Healthy volunteers Other
Conditions
Interventions
This was a Phase 1, open-label study to characterise the PK of adrenaline from ADD008 (test IMP) and EpiPen® (reference IMP) (Part 1 [1a and 1b) and to determine the recommended dose of ADD008 for com
Sponsors
Theravia
Eligibility
Sex/Gender
All
Age
18 Years to 60 Years
Inclusion criteria
Inclusion criteria: 1. Healthy male and female participant, between 18 and 60 years of age, inclusive. 2. a) Female participant of childbearing potential willing to use an effective method of contraception, if applicable (unless of non-childbearing potential or where abstaining from sexual intercourse was in line with the preferred and usual lifestyle of the participant) from screening until 2 weeks after the last dose of IMP. b) Female participant of non-childbearing potential. For the purposes of this study, this was defined as the participant being postmenopausal with no menses for at least 12 consecutive months without an alternative medical cause, or at least 4 months post-surgical sterilisation (including bilateral salpingectomy or bilateral oophorectomy with or without hysterectomy). 3. Female participant with a negative pregnancy test at screening. 4. Female participant of menopausal status confirmed by demonstrating at screening that the serum level of follicle stimulating hormone (FSH) fell within the respective pathology reference range. A high FSH level in the postmenopausal range may have been used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement was insufficient. 5. Male participant (and partner of childbearing potential) willing to use an effective method of contraception, if applicable (unless anatomically sterile or where abstaining from sexual intercourse was in line with the preferred and usual lifestyle of the participant) from screening until 2 weeks after last dose of IMP. 6. Participant with a body mass index (BMI) of 18-32 kg/m². BMI = body weight (kg) / [height (m)]². 7. No clinically significant history of previous allergy / sensitivity to adrenaline or any of the excipients contained within the IMP(s). 8. No clinically significant abnormal test results for serum biochemistry, haematology and/or urine analyses within 35 days before the first dose administration of the IMP. 9. No clinically significant medical history of cardiovascular disease/identified cardiovascular risks or clinically significant medical history of any other condition/disease, as determined by medical history evaluation by the Investigator within 35 days before the first dose administration of the IMP (i.e., during screening). 10. Participant with a negative urinary drugs of abuse screen (including alcohol) test results, determined within 35 days before the first dose administration of the IMP (N.B.: A positive test result may be repeated at the Investigator’s discretion). 11. Participant with negative human immunodeficiency virus, hepatitis B surface antigen and hepatitis C virus antibody test results at screening. 12. No clinically significant abnormalities in 12-lead electrocardiogram (ECG) determined within 35 days before first dose of IMP including a PR interval = 220 ms, QRS width = 120 ms and QT interval corrected using Fredericia’s formula (QTcF) = 450 ms. 13. No clinically significant abnormalities in vital signs (blood pressure/heart rate, oral temperature) determined within 35 days before first dose of IMP. 14. Participant was available to complete the study (including all follow-up visits). 15. Participant satisfied an Investigator about his/her fitness to participate in the study i.e., participant was able to understand the informed consent form and associated study restrictions, and willing to participate on thi
Exclusion criteria
Exclusion criteria: 1. Participants who had a clinically significant maxillofacial pathology (including of the oral mucosa and/or dentition) or were still in convalescence following recent maxillofacial surgery as deemed by the Investigator. 2. Presence of any tongue piercings or history of any tongue piercings in the last 90 days prior to Day -1. 3. Use of prescription or non-prescription drugs, within 35 days or 5 half-lives (whichever is longer) prior to the first dose of IMP. 4. Use of dietary and herbal supplements within 14 days prior to the first dose of IMP. 5. Evidence of ongoing or clinical history of renal, hepatic, central nervous system, respiratory, cardiovascular, or metabolic comorbidities. 6. A clinically significant history of drug or alcohol abuse (defined as the consumption of more than 14 units for male and female participants of alcohol a week) within the past two years. 7. Inability to communicate well with the Investigators (i.e., language problem, poor mental development, or impaired cerebral function). 8. Participation in a new chemical entity clinical study within the previous 3 months or five half-lives whichever was the longest, or a marketed drug clinical study within the 30 days or five half-lives whichever was the longest, before the first dose of IMP.(Washout period between studies was defined as the period of time elapsed between the last dose of the previous study and the first dose of the next study). 9. Donation of 450 mL or more blood within the 3 months before the first dose of IMP. 10. Users of nicotine products i.e., current smokers or ex-smokers who had smoked within 6 months prior to first dose administration with the study medication or users of cigarette replacements (i.e., e-cigarettes, nicotine patches or gums). 11. Female participants who were pregnant, breastfeeding or lactating. 12. Participants with veins unsuitable for venepuncture and cannulation. 13. Participants who had received either any live vaccine(s) within 1 month prior to screening or inactivated vaccine(s) 1-2 weeks prior to screening or planned to receive such vaccines during the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoints for Part 1a and Part 1b of this study were pharmacokinetic parameters derived from analysis of plasma samples for concentrations of epinephrine from ADD008, EpiPen® & Anapen and were defined as follows: 1. Maximum plasma concentration (Cmax) 2. First maximum plasma concentration (Cmax1) 3. Time to Cmax (Tmax) 4. Time to Cmax1 (Tmax1) 5. Endogenous adrenaline levels at baseline, prior to adrenaline (unadjusted C0) 6. Time delay between drug administration and the last time prior to first observed concentration above baseline (Tlag) 7. Area under the concentration-time curve (AUC) from time of dosing to 10 min post-dose (AUC0-10) 8. AUC from time of dosing to 20 min post-dose (AUC0-20) 9. AUC from time of dosing to 30 min post-dose (AUC0-30) 10. AUC from time of dosing to time of last measurable concentration (AUC0-t) Timepoints for Assessment in Part 1a and Part 1b were as follows: Day 1: -60, -30, immediately pre-dose and 2, 4, 6, 8, 10, 12, 15, 20, 30 min, 1h, 2h & 4h post-dose (applies across all 6 treatment periods). | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary endpoints for Part 1a and Part 1b of this study were PK endpoints and safety endpoints and were defined as follows: PK Endpoints: 1. Elimination rate constant (?z) 2. Terminal elimination half-life (t1/2) 3. AUC extrapolated to infinity (AUC0-inf) 4. AUC%extrapolated (residual area) Safety Endpoints: 1. Adverse Events (AEs) 2. Vital Signs (systolic/diastolic pressure, heart rate, oral temperature) 3. 12-lead ECG (heart rate, PR interval, QRS width, QT interval and QT interval corrected using Fridericia’s (QTcF interval) formula 4. Laboratory safety (biochemistry, haematology, and urinalysis) 5. Oral Cavity assessments 5.1. Oral Cavity (4-point scoring scale) 5.2. Irritation (8-point scoring scale) 5.3. Blanching (Yes or No) Timepoints for Assessment in Part 1a and Part 1b were as follows: PK: Day 1: -60, -30, immediately pre-dose and 2, 4, 6, 8, 10, 12, 15, 20, 30 min, 1h, 2h & 4h post-dose (applies across all 6 treatment periods). Adverse Events: AEs will be recorded from the point of informed consent up to final post-study follow up visit. Vital Signs (All Parts): Screening, Day -1, Day 1 of each Treatment Period at pre-dose and 10, 15, 45 min, 1, 2, 4 h post-dose & post-study follow up visit. 12 Lead ECG (All Parts): Screening, Day -1 of each Treatment Period & post-study follow up visit. Laboratory Safety Testing (All Parts): Screening, Day -1 of each Treatment Period & post-study follow up visit. Oral Cavity Assessments (All Parts): Day 1 of each Treatment Period where ADD008 is administered at pre-dose and 3 min, 10 min, 30 min & 1 h post-dose. | — |
Countries
United Kingdom, Wales
Contacts
Public ContactRichard Ng
Outcome results
None listed