Acute Effects of Partial GABA(A)-Receptor Modulation by GT-002 on Psychophysiological Measures: The TOTEMS Phase II Clinical Trial Targeting Cognitive Impairment Associated with Schizophrenia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Hovedstadens Psykiatriske

Participant type

Patients, Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

7 May 2026 → ongoing

Decision date (initial)

2025-02-14

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

The overall objective of the TOTEMS clinical trial is to investigate the acute effects of partial GABA(A)-receptor modulation by GT-002 on psychophysiological measures in schizophrenia spectrum patients, including event-related EEG and EMG, as well as resting-state EEG. Collectively, these psychophysiological parameters provide proxy measures of hypofrontality, which is considered a key mechanism underlying cognitive impairment in schizophrenia.

Conditions and MedDRA coding

Patients must meet diagnostic criteria for schizophrenia, persistent delusional disorder, acute and transient psychotic disorders, induced delusional disorders, schizoaffective disorders, other non-organic psychotic disorders or unspecified non-organic psychosis (ICD-10: F20.x; F22.x; F23.x; F24.x; F25.x; F28; F29)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. General inclusion criteria (for all participants): 1. Legally competent (in Danish: 'myndige og habile i retslig forstand').
2. General inclusion criteria (for all participants): 2. Males or non-pregnant, non-lactating females aged between 18 and 45 years.
3. Additional inclusion criteria for healthy controls: 1. No current or previous diagnosed mental disorder.
4. Additional inclusion criteria for healthy controls: 2. No first-degree relative with known major psychiatric disorder (ICD-10: F1x; F2x; F3x), defined as having received medical treatment for and/or hospitalizations related to these diagnoses.
5. Additional inclusion criteria for patients: 1. Fulfilling the diagnostic criteria for schizophrenia, persistent delusional disorder, acute and transient psychotic disorders, induced delusional disorders, schizoaffective disorders, other non-organic psychotic disorders or unspecified non-organic psychosis (ICD-10: F20.x; F22.x; F23.x; F24.x; F25.x; F28; F29), prioritizing patients with a shorter antipsychotic history.
6. Additional inclusion criteria for patients: 2. Treated with antipsychotic monotherapy for at least the last three months, including pro re nata (PRN) antipsychotic medication, and prioritizing patients treated specifically with dopamine receptor partial agonists, irrespective of formulation.
7. Additional inclusion criteria for patients: 3. Clinically stable for a minimum of the last three months, i.e., without hospitalizations for schizophrenia or recently intensified psychiatric care (as judged by the TOTEMS investigators).

Exclusion criteria 19

1. General exclusion criteria (for all participants): 1. Prior serious adverse reaction, hypersensitivity, or intolerance to benzodiazepines, GT-002, placebo, or their excipients.
2. General exclusion criteria (for all participants): 2. Ongoing treatment with benzodiazepines (see also concomitant treatment/medication).
3. General exclusion criteria (for all participants): 3. Severe (co-morbid) physical condition (as judged by the TOTEMS investigators), including but not limited to kidney disease, liver disease, chronic obstructive pulmonary disease (COPD), sleep apnea, hypotension, heart failure, and suicidal behavior.
4. General exclusion criteria (for all participants): 4. Pregnancy (assessed by urine pregnancy test).
5. General exclusion criteria (for all participants): 5. Lactation
6. General exclusion criteria (for all participants): 6. Unwillingness or inability to use contraception methods during the study period and until the end of the relevant systemic exposure period, defined as 5 days after the last study drug administration. This applies only to women of childbearing potential.
7. General exclusion criteria (for all participants): 7. Hearing impairment compromising the planned EEG assessments.
8. General exclusion criteria (for all participants): 8. Physical or language impairments that negatively impact the accuracy of cognitive assessment data or verified mental retardation (IQ ≤ 70).
9. General exclusion criteria (for all participants): 9. Clinically relevant findings on physical examination at the screening visit (as judged by the TOTEMS investigators).
10. General exclusion criteria (for all participants): 10. Clinically relevant abnormalities on 12-lead ECG at the screening visit (as judged by the TOTEMS investigators).
11. General exclusion criteria (for all participants): 11. Clinically relevant findings in laboratory samples at screening (as judged by the TOTEMS investigators).
12. General exclusion criteria (for all participants): 12. Participation in a clinical study involving study medical treatment administration within three months prior to screening or in more than 2 clinical studies within 1 year prior to the screening visit.
13. General exclusion criteria (for all participants): 13. Positive results from urine drug tests.
14. General exclusion criteria (for all participants): 14. Unwillingness to refrain from donating blood or blood products during the study
15. Additional exclusion criteria for healthy controls: 1. Lifetime substance dependence (ICD-10: F1x.2) (exception: nicotine dependence, F17.x) or any use of illicit drugs within the 12 months prior to inclusion.
16. Additional exclusion criteria for healthy controls: 2. Any prescribed medications and over-the-counter medications (exceptions specified in the protocol) within 3 weeks prior to the first study drug administration.
17. Additional exclusion criteria for patients: 1. Current substance dependence (ICD-10 F1x.2) (exception: nicotine dependence, F17.x) or any use of illicit drugs within the three months prior to inclusion.
18. Additional exclusion criteria for patients: 2. Any previous or current coercive measure as per Danish legislation ('Lov om Tvang i Psykiatrien').
19. Additional exclusion criteria for patients: 3. Electroconvulsive therapy (ECT) in the last three months.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in Pre-pulse Inhibition of the Startle Reflex (PPI) in schizophrenia spectrum patients following exposure to GT-002, placebo, or oxazepam. The primary analysis will assess the difference between 2 mg GT-002 and placebo.

Secondary endpoints 5

1. Changes in the Mismatch Negativity (MMN) paradigm, Selective Attention (SA) paradigm, 40-Hz Auditory Steady-State Response (40-Hz ASSR) paradigm, and frequency bands at resting state in schizophrenia spectrum patients following exposure to GT-002, oxazepam, or placebo.
2. Safety and tolerability in both antipsychotic-treated schizophrenia spectrum patients and healthy controls, as measured by reported adverse events (AEs) and visual analogue mood scales (VAMS).
3. Changes in the EEG paradigms due to the differential acute effects between GT-002, oxazepam, and placebo in healthy controls.
4. Changes in cognition due to GT-002 compared to oxazepam and placebo in both schizophrenia spectrum patients and healthy controls.
5. The impact of antipsychotic medication type and its duration, sex, age, diagnosis, and duration of illness (DOI) on the acute effect of GT-002 on the EEG paradigms in schizophrenia spectrum patients.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Hovedstadens Psykiatriske

Sponsor organisation

Region Hovedstadens Psykiatriske

Address

Nordre Ringvej 69

City

Glostrup

Postcode

2600

Country

Denmark

Scientific contact point

Organisation

Region Hovedstadens Psykiatriske

Contact name

Bjørn H. Ebdrup

Public contact point

Organisation

Region Hovedstadens Psykiatriske

Contact name

Center for Neuropsychiatric Schizophrenia Research

Third parties 1

Sponsor responsibilities

Article 77 compliance

Region Hovedstadens Psykiatriske

Contact point sponsor

Region Hovedstadens Psykiatriske

Article 77 implementation

Region Hovedstadens Psykiatriske

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 20 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications