*A 3-part study to investigate ADD008 in comparison with EpiPen® in healthy volunteers
Research type
Research Study
Full title
*A Phase 1, three-part, open label, single centre study to investigate the safety, tolerability, and pharmacokinetics of ADD008 in comparison with EpiPen®.
IRAS ID
1008056
Contact name
Amie Gledhill
Contact email
Sponsor organisation
THERAVIA
ISRCTN Number
ISRCTN40495811
Research summary
Summary of Research\n\nThe purpose of this study is to investigate ADD008 (active ingredient adrenaline, herein referred to as epinephrine).\n\nThe overall objectives are to determine the safety, tolerability (degree to which side effects of a drug can be tolerated) and concentration in the blood of epinephrine when evaluated in different conditions i.e., single and repeat doses, different dose strengths and in different forms i.e., in the form of a sublingual tablet (which dissolves under the tongue – test drug ADD008) in comparison with EpiPen® (a marketed form of injectable epinephrine used in the treatment of severe allergic reactions). \n\nThe study will be split into 3 parts as follows:\n\n- Part 1 - enrolling up to 10 healthy participants, evaluating 5 single doses of ADD008 (ranging from 2 mg-30 mg), in comparison with a single dose of EpiPen® across 6 treatment periods.\n\n- Part 2a - enrolling up to 40 healthy participants, evaluating a single dose of ADD008 (optimal dose selected from Part 1 data), in comparison with a single dose of EpiPen® across 2 randomised treatment periods.\n\n- Part 2b - enrolling up to 40 healthy participants, evaluating a repeat dose of ADD008 (optimal dose selected from Part 1 data and doses administered twice, 10 minutes apart), in comparison with a repeat dose of EpiPen® (administered twice, 10 minutes apart) across 2 randomised treatment periods.\n\nBlood samples will be taken at set timepoints to measure the levels of epinephrine in the blood. The results will be compared between each treatment period and each study part to determine if there are any significant differences in the safety of epinephrine, the concentration of epinephrine in the blood or when epinephrine is administered in different forms and conditions. The purpose of this is to determine as to which dose of ADD008 is most comparable to the dose of the standard treatment for allergic reactions (EpiPen®) to support developing ADD008 as an alternative form of epinephrine.\n\nSummary of Results\nThe purpose of this study was to investigate the study drug ADD008 (active ingredient adrenaline, herein referred to as epinephrine as this is the applied term for the synthetic (man-made) form of adrenaline), in comparison with EpiPen®.\n\nThis study was split into four parts and the overall objectives of the study were to determine the safety, tolerability (degree to which side effects of a drug can be tolerated) and concentration in the blood of epinephrine when evaluated in different conditions i.e., single and repeat doses, different dose strengths and in different forms i.e., in the form of a sublingual tablet (which dissolves under the tongue – test drug ADD008) in comparison with EpiPen® (a marketed form of injectable epinephrine used in the treatment of severe allergic reactions) and another marketed form of injectable epinephrine similar to EpiPen® (at a higher dose). The purpose of the overall study was to determine as to which dose strength of ADD008 demonstrated the most comparable concentrations in the blood to the standard dose of the current recommended standard treatment for allergic reactions (EpiPen®).\n\nThe study was planned to consist of up to 100 participants across the four parts of the study; however, only Parts 1a and 1b of the study completed and therefore only 24 participants were enrolled (10 within Part 1a and 14 within Part 1b). Of the 24 participants who were enrolled, 8 completed Part 1a and 10 completed Part 1b.\n\nBlood samples were taken at set timepoints throughout each part of the study in order to measure the levels of epinephrine in the blood. The results between each treatment period and each study part have been compared to determine if there are any significant differences in the safety of epinephrine, the concentration of epinephrine in the blood and how this concentration changed over time or when epinephrine was administered in different conditions i.e., single and repeat doses, different dose strengths and in different forms. The below section outlines the key outcomes based on the study data generated.\n\nWith respect to the safety objectives of the study, it was determined that ADD008 was not considered to be well tolerated owing to a high occurrence of side effects at all dose strengths evaluated (from 2 mg – 30 mg). With respect to side effects reported, the majority of side effects were considered related to the study drug; however, no effects were classified as serious in severity (the majority of effects were considered to be mild in nature). In addition, all effects reported resolved before the study concluded.\n\nWith respect to the other objectives of the study the following outcomes were reported:\n\nThere was insufficient data generated to reliably generate a profile for the concentration of epinephrine at any of the ADD008 dose strengths evaluated in Part 1a or Part 1b.\n\nThere were no significant safety findings in any of the vital signs or laboratory safety testing conducted during Part 1a or Part 1b.\n\nThere were no effects seen in the mouth as a result of administration of ADD008 at any of the dose strengths administered.\n\nIn summary, the data gathered during the study was considered insufficient to meet the objectives of the study.
REC name
Wales REC 2
REC reference
23/WA/0204
Date of REC Opinion
16 Jan 2024
REC opinion
Further Information Favourable Opinion