TMC435-TiDP16-C107: This Study Measures the (Possible) Influence of TMC435 on the Activity of a Selected Set of Drug-degrading Proteins by Measuring the Blood Levels of Drugs That Have Been Taken Together With TMC435 and That Are Known to be Specifically Degraded by These Drug-degrading Proteins.

NCT00866853 | Completed Phase 1

• 1 other identifier: CR015949
• Study Type: interventional
• Target: 16
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to determine whether TMC435 influences the activity of certain drug-degrading proteins in the human body. The drug-degrading proteins investigated in this study belong to the Cytochrome P (CYP) family and are called CYP1A2, CYP2C9, CYP2D6, CYP3A4 and CYP2C19. The activity of these drug-degrading enzymes are determined by measuring the blood levels of a selected set of drugs, which are taken together with TMC435, and, which are known to be specifically degraded by a certain member of the CYP family. This selected set of drugs (which are taken together and therefore called a "drug cocktail") are considered as "probes" of these respective drug-degrading enzymes. By measuring the levels of these probes in human blood, the activity of these degrading enzymes are being revealed. In this way, we can determine if TMC435 influences in one way or another the activity of one or several of these selected drug-degrading proteins.

Conditions

Hepatitis C; Viruses

Keywords

TMC435350; HCV; Hepatitis C; TMC435; protease inhibitor; CYP; Cooperstown 5+1 cocktail

Outcome Measures

Primary Outcomes (1)

• Plasma levels of TMC435, midazolam and the compounds of the cocktail (+ metabolites) will be assessed.

  On defined time points on Day1-6 (Treatment A) and Day1-15 (Treatment B).

Secondary Outcomes (2)

• To determine the short-term safety and tolerability of the concomitant use of TMC435 and oral midazolam or a cocktail of representative probes of drug-degrading enzymes of the CYP family

  On days 1, 2, 3 and 5 of Treatment A and on days 1, 2, 10, 11, 12 and 15 of Tretament B

• To determine the steady-state pharmacokinetics of TMC435 given 150 mg once daily

  On days 9, 10, 11, 12, 13, 14 and 15 of Treatment B

Interventions

TMC435 DRUG

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Volunteer is a non-smoker for at least 3 months prior to screening
• Healthy on the basis of a physical examination, medical history, electrocardiogram, vital signs and the results of blood biochemistry, blood coagulation, and hematology tests and a urinalysis carried out at screening
• Normal weight as defined by a Body Mass Index (BMI, weight in kg divided by the square of height in meters) of 18.0 to 30.0 kg/m2, extremes included

You may not qualify if:

• No volunteers who carry certain forms of the CYP2D6, CYP2C9 and CYP2C19 genes, which cause a weak activity of these drug-degrading proteins. These forms are: genotype \*3, \*4, \*5, \*6 for CYP2D6, \*2, \*3 for CYP2C9 or \*2, \*3, \*4, \*8 for CYP2C19
• No Hepatitis A, B, or C infection at screening
• No history and/or clinical signs and symptoms of hereditary or acquired coagulation disorders
• No positive Human Immunodeficiency Virus (HIV) 1 or 2 test
• No positive pregnancy test or breast-feeding at screening
• No subjects not using adequate birth control methods.

Sponsors & Collaborators

• Tibotec Pharmaceuticals, Ireland: lead

MeSH Terms

Conditions

Hepatitis C; Virus Diseases

Interventions

Simeprevir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Tibotec Pharmaceuticals Limited Clinical Trial

  Tibotec Pharmaceutical Limited

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: March 19, 2009
• First Posted: March 23, 2009
• Study Start: March 1, 2009
• Primary Completion: July 1, 2009
• Study Completion: July 1, 2009
• Last Updated: April 28, 2010

Record last verified: 2010-04