Schizophrenia MedDRA version: 19.0 Level: PT Classification code 10039626 Term: Schizophrenia System Organ Class: 10037175 - Psychiatric disorders
Conditions
Interventions
Product Name: AUT00206 200 mg capsules
Product Code: AUT00206
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: AUT00206
Current Sponsor code: AUT00206
Other descriptive name: N/A
Concentration
Sponsors
Autifony Therapeutics Limited
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: Male aged 18 to 45 years, inclusive at Visit 1 Healthy on the basis of medical history, psychiatric history, physical examination, vital signs, 12-lead electrocardiogram (ECG), haematology, blood chemistry and urinalysis within 6 weeks of Visit 2 Right-handed Not a regular smoker (maximum 5 cigarettes per week or equivalent) Competent English speakers Acceptable weight as defined by Body Mass Index (BMI) (weight [kg]/height [m]²) range of 18 to 30 kg/m², inclusive at Visit Participants with partner(s) of childbearing potential must take appropriate precautions to avoid fathering a child from Visit 1 until 4 months after the last dose of study drug and use barrier contraception, in addition to their partner(s) using another method. Acceptable forms of contraception are as follows: Barrier methods: condoms, diaphragms, cervical caps; with a spermicide foam, gel, film, cream or suppository; Non-hormone containing intrauterine methods: intrauterine devices or systems. Provision of written informed consent before initiation of any study related procedures. Be able to understand and comply with the requirements of the study, as judged by the Investigator. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 16 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: History of positive test for hepatitis B, hepatitis C, human immunodeficiency virus (HIV)-1 or HIV-2. Sitting (5 minutes) blood pressure outside the ranges of 90 to 150 mmHg systolic, inclusive, and 60 to 90 mmHg diastolic, inclusive, unless judged not clinically significant by the responsible physician. Corrected QT interval (QTcF) > 450 msec (based on the Fridericia correction where QTcF = QT/RR0.33). Known contraindication to the use of ketamine Participants in whom an elevation of blood pressure would constitute a serious hazard Hypersensitivity to the drug or its components Participants with severe coronary or myocardial disease, cerebrovascular accident or cerebral trauma History of, or presents (in the opinion of the responsible physician) with, significant neurological or psychiatric conditions (such as stroke, traumatic brain injury, depression, epilepsy, space occupying lesions, multiple sclerosis, Parkinson’s disease, vascular dementia, transient ischemic attack, schizophrenia, blackouts requiring hospitalisation). History of, or current condition of, migraine headaches or has undergone operations to the head. History of significant claustrophobia. Recreational drug use within 3 months prior to Visit 1. Intake of more than 21 units of alcohol weekly. Positive alcohol breath test at Visit 1 or Visit 2. Positive urine drug screen at Visit 1 or Visit 2. Consumption of large amounts of caffeinated drinks (more than 8 cups of standard caffeinated drinks [tea, instant coffee] or 6 cups of stronger coffee or other drinks containing methylxanthines such as Coca Cola or Red Bull per day). Consumption of any food or any drinks containing cranberry, pomegranate, star fruit, grapefruit, pomelos, exotic citrus fruits or Seville oranges within 3 days prior to Visit 2. Use of a prescription medicine in the 28 days before Visit 2, unless the responsible physician considers that it would not interfere with the study (e.g. acetaminophen). Use of an over-the-counter medicine, with the exception of acetaminophen (paracetamol), in the 7 days before Visit 2, unless the responsible physician considers that it would not interfere with the study. Has participated in another study and/or taken experimental drugs and/or used experimental medical devices within 30 days of Visit 1 or within a period less than 5 times the drug’s half-life, whichever is longer Previous randomisation in the present study. Fulfils any of the MRI contraindications on the standard site radiography screening questionnaire (e.g. history of surgery involving metal implants).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether AUT00206 compared to placebo attenuates the effects of ketamine on the Blood Oxygen Level Dependent (BOLD) pharmacological Magnetic Resonance Imaging (phMRI) signal in regions known to be sensitive to ketamine challenge, including the cingulate gyrus, thalamus, and precuneus, in healthy male participants;Secondary Objective: AUT00206 compared to placebo attenuates the effects of ketamine, as assessed by: the whole-brain ketamine signal to train a Gaussian Process Classifier; the BOLD functional Magnetic Resonance Imaging (fMRI) signal in brain areas associated with executive function (working memory) during performance of the N-back task; modulation of resting state connectivity in the default mode and salience networks; modulation of cerebral blood flow (CBF) and arterial arrival time (AAL) as determined by arterial spin labelling (ASL); arterial blood flow as determined by ASL. To explore the effects of AUT00206 compared to placebo on deficits induced by ketamine on performance of the N-back task, as measured by reaction time, response accuracy, sensitivity (d’) and bias (criterion). To determine whether AUT00206 compared to placebo modulates the dissociative and subjective effects induced by ketamine as determined by questionnaire measures (PSI, PANSS and CADSS). Safety and tolerability of AUT00206;Primary end point(s): BOLD phMRI signals within the pre-specified regions of interest (ROI) derived from Deakin et al. (2008) and detailed in the supplementary material of Doyle et al. (2013).;Timepoint(s) of evaluation of this end point: At baseline (infusion of saline) and during treatment period scanning. Participants will enter the scanner 3 hours (±15 minutes) after administration of AUT00206/placebo. All treatment period scanning activities must be completed 5 minutes prior to the end of treatment infusion. Expected total scanning durations are approximately 50 minutes at Visit 2 and approximately 45 minutes at Visits 3 to 5. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: At Visits 2 to 5. ;Secondary end point(s): Change in accuracy of the GPC from saline-ketamine to AUT00206-ketamine (high and low dose). BOLD fMRI signals in the frontal and parietal cortex during performance of the N-back task. Changes in resting-state connectivity before and after the bolus infusion in the default mode network and salience network. ASL measurements of CBF and AAT. Behavioural performance in the N-back task, including measurements of accuracy (% correct for each trial type), reaction time and target sensitivity (d’). PSI scores before and after MRI scanning at Visits 2 to 5. PANSS scores before and after MRI scanning at Visits 2 to 5. CADSS scores before and after MRI scanning at Visits 2 to 5. | — |
Countries
United Kingdom
Contacts
Public ContactAnil Sajjala
Autifony Therapeutics Limited
Outcome results
None listed