A Phase I, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of RO6864018 Following Oral Administration in Asian Healthy Subjects

Hoffmann-La Roche1 site in 1 country48 target enrollmentDecember 2013

ConditionsHealthy Volunteer

InterventionsPlacebo RO6864018

DrugsRO6864018 Placebo

Overview

Phase: Phase 1
Intervention: Placebo
Conditions: Healthy Volunteer
Sponsor: Hoffmann-La Roche
Enrollment: 48
Locations: 1
Primary Endpoint: Number of Participants With Adverse Events
Status: Completed
Last Updated: 9 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

December 2013

End Date

November 2014

Last Updated

9 years ago

Study Type

Interventional

Study Design

Parallel

Sex

Male

Investigators

Sponsor

Hoffmann-La Roche

Responsible Party

Sponsor

Eligibility Criteria

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

Arms & Interventions

Placebo

Participants will receive a single oral dose of placebo matching to RO6864018.

Intervention: Placebo

RO6864018

Asian participants will receive a single oral dose of RO6864018 capsule on Day 1. The first dose escalation cohort will receive a single 400 mg oral dose. Dose will be escalated in subsequent cohorts (up to Cohort 4) up to a maximum of 1600 mg, based on safety, pharmacokinetic, and pharmacodynamic data available from lower dose cohorts. The Cohort 5 will include Caucasian participants who will receive a single 1200 mg (or the highest dose well-tolerated by Asian participants, if lower than 1200 mg) oral dose of RO6864018 capsules on Day 1.

Intervention: RO6864018

Outcomes

Primary Outcomes

Number of Participants With Adverse Events

Time Frame: Baseline up to Day 29

Secondary Outcomes

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)
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)
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)
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 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)
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)
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)
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)
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)
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)
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)
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)
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)