Healthy participants Not Applicable
Conditions
Interventions
Part 1: MAD and DDI:
Participants enrolled in multiple dose groups will be randomized in a 3:1 ratio to receive RO7308480 or matching placebo, orally, once daily (QD) for 14 days. Part
RO7308480 high dose oral capsule
lorazepam oral tablet and placebo) in four periods. Participants will receive a single dose of one of the four treatments on Day 1 in each cross-over period. Each period will be followed by a wash-out
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participants who are overtly healthy (defined by absence of evidence of any active or chronic disease). 2. Body mass index (BMI) of 18.5 to 30 kilogram metered square (kg/m²) inclusive. 3. Affiliated with a social security scheme.
Exclusion criteria
Exclusion criteria: 1. Any condition or disease detected during the medical interview/physical examination that could relapse during or immediately after the study, or would render the participant unsuitable for the study, place the participant at undue risk, or interfere with the ability of the participant to complete the study, as determined by the Investigator. 2. History or evidence of any medical condition potentially altering the absorption, metabolism, or elimination of drugs. This includes a surgical history of the gastrointestinal tract affecting gastric motility or altering the gastrointestinal tract. 3. Use of any psychoactive medication, or medications known to have effects on central nervous system (CNS), or blood flow taken within 4 weeks prior to dosing with RO7308480. 4. Use of any psychoactive medication, or medications known to have effects on CNS or blood flow taken within 4 weeks (or within 5 × the elimination half-life of the medication, whichever is longer) prior to dosing with RO7308480. 5. History of convulsions (other than benign febrile convulsions of childhood) including epilepsy, or personal history of significant cerebral trauma or CNS infections (e.g., meningitis). 6. Part 2 only: abnormalities in the brain known at time of screening which would adversely affect the MRI data analysis. 7. Part 2 only: any condition or disease detected during the medical interview/physical examination which are contraindications for lorazepam such as acute narrow-angle glaucoma, hypersensitivity to benzodiazepines or to any of the other ingredients, acute pulmonary insufficiency: respiratory depression; sleep apnea (risk of further respiratory depression), obsessional states (inadequate evidence of safety and efficacy), severe hepatic insufficiency (may precipitate encephalopathy) and/or myasthenia gravis. 8. Participation in an investigational drug or device study within 90 days (or within 5 times the elimination half-life of the investigational drug, whichever is longer) prior to screening, as calculated from the day of follow-up from the previous study, or more than 4 times per year. 9. Dietary restrictions that would prohibit the consumption of standardized meals. 10. Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that contraindicates the participation in the study. 11. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and/or total bilirubin outside of normal range (with the exception of Gilbert’s syndrome with total bilirubin 5 cups per day or methylxanthine (e.g., Coca-Cola) containing drinks > 1 liter/day or > 250 grams/day of chocolate. 15. Participants under judicial supervision, guardianship, or curatorship. 16. Part 2 only: any con
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Part 1: Number of Participants with Adverse Events (AEs) and Severity of AEs Graded on a Scale From Mild, Moderate or Severe From Screening up to Follow-up Visit (up to Approximately 8 Weeks) 2. Part 2: Difference in Regional Amygdala Activity During Emotional Face Matching Task from Placebo Measured by Functional Magnetic Resonance Imaging (fMRI) on Day 1 | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Part 1: Plasma Pharmacokinetics (PK) Parameters of RO7308480 (and its Metabolite[s] as Appropriate) Measured Using Specific and Validated Liquid Chromatography–Mass Spectrometry/Mass Spectrometry (LC-MS/MS) from Day 1 up to Day 22 2. Part 1: Urine PK Parameters of RO7308480 (and its Metabolite[s] as Appropriate) Measured Using Specific and Validated LC-MS/MS on Multiple Time-Points from Day 1 up to Day 15 3. Part 1: Plasma PK parameters of RO7308480 (and its Metabolite[s] as Appropriate) Measured Using Specific and Validated LC-MS/MS on Day 1 vs Steady-State-Cmax, AUCtau From Day 1 up to Day 22 4. Part 1: Plasma PK parameters of Midazolam With and Without Concomitant Administration of RO7308480 Measured Using Specific and Validated LC-MS/MS on Multiple Time-Points from Day -2 (2 Days Prior to the First Dose of RO7308480 [or Matching Placebo]) up to Day 15 5. Part 2: Number of Participants with Adverse Events (AEs) and Severity of AEs Graded on a Scale From Mild, Moderate or Severe From Screening up to Follow-up Visit (Approximately 12 Weeks) | — |
Countries
France
Contacts
Public ContactClinical Trials
Outcome results
None listed