Safety, tolerability, pharmacokinetics, and food effects of single-ascending oral doses of RO7308480 in healthy participants Not Applicable
Conditions
Interventions
Part 1: RO7308480-SAD Cohorts: Participants will receive a single dose of RO7308480 capsule, orally, under fasted conditions on Day 1 in cohort 1. The dose will be escalated in subsequent cohorts in s
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 18 to 55 years of age inclusive, at the time of signing the informed consent 2. Male and female participants who are overtly healthy (defined by the absence of evidence of any active or chronic disease) as determined by medical evaluation 3. Participants able to communicate with the study staff 4. Body mass index (BMI) of 18 to 30 kg/m² inclusive
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 2. 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 first dosing 3. 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) 4. Any major illness within one month before the screening examination (e.g., COVID-19 infection) or any febrile illness within 1 week prior to screening and up to first study drug administration 5. Clinically significant abnormalities in laboratory test results 6. Current or chronic history of liver disease, or known hepatic or biliary abnormalities 7. Participants who, in the Investigator's judgment, pose a suicidal or homicidal risk, or any participant with a history of suicidal or homicidal attempts 8. Participants likely to need concomitant medication during the study period 9. Use of isotretinoin within 2 years prior to screening 10. Incomplete SARS-CoV-2/COVID-19 vaccinations scheme 2 weeks prior to administration of the first dose 11. Participation in an investigational drug or device study within 90 days prior to screening, as calculated from the day of follow-up from the previous study, or more than four times a year 12. Show evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies 13. Positive result on hepatitis B virus (HBV) or hepatitis C virus (HCV) at screening or within 3 months prior to starting study treatment 14. Any suspicion or history of alcohol abuse 15. Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that contraindicates the participation in the study 16. Participants who regularly smoke more than 5 cigarettes daily or equivalent amount of tobacco and nicotine substitutes as determined by history, and unable or unwilling not to smoke during the in-house period
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Part 1 and 2: Percentage of participants with adverse event (AEs), recorded by non-leading verbal questioning of the participant, from screening up to Day 14 and 28 days after study drug administration (up to approximately 6 months) in single-ascending dose (SAD) and food effect assessment (FE) stages, respectively 2. Part 1 and 2: Percentage of participants with the severity of AEs as assessed by the investigator (mild, moderate, or severe) from screening up to Day 14 and 28 days after study drug administration (up to approximately 6 months) in SAD and FE stages, respectively 3. Part 1 and 2: Percentage of participants with clinically significant changes in vital signs values measured using body temperature (tympanic), pulse rate, respiratory rate, and blood pressure from screening up to Day 14 and 28 days after study drug administration (up to approximately 6 months) in SAD and FE stages, respectively 4. Part 1 and 2: Percentage of participants with clinically significant changes in physical findings measured by assessment of cardiovascular, respiratory, gastrointestinal, dermatological, neurological, and musculoskeletal systems in addition to head, eyes, ears, nose, throat, neck, and lymph nodes from screening up to Day 14 and 28 days after study drug administration (up to approximately 6 months) in SAD and FE stages, respectively 5. Part 1 and 2: Percentage of participants with clinically significant changes in neurological findings assessed using measurement of motor and sensory skills, functioning of cranial nerves (including pupillary responses), coordination, gait, reflexes, and mental status from screening up to Day 14 and 28 days after study drug administration (up to approximately 6 months) in SAD and FE stages, respectively 6. Part 1 and 2: Percentage of participants with clinically significant changes in electrocardiogram (ECG) parameters measured using 12-lead ECG and Ho | — |
Secondary
| Measure | Time frame |
|---|---|
| Measured from blood samples using a specific and validated liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method: 1. Part 1: Maximum observed plasma concentration (Cmax) of RO7308480 and its metabolites, as appropriate, measured using blood samples at pre-dose and multiple time-points post-dose on Day 1 and every 12 hours (h) thereafter up to Day 14 in SAD stage 2. Part 1: Time to maximum observed concentration (Tmax) of RO7308480 and its metabolites, as appropriate, measured using blood samples at pre-dose and multiple time-points post-dose on Day 1 and every 12 h thereafter up to Day 14 in SAD stage 3. Part 1: Area under the plasma concentration-time curve from time zero up to the last measurable concentration (AUClast) of RO7308480 and its metabolites, as appropriate, measured using blood samples at pre-dose and multiple time-points post-dose on Day 1 and every 12 h thereafter up to Day 14 in SAD stage 4. Part 1: Area under the plasma concentration-time curve from time zero up to 24 h (AUC0-24h) of RO7308480 and its metabolites, as appropriate, measured using blood samples at pre-dose and multiple time-points post-dose on Day 1 and every 12 h thereafter up to Day 14 in SAD stage 5. Part 1: Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUCinf) of RO7308480 and its metabolites, as appropriate, measured using blood samples at pre-dose and multiple time-points post-dose on Day 1 and every 12 h thereafter up to Day 14 in SAD stage 6. Part 1: Area under the plasma concentration-time curve from zero up to a given time (AUC0-t) of RO7308480 and its metabolites, as appropriate, measured using blood samples at pre-dose and multiple time-points post-dose on Day 1 and every 12 h thereafter up to Day 14 in SAD stage 7. Part 1: Terminal rate constant (?z) calculated by linear regression of the log-transf | — |
Countries
France
Contacts
Public ContactClinical Trials
Outcome results
None listed