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

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

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 Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: RO6864018; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 529889
  • Singapore, Singapore, 529889
    • Changi General Hospital; Clinical Trial & Research unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: RO6864018; A single oral ascending dose of RO6864018 capsules on Day 1.
Placebo Comparator: Placebo; Participants will receive a single oral dose of placebo matching to RO6864018.	Drug: Placebo; A single oral dose of placebo matching RO6864018 capsules on Day 1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Adverse Events	Baseline up to Day 29

Secondary Outcome Measures

Outcome Measure	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: November 28, 2013
• First Submitted That Met QC Criteria: December 13, 2013
• First Posted (Estimate): December 19, 2013

Study Record Updates

• Last Update Posted (Actual): March 1, 2017
• Last Update Submitted That Met QC Criteria: February 28, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Other Study ID Numbers: YP29017