Healthy volunteers Other
Conditions
Interventions
In Part 1 volunteers receive reconstituted 5-HTP powder for oral solution alone in a sipping regimen split into 10 equal doses administered over 9 hours on one occasion, in combination with reconstitu
Sponsors
Evecxia Therapeutics Inc.
Eligibility
Sex/Gender
All
Age
18 Years to 60 Years
Inclusion criteria
Inclusion criteria: 1. Healthy males or healthy females of non-childbearing potential 2. Age 18 to 60 years (Part 1) or 30 to 60 years (Part 2) of age at the time of signing informed consent 3. Body mass index (BMI) of 18.0 to 32.0 kg/m² inclusive, and a body weight of at least 50 kg at screening 4. Must be willing and able to communicate and participate in the whole study 5. Must provide written informed consent 6. Must agree to adhere to the contraception requirements defined in the clinical protocol
Exclusion criteria
Exclusion criteria: 1. Subjects who have received any IMP in a clinical research study within the 90 days prior to Day 1 2. Subjects who are study site employees, or immediate family members of a study site or sponsor employee 3. History of any drug or alcohol abuse in the past 2 years 4. Regular alcohol consumption in males >21 units per week and females >14 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 units = 125 mL glass of wine, depending on type) 5. A confirmed positive alcohol breath test at screening or admission 6. Current smokers and those who have smoked within the last 12 months. A confirmed breath carbon monoxide reading of greater than 10 ppm at screening or admission 7. Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months 8. Females of childbearing potential including those who are pregnant or lactating (all female subjects must have a negative serum pregnancy test at screening and a negative urine pregnancy test at each admission). A woman is considered of childbearing potential unless she is permanently sterile (hysterectomy, bilateral salpingectomy, and bilateral oophorectomy) or is postmenopausal (had no menses for 12 months without an alternative medical cause and a serum follicle stimulating hormone [FSH] concentration =40 IU/L). Bilateral tubal ligation/occlusion is not considered a form of permanent sterilisation 9. Subjects with pregnant partners 10. Part 2 only: Radiation exposure, including that from the present study, excluding background radiation but including diagnostic x-rays and other medical exposures, exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years. No occupationally exposed worker, as defined in the Ionising Radiation Regulations 2017, shall participate in the study (not applicable for Part 1) 11. Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening 12. Clinically significant abnormal clinical chemistry, haematology or urinalysis as judged by the investigator. Subjects with Gilbert’s Syndrome are allowed 13. Confirmed positive drugs of abuse test result 14. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results 15. Presence or history of clinically significant cardiovascular, renal, hepatic, respiratory disease, neurological or psychiatric disorder, or other significant diseases as judged by the investigator 16. Presence of history of any GI disease including peptic ulceration, GI bleeding, ulcerative colitis, Crohn’s Disease or Irritable Bowel Syndrome 17. Part 2 only: History of clinically relevant GI surgery (with the exception of appendectomy unless it was performed within the previous 12 months; not applicable for Part 1) 18. Acute diarrhoea or constipation in the 7 days before the predicted Day 1. If screening occurs >7 days before the Day 1, this criterion will be determined on Day 1. Diarrhoea will be defined as the passage of liquid faeces and/or a stool frequency of greater than 3 times per day. Constipation will be defined as a failure to open the bowels more frequently than every other day 19. Subjects must be able to eat 90% of the FDA-approved high-fat breakfast, including bacon, in order to be eligible for dosing 20. Subjects with a history of cholecystectomy or gall stones 21. Subject answers "yes" to "Suicidal Ideation" Items
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 1: Measurement of the appropriate pharmacokinetic (PK) parameters of 5-HTP and carbidopa following administration of 5-HTP Powder for Oral Solution and Carbidopa Powder for Oral Solution in a sipping regimen including but not limited to: Tmax, Cmax, AUC(0-last), AUC(0 inf) and T1/2 measured using analysis of plasma samples at timepoints from pre-dose until 36 hours post-dose;Part 1: Measurement of Frel (exposure) of 5 HTP at different dose levels based on Cmax, AUC(0 last) and AUC(0-inf) measured using analysis of plasma samples at timepoints from pre-dose until 36 hours post-dose;Part 1: Measurement of Frel (exposure) of 5 HTP at different dose levels of carbidopa based on Cmax, AUC(0-last) and AUC(0-inf) measured using analysis of plasma samples at timepoints from pre-dose until 36 hours post-dose;Part 1: Measurement of Frel (exposure) of 5-HTP at different 5-HTP:carbidopa ratios based on Cmax, AUC(0-last) and AUC(0-inf) measured using analysis of plasma samples at timepoints from pre-dose until 36 hours post-dose;Part 2: A comparison of the in vivo transit and disintegration of 5-HTP/carbidopa GR prototype tablet formulations by measuring the following scintigraphic parameters: last time in stomach, gastric emptying (GE), small intestinal transit, colon arrival (CA), time and location of initial tablet disintegration (ITD) and complete tablet disintegration (CTD) measured using analysis of scintigraphic images at timepoints from immediately after dosing until 24 hours post-dose;Part 2: Measurement of the appropriate PK parameters of 5-HTP and carbidopa following administration of 5-HTP/carbidopa GR prototype tablet formulations including but not limited to: Tmax, Cmax, AUC(0-last), AUC(0 inf) and T1/2 measured using analysis of plasma samples at timepoints from pre-dose until 36 hours post-dose | — |
Secondary
| Measure | Time frame |
|---|---|
| Part 1: Safety and tolerability measured using incidence of adverse events (AEs), and assessment of physical examinations, safety laboratory tests, vital signs, and electrocardiograms (ECGs) at timepoints from written informed consent until discharge from the study at the final follow up call or unscheduled follow-up visit;Part 1: Comparison of the PK parameters AUC(0 last), AUC(0-inf) and Cmax of 5 HTP and carbidopa in the fed state versus fasted state (optional) measured using analysis of plasma samples at timepoints from from pre-dose until 36 hours post-dose;Part 1: Measurement of Frel of the sustained release delivery (as mimicked by the sipping schedule) vs the IR administration of 5 HTP and carbidopa, based on Cmax, AUC(0-last) and AUC(0-inf) (optional) measured using analysis of plasma samples at timepoints from pre-dose until 36 hours post-dose;Part 2: A comparison of the in vivo transit and disintegration of 5-HTP/carbidopa GR prototype tablet formulations by measuring the following: scintigraphic parameters – last time in stomach, GE, small intestinal transit, CA, time and location of ITD, and CTD; PK parameters - Tmax, Cmax, AUC(0-last), AUC(0 inf) and T1/2 measured using analysis of scintigraphic images at timepoints from immediately after dosing until 24 hours post-dose;Part 2: Safety and tolerability measured using incidence of AEs, and assessment of physical examinations, safety laboratory tests, vital signs, and ECGs. at timepoints from written informed consent until discharge from the study at the final follow up call or unscheduled follow-up visit | — |
Countries
England, United Kingdom
Contacts
Public ContactJacob Jacobsen
Outcome results
None listed