Social anxiety disorder Mental and Behavioural Disorders
Conditions
Interventions
Participants will receive a single dose of RO7308480 capsule, orally on Day 1. Multiple dose levels of RO7308480 will be tested in Part 1 and Part 2 of the study.
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participants aged 23- 55 years 2. Body mass index 18-32 kg/m² 3. In good health, as judged by medical history, medical examination, vital signs, ECG and clinical laboratory tests 4. Able to communicate with study personnel 5. Reliable, willing, and likely to comply with the protocol 6. Willing to comply with the contraception requirements of the protocol 7. Consent to inform their GP of their participation in the study, and to enter their details into the over-volunteering database (TOPS).
Exclusion criteria
Exclusion criteria: 1. Not healthy (clinically significant abnormality in our screening tests, which include ECG, vital signs, physical examination, MRI scan and laboratory safety tests of blood and urine); 2. Abuse of alcohol or drugs; 3. Serious reaction to any medicine; 4. Taken certain medicines (ones that could affect the breakdown of the study medicine or that affect the central nervous system or blood flow) during the 30 days before dosing; taken any medicine (except paracetamol), herbal remedies or dietary supplements during the 2 weeks before dosing; taken isotretinoin 2 years prior to screening; 5. History of ophthalmologic conditions that might affect the corneal surface (such as keratoconus, severe dry eye disease and/or corneal dystrophy); wear prescription contact lenses on a daily basis, unless they are not willing to switch to prescription glasses during the study, including the follow-up visit; 6. Have had any condition or operation that might affect the way the body absorbs medicines; have had any clinically significant disease; history of seizures or convulsion ‘fits’ (other than single benign febrile convulsion of childhood); 7. Objection by GP on medical grounds — because they might increase the risk, or confound the assessment of receptor occupancy 8. Tried to commit suicide or homicide, had suicidal or homicidal thoughts; mental illness might compromise consent; 9. Pregnant or breastfeeding; unwilling to comply with the contraception requirements of the protocol — because of the potential risk to the unborn or breastfed baby; 10. Claustrophobia; any condition which would make it difficult to lie still for very long; 11. Metal in the body (eg pacemaker, mechanical heart valve, replacement hip joint, shrapnel); have worked as a metal worker, machinist or welder — due to increased risk from MRI scans 12. Exposure to ionising radiation as part of a research study, such that combined with the exposure from this study their effective dose in a 12 month period would exceed 10 mSv. 13. Unsatisfactory venous access or contraindication for arterial cannulation; 14. Participants who have donated ?500 mL of blood or blood products or had significant blood loss within 3 months prior to screening. 15. participants who use 5 or more cigarettes per day or equivalent amount of tobacco or nicotine products — because participants must be able comfortably to abstain from smoking during the study. 16. Alanine aminotransferase and total bilirubin above the upper limit of normal (ULN) (added 27/06/2023) Criteria are designed to select healthy young participants, who are robust enough to recover quickly from any adverse effects of RO7308480.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Pharmacodynamic (PD): Occupancy of brain GABAA ?1 and GABAA ?2 subunit containing receptors by RO7308480 measured using 1 baseline and 2 post-dose PET scans to assess GABAA receptor occupancy. The baseline PET scan will be carried out on Day -7 or predose on Day 1. The second and third PET scans will be approximately 1.5-2.5 hours and 24-36 hours post-dose. The timing of the on-treatment PET scans may or may not be adjusted after the review of the results from the previous groups. 2. Pharmacokinetic (PK): RO7308480 plasma concentrations measured using blood samples for plasma concentration of RO7308480 will be taken before and after each on-treatment PET scan. | — |
Secondary
| Measure | Time frame |
|---|---|
| Safety and tolerability of single oral doses of RO7308480, as judged by adverse events, vital signs, physical, and neurological exams, ECG parameters, clinical laboratory results, and C-SSRS. Vital signs, medical examination (including weight), laboratory safety tests, ECGs and adverse events will be assessed frequently until the subject's final visit, 10-14 days after their dose of RO7308480. Serious adverse events (SAEs) will be assessed up to 2 weeks after the last dose of RO7308480. If the Investigator learns of an SAE at any time after the follow up period that they considered reasonably related to study treatment or study participation, the Investigator will notify the Sponsor. | — |
Countries
United Kingdom
Outcome results
None listed