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

NCT07478744 | Not Yet Recruiting Phase 2

• 2 other identifiers: SYN510CT-GAD2011013320
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Generalized Anxiety Disorder

Outcome Measures

Primary Outcomes (9)

• 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 Outcomes (6)

• 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

Study Arms (2)

SYT-510

EXPERIMENTAL

Drug: SYT-510

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

SYT-510 DRUG

SYT-510 will be administered as a single oral dose in the morning with liquid.

SYT-510

Placebo DRUG

Matching placebo will be administered as a single oral dose in the morning with liquid.

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Males or females aged 18 to 55 years old (inclusive) at the date of signing the ICF.
• Participants who are currently unmedicated and meet the criteria for GAD as defined in the DSM-5 by using the MINI.
• Participants must be right-handed.
• BMI between 18 and 30 kg/m2, inclusive, at Screening and a minimum weight of 50 kg.
• Contraception use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• 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.
• 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.
• Have an understanding, ability, and willingness to fully comply with study procedures as detailed in the Study Protocol and ICF.

You may not qualify if:

• 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.
• 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.
• Participants with significant learning difficulties, uncorrected visual and auditory problems and history of dyslexia.
• Participants with a current DSM-5 diagnosis of major depressive disorders or severe depressive symptoms determined by MADRS score \> 20.
• Substance use disorder within the past 6 months before Screening.
• Any primary diagnosis other than GAD e.g., bipolar disorder, obsessive compulsive disorder, PTSD, psychotic disorder, cognitive impairment, or pervasive development disorder.
• Any psychotic features, including dementia or delirium.
• Experienced suicidal ideation with some intent to act within the 6 months preceding screening or any history of suicidal behavior.
• Other current or relevant history of physical, neurological or psychiatric illness that may require treatment (e.g., any history of epilepsy).
• Participants with contraindications for MRI.
• 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.
• Positive test for HBsAg, hepatitis C virus antibody, or human immunodeficiency virus antibody at Screening.
• 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
• Laboratory parameters outside of the laboratory normal range (hematology, biochemistry, coagulation, urinalysis), unless deemed NCS by the Investigator.

Sponsors & Collaborators

• Synendos Therapeutics AG: lead

MeSH Terms

Conditions

Generalized Anxiety Disorder

Condition Hierarchy (Ancestors)

Anxiety Disorders; Mental Disorders

Study Officials

• Allan Young

  SLaM

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrea Chicca

CONTACT

+41783008789; andrea.chicca@synendos.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2026
• First Posted: March 17, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: March 17, 2026

Record last verified: 2026-03