Primary objectives: • To determine the safety and tolerability of a single administration and single-day IDR of intravenous GH002.• To determine the pharmacokinetics (PK) of 5-MeO-DMT in healthy volunteers following a single administration and…
Source
Brief title
Phase 1 clinical trial of IV GH002 in healthy volunteers
Condition
- Mood disorders and disturbances NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
• 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 outcome
• 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.
Background summary
Serotonergic psychedelic drugs such as the phenethylamine mescaline, the
tryptamine psilocybin and the ergoline lysergic acid diethylamide (LSD) were
used extensively in psychiatry before they were placed in Schedule I of the
United Nations Convention on Psychotropic Substances in 1971. After decades of
dormancy, there is now a major revival of human psychedelic research driven by
modern brain imaging studies and clinical trials providing promising efficacy
and safety data for the use of psychedelics in the treatment of mental
disorders (Andersen, Carhart-Harris et al. 2021).
5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a psychoactive substance from
the class of tryptamines with high potency, fast onset (generally within 30
seconds) and short duration (generally 5 to 30 minutes) of psychedelic effects,
with no apparent tachyphylaxis (based on assessment of psychedelic effect
intensity) even after short-term re-administration. 5-MeO-DMT acts as a
serotonin (5-HT) agonist and both the 5-HT1A and the 5-HT2A receptor have been
suggested to contribute to 5-MeO-DMT-mediated activity (Shen, Jiang et al.
2010), where it appears to have a higher affinity for the 5-HT1A receptor
subtype (sponsor trial GHNC-API-002; further details are provided in the
current GH001 and GH002 Investigator*s Brochure, (Spencer, Glaser et al. 1987,
Ray 2010).
Study objective
Primary objectives:
• To determine the safety and tolerability of a single administration and
single-day IDR of intravenous GH002.
• To determine the pharmacokinetics (PK) of 5-MeO-DMT in healthy volunteers
following a single administration and single-day IDR of intravenous GH002.
Secondary objectives:
• To investigate the PK/pharmacodynamic (PD) relationship(s), the PD profile of
GH002 as evaluated by its psychoactive effects (PsE), and the impact on
cognitive performance of a single administration and single-day IDR of
intravenous GH002 in healthy volunteers.
• To determine the PK of the metabolite bufotenine in healthy volunteers
following a single administration and single-day IDR of intravenous GH002.
• To evaluate the effect of GH002 on ECG parameters following a single
administration and single-day IDR of intravenous GH002.
Study design
Part A is a double-blind, placebo-controlled, randomized dose-escalation
design, and Part B is an open-label, non-randomized design utilizing an
Individualized Dosing Regimen (IDR).
Intervention
intravenous GH002 or placebo
Study burden and risks
Since the study is executed in healthy volunteers, there are no anticipated
benefits of the IMP. Please see the IB for further information.
Lower Baggot Street 28
Dublin D02 NX43
IE
Lower Baggot Street 28
Dublin D02 NX43
IE
Listed location countries
Age
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
- 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
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 | EUCTR2022-002620-13-NL |
CCMO | NL82760.056.22 |