A Phase 2a Efficacy, Safety, Tolerability, and PK Study of SYT-510 in Participants With Generalized Anxiety Disorder

A Study Investigating the Efficacy, Safety, Tolerability, and Pharmacokinetics of a Single Dose of SYT-510 in Participants Who Meet DSM-5 Diagnostic Criteria for Generalized Anxiety Disorder

This is a single dose study to investigate the efficacy, safety, tolerability and the PK, of SYT-510 in participants who meet diagnostic criteria of GAD. This study represents an evaluation of the effects of SYT-510 in participants meeting DSM-5 GAD diagnostic criteria. As a single dose study, it is designed to evaluate the efficacy of SYT-510 on neurobiological and behavioral markers associated with anxiety and will inform the design of future clinical trials in anxiety disorders. By integrating efficacy / PD, safety, tolerability, and PK measures within the same study framework, the study enables the translational value of the program, ensuring a more comprehensive understanding of SYT-510 effects in patients with generalized anxiety disorders. The plan is to evaluate a single dose of SYT-510 as compared with its matching placebo in a two-way crossover design, separated by a washout period of 7 to 14 days.

Study Overview

• Status: Not yet recruiting
• Conditions: Generalized Anxiety Disorder
• Intervention / Treatment: Drug: SYT-510; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Andrea Chicca; Phone Number: +41783008789; Email: andrea.chicca@synendos.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Males or females aged 18 to 55 years old (inclusive) at the date of signing the ICF.
2. Participants who are currently unmedicated and meet the criteria for GAD as defined in the DSM-5 by using the MINI.
3. Participants must be right-handed.
4. BMI between 18 and 30 kg/m2, inclusive, at Screening and a minimum weight of 50 kg.
5. Contraception use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
6. Participants must agree not to donate sperm or ova from the time of the first administration of study drug (T1, D2) until 3 months after the participant's last visit.
7. Ability to provide written, personally signed, and dated informed consent to participate in the study, in accordance with the current version of the ICH GCP Guideline E6 and applicable regulations, before completing any study-related procedures.
8. Have an understanding, ability, and willingness to fully comply with study procedures as detailed in the Study Protocol and ICF.

Exclusion Criteria:

1. Current or past diseases (e.g., cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematologic, neurologic, endocrine, immunologic, rheumatologic, dermatologic or other conditions) that may interfere with the execution of the conduct of the study, as per the Investigator's judgment.
2. Participants with current or recurrent disease or treatment that can interfere with the absorption, metabolism, and elimination of SYT-510. Examples include participants with partial gastrostomy or impaired renal functions.
3. Participants with significant learning difficulties, uncorrected visual and auditory problems and history of dyslexia.
4. Participants with a current DSM-5 diagnosis of major depressive disorders or severe depressive symptoms determined by MADRS score > 20.
5. Substance use disorder within the past 6 months before Screening.
6. Any primary diagnosis other than GAD e.g., bipolar disorder, obsessive compulsive disorder, PTSD, psychotic disorder, cognitive impairment, or pervasive development disorder.
7. Any psychotic features, including dementia or delirium.
8. Experienced suicidal ideation with some intent to act within the 6 months preceding screening or any history of suicidal behavior.
9. Other current or relevant history of physical, neurological or psychiatric illness that may require treatment (e.g., any history of epilepsy).
10. Participants with contraindications for MRI.
11. Conditions that make the participant unlikely to fully comply with the requirements of the study or complete the study, or any condition that presents undue risk from the study drug or study procedures.
12. Positive test for HBsAg, hepatitis C virus antibody, or human immunodeficiency virus antibody at Screening.

13. Active systemic bacterial, viral, or fungal infection within 14 days prior to dosing on T1, D2 or presence of fever (confirmed body temperature > 38 ºC) within 14 days prior to dosing on T1, D2.

    Diagnostic Assessments

14. Laboratory parameters outside of the laboratory normal range (hematology, biochemistry, coagulation, urinalysis), unless deemed NCS by the Investigator.
15. Has vital signs outside of the following normal range at Screening or Baseline, unless considered NCS by the Investigator: supine SBP 90-140 mmHg, supine DBP 50-90 mmHg, supine PR 40-100 bpm.
16. Has any clinically significant abnormalities in rhythm, conduction or morphology of resting ECG or clinically important abnormalities that may interfere with the interpretation of QTc interval changes, or values outside of the normal range, unless considered NCS by the Investigator.
17. Positive test results for alcohol or drugs of abuse at Screening or Baseline. Prior/Concomitant Therapies
18. Has used any prescription medication (excluding hormonal therapy for postmenopausal women or contraception for WOCBP) within 30 days prior to Screening and any medication for the treatment of anxiety within 6 months prior to screening.
19. Consumption of herbal remedies or dietary supplements which may interact with the study drug (for example containing St. John's Wort) in the 30 days prior to first dose and until the end of the study.
20. Use of cannabis, tetrahydrocannabinol or cannabidiol containing products in the 28 days before the Study T1, D2.

21. Participants who have received a live vaccine within 30 days prior to the first dose administration or who plan to receive a live vaccine during the study period.

    Prior / Concurrent Clinical Study Experience

22. Treatment with an investigational drug within 90 days or 5 half-lives preceding the first dose of trial intervention (or as determined by the local requirement, whichever is the longer) or will start any other investigational product or device study within 90 days after last study drug administration.

    Other Exclusion Criteria

23. Known or suspected intolerance or hypersensitivity to the investigational product, any closely related compound, or any of the stated ingredients.
24. History of significant allergic reactions (anaphylaxis, angioedema) to any product (food, pharmaceutical, etc.).
25. Donation of blood or blood products within 90 days, or plasma within 7 days prior to study drug administration on T1, D2.
26. Underwent general anesthesia in the 30 days prior to study drug administration on T1, D2.
27. Nicotine consumption (in any form) equivalent to > 5 cigarettes or vapes per week.
28. Weekly intake of more than 14 units of alcohol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Matching placebo will be administered as a single oral dose in the morning with liquid.
Experimental: SYT-510	Drug: SYT-510; SYT-510 will be administered as a single oral dose in the morning with liquid.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BOLD fMRI signal in the amygdala in response to fearful stimuli		7 hours post-dose on Day 2 Treatment period 1 and Day 2 Treatment period 2
Defensive behavior: Joystick Operated Runway Task (JORT) Flight Intensity	The JORT uses a force sensing joystick combined with a two-dimensional runway positioned vertically on a computer monitor to measure one-way active avoidance and two-way active avoidance in response to threat of a white noise burst. Each JORT session generates a time series datafile. These time series files are fed into custom programmed scoring software. This software calculates Flight Intensity and RAI for that session	4 hours post-dose, Day 2 Treatment period 1 and Day 2 Treatment period 2
Defensive behavior: Joystick Operated Runway Task Risk Assessment Intensity	The JORT uses a force sensing joystick combined with a two-dimensional runway positioned vertically on a computer monitor to measure one-way active avoidance and two-way active avoidance in response to threat of a white noise burst. Each JORT session generates a time series datafile. These time series files are fed into custom programmed scoring software. This software calculates Risk Assessment Intensity for that session	4 hours post-dose, Day 2 Treatment Period 1 and Day 2 Treatment period 2
Subjective dread during Joystick Operated Runway Task (JORT)	Dread rating on a scale of 1 (no threat) to 10 (maximum dread) .	4 hours post-dose, Day 2 Treatment Period 1 and Day 2 Treatment period 2
Approach-avoidance learning: reward-punishment sensitivity index		4 hours post-dose, Day 2 Treatment period 1 and Day 2 Treatment period 2
Approach-avoidance learning: punishment sensitivity index		4 hours post-dose, Day 2 Treatment period 1 and Day 2 Treatment period 2
Default Mode Network connectivity (fMRI)		7 hours post dose, Day 2 Treatment period 1 and Day 2 Treatment period 2
Reaction time to fearful faces (fMRI task)		7 hours post-dose, Day 2 Treatment period 1 and Day 2 Treatment period 2
Self reported State Trait Anxiety Inventory (STAI) subscale score	The STAI sub-scale is a questionnaire that consists of 20 self-report items that assess current symptoms of anxiety, each item is rated on a four-point Likert scale from "Not at all" to "Very much so".	1 day post-dose, on Day 3 Treatment period 1 and Day 3 treatment period 2

Secondary Outcome Measures

Outcome Measure	Time Frame
EEG power across frequency bands	3 and 6 hours post-dose
Plasma concentrations of endocannabinoids and ECS related biomarkers	pre-dose to 24 hours post-dose, Day 2 to Day 3 Treatment period 1 and 2
Maximum Observed Concentration (Cmax) of SYT 510	Up to 24 hours post-dose, Day 2 to Day3 Treatment period 1 and 2
Time of maximal plasma concentration (tmax) of SYT-510	From dosing to follow-up visit, up to 11 weeks
Area Under the SYT-510 concentration -time Curve (AUC) from time 0 to 24 hours	pre-dose to 24 hours post dose, on Day 2 to Day 3 Treatment periods 1 and 2
14. Incidence and severity of Treatment Emergent Adverse Events and Serious Adverse Events, changes and/or abnormalities in clinical laboratory tests, physical examination findings, vital signs, and ECGs.	From Day 2 treatment period 1 to follow-up visit, up to 11 weeks

Collaborators and Investigators

• Sponsor: Synendos Therapeutics AG
• Investigators: Principal Investigator: Allan Young, SLaM

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: March 9, 2026
• First Submitted That Met QC Criteria: March 13, 2026
• First Posted (Actual): March 17, 2026

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 13, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Anxiety Disorders; Generalized Anxiety Disorder
• Other Study ID Numbers: SYN510CT-GAD201; 1013320 (Other Identifier: IRAS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No