Major Depressive Disorder
Conditions
Keywords
MDD
Brief summary
The aim of this Phase 2a study in patients with MDD is to assess safety and tolerability and preliminary antidepressant efficacy.
Interventions
DRUGGM-1020
N-methyl-D-aspartate (NMDA) receptor antagonist
Sponsors
Gilgamesh Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Patient is male or female, of any ethnic origin. 2. Patient is aged between 18 to 65 years, inclusive. 3. Patient has a body mass index (BMI) of 18.0 to 35.0 kg/m2, inclusive. 4. Patient is ≥50 kg. 5. Patient meets the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria for recurrent MDD without psychotic features based on the Mini-International Neuropsychiatric Interview (MINI) at Screening. Comorbid anxiety disorders (e.g., social anxiety disorder, panic disorder, generalised anxiety disorder, specific phobia, agoraphobia) and cluster C personality disorders (avoidant, dependent and obsessive-compulsive) are allowed, provided that MDD is considered the primary diagnosis. 6. Current moderate to severe MDD as confirmed with a MADRS-SIGMA total score \>22 and CGI-S score \>3 at Screening and Day -1. 7. Patient is either not currently taking antidepressants (and hasn't for at least 6 weeks prior to Screening) or is being treated with an SSRI or SNRI antidepressant drug according to national guidelines during the current MDD episode. a. If the patient is currently being treated with SSRI or SNRI antidepressants, these have been prescribed at a stable dose and the dose has remained unchanged for at least 6 weeks prior to Screening. However, the following medications are not permitted during the study at any time: NMDA receptor antagonists (including ketamine, esketamine) and 5-HT2A receptor agonists (including psilocybin, DMT, 5-MeO-DMT). No augmentation strategies will be permitted. 8. Changes in current drug treatment or psychological treatment for depression are not foreseen for the duration of the study. Key
Exclusion criteria
1. Current or recent history of clinically significant suicidal ideation or behaviours as defined by: 1. Suicidal ideation as endorsed on items 4 or 5 on the C-SSRS within 6 months prior to Screening, or 2. Suicidal behaviours within 1 year prior to Screening, or 3. Clinical assessment of significant suicidal risk. Patients with a prior suicide attempt of any sort, or prior serious suicidal ideation/plan \>6 months ago, should be carefully screened for current suicidal ideation and only included at the discretion of the Investigator. 2. Involuntary psychiatric hospitalisation in the current episode. Previous involuntary psychiatric hospitalisation should be carefully considered and only included at the discretion of the Investigator. 3. Lifetime diagnosis of any DSM-5 psychotic disorders, bipolar or related disorders, post-traumatic stress disorder (PTSD), complex-PTSD and borderline personality disorder. Other psychiatric disorders besides MDD should not be the primary disorder. 4. Patient has failed previous treatment with rapidly acting antidepressant drugs, such as NMDA receptor antagonists (e.g., ketamine, esketamine) or 5-HT2A receptor agonists (e.g., psilocybin, DMT, 5-MeO-DMT) or neuromodulating treatments, such as electroconvulsive therapy, transcranial magnetic stimulation, vagus nerve stimulation, or deep brain stimulation. 5. Patient is currently or has recently (within 6 weeks prior to Day 1) been treated with antipsychotic medication. 6. Use of psychoactive substances (including ketamine, esketamine or psychedelics, excluding cannabis) during the 6 weeks prior to Screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment Emergent Adverse Events | Baseline, Day 29 | Clinical monitoring of safety data from AE reporting, 12-lead ECG, vital signs, clinical laboratory evaluations, emergence of suicidal thoughts and ideations (Columbia-Suicidal Severity Rating Scale) and sedation (Modified Observer's Assessment of Alertness and Sedation). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MADRS Total Score Change From Baseline to 24 Hours | Baseline, 24 hours | The Structured Interview Guide for the Montgomery-Åsberg Depression Rating Scale (MADRS) is a 10-item clinician-rated scale used to assess the severity of depressive symptoms in patients. It consists of 10 items, each scored from 0 to 6, yielding a total score ranging from 0 to 60, with higher scores indicating greater depression severity. Part A change from baseline MADRS was analyzed for Period 1 due to carryover effects as per SAP-defined analysis. |
| MADRS Total Score Change From Baseline to Day 8 | Day 8 | The Structured Interview Guide for the Montgomery-Åsberg Depression Rating Scale (MADRS) is a 10-item clinician-rated scale used to assess the severity of depressive symptoms in patients. It consists of 10 items, each scored from 0 to 6, yielding a total score ranging from 0 to 60, with higher scores indicating greater depression severity. Part A change from baseline MADRS was analyzed for Period 1 due to carryover effects as per SAP-defined analysis. |
Countries
United Kingdom
Contacts
STUDY_CHAIRGerard Marek, MD
Gilgamesh Pharmaceuticals
Participant flow
Recruitment details
Subjects with recurrent MDD with Montgomery-Asberg Depression Rating Scale (MADRS) score ≥23 and a CGI ≥ 4 were randomized. Participants had either been antidepressant-free for at least 6 weeks or were receiving an adequate dose of a single SSRI or SNRI for at least 6 weeks, prior to screening and had to maintain this treatment unchanged during the study. SAFER interviews verified MDD diagnosis and severity and antidepressant medication status.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 46 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 41 Participants |
| Region of Enrollment United Kingdom | 13 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 44 | 0 / 43 | 0 / 18 | 0 / 19 |
| other Total, other adverse events | 23 / 44 | 43 / 43 | 18 / 18 | 19 / 19 |
| serious Total, serious adverse events | 0 / 44 | 0 / 43 | 0 / 18 | 0 / 19 |
Outcome results
None listed