Inflammatory bowel disease (IBD), respiratory diseases including chronic obstructive pulmonary disease (COPD) and severe asthma, and Parkinson’s disease Not Applicable
Conditions
Interventions
Part 1:
Participants will be randomised to receive a single dose of each of reference Hard Capsules RO7486967 200 mg (2 x 100 mg) in the fasted state, RO7486967 Immediate Release Tablet, 200 mg in the
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Healthy males or non-pregnant, non-lactating healthy females 2. Aged 18 to 55 years inclusive at the time of signing the informed consent 3. Body mass index (BMI) of 18.0 to 30.0 kg/m², inclusive, as measured at screening 4. Participants must be willing and able to communicate and participate in the whole study and comply with study requirements 5. Participants must provide written informed consent 6. Participants must agree to adhere to the contraception requirements defined in the clinical protocol
Exclusion criteria
Exclusion criteria: 1. Participants who have received any IMP in a clinical research study within the 90 days prior to the planned first dose date of this study (i.e., Day 1 of Period 1), or less than 5 elimination half-lives prior to Day 1 of Period 1, whichever is longer. Participants who are enrolled and dosed in Part 1 are permitted to be enrolled in Part 2, only if there is a minimum of 90 days washout between the final dose of RO7486967 in Part 1 and the first dose of RO7486967 in Part 2. 2. Participants who are, or are immediate family members of, a study site or sponsor employee. 3. Positive test for SARS-CoV-2 within 30 days prior to Day 1 of Period 1 or evidence of recent SARS-CoV-2 symptomatic infection within the last 3 months. Participants who had asymptomatic, incidental, positive findings can be included if tested more than 30 days prior to screening and test negative at screening and prior to admission to the clinical unit. 4. Fever (body temperature >38°C) or symptomatic viral or bacterial infection within 2 weeks prior to screening. 5. History of any drug or alcohol abuse in the past 2 years. 6. Regular alcohol consumption in males >21 units per week and females >14 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 units = 125 ml glass of wine, depending on type) 7. A confirmed positive alcohol breath test at screening or admission. 8. Current smokers and those who have smoked within the last 12 months. A confirmed breath carbon monoxide reading of greater than 10 ppm at screening or admission. 9. Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months. 10. Females who are pregnant or lactating (all female participants must have a negative highly sensitive serum [screening] and urine [admission] pregnancy test). A woman is considered of childbearing potential unless she is permanently sterile (hysterectomy, bilateral salpingectomy, and bilateral oophorectomy) or is postmenopausal (had no menses for 12 months without an alternative medical cause and a serum follicle-stimulating hormone [FSH] concentration =40 IU/l). Female subjects who are currently receiving HRT and have a serum FSH concentration ULN, INR >1.5 or albumin <34 g/l at screening. Repeat testing (one repeat test at screening and one repeat test at admission) is acceptable for out of range values following approval by the investigator or delegate. 15. Confirmed positive drugs of abuse test result. 16. Positive QuantiFERON test at the screening visit or within 2 months prior to screening. 17. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) antibody results. 18. Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance (CLcr) of <70 mL/min using the Cockcroft-Gault equation 19. Abnormal ECG findings at screening and pre-dose that are considered by the investigator to be cl
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Parts 1 and 2: 1. Pharmacokinetic (PK) parameters, including (but not limited to) Tmax, Cmax, AUC(0-last), AUC(0-inf), lambda-z and T1/2 for RO7486967 in plasma, as applicable, measured using blood samples at pre-dose and at multiple time points, up to 16 hours post-dose on Day 1, and thereafter on Days 2 and 3. 2. Assessment of food effect on plasma PK parameters Cmax, AUC(0-last) and AUC(0-inf) for RO7486967 and RO7428130, as applicable, in the fed state (test regimens) compared to the fasted state (reference regimens), for RO7486967 in plasma measured using blood samples at pre-dose and at multiple time points, up to 16 hours post-dose on Day 1, and thereafter on Days 2 and 3. Part 1 and Part 2b only: 1. Relative bioavailability of plasma PK parameters Cmax, AUC(0-last) and AUC(0-inf) for RO7486967 and RO7428130, as applicable, for tablet formulations (test regimens) compared to a capsule formulation (reference regimen), in plasma measured using blood samples at pre-dose and at multiple time points, up to 16 hours post-dose on Day 1, and thereafter on Days 2 and 3. Part 2 only: 1. Dose proportionality of plasma PK parameters Cmax, AUC(0-last) and AUC(0-inf) for RO7486967 and RO7428130, as applicable, in the chosen 25 mg RO7486967 tablet formulation (test regimen) compared to the chosen 200 mg RO7486967 tablet formulation (reference regimen), in plasma measured using blood samples at pre-dose and at multiple time points, up to 16 hours post-dose on Day 1, and thereafter on Days 2 and 3. | — |
Secondary
| Measure | Time frame |
|---|---|
| Parts 1 and 2: 1. Additional safety and tolerability information for RO7486967 collected by assessing the incidence of adverse events (AEs), and change from baseline for Columbia-Suicide Severity Rating Scale (C-SSRS), vital signs, electrocardiograms (ECGs), and laboratory safety tests, from the time of signing the informed consent form to up to 21 days post-final dose (approximately 11 weeks) | — |
Countries
England, United Kingdom
Contacts
Public ContactTrial Information Support Line (TISL)
Outcome results
None listed