TMC435350-TiDP16-C109: A Safety Study for TMC435350 in an Oral Solution Containing Either 100, 200 or 400 mg Equivalent of TMC435350 or Placebo in Healthy Japanese Male Volunteers

Phase I, Double-blind, Randomized, Placebo-controlled Trial to Examine the Safety, Tolerability and Plasma Pharmacokinetics of Ascending Oral Doses of TMC435350 After Single and Repeated Dosing in Healthy Japanese Male Subjects

The purpose of this study is to evaluate the safety and tolerability of three different doses of TMC435350 compared to placebo in healthy Japanese males.

Study Overview

• Status: Completed
• Conditions: HCV
• Intervention / Treatment: Drug: TMC435350

Detailed Description

This is a Phase I, double-blind (neither the physician or the volunteer knows the dose of the study medication), randomized (study medication assigned by chance), placebo-controlled (dose without the study medication present) trial to determine the safety, tolerability and plasma pharmacokinetics (amount of medication in the blood) of TMC435350 after single and multiple oral doses in healthy male Japanese volunteers. 100 mg, 200 mg and 400 mg doses will be given as an oral solution. Six (6) doses will be given with a 3 day follow-up between the first and second dose. Additional follow-up will be done for 3 days after the last dose and at approximately 2 and 4 weeks after the last dose.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy Japanese male volunteers between the ages of 20 and 55 years
• Japanese healthy volunteers who have resided outside of Japan for no more than five years and whose parents and maternal and paternal grandparents are Japanese
• Non-smoking or smoking no more than 10 cigarettes, or 2 cigars, or 2 pipes per day for at least 3 months prior to selection
• Normal weight as defined by a Body Mass Index (BMI: weight in kg divided by square of height in meters) of 18.0 to 30.0 kg/m2
• Body weight above 50 kg at screening
• Informed Consent Form (ICF) signed voluntarily before any trial-related activity
• Normal 12-lead electrocardiogram (ECG) at screening
• Healthy on the basis of a medical evaluation that reveals the absence of any clinically relevant abnormality.

Exclusion Criteria:

• Healthy volunteers must not have any of the following characteristics: Past history of heart arrhythmias (extrasystoli, tachycardia at rest) or having baseline prolongation of QTc interval > 450 ms, history of risk factors for Torsade de Pointes syndrome (hypokalemia, hypomagnesemia, family history of long QT Syndrome) or echographically suspected cardiomyopathy
• History or evidence of current use of alcohol, barbiturate, amphetamine, recreational or narcotic drug use which in the investigator's opinion would compromise healthy volunteer's safety and/or compliance with the trial procedures
• Hepatitis A, B, or C infection (confirmed by hepatitis A antibody, hepatitis B surface antigen, or hepatitis C virus antibody, respectively) or human immunodeficiency virus - type 1 (HIV-1) or HIV-2 infection at screening
• A positive urine drug test at screening. Urine will be tested for the presence of amphetamines, benzodiazepines, cocaine, cannabinoids, and opioids
• Currently active or underlying gastrointestinal, cardiovascular, neurologic, psychiatric, metabolic, renal, hepatic, respiratory, inflammatory, or infectious disease
• Any history of clinically relevant skin disease such as, but not limited to, dermatitis, eczema, drug rash, drug allergy, psoriasis, food allergy, urticaria
• History of drug allergy such as, but not limited to, sulfonamides and penicillins, or drug allergy
• Use of concomitant medication, including herbal medications and dietary supplements and products containing Hypericum perforatum (e.g. St. John's wort), except for paracetamol (acetaminophen) or ibuprofen in a period of 14 days before the first trial medication intake
• Participation in another investigational drug trial within 30 days prior to the first intake of trial medication
• Donation of blood or plasma within 60 days preceding the first intake of trial medication

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Determine the short-term safety and tolerability of TMC435350 in healthy Japanese male volunteers after single and multiple doses and determine the plasma pharmacokinetics of TMC435350 after single and multiple doses.

Collaborators and Investigators

• Sponsor: Tibotec Pharmaceuticals, Ireland

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): November 1, 2008
• Study Completion (Actual): November 1, 2008

Study Registration Dates

• First Submitted: September 11, 2008
• First Submitted That Met QC Criteria: September 12, 2008
• First Posted (Estimate): September 15, 2008

Study Record Updates

• Last Update Posted (Estimate): April 28, 2010
• Last Update Submitted That Met QC Criteria: April 26, 2010
• Last Verified: April 1, 2010

More Information

Terms related to this study

• Keywords: HCV; Hepatitis C; TMC435350; TMC435350-TiDP16-C109; TMC435350-C109
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Protease Inhibitors; Simeprevir
• Other Study ID Numbers: CR015418