Treatment-resistant depression
Conditions
Interventions
intravenous GH002 or placebo
Sponsors
GH Research Ireland Limited
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Is informed about the trial, has given informed consent in writing, and is willing and able to comply with all requirements and rules of the trial. 2. Is in the age range between 18 and 45 years (inclusive) at the time of informed consent. 3. Has a body mass index (BMI) in the range of 18.5 and 35 kg/m2 (inclusive) at Screening.
Exclusion criteria
Exclusion criteria: - Has any current or past clinically significant condition (e.g., severe infection, severe pulmonary disease, uncontrolled hypertension, uncontrolled diabetes, severe cardiovascular disease, myocardial infarction or clinically significant arrythmia within the past year, severe hepatic or severe renal failure, brain disorder [including seizure, stroke, dementia, degenerative neurologic diseases, meningitis, encephalitis, and head injury with loss of consciousness]) that may interfere with the interpretation of the trial results, constitute a health risk for the subject, or that otherwise renders the subject unsuitable for the trial according to the investigator*s judgement. - Current or previously diagnosed psychiatric disorder (e.g., a history of major depressive disorder [MDD], bipolar disorders, psychotic disorders, post-traumatic stress disorder [PTSD], obsessive compulsive disorder, autism spectrum disorder, borderline personality disorder, clinically significant intellectual disability). - Has one or more first degree relatives with a current or prior diagnosis of bipolar disorder, psychotic disorder or other mood disorder (including MDD) with psychotic features.-. Has one or more first-degree relatives with current or past history of seizures (uncomplicated childhood febrile seizures with no sequelae are not exclusionary). - If a smoker, is unwilling or unable to abstain from cigarette smoking or vaping for the duration of stay at the trial site (nicotine replacement therapy is permitted).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| • The safety and tolerability of GH002 will be evaluated by: o Incidence of treatment emergent adverse events (TEAEs); o Local tolerance (injection site reactions); o Clinically significant changes from Baseline in ECG, vital signs and safety laboratory assessments assessed as part of the discharge evaluation on Day 0, and at Day 7; o Assessment of sedation (Modified Observer*s Assessment of Alertness and Sedation [MOAA/S]) following each dose and as part of the discharge evaluation on Day 0; o Change from Baseline in Clinician Administered Dissociative Scale (CADSS) assessed as part of the discharge evaluation on Day 0 and at Day 7; o Assessment of subject-discharge readiness at discharge on Day 0 using the Clinical Assessment of Discharge Readiness (CADR). o C-SSRS categorization based on the Columbia Classification Algorithm of Suicide Assessment (C-CASA). o Change from Baseline in Brief Psychiatric Rating Scale (BPRS) assessed as part of the discharge evaluation on Day 0, and at Day 7. • The PK parameters (Cmax, Tmax, t1/2, AUC0-t, AUC0-*, *z, CL, VSS, and Cmax/ AUC0-*) derived from laboratory assay results of the systemic levels of 5-MeO-DMT assessed up to 6 hours post any administration of GH002. | — |
Secondary
| Measure | Time frame |
|---|---|
| • The PD profile of GH002 as evaluated by its PsE as reported 30 to 60 minutes after each dosing, when the PsE have subsided: o PsE assessment using the peak experience (PE) scale (PES) to assess the achievement of a PE (PES score >=75); o Challenging Experience Questionnaire (CEQ); o 30-Question Mystical Experience Questionnaire (MEQ30); o Duration of the PsE defined as the time from GH002 administration to the time when the PsE have subsided as assessed by the investigator. • The PK/PD relationship(s) of 5-MeO-DMT, in particular the correlation between Cmax and AUC with PES score and duration of PsE as scored by the investigator. • The impact on cognitive performance, as evaluated by the change from Baseline to post-dose on Day 0 and to Day 7 in: o Rapid visual information processing (RVP) test; o Verbal recognition memory (VRM) test; o Spatial working memory (SWM) task; o Digit symbol substitution test (DSST). • The PK parameters (Cmax, Tmax, t1/2, AUC0-t, AUC0-*, *z, CL, VSS, and Cmax/ AUC0-*) derived from laboratory assay results of the systemic levels of bufotenine assessed up to 6 hours post any administration of GH002. • ECG parameters as measured from replicate ECGs extracted at pre-defined time points from Holter ECG recordings will include: o Change-from-baseline in HR, QTcF, QTcB, PR, and QRS (ΔHR, ΔQTcF, ΔQTcB, ΔPR, and ΔQRS); o Placebo-corrected ΔHR, ΔQTcF, ΔQTcB, ΔPR, and ΔQRS (ΔΔHR, ΔΔQTcF, ΔΔQTcB, ΔΔPR, and ΔΔQRS); o Categorical outliers for HR, QTcF, QTcB, PR, and QRS; o Frequency of treatment-emergent changes of T-wave morphology and U-wave presence; o Placebo-corrected baseline-adjusted QTcF (ΔΔQTcF), computed from a concentration-response (C-R) model between plasma concentration and changes from baseline in QTcF parameter. | — |
Countries
Netherlands
Outcome results
None listed