A Study in Healthy Participants Investigating the Effect of TMC435 on the Pharmacokinetics of Immunosuppressants Cyclosporine and Tacrolimus

NCT01479881 | Completed Phase 1

• 3 other identifiers: CR100686TMC435-TIDP16-C1202011-003021-96
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate the effect of steady-state concentrations of TMC435 (administered once a day) on the single-dose pharmacokinetics of the immunosuppressants cyclosporine and tacrolimus in healthy participants. Cyclosporine and tacrolimus are immunosuppressants used to prevent transplant rejection and may therefore potentially be coadministered with TMC435 in patients infected with hepatitis C virus that undergo liver transplantation. We will also explore the short-term safety and tolerability following coadministration of TMC435 at steady-state and (1) cyclosporine or (2) tacrolimus after single dosing in healthy participants. Steady-state is a term that means that the drug has been given long enough so that the plasma concentrations will remain the same with each subsequent dose. Pharmacokinetics (PK) means how the drug is absorbed into the bloodstream, distributed in the body and eliminated from the body.

Conditions

Hepatitis C Virus

Keywords

Hepatitis C Virus; TMC435; TMC435-TiDP16-C120; TMC435-C120; HCV; Hepatitis C; Hep C; Healthy participants

Outcome Measures

Primary Outcomes (1)

• Change in the steady-state plasma concentration (PK) of cyclosporine and tacrolimus following co-administration with TMC435.

  Change in the steady-state plasma PK of cyclosporine and tacrolimus following co-administration with TMC435. PK characteristics of cyclosporine and tacrolimus are determined based on their respective plasma levels at one time point (Day 1 and Day 7 for respectively panel 1 and panel 2) and at 17 other time points. Standard PK parameters such as C0h, Cmin, Cmax, Tmax, AUC24h etc. will be determined.

  Measured on Day1 till and including Day 7 for panel 1, and till and including Day 13 for panel 2. Reference is Day 1 for panel 1 and Day 7 for panel 2.

Secondary Outcomes (1)

• Number of participants with adverse events as a measure of safety and tolerability when combining TMC435 (150 mg, q.d.) with cyclosporine or tacrolimus.

  Up to Day 50.

Study Arms (4)

001

EXPERIMENTAL

a single 100-mg dose of cyclosporine, and after a wash out period of at least 10 days, TMC435 150 mg once daily (q.d.) for 10 days on Days 1 to 10, coadministered with a single 100-mg dose of cyclosporine on Day 7.

Drug: cyclosporine; Drug: TMC435

002

EXPERIMENTAL

TMC435 150 mg once daily (q.d.) for 10 days on Days 1 to 10, coadministered with a single 100-mg dose of cyclosporine on Day 7 and after a wash out period of at least 10 days, a single 100-mg dose of cyclosporine.

Drug: cyclosporine; Drug: TMC435

003

EXPERIMENTAL

a single 2-mg dose of tacrolimus on Day 1. After a wash out period of at least 10 days, participants will receive TMC435 150 mg q.d. for 12 days on Days 1 to 12, coadministered with a single 2-mg dose of tacrolimus on Day 7.

Drug: tacrolimus; Drug: TMC435

004

EXPERIMENTAL

TMC435 150 mg q.d. for 12 days on Days 1 to 12, coadministered with a single 2-mg dose of tacrolimus on Day 7. After a wash out period of at least 10 days, participants receive a single 2-mg dose of tacrolimus.

Drug: tacrolimus; Drug: TMC435

Interventions

tacrolimus DRUG

a single 2-mg dose of tacrolimus (on Day 1 in treatment C and on Day 7 in treatment D).

003; 004

TMC435 DRUG

TMC435, 150 mg daily for 12 days (Days 1 to 12 in treatment D).

003; 004

cyclosporine DRUG

A single 100-mg dose of cyclosporine (on Day 1 of treatment A and on Day 7 of treatment B).

001; 002

Eligibility Criteria

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

You may qualify if:

• Women must be postmenopausal for at least 2 years, OR be surgically sterile, OR be not heterosexually active for the duration of the study or have a vasectomized partner OR if of childbearing potential and heterosexually active, be practicing a highly effective method of birth control before entry, and agree to continue to use the same method of contraception throughout the study and for at least 30 days after the last administration of study drug(s).

You may not qualify if:

• A positive Human Immunodeficiency Virus (HIV)-1 or HIV-2 test at screening;
• A positive Hepatitis A, B and C test at screening

Sponsors & Collaborators

• Tibotec Pharmaceuticals, Ireland: lead

Study Sites (1)

Unknown Facility

Merksem, Belgium

Location

MeSH Terms

Conditions

Hepatitis C

Interventions

Tacrolimus; Simeprevir; Cyclosporine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Sulfonamides; Sulfones; Sulfur Compounds; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Tibotec Pharmaceuticals, Ireland Clinical Trial

  Tibotec Pharmaceuticals, Ireland

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: October 20, 2011
• First Posted: November 28, 2011
• Study Start: October 1, 2011
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: November 1, 2012

Record last verified: 2012-10

Locations

BE (1)