Healthy Subjects
Conditions
Keywords
Relative Bioavailability
Brief summary
This is a randomised, open-label, 3-period, crossover single dose study to assess the relative bioavailability of two formulations of HTL0016878: an oral solution of HCl salt form (the reference product) and an oral capsule containing citrate salt (the test product); and of the effect of food on the pharmacokinetics of the capsule formulation.
Detailed description
Fifteen healthy male or female subjects will be enrolled. Each subject will have 3 study sessions and receive a single oral dose of 10 mg HTL0016878 on Day 1 of each study session. Subjects will receive the HTL0016878.HCl oral solution in the fasted state in 1 session, and the HTL0016878.citrate capsule, in the fasted state and after a high-fat meal, respectively, in the other 2 sessions. Each subject will be randomised to 1 of 3 treatment sequences (5 subjects to each sequence). There will be a washout of at least 10 days between doses. Subjects will be screened within 35 days before their first dose of HTL0016878. In each study session, subjects will be resident on the ward from the day before dosing (Day -1) until completion of procedures 72 h after their dose (Day 4). Subjects will return for a follow up visit 10-13 days after their final dose of trial medication.
Interventions
DRUGHTL0016878.HCl Solution 10 mg
Oral solution fasted
DRUGHTL0016878.Citrate Capsule 10 mg
Oral capsule fed or fasted
Sponsors
Nxera Pharma UK Limited
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy male or females, aged 18-50 years 2. Female subjects must agree to use highly effective contraception 3. Weigh 60 kg or more, with a BMI in the range 18.0-30.0 kg/m2 4. Sufficient intelligence to understand the nature of the trial 5. Willingness to give written consent to participate 6. Agree to use the contraception requirements of the trial 7. Agree not to donate blood or blood products during the study and for up to 3 months after the administration of the trial medication 8. Willingness to give written consent to have data entered into The Overvolunteering Prevention System
Exclusion criteria
1. Woman who is pregnant or lactating 2. Clinically relevant abnormal history, physical findings, ECG, or laboratory values 3. Presence or history of acute or chronic illness, or mental health problem 4. Impaired neurological, endocrine, thyroid, cardiovascular, respiratory, gastrointestinal, hepatic or renal function, diabetes mellitus, coronary heart disease, or history of any psychiatric disorder or psychotic mental illness 5. Cancer during the 5 years before screening 6. Supine blood pressure and heart rate outside the ranges: 90-140 mm Hg systolic and 50-90 mm Hg diastolic blood pressure; heart rate 45-80 beats/min 7. Supine QT interval (QTcF) outside the ranges 300-450 msec (men) and 300-470 msec (women) 8. Personal or family history of long QT syndrome or family sudden death 9. Positive test for hepatitis B, hepatitis C or HIV 10. Aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase or total bilirubin levels \> 1.5 times the upper limit of normal 11. Creatinine clearance \< 80 mL/min/1.73 m2 12. Presence or history of drug or alcohol abuse in the past 5 years; or regular intake of more than 21 units of alcohol weekly (for men) or 14 units of alcohol weekly (for women); or use of cigarettes, tobacco and/or nicotine-containing products during the 3 months before dosing 13. Evidence of drug abuse or positive alcohol or cotinine test results 14. Positive pregnancy test 15. Habitual and heavy consumption of caffeinated beverages 16. Use of a prescription or over-the-counter medicine, any herbal remedy, or nutritional supplement 17. Receipt of a vaccine against COVID-19 in the 14 days before dosing 18. Received live attenuated vaccination within 6 weeks prior to Screening 19. History of severe allergies 20. Use of any drugs that are inhibitors of CYP2D6 21. Poor metaboliser of CYP2D6 22. History of epilepsy or seizures 23. Any disease associated with cognitive impairment and/or psychosis 24. Suicidal thoughts or ideation, or insomnia 25. Any history of mental illness (including anxiety, depression), which required medical intervention 26. Presence or history of severe adverse reaction to any drug 27. Surgery or medical condition that might affect absorption of medicines 28. Receipt of an investigational product as part of another clinical trial within the 3 months before dosing in this study 29. Receipt of HTL0016878 in a previous clinical trial 30. Loss of more than 400 mL blood during the 3 months before dosing 31. Unwilling to eat a high-fat breakfast 32. Possibility that the volunteer will not cooperate with the requirements of the protocol 33. Objection by GP to volunteer entering trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of HTL0016878 in plasma Cmax | 0-72 hours | Pharmacokinetics |
| Concentration of HTL0016878 in plasma AUC | 0-72 hours | Pharmacokinetics |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Emergent Adverse Events | Baseline up to 13 days post-dose | Safety and Tolerability |
Countries
United Kingdom
Outcome results
None listed