rBA/FE and MAD study of SYT-510 in healthy participants
Research type
Research Study
Full title
A Two-Part Study Investigating The Relative Bioavailability And The Potential Food Effect After A Single Oral Dose Administration Of A New Formulation of SYT-510, And The Safety, Tolerability, Pharmacokinetics and Pharmacodynamics After Multiple Oral Dose Administration Of SYT-510 in Healthy Subjects
IRAS ID
1010456
Contact name
Andrea Chicca
Contact email
Sponsor organisation
Synendos Theraputics AG
Clinicaltrials.gov Identifier
Research summary
SYT-510 is a selective endocannabinoid reuptake inhibitor, intended to increase levels of endocannabinoids in the central nervous system (CNS). It is intended as a potential treatment for CNS disorders, such as Tourette syndrome and post-traumatic stress disorder, which are characterised by altered endocannabinoid levels and have a high unmet medical need.
An ongoing study of SYT-510 is using a flavoured emulsion. The intention is to replace the flavoured formulation with a powder for suspension for further investigations. Part 1 of the current study will enrol up to 18 healthy participants to assess how the powder formulation is absorbed by the body, with and without food, compared to the flavoured emulsion. All participants will receive each of the formulations, in a randomly assigned sequence, separated by 14-day washout periods.
This will then guide dosing in Part 2, a multiple dose study enrolling up to 12 healthy participants per cohort using the flavoured emulsion or powder for suspension formulation. It will investigate the safety and tolerability of SYT-510 and the way it is processed in the body. Participants will have a 3:1 chance of receiving daily doses of either SYT-510 or placebo for 14 days, during a 22 day in-unit admission. Cerebrospinal fluid (CSF) sampling will be performed by an experienced consultant prior to dosing, and at specified points post dosing to assess the levels of endocannabinoids and other biomarkers in the fluid around the brain and spinal cord. Part 2 is a double-blinded study, whereby neither the study doctor nor the participants know which treatment they receive, and the treatments will be randomly assigned.
SYT-510 has so far shown a favourable safety profile based on an ongoing single dose study and the pre-clinical data. Prior to enrolment, participants for Part 1 and Part 2 will be assessed to ensure they are safe to dose and will be closely monitored throughout the study.
Lay Summary:
"The study had two parts and evaluated the study drug SYT-510.
Part 1: looked at how the body absorbs and processes SYT-510 when it was given as a single dose in two different forms and under different conditions (with or without food) in healthy participants.
Part 2: looked at how the body processes SYT-510 after repeated doses in healthy participants.
Both parts also assessed the safety of SYT-510 and how well participants tolerated it after both single and repeated doses.
The results showed that when SYT-510 was given as a Powder for Suspension (PfS) without food (fasted state), only about 30 to 40% of the amount of drug was present in the body compared to when it was given as a flavoured emulsion without food.
PfS was being tested as it would be easier for the patients to take at home compared to the existing form of flavoured emulsion.
Food had a strong effect on how SYT-510 (as PfS) was absorbed in the body, increasing both how quickly and how much of the drug entered the bloodstream. When SYT-510 was given as PfS with food, a higher amount of the drug was present in the body compared to taking it without food.
When PfS was taken with a high-fat meal, the amount of drug available in the body was similar to that seen with the flavoured emulsion taken without food. These findings suggest that taking SYT-510 with food can help improve how much of the drug becomes available in the body when using the PfS form.
After both single and repeated doses, higher doses of SYT-510 led to higher amounts of the drug in the body. This increase was broadly proportional to the dose across the doses tested. When SYT-510 was taken once daily over several days, stable levels of the drug in the body were reached by approximately Day 8. Overall, the way the drug behaved in the body was predictable and consistent across different doses.
SYT-510 was well tolerated by the participants in this study. There were no serious or severe side effects reported. Most side effects were mild and were generally not considered to be related to the study drug. The treatment was well tolerated across tested doses, formulations, durations of use, and whether it was taken with or without food."REC name
London - London Bridge Research Ethics Committee
REC reference
24/LO/0524
Date of REC Opinion
7 Oct 2024
REC opinion
Further Information Favourable Opinion