Depression, Major Depressive Disorder, Treatment Resistant Depression
Conditions
Keywords
Treatment, 5-MeO-DMT, 5-methoxy-dimethyltryptamine
Brief summary
The aim of the study is to investigate the safety of GH001 (containing 5-methoxy-dimethyltryptamine; 5-MeO-DMT), and to investigate its effects on severity of depressive symptoms, and its dose-related psychoactive effects in patients with Treatment-Resistant Depression (TRD). The study is comprised of two open-label, single-arm study parts where Part A evaluates single doses of GH001 at two dose levels and Part B evaluates a specific individualized dosing regimen of GH001.
Detailed description
Phase 1 (Part A): The primary objective of this study is to assess the safety and tolerability of single doses of GH001 (containing 5-methoxy-dimethyltryptamine; 5-MeO-DMT) in patients with TRD. The secondary objectives of the study are to assess the effects of single doses of GH001 on various measures of depression, and on dose-related psychoactive effects. Phase 2 (Part B): The primary objective of this study is to assess the effects of an individualized dosing regimen of GH001 on the severity of depression. The secondary objectives of the study are to assess the safety and tolerability of an individualized dosing regimen of GH001 in patients with TRD and its effects on the severity of depression, other measures of depression, and on dose-related psychoactive effects. Study design: Phase 1/2 study in two parts. Intervention: In the Phase 1 (Part A), a single dose of GH001 will be administered per patient. Two different dose levels will be investigated with four patients at each dose level. In the Phase 2 (Part B), an individualized dosing regimen will be administered. In both parts, GH001 will be administered via inhalation.
Interventions
GH001 administered via inhalation
Sponsors
GH Research Ireland Limited
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Phase 1 (Part A): Two dose levels of GH001 investigated in single doses. Phase 2 (Part B): GH001 investigated in an individualized dosing regimen.
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Has a body mass index (BMI) in the range of 18.5 and 35.0 kg/m2 (inclusive); * Meets the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnostic criteria for single-episode major depressive disorder (MDD) or recurrent MDD, without psychotic features confirmed by the Mini-International Neuropsychiatric Interview (MINI); * Treatment-Resistant Depression as evaluated by the Antidepressant Treatment History Form - Short Form (ATHF-SF); * Has outpatient status at screening and enrolment visits;
Exclusion criteria
* Has a current or prior diagnosis of a psychiatric comorbidity that renders the patient unsuitable for the study according to a study psychiatrist or registered psychologist; * Has received any investigational medication within the last 1 month; * Has a current medically significant condition (e.g., severe infection) or has a history of a medically significant condition (e.g., medical history of seizure, uncontrolled hypertension, uncontrolled diabetes, severe cardiovascular disease, hepatic or renal failure, etc.) that renders the patient unsuitable for the study according to the medical supervisor's judgment; * Takes any medication or other substance that renders the patient unsuitable for the study according to the medical supervisor's judgment; * Has a clinically significant abnormality in physical examination, vital signs, ECG, or clinical laboratory parameters, which renders the patient unsuitable for the study according to the medical supervisor's judgment;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: The safety and tolerability of GH001 as a combined measure of outcomes 5 to 13. | up to 7 days | Phase 1: The primary endpoint is a binary variable (yes/no) reflecting a combined medical/clinical evaluation of the occurrence of Outcomes 5 to 13. The endpoint will be considered met for any dose level or regimen if the Study Safety Group (SSG) - through a qualitative medical/clinical evaluation - considers that dose level or regimen sufficiently safe and tolerable for potential further clinical development in a subsequent study. |
| Phase 2: The effects of GH001 on the severity of depression evaluated by the Montgomery-Asberg Depression Rating Scale (MADRS) | up to 7 days | Phase 2: The assessment is done with the Montgomery-Asberg Depression Rating Scale (MADRS), a diagnostic questionnaire with ten items for measuring the severity of depressive episodes in patients with mood disorders. A higher MADRS score indicates more severe depression, and each item is scored from 0 to 6. The overall score ranges from 0 to 60. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: The effects of GH001 on the severity of depression evaluated by the Montgomery-Asberg Depression Rating Scale (MADRS) | up to 7 days | Phase 1: The assessment is done with the Montgomery-Asberg Depression Rating Scale (MADRS), a diagnostic questionnaire with ten items for measuring the severity of depressive episodes in patients with mood disorders. A higher MADRS score indicates more severe depression, and each item is scored from 0 to 6. The overall score ranges from 0 to 60. |
| Phase 2: The safety and tolerability of GH001 as a combined measure of outcomes 5 to 13 | up to 7 days | Phase 2: The secondary endpoint is a binary variable (yes/no) reflecting a combined medical/clinical evaluation of the occurrence of Outcomes 5 to 13. The endpoint will be considered met for any dose level or regimen if the Study Safety Group (SSG) - through a qualitative medical/clinical evaluation - considers that dose level or regimen sufficiently safe and tolerable for potential further clinical development in a subsequent study. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in the Brief Psychiatric Rating Scale (BPRS) | up to 7 days | Change from baseline in the Brief Psychiatric Rating Scale (BPRS). A scale to measure psychiatric symptoms. Each symptom is rated 1-7 and a total of 18 symptoms are scored. Combined score ranges from 18 to 126. |
| Change from baseline in the Clinician Administered Dissociative States Scale (CADSS) | up to 7 days | Change from baseline in the Clinician Administered Dissociative States Scale (CADSS). The CADSS comprises 19 subjective items, ranging from 0 'not at all' to 4 'extremely. Summed together, these subscales form a total dissociative score. Combined score ranges from 0 to 76. |
| Type and Frequency of Adverse Events | up to 7 days | Adverse events reported in the study and coded by MedDRA. |
| Change from baseline in the Psychomotor Vigilance Test (PVT) | up to 7 days | Change from baseline in the Psychomotor Vigilance Test (PVT). A computerized test assessing the reaction time in response to a visual stimulus. Outcome measures are Response Time and the number of attentional lapses (Response Time ≥ 500 msec). |
| Change from baseline in Digit Symbol Substitution Test (DSST) | up to 7 days | Change from baseline in the Digit Symbol Substitution Test (DSST). A computerized test with the task is to match digits with symbols from encoding list. The number of digits correctly encoded within 3 minutes is the performance measure. |
| Change from baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) | up to 7 days | Change from baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS). A detailed questionnaire assessing both suicidal behaviour and suicidal ideation. No combined score is created. |
| Frequency of clinically significant changes from baseline in the safety laboratory analyses (biochemistry, hematology, urinalysis) | up to 7 days | Safety laboratory analyses are analyses of blood samples (biochemistry, hematology) and urine samples (urinalysis). Changes are defined as any clinically significant change from baseline as determined by the medical supervisor at the site. |
| Frequency of clinically significant changes from baseline in Vital Signs | up to 7 days | Vital signs include heart rate (beats per minute), blood pressure (mmHg), respiratory rate (breaths per minute), oxygen saturation (%), and temperature (degrees celsius). Changes are defined as any clinically significant change from baseline as determined by the medical supervisor at the site. |
| Frequency of clinically significant changes from baseline in Electrocardiogram (ECG) parameters | up to 3 hours after administration of GH001 | Clinically significant changes in ECG include any significant change in rate or rhythm as determined by the medical supervisor at the site. |
Countries
Netherlands
Outcome results
None listed