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

Healthy Volunteer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02015715
• Other study ID #: YP29017
• Status: Completed
• Phase: Phase 1
• First received: November 28, 2013
• Last updated: February 28, 2017
• Start date: December 2013
• Est. completion date: November 2014

Study information

• Verified date: February 2017
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 21 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Volunteer

Intervention

Drug:
• RO6864018
A single oral ascending dose of RO6864018 capsules on Day 1.
• Placebo
A single oral dose of placebo matching RO6864018 capsules on Day 1.

Locations

Country	Name	City	State
Singapore	Changi General Hospital; Clinical Trial & Research unit	Singapore

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events		Baseline up to Day 29
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Serum Interferon alpha Levels		Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose
Secondary	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
Secondary	Serum Interleukin (IL)-6 Levels		Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose
Secondary	Serum IL-10 Levels		Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose
Secondary	Serum IL-12 Levels		Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose
Secondary	Serum Neopterin Levels		Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose
Secondary	Serum p40 (IL-12B) Levels		Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Serum Tumor Necrosis Factor Alpha Levels		Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose