whether there are differences in the concentration between different forms of adrenaline.\n \n- To evaluate and compare how the position of KL-01401 in the mouth affects the concentration of adrenaline in the blood.\n\n- To assess different factors for the KL-01401 film including the irritation in the mouth and how the film ‘sticks’ to the inside of the mouth based on where the film is placed.\n\n- To evaluate the bioavailability (the degree and rate at which a substance (such as a drug) is absorbed into the body or is made available at the site of its’ desired effect) of adrenaline as an oral mucosal film in comparison with a marketed product (EpiPen®).\n\nThis study will be split into 2 parts: Parts A & B.\nPart A will investigate adrenaline when it is given as single doses in 3 different forms and Part B will investigate adrenaline when it is given as single doses in 2 different forms. Part A will enrol 12 participants and Part B will enrol a minimum of 12 participants.\n\nBlood samples will be taken in order to measure the concentration of adrenaline in the blood and this will be compared between the different forms of adrenaline.
Lay summary of study results:
The purpose of this study was to investigate the active product adrenaline being administered in a different form as an oral mucosal film. The study was split into two parts: Part A & Part B. The main objectives of the overall study were:
- To determine the safety and tolerability of adrenaline when it was administered as single doses in up to 3 different formulations i.e., as an oral mucosal film, an EpiPen® Auto Injector and as a subcutaneous injection.
- To investigate the pharmacokinetic (PK) profile of adrenaline in the blood, how this changed over a period of time and to evaluate whether there were differences in the PK profile between the different adrenaline formulations.
- To evaluate and compare how the position and placement of the film in the mouth affected the PK profile of adrenaline in the blood.
- To assess different factors for the film including the level of irritation in the mouth, level of adhesion based on film placement and how the application of 2 films of the same dose strength affected the PK profile of adrenaline in the blood when compared to application of 1 film.
- To evaluate and compare the bioavailability of adrenaline as an oral mucosal film in comparison with a marketed product (EpiPen®).Note: Part B of the study did not proceed and therefore the information presented relates to Part A of the study only.
Part A consisted of one group of 12 participants with participants receiving all three adrenaline products across 8 treatment periods in a randomised fashion. For 6 of the 8 treatment periods, participants received the OMF and for the remaining 2 treatment periods, participants received either the EpiPen® or the subcutaneous injection. Part A of the study consisted of a screening visit (between 50 and 2 days prior to first dose), 8 treatment periods (consisting of a maximum of 3 days with 2 overnight stays for treatment period 1 and a maximum of 2 days with 1 overnight stay per subsequent treatment period) and a post-study follow-up visit 5-7 days after the last dose of adrenaline in treatment period 8. Each treatment period was separated by a washout period of at least 2 days (48 hours).
The below section outlines the key outcomes based on the study data generated.
With respect to the safety objectives of the study, it was determined that all of the adrenaline products were considered to be safe and well tolerated in the study.
With respect to the other objectives of the study the following outcomes were reported:
• The data generated for the measurement of adrenaline in the blood was insufficient and therefore the study objectives could not be assessed.
In summary, the data gathered during the study was considered insufficient to meet the objectives of the study.
REC name
Wales REC 2
REC reference
21/WA/0348
Date of REC Opinion
16 Nov 2021
REC opinion
Favourable Opinion