A Study Evaluating the Safety, Pharmacokinetics, and Pharmacodynamics of RO6864018 in Male, Healthy, Asian Participants

Phase 1CompletedNCT02015715

Hoffmann-La Roche48 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Healthy Volunteer

Interventions

RO6864018DRUG

A single oral ascending dose of RO6864018 capsules on Day 1.

PlaceboDRUG

A single oral dose of placebo matching RO6864018 capsules on Day 1.

Eligibility

Sex: MALEMin age: 21 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (2)

Changi General Hospital; Clinical Trial & Research unit

Singapore, Singapore

Unnamed facility

Singapore, Singapore

Outcomes

Primary Outcomes

Number of Participants With Adverse Events

Time frame: Baseline up to Day 29

Secondary Outcomes

Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of RO6864018

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Data from ClinicalTrials.gov

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Maximum Observed Plasma Concentration (Cmax) of RO6864018

Time frame: 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

Time frame: 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 Prodrug Metabolite RO6870868

Time frame: 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 Minor Metabolite RO6872373

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Minor Metabolite RO6872373 Urine Concentration

Time frame: 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

Apparent Terminal Elimination Half-Life (T1/2) of RO6864018

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose

Serum Interleukin (IL)-6 Levels

Time frame: Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose

Serum IL-10 Levels

Time frame: Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose

Serum IL-12 Levels

Time frame: Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose

Serum Neopterin Levels

Time frame: Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose

Serum p40 (IL-12B) Levels

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose

Tmax of Prodrug Metabolite RO6870868

Time frame: 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

Time frame: Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose