To characterize the safety and tolerability of ascending single oral doses (part A) and ascending repeated oral doses (part B) of GM-1020 and the effect of food on single dose GM-1020 (part C) in healthy volunteers.
ID
Source
Brief title
Condition
- Mood disorders and disturbances NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Part A, Part B
Safety and tolerability endpoints:
AE*s, vital signs, 12-lead ECG, , laboratory safety tests (routine
haematology, biochemistry and urinalysis), occurrence of psychotic symptoms
(BPRS),emergence of suicidal thoughts and ideations (CSSRS) modified observer*s
assessment of alertness and sedation scale (MOAA/S), and concomitant
medications.
Part C
Plasma and urine PK endpoints GM-1020 and metabolites
Secondary outcome
Part A
Plasma and urine PK endpoints GM-1020 and metabolites.
PD endpoints: Neurophysiological/neuropsychological test battery (Neurocart);
Rating scales; and behavioral assessments
Part B
Plasma and urine PK endpoints GM-1020 and metabolites.
PD endpoints:
o Visual Analogue Scales Bond and Lader (VAS B&L)
o VAS Bowdle (VAS Bowdle) and VAS Drug rating (subjective drug effects) and
Drug Effects Questionnaire (DEQ)
o Pharmaco-EEG (pEEG)
Rating scales:
o Clinician-Administered Dissociative Symptoms Scale (CADSS)
o 5-Dimension Altered States of Consciousness Rating Scale (5D-ASC)
o Mystical Experiences Questionnaire (MEQ30)
o Real-time intensity scale
behavioral assessments
Part C
Safety and tolerability endpoints
AE*s, vital signs, 12-lead ECG, , laboratory safety tests (routine
haematology, biochemistry and urinalysis), occurrence of psychotic symptoms
(BPRS),emergence of suicidal thoughts and ideations (CSSRS) modified observer*s
assessment of alertness and sedation scale (MOAA/S), and concomitant medications
PD endpoints:
o Visual Analogue Scales Bond and Lader (VAS B&L)
o VAS Bowdle (VAS Bowdle) en Drug Effects Questionnaire (DEQ)
Rating scales:
o Clinician-Administered Dissociative Symptoms Scale (CADSS)
o 5-Dimension Altered States of Consciousness Rating Scale (5D-ASC)
Background summary
The pharmacological treatment of major depressive disorder (MDD) with currently
available antidepressant drugs is characterized by considerable
ineffectiveness. Therapeutic effects with conventional antidepressants are only
achieved following several weeks of treatment, and patients who do achieve
adequate symptomatic relief often experience burdensome adverse effects and/or
residual depressive symptoms. In addition, a significant proportion of patients
with MDD are considered treatment resistant since they fail to recover despite
(sequential) treatment with monoamine modulating drugs, and/or various
augmentation strategies with lithium and/or second-generation antipsychotic
drugs. Taken together, the development of more effective and rapidly acting
antidepressant drugs with favorable side-effect profiles is needed.
The non-competitive glutamate N-Methyl-D-aspartate receptor (NMDAR) antagonist
ketamine exists in two enantiomers (R-) and (S-) ketamine. Racemic
(R,S)-ketamine demonstrates robust and rapidly occurring antidepressant
efficacy 24h after intravenous (IV) administration in MDD patients that do not
respond to monoamine-based drugs. It is therefore unique in terms of
mechanism-of-action and onset of antidepressant effects compared to
conventional antidepressant drugs
GM-1020 is a novel synthetic arylcyclohexylamine structural analog of
arketamine that has been optimized to be orally bioavailable while exhibiting a
similar pharmacological profile to (R-)ketamine
Study objective
To characterize the safety and tolerability of ascending single oral doses
(part A) and ascending repeated oral doses (part B) of GM-1020 and the effect
of food on single dose GM-1020 (part C) in healthy volunteers.
Study design
Part A (single ascending dose (SAD)) of this study will evaluate the safety, PK
and PD of ascending single oral doses of GM-1020 by applying a double-blind,
randomized, placebo-controlled design in healthy male and female volunteers.
Part B (multiple ascending dose (MAD)) of this study will evaluate the safety,
PK and PD of ascending repeated oral doses of GM-1020 by applying a randomized,
double-blind, placebo-controlled design in healthy male and female volunteers.
Part C (single dose (SAD)) will consist of an open-label, randomized, 2-period
crossover study in healthy male and female volunteers.
Intervention
Part A: single dose of GM-1020 or placebo
Part B: 4 doses of GM-1020 or placebo (every other day in a timespan of 1 week)
Part C: single dose of GM-1020, 2 times
Study burden and risks
The target disease population for future treatment with GM-1020 is MDD
patients. Therefore, a study population of healthy volunteers between 18 and 55
years is deemed appropriate for this first-in-human ascending single dose and
repeat dose study as these subjects are best to reflect the target population.
The population is not expected to derive any benefit from participating in this
study. The following effects are anticipated in healthy human subjects in the
current study: changes in heart rate and/or blood pressure, shortening of PR
and QT interval, changes in appetite, vomiting, tremors, ataxia and
dissociative effects. This phase 1 trial has been designed to mitigate the
known risks associated with NMDA-receptor antagonists as a class in general and
the potential risks based on the nonclinical toxicity data GM-1020 in
particular. All study drug administrations will be done in the clinic under
medical supervision. The subjects receiving any study drug will remain in the
clinic for at least 24 hours after each study drug administration. Thus, the
subjects can be closely monitored for any adverse signs during the different
treatments. Therefore, providing the protocol is adhered to, careful
observation and medical management will minimize any associated risk in this
study.
University Place Suite 1019 113
New York NY 100003
US
University Place Suite 1019 113
New York NY 100003
US
Listed location countries
Age
Inclusion criteria
1. Healthy female or male subjects, 18 to 55 years of age, inclusive. Healthy
status is defined by absence of evidence of any active or chronic disease
following a detailed medical, surgical a complete physical examination
including vital signs, 12-lead ECG, hematology, blood chemistry, and
urinalysis. If the results of the serum chemistry panel, hematology, or
urinalysis are outside the normal reference ranges, the subject may be included
only if the investigator judges the abnormalities to be not clinically
significant.
2. Subject has a body mass index (BMI) between 18.0 and 30.0 kg/m2 inclusive
(BMI=weight/height2) at screening.
3. Subjects must be willing to adhere to the prohibitions and restrictions
specified in the protocol, including attending all study visits and completing
all study evaluations.
4. Each subject must sign an informed consent form (ICF) indicating that he or
she understands the purpose and procedures required for the study and are
willing to participate in the study. Agree to refrain from using any
psychoactive drugs from 30 days before first dosing and until the last follow
up visit and to refrain from using alcoholic beverages within 48 hours prior to
admission of each treatment period.
Exclusion criteria
1. Clinically significant current or previous liver or renal insufficiency,
cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic,
hematologic, rheumatologic, metabolic or inflammatory illness, or any other
illness that would compromise the well-being of the subject or the study or
prevent the subject from meeting or performing study requirements according to
the investigator.
3.Subject has a history of or current hypertension (resting systolic blood
pressure > 130 mmHg or diastolic blood pressure >90 mmHg) at screening.
5. Resting heart rate (HR) greater than 100 or less than 45 beats per minute
(bpm) at screening.
7. Clinically significant current or previous psychiatric disorder according to
DSM 5.
8. Family history of a psychotic disorder in first-degree and second-degree
relatives.
9. Clinically significant current or previous suicidality based on the C-SSRS
and psychiatric history indicating current suicidal ideation or a history of
active suicidal ideation or suicide attempts
10. Subject has a current or history of drug or alcohol use disorder according
to DSM 5 within the past 12 months.
11. Structural use of psychoactive substances (including ketamine, esketamine,
MDMA, cannabinoids, or psychedelics) during the 6 weeks prior to screening.
Ingestion of psilocybin, DMT, LSD, MDMA, or another serotonergic psychedelic
within the last 4 weeks.
12. Persistent psychological effects following the previous use of psilocybin,
LSD, DMT, ayahuasca, mescaline, ibogaine, 2C-drugs (such as 2CB, 2CI and 2CE)
and/or ketamine. Such effects might include but are not limited to anxiety,
depressed mood, paranoid ideation and/or hallucinations (including hallucinogen
persisting perception disorder - HPPD) or recurrent flashbacks related to use.
13. Subject has a positive test result(s) for alcohol and/or drugs of abuse
(including opiates, cocaine, amphetamines, methamphetamines, cannabinoids,
ketamine and benzodiazepines) at screening or admission to the clinical unit.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2022-003013-11-NL |
| CCMO | NL82520.056.22 |