Healthy Volunteer
Conditions
Brief summary
This randomized, double-blind, placebo-controlled, single ascending dose study will assess the safety, pharmacokinetics, and pharmacodynamics of RO6864018 in healthy, male, Asian and Caucasian participants. Participants will be enrolled in cohorts and randomized 8:2 to receive a single oral administration of RO6864018 or placebo. Total study duration for each participant is up to 9 weeks.
Interventions
DRUGRO6864018
A single oral ascending dose of RO6864018 capsules on Day 1.
DRUGPlacebo
A single oral dose of placebo matching RO6864018 capsules on Day 1.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
21 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male participants of ethnic Chinese, Korean, Japanese origin or Caucasian * No signs of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead electrocardiogram (ECG), hematology, blood chemistry, serology and urinalysis * Body Mass Index (BMI) between 18 to 30 kilograms per square meter (kg/m\^2) inclusive, and a weight range of 50 to 100 kilograms (kg) (110 to 220 pounds \[lb\]) inclusive at screening * Non-smokers, or use of less than (\<) 10 cigarettes (or equivalent nicotine-containing product) per day
Exclusion criteria
* History or symptoms of any significant disease * Personal or family history of congenital long QT syndrome or sudden death * Any confirmed significant allergic reactions against any drug, or multiple drug allergies (non-active hay fever is acceptable) * Positive results for anti-nuclear antibody (ANA), anti-mitochondrial antibody (AMA), anti-smooth muscle antibody (ASMA) and thyroid peroxidase antibody * Suspicion of regular consumption of drug of abuse * History (within 3 months of screening) of alcohol consumption exceeding 14 units per week on average (1 unit = 10 grams of alcohol) * Participants who have received Interferon (IFN) or peginterferon within 8 weeks prior to dosing * Use of any medication (prescription or over the counter \[OTC\], including health supplements and herbal remedies) within 2 weeks before the first dose of study medication * Positive Hepatitis A immunoglobulin M antibody (HAV IgM Ab), Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab) or human immunodeficiency virus antibody (HIV Ab) at screening * Donation or loss of blood of greater than 500 milliliters (mL) within 90 days prior to dosing * Have participated in other clinical studies within 60 days prior to study randomization
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Adverse Events | Baseline up to Day 29 |
Secondary
| Measure | Time frame |
|---|---|
| Cmax of Minor Metabolite RO6872373 | Pre-dose (0 hour), 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 18, 24, 36 and 48 hours post-Day 1 dose |
| Time to Maximum Plasma Concentration (Tmax) of RO6864018 | Pre-dose (0 hour), 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 18, 24, 36 and 48 hours post-Day 1 dose |
| Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of RO6864018 | Pre-dose (0 hour), 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 18, 24, 36 and 48 hours post-Day 1 dose |
| AUC0-inf of Active Metabolite RO6871765 | Pre-dose (0 hour), 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 18, 24, 36 and 48 hours post-Day 1 dose |
| AUC0-inf of Prodrug Metabolite RO6870868 | Pre-dose (0 hour), 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 18, 24, 36 and 48 hours post-Day 1 dose |
| AUC0-inf of Minor Metabolite RO6872373 | Pre-dose (0 hour), 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 18, 24, 36 and 48 hours post-Day 1 dose |
| Area Under the Plasma Concentration Time Curve From Time Zero to Last Measurable Concentration (AUClast) of RO6864018 | Pre-dose (0 hour), 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 18, 24, 36 and 48 hours post-Day 1 dose |
| AUClast of Active Metabolite RO6871765 | Pre-dose (0 hour), 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 18, 24, 36 and 48 hours post-Day 1 dose |
| AUClast of Prodrug Metabolite RO6870868 | Pre-dose (0 hour), 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 18, 24, 36 and 48 hours post-Day 1 dose |
| AUClast of Minor Metabolite RO6872373 | Pre-dose (0 hour), 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 18, 24, 36 and 48 hours post-Day 1 dose |
| Maximum Observed Plasma Concentration (Cmax) of RO6864018 | Pre-dose (0 hour), 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 18, 24, 36 and 48 hours post-Day 1 dose |
| Cmax of Active Metabolite RO6871765 | Pre-dose (0 hour), 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 18, 24, 36 and 48 hours post-Day 1 dose |
| Tmax of Active Metabolite RO6871765 | Pre-dose (0 hour), 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 18, 24, 36 and 48 hours post-Day 1 dose |
| Tmax of Minor Metabolite RO6872373 | Pre-dose (0 hour), 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 18, 24, 36 and 48 hours post-Day 1 dose |
| RO6864018 Urine Concentration | Pre-dose (0-4 hours before dosing), 0-4, 4-8, 8-12, 12-24, 24-36, and 36-48 hours post-Day 1 dose |
| Active Metabolite RO6871765 Urine Concentration | Pre-dose (0-4 hours before dosing), 0-4, 4-8, 8-12, 12-24, 24-36, and 36-48 hours post-Day 1 dose |
| Prodrug Metabolite RO6870868 Urine Concentration | Pre-dose (0-4 hours before dosing), 0-4, 4-8, 8-12, 12-24, 24-36, and 36-48 hours post-Day 1 dose |
| Cmax of Prodrug Metabolite RO6870868 | Pre-dose (0 hour), 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 18, 24, 36 and 48 hours post-Day 1 dose |
| Apparent Terminal Elimination Half-Life (T1/2) of RO6864018 | Pre-dose (0 hour), 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 18, 24, 36 and 48 hours post-Day 1 dose |
| T1/2 of Active Metabolite RO6871765 | Pre-dose (0 hour), 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 18, 24, 36 and 48 hours post-Day 1 dose |
| T1/2 of Prodrug Metabolite RO6870868 | Pre-dose (0 hour), 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 18, 24, 36 and 48 hours post-Day 1 dose |
| T1/2 of Minor Metabolite RO6872373 | Pre-dose (0 hour), 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 18, 24, 36 and 48 hours post-Day 1 dose |
| Serum Interferon alpha Levels | Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose |
| Serum Interferon-Gamma-Inducible Protein-10 (IP-10) Levels | Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose |
| Serum Interleukin (IL)-6 Levels | Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose |
| Serum IL-10 Levels | Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose |
| Serum IL-12 Levels | Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose |
| Serum Neopterin Levels | Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose |
| Serum p40 (IL-12B) Levels | Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose |
| Interferon-Stimulated Gene-15 (ISG-15) Messenger Ribonucleic Acid (mRNA) Levels in Whole Blood | Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose |
| Myxovirus Resistance 1 (MX-1) Gene mRNA Levels in Whole Blood | Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose |
| Oligoadenylate Synthetase 1 (OAS 1) Gene mRNA Levels in Whole Blood | Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose |
| Toll-Like Receptor 7 (TLR7) Gene mRNA Levels in Whole Blood | Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose |
| Tmax of Prodrug Metabolite RO6870868 | Pre-dose (0 hour), 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 18, 24, 36 and 48 hours post-Day 1 dose |
| Serum Tumor Necrosis Factor Alpha Levels | Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose |
| Minor Metabolite RO6872373 Urine Concentration | Pre-dose (0-4 hours before dosing), 0-4, 4-8, 8-12, 12-24, 24-36, and 36-48 hours post-Day 1 dose |
Countries
Singapore
Outcome results
None listed