Clinical trial NCT02015715: A Study Evaluating the Safety, Pharmacokinetics, and Pharmacodynamics of RO6864018 in Male, Healthy, Asian Participants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2013-12-19
Enrollment: 48
Sex: MALE
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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
* Have participated in other clinical studies within 60 days prior to study randomization

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: Baseline up to Day 29
Secondary outcomes:
measure: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of RO6864018
timeFrame: 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
measure: AUC0-inf of Active Metabolite RO6871765
timeFrame: 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
measure: AUC0-inf of Prodrug Metabolite RO6870868
timeFrame: 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
measure: AUC0-inf of Minor Metabolite RO6872373
timeFrame: 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
measure: Area Under the Plasma Concentration Time Curve From Time Zero to Last Measurable Concentration (AUClast) of RO6864018
timeFrame: 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
measure: AUClast of Active Metabolite RO6871765
timeFrame: 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
measure: AUClast of Prodrug Metabolite RO6870868
timeFrame: 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
measure: AUClast of Minor Metabolite RO6872373
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax) of RO6864018
timeFrame: 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
measure: Cmax of Active Metabolite RO6871765
timeFrame: 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
measure: Cmax of Prodrug Metabolite RO6870868
timeFrame: 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
measure: Cmax of Minor Metabolite RO6872373
timeFrame: 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
measure: Time to Maximum Plasma Concentration (Tmax) of RO6864018
timeFrame: 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
measure: Tmax of Active Metabolite RO6871765
timeFrame: 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
measure: Tmax of Minor Metabolite RO6872373
timeFrame: 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
measure: RO6864018 Urine Concentration
timeFrame: 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
measure: Active Metabolite RO6871765 Urine Concentration
timeFrame: 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
measure: Prodrug Metabolite RO6870868 Urine Concentration
timeFrame: 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
measure: Minor Metabolite RO6872373 Urine Concentration
timeFrame: 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
measure: Apparent Terminal Elimination Half-Life (T1/2) of RO6864018
timeFrame: 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
measure: T1/2 of Active Metabolite RO6871765
timeFrame: 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
measure: T1/2 of Prodrug Metabolite RO6870868
timeFrame: 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
measure: T1/2 of Minor Metabolite RO6872373
timeFrame: 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
measure: Serum Interferon alpha Levels
timeFrame: Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose
measure: Serum Interferon-Gamma-Inducible Protein-10 (IP-10) Levels
timeFrame: Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose
measure: Serum Interleukin (IL)-6 Levels
timeFrame: Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose
measure: Serum IL-10 Levels
timeFrame: Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose
measure: Serum IL-12 Levels
timeFrame: Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose
measure: Serum Neopterin Levels
timeFrame: Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose
measure: Serum p40 (IL-12B) Levels
timeFrame: Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose
measure: Interferon-Stimulated Gene-15 (ISG-15) Messenger Ribonucleic Acid (mRNA) Levels in Whole Blood
timeFrame: Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose
measure: Myxovirus Resistance 1 (MX-1) Gene mRNA Levels in Whole Blood
timeFrame: Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose
measure: Oligoadenylate Synthetase 1 (OAS 1) Gene mRNA Levels in Whole Blood
timeFrame: Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose
measure: Toll-Like Receptor 7 (TLR7) Gene mRNA Levels in Whole Blood
timeFrame: Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose
measure: Tmax of Prodrug Metabolite RO6870868
timeFrame: 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
measure: Serum Tumor Necrosis Factor Alpha Levels
timeFrame: Pre-dose (0 hours), 3, 6, 12, 18, 24, 36, and 48 hours post-Day 1 dose
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: Changi General Hospital; Clinical Trial & Research unit
city: Singapore
country: Singapore
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: