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

Официальное название

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

Обзор

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.

Вмешательства

• Препарат SYT-510
  SYT-510 will be administered as a single oral dose in the morning with liquid.
• Препарат Placebo
  Matching placebo will be administered as a single oral dose in the morning with liquid.

Первичные конечные точки

• BOLD fMRI signal in the amygdala in response to fearful stimuli [Срок оценки: 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 [Срок оценки: 4 hours post-dose, Day 2 Treatment period 1 and Day 2 Treatment period 2]
• Defensive behavior: Joystick Operated Runway Task Risk Assessment Intensity [Срок оценки: 4 hours post-dose, Day 2 Treatment Period 1 and Day 2 Treatment period 2]
• Subjective dread during Joystick Operated Runway Task (JORT) [Срок оценки: 4 hours post-dose, Day 2 Treatment Period 1 and Day 2 Treatment period 2]
• Approach-avoidance learning: reward-punishment sensitivity index [Срок оценки: 4 hours post-dose, Day 2 Treatment period 1 and Day 2 Treatment period 2]
• Approach-avoidance learning: punishment sensitivity index [Срок оценки: 4 hours post-dose, Day 2 Treatment period 1 and Day 2 Treatment period 2]
• Default Mode Network connectivity (fMRI) [Срок оценки: 7 hours post dose, Day 2 Treatment period 1 and Day 2 Treatment period 2]
• Reaction time to fearful faces (fMRI task) [Срок оценки: 7 hours post-dose, Day 2 Treatment period 1 and Day 2 Treatment period 2]
• Self reported State Trait Anxiety Inventory (STAI) subscale score [Срок оценки: 1 day post-dose, on Day 3 Treatment period 1 and Day 3 treatment period 2]

Вторичные конечные точки (6)

• EEG power across frequency bands [Срок оценки: 3 and 6 hours post-dose]
• Plasma concentrations of endocannabinoids and ECS related biomarkers [Срок оценки: pre-dose to 24 hours post-dose, Day 2 to Day 3 Treatment period 1 and 2]
• Maximum Observed Concentration (Cmax) of SYT 510 [Срок оценки: Up to 24 hours post-dose, Day 2 to Day3 Treatment period 1 and 2]
• Time of maximal plasma concentration (tmax) of SYT-510 [Срок оценки: 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 [Срок оценки: 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. [Срок оценки: From Day 2 treatment period 1 to follow-up visit, up to 11 weeks]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.
• 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.
• 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.
• Positive test results for alcohol or drugs of abuse at Screening or Baseline. Prior/Concomitant Therapies
• 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.
• 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.
• Use of cannabis, tetrahydrocannabinol or cannabidiol containing products in the 28 days before the Study T1, D2.
• 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

• 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

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Великобритания · 1 центр

• SLaM — London

Идентификаторы

NCT: NCT07478744 · SYN510CT-GAD201 · 1013320

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗