A Clinical Study to Evaluate of Single and Multiple Oral... | NCT06309277

NCT06309277

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Label	Type	Description	Intervention Names
Active	Experimental	GM-1020 (oral)	Drug: GM-1020
Placebo	Placebo Comparator	Placebo (oral)	Drug: GM-1020

Name	Type	Description	Arm Group Labels	Other Names
GM-1020	Drug	N-methyl-D-aspartate (NMDA) receptor antagonist	Active Placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Incidence of Treatment Emergent Adverse Events	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).	Baseline, Day 29

Secondary Outcomes

Measure	Description	Time Frame
MADRS Total Score Change From Baseline to 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.

Other Outcomes

Measure	Description	Time Frame
Part B Remission Rate, Day 42	Observed percentage of participants with a MADRS total Score <= 10.	Day 42
Part B Remission Rate at Day 67	Observed percentage of participants with a MADRS total Score <= 10.

Eligibility Module

Eligibility Criteria

Key Inclusion Criteria:

Patient is male or female, of any ethnic origin.
Patient is aged between 18 to 65 years, inclusive.
Patient has a body mass index (BMI) of 18.0 to 35.0 kg/m2, inclusive.
Patient is ≥50 kg.
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.
Current moderate to severe MDD as confirmed with a MADRS-SIGMA total score >22 and CGI-S score >3 at Screening and Day -1.
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.
Changes in current drug treatment or psychological treatment for depression are not foreseen for the duration of the study.

Key Exclusion Criteria:

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.
Involuntary psychiatric hospitalisation in the current episode. Previous involuntary psychiatric hospitalisation should be carefully considered and only included at the discretion of the Investigator.
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.
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.
Patient is currently or has recently (within 6 weeks prior to Day 1) been treated with antipsychotic medication.
Use of psychoactive substances (including ketamine, esketamine or psychedelics, excluding cannabis) during the 6 weeks prior to Screening.

Name	Affiliation	Role
Gerard Marek, MD	Gilgamesh Pharmaceuticals	Study Chair

Arm/Group Information

ID	Title	Description
FG000	Treatment Sequence 1	Part A: GM-1020 140 mg → Placebo → Part B: GM-1020 140 mg This proof-of-concept study had two parts: Part A was a randomized, double-blind, placebo-controlled, single-dose, cross-over study of GM-1020. In Part A Period 1, patients received GM-1020 140 mg p.o. or placebo and were monitored for 2 weeks. Participants then received the cross-over treatment and were monitored for another 2 weeks (Part A Period 2). Part B was a multiple-dose extension period; patients remained blinded to the treatment assignment and were randomized to receive GM-1020 at either 140 or 210 mg p.o., twice a week for 2 weeks. Following completion of Part B, all participants were followed for 28 days.
FG001	Treatment Sequence 2	Part A: GM-1020 140 mg → Placebo → Part B: GM-1020 210 mg This proof-of-concept study had two parts: Part A was a randomized, double-blind, placebo-controlled, single-dose, cross-over study of GM-1020. In Part A Period 1, patients received GM-1020 140 mg p.o. or placebo (PBO) and were monitored for 2 weeks. Participants then received the cross-over treatment and were monitored for another 2 weeks (Part A Period 2). Part B was a multiple-dose extension period; patients remained blinded to the treatment assignment and were randomized to receive GM-1020 at either 140 or 210 mg p.o., twice a week for 2 weeks. Following completion of Part B, all participants were followed for 28 days.
FG002	Treatment Sequence 3	Part A: Placebo → GM-1020 140 mg → Part B: GM-1020 140 mg This proof-of-concept study had two parts: Part A was a randomized, double-blind, placebo-controlled, single-dose, cross-over study of GM-1020. In Part A Period 1, patients received GM-1020 140 mg p.o. or placebo (PBO) and were monitored for 2 weeks. Participants then received the cross-over treatment and were monitored for another 2 weeks (Part A Period 2). Part B was a multiple-dose extension period; patients remained blinded to the treatment assignment and were randomized to receive GM-1020 at either 140 or 210 mg p.o., twice a week for 2 weeks. Following completion of Part B, all participants were followed for 28 days.
FG003	Treatment Sequence 4	Part A: Placebo → GM-1020 140 mg → Part B: GM-1020 210 mg This proof-of-concept study had two parts: Part A was a randomized, double-blind, placebo-controlled, single-dose, cross-over study of GM-1020. In Part A Period 1, patients received GM-1020 140 mg p.o. or placebo (PBO) and were monitored for 2 weeks. Participants then received the cross-over treatment and were monitored for another 2 weeks (Part A Period 2). Part B was a multiple-dose extension period; patients remained blinded to the treatment assignment and were randomized to receive GM-1020 at either 140 or 210 mg p.o., twice a week for 2 weeks. Following completion of Part B, all participants were followed for 28 days.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Treatment Sequence 1	Part A: GM-1020 140 mg → Placebo → Part B: GM-1020 140 mg This proof-of-concept study had two parts: Part A was a randomized, double-blind, placebo-controlled, single-dose, cross-over study of GM-1020. In Part A Period 1, patients received GM-1020 140 mg p.o. or placebo (PBO) and were monitored for 2 weeks. Participants then received the cross-over treatment and were monitored for another 2 weeks (Part A Period 2). Part B was a multiple-dose extension period; patients remained blinded to the treatment assignment and were randomized to receive GM-1020 at either 140 or 210 mg p.o., twice a week for 2 weeks. Following completion of Part B, all participants were followed for 28 days.

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Incidence of Treatment Emergent Adverse Events

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).

Safety analysis set, defined as all participants who receive at least one dose of study treatment.

Posted

Count of Participants

Participants

Baseline, Day 29

ID	Title	Description
OG000	Part A, Placebo	This proof-of-concept study had two parts: Part A was a randomized, double-blind, placebo-controlled, single-dose, cross-over study of GM-1020. In Part A Period 1, patients received a single oral dose of GM-1020 140 mg or placebo and were monitored for 2 weeks. Participants then received the cross-over treatment and were monitored for another 2 weeks (Part A Period 2).

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Part A Placebo	This proof-of-concept study had two parts: Part A was a randomized, double-blind, placebo-controlled, single-dose, cross-over study of GM-1020. In Part A Period 1, patients received a single oral dose of GM-1020 140 mg or placebo and were monitored for 2 weeks. Participants then received the cross-over treatment and were monitored for another 2 weeks (Part A Period 2).

ID	Term
D003866	Depressive Disorder
D019964	Mood Disorders
D001523	Mental Disorders