Schizophrenia Mental and Behavioural Disorders Schizophrenia
Conditions
Interventions
Participants will be randomly assigned 2:1 by an independent statistician using SAS to take either AUT00206 or AUT00206 placebo oral capsules as follows:
1. A single dose of 2000 mg on the first day
2
Sponsors
Autifony Therapeutics (United Kingdom)
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Aged 18–50 years 2. Schizophrenia diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5); no more than 5 years (before screening) since first contact, diagnosis, and treatment with the psychiatric services for a psychotic illness. Subjects up to 5 years and 6 months post-diagnosis may be included if considered otherwise suitable, at the discretion of the investigator. 3. One positive symptom >3, or two or more positive symptoms =3, AND one negative symptom >3, or two or more negative symptoms =3 on the PANSS 4. Medically and psychiatrically stable (in the opinion of the investigator) and no significant relapse of schizophrenia (i.e. requiring hospitalisation) for the 2 months before admission 5. On a stable dose of one or two antipsychotic drugs (excluding clozapine) for 1 month before screening 6. Agree to use appropriate contraception 7. Sufficient understanding of the nature of the trial and any hazards of participating in it. Ability to communicate satisfactorily with the investigator and to participate in, and comply with the requirements of, the entire trial. 8. Willingness to give written consent to participate after reading the information and consent form, and after having the opportunity to discuss the trial with the investigator or his delegate 9. Capacity to provide informed consent, as judged by an investigator
Exclusion criteria
Exclusion criteria: 1. Female 2. Severely underweight, or morbidly obese, as judged by the investigator 3. Clinically relevant abnormal history, physical findings, ECG, or laboratory values at the pre-trial screening assessment that could interfere with the objectives of the trial or the safety of the subject 4. Presence of acute or chronic illness or history of chronic illness sufficient to invalidate the subject’s participation in the trial or make it unnecessarily hazardous 5. Impaired endocrine, cardiac, pulmonary, thyroid, haematological, hepatic, respiratory, neurological, immunological or renal function, or another major disease (e.g. cancer) deemed clinically significant at the time of the study 6. Type 1 diabetes or type 2 diabetes requiring therapeutic intervention (type 2 diabetes controlled by diet alone is permitted if HbA1c 450 msec at the screening examination, unless judged not clinically significant by an investigator 17. Likelihood that the subject will not comply with the requirements of the protocol 18. Positive test for hepatitis B, hepatitis C or HIV 19. Loss of more than 400 ml blood during the 3 months before the admission, e.g. as a blood donor 20. Objection by a General Practitioner (GP), or another doctor responsible for their treatment, to the patient entering the trial Additional exclusion criteria for PET and MRI only: 1. Exposure to radiation, such that in combination with this trial, exposure would be more than 10 mSv within the previous 12 months (PET exclusion only) 2. Presence of a cardiac pacemaker or other implanted electronic device 3. Contradictions to having an MRI scan, such as (but not limited to) ferromagnetic foreign bodies, pacemaker, shrapnel, etc. (MRI exclusion only)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Pharmacokinetic (PK) profile of AUT00206 after single oral doses measured using blood samples taken before and at several timepoints during the 28-day dosing period – at 0.5, 1, 2, 4, 6, 8, 12 and 16 h after morning dosing on Day 1. Pre-dose samples will be taken before morning dosing on Days 2–6 and on Days 14, 21 and 28 (before morning dosing, if possible) 2. Safety measured using the following at frequent intervals during the study: 2.1. Vital signs (blood pressure, heart rate, tympanic temperature, and respiratory rate) recorded before each morning and evening dose administered during residence, and at 4 h after the morning dose on Days 1–5 and pre-morning dose on Day 6, 14, 21, 28 and at follow up visit. 2.2. 12-lead electrocardiogram (ECG) (single measurements) will be recorded before each morning and evening dose administered during residence, and at 4 h after the morning dose on Days 1–5 and pre-morning dose on Day 21 and follow up. 2.3. Physical examinations on day -2 and on Day 6, 14,21, 28 and at follow up 2.4. Laboratory safety tests (haematology, biochemistry, and urinalysis) on Day 1, 5,14,21 and at follow up 2.5. Suicidal ideation with some intent to act measured using the Columbia-Suicide Severity Rating Scale (C-SSRS) at screening, Day -1, Day 6 2.6. Adverse events (AEs) reported throughout the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary outcome measures: The effects of repeated doses of AUT00206 on Mismatch Negativity (MMN) as a biomarker for schizophrenia measured using MMN at baseline (day -2) and Day 1, Day 4 or 6, Day 14, Day 21 and Day 28 during the study whilst subjects receive treatment Exploratory outcome measures: 1. The effects of repeated doses of AUT00206 on several clinical rating scales measured using the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression (CGI) scale, and Hospital Anxiety and Depression Scale (HADS) at screening, baseline, and 6 weeks 2. The effects of repeated doses of AUT00206 on the electrical activity of the brain and cognition assessed using EEGs and cognitive tests at baseline and 2, 3, 4, and 6 weeks and some optional assessments which include Audiology at baseline and 2, 3, 4, and 6 weeks, and fMRI, and PET scans at one of the visits at baseline and 2, 3, 4, or 6 weeks | — |
Countries
England, United Kingdom
Contacts
Public ContactAlice Sharman
Outcome results
None listed