Generalized Anxiety Disorder MedDRA version: 18.1 Level: LLT Classification code 10018105 Term: Generalized anxiety disorder System Organ Class: 100000004873
Conditions
Interventions
Product Code: BNC210 300mg
Pharmaceutical Form: Powder for oral suspension
Pharmaceutical form of the placebo: Oral solution
Route of administration of the placebo: Oral use
Product Code: BNC210 2000
Sponsors
BIONOMICS LIMITED
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Male or female volunteers 18 to 50 years of age who are un-medicated but meet the criteria for Generalized Anxiety Disorder (GAD) as defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM) IV by using the Mini-International Neuropsychiatric Interview (MINI). Subjects must have a depression score of 15 or lower, as measured by the Montgomery–Åsberg Depression Rating Scale (MADRS). Subjects must also undertake the Hamilton Anxiety Rating Scale (HAM-A) during the screening visit to score the severity of their anxiety symptoms. 2.A male subject who is non-sterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception* from signing of informed consent throughout the duration of the study and for 16 weeks after last dose. 3.Male subjects must agree not to donate sperm or blood from signing of informed consent to 16 weeks after the last dose of study medication. 4.Female subjects must agree not to donate blood from signing of informed consent to 16 weeks after the last dose of study medication. 5.Female subjects of childbearing potential must agree to use adequate contraception* from signing of informed consent throughout the duration of the study and for 16 weeks after last dose. 6.Female subject of childbearing potential must have a negative serum pregnancy test result at screening and a negative urine pregnancy test prior to each dose. 7.Female subjects must not be breast-feeding. 8.Body weight =50 kg with a body mass index (BMI) calculated as weight in kg/(height in m)2 from 18 to 30 kg/m2 (inclusive) at screening. 9.A signed and dated informed consent form before any study-specific screening procedure is performed. 10.Apart from meeting the criteria for GAD, subjects must be healthy as determined by the Investigator on the basis of medical history, physical examination findings, clinical laboratory test results, vital sign measurements, digital 12-lead electrocardiogram (ECG) readings, and mental health based on responses to the MINI, a screening instrument which evaluates a broad range of psychological problems and symptoms of psychopathology (all results should be normal or, if out of range, non-clinically significant as determined by the Investigator). 11.Normal thyroid function based on thyroid-stimulating hormone (TSH). 12.Non-smoker. Ex-smokers are eligible after 3 months of smoking cessation. 13.Subjects must be judged by the investigators to have a high probability for compliance with and completion of the study. For example, subjects must be fluent in English and have a cooperative attitude, as they must be able to fully understand written and verbal instructions and the nature of the study, have the capacity to make an informed decision about whether to take part and sign the consent form. Assessments require the completion of English language questionnaires. 14.Subjects must be suitable for magnetic resonance imaging (MRI). For example, the subject must not have claustrophobia, any metal objects in their body, nor have undergone recent surgery. Subjects must be able-bodied enough to perform the required tasks in the MRI scanner. The subjects must also have no learning difficulties, no uncorrected visual problems, no auditory problems and no history of dyslexia, serious head injury or seizure. Participants will undergo a session in the mock scanner in order to assess their capacity to undergo the somewhat claustrophobic conditions that exi
Exclusion criteria
Exclusion criteria: Medical History 1.Any significant cardiovascular (e.g., heart failure), hepatic, renal, respiratory (e.g., asthma), gastrointestinal, endocrine (e.g., diabetes, dyslipidaemia), immunologic, dermatological, haematological, neurologic, psychiatric disease (except GAD) or history of any clinically important drug allergy. 2.The subject has a positive test result for hepatitis B surface antigen (HBsAg), antibody to hepatitis C virus (anti-HCV), or human immunodeficiency virus (HIV) antibody/antigen at Screening. 3.Substance use disorder or post-traumatic stress disorder (PTSD) within the past 6 months. 4.Lifetime bipolar disorder, obsessive-compulsive disorder (OCD), psychotic disorder, mental retardation, or pervasive development disorder. 5.Any psychotic features, including dementia or delirium. 6.Current serious suicidal ideation, and/or suicidal attempt within the past 6 months. 7.Acute disease state (e.g., vomiting, fever, diarrhoea) within 7 days before the first dosing visit. 8.Presence of orthostatic hypotension (decrease in systolic blood pressure = 20 mmHg from supine to standing position) at screening. 9.Current drug abuse or history of drug abuse within 1 year before the first dosing visit. 10.Current alcoholism or history of alcoholism within 1 year before the first dosing visit. Consumption of more than 50 g of ethanol per day [12.5 cL glass of 10° (10%) wine = 12 g; 4 cL of aperitif, 42° (42%) whiskey = 17 g; 25 cL glass of 3° (3%) beer = 7.5 g; 25 cL glass of 6° (6%) beer = 15 g]. 11.A low likelihood of completing the study, according to the judgement of the investigator. Prohibited Treatments: 12.Use of any investigational drug within 30 days before first dose. 13.Use of any prescription or over-the counter drug [including herbal medications (especially St. John’s wort), herbal supplements and herbal teas] within less than 5 times the elimination half-life before first dose. 14.Use of any prescribed drug that is a potential cytochrome P450 3A4 inducer within the previous 30 days (carbamazepine, efavirenz, nevirapine, phenobarbital, phenytoin, rifabutin, rifampin). 15.The subject has a known contraindication to the use of lorazepam or hypersensitivity to any component of the formulation of BNC210 or lorazepam.. Other 16.Regular consumption of any caffeine-containing products (e.g., coffee, tea, chocolate, or cola) in excess of 6 cups per day (or equivalent). 17.Donation of blood (i.e., 450 mL) within 60 days before first dose. 18.The subject is an immediate family member, study site employee, or is in a dependant relationship with a study site employee who is involved in the conduct of this study (e.g., spouse, parent, child, sibling) or may consent under duress.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether BNC210 causes significant changes in cerebral perfusion using Arterial Spin Labelling in the resting state. To determine whether BNC210 causes significant changes in task-related brain activity using the emotional faces task during fMRI. ;Secondary Objective: To determine the effect of BNC210 on defensive behaviour. To determine whether BNC210 alters affective self-report in a way that is consistent with reduced anxiety. To contribute safety and tolerability information on BNC210. The exploratory objective is to determine the correlation between BNC210-related brain activity changes and affective self-report.;Primary end point(s): The primary endpoints of this study are the effect of BNC210 administration, compared to placebo on the following parameters: -resting fMRI blood-oxygen-level-dependent (BOLD) and arterial spin labelling (ASL) response in the amygdala. -fMRI BOLD response in the amygdala during the Emotional Faces Task. ;Timepoint(s) of evaluation of this end point: Throughout the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints of this study are the effect of BNC210 administration, compared to placebo on: -the intensity of defensive behavior as measured by the Joystick Operated Runway Task (JORT). -affective self-report using the Spielberger State-Trait Anxiety Inventory (STAI). -safety (i.e., adverse events, vital signs measurements, 12-lead electrocardiograms (ECGs), physical examination findings, blood safety tests, urine safety tests). The exploratory endpoints of this study are to determine the correlation between BNC210 related brain activity changes and affective self-report.;Timepoint(s) of evaluation of this end point: Throughout the study | — |
Countries
United Kingdom
Contacts
Public ContactLiz Doolin
BIONOMICS LIMITED
Outcome results
None listed