- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01479881
A Study in Healthy Participants Investigating the Effect of TMC435 on the Pharmacokinetics of Immunosuppressants Cyclosporine and Tacrolimus
October 31, 2012 updated by: Tibotec Pharmaceuticals, Ireland
A Phase I, 2-panel, Open-label, Randomized, Cross-over Trial in Healthy Subjects to Investigate the Effect of TMC435 at Steady-state on the Pharmacokinetics of the Immunosuppressants Cyclosporine and Tacrolimus
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
TMC435 is a protease inhibitor (PI) and is being investigated for treatment of chronic hepatitis C virus (HCV) infection, in combination with Peg-IFN (pegylated interferon) and RBV (ribavirin).
This is a Phase I, open-label (both participant and investigator know the name of the medication given at a certain moment) trial in 28 healthy participants to investigate the effect of TMC435 at steady-state on the single dose pharmacokinetics of the immunosuppressants cyclosporine and tacrolimus.
The trial population will consist of a total of 28 healthy participants, equally divided over 2 panels.
In Panel 1, each participant will receive 2 treatments: a single 100-mg dose of cyclosporine on Day 1 and TMC435 150 mg once daily for 10 days on Days 1 to 10, coadministered with a single 100-mg dose of cyclosporine on Day 7. In Panel 2, each participant will receive 2 treatments: a single 2-mg dose of tacrolimus on Day 1 and TMC435 150 mg each day for 12 days on Days 1 to 12, coadministered with a single 2-mg dose of tacrolimus on Day 7. Safety and tolerability will be assessed during the study period and during follow up.
Blood and urine safety samples, electrocardiogram (ECG) and vital signs (blood pressure and heart rate) will be taken at screening, Day1, Day 2 (only panel 1), Day 7(only panel 2), Day 8 (only panel 2) and at the follow-up visit about 5 to 7 days after last TMC435 intake.
Study Type
Interventional
Enrollment (Actual)
29
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Merksem, Belgium
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 55 years (Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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).
Exclusion Criteria:
- A positive Human Immunodeficiency Virus (HIV)-1 or HIV-2 test at screening;
- A positive Hepatitis A, B and C test at screening
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 001
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.
|
TMC435, 150 mg daily for 12 days (Days 1 to 12 in treatment D).
A single 100-mg dose of cyclosporine (on Day 1 of treatment A and on Day 7 of treatment B).
TMC435, 150 mg daily for 10 days (Day 1 - 10 in treatment B).
|
Experimental: 002
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.
|
TMC435, 150 mg daily for 12 days (Days 1 to 12 in treatment D).
A single 100-mg dose of cyclosporine (on Day 1 of treatment A and on Day 7 of treatment B).
TMC435, 150 mg daily for 10 days (Day 1 - 10 in treatment B).
|
Experimental: 003
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.
|
TMC435, 150 mg daily for 12 days (Days 1 to 12 in treatment D).
TMC435, 150 mg daily for 10 days (Day 1 - 10 in treatment B).
a single 2-mg dose of tacrolimus (on Day 1 in treatment C and on Day 7 in treatment D).
|
Experimental: 004
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.
|
TMC435, 150 mg daily for 12 days (Days 1 to 12 in treatment D).
TMC435, 150 mg daily for 10 days (Day 1 - 10 in treatment B).
a single 2-mg dose of tacrolimus (on Day 1 in treatment C and on Day 7 in treatment D).
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in the steady-state plasma concentration (PK) of cyclosporine and tacrolimus following co-administration with TMC435.
Time Frame: 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.
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of participants with adverse events as a measure of safety and tolerability when combining TMC435 (150 mg, q.d.) with cyclosporine or tacrolimus.
Time Frame: Up to Day 50.
|
to explore the short-term safety and tolerability following coadministration of TMC435 at steady-state and (1) 100-mg dose cyclosporine or (2) 2-mg dose tacrolimus after single dosing in healthy subjects.
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Up to Day 50.
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
October 1, 2011
Primary Completion (Actual)
December 1, 2011
Study Completion (Actual)
December 1, 2011
Study Registration Dates
First Submitted
October 20, 2011
First Submitted That Met QC Criteria
November 22, 2011
First Posted (Estimate)
November 28, 2011
Study Record Updates
Last Update Posted (Estimate)
November 1, 2012
Last Update Submitted That Met QC Criteria
October 31, 2012
Last Verified
October 1, 2012
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Liver Diseases
- Flaviviridae Infections
- Hepatitis, Viral, Human
- Hepatitis
- Hepatitis C
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antirheumatic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Protease Inhibitors
- Dermatologic Agents
- Antifungal Agents
- Calcineurin Inhibitors
- Tacrolimus
- Cyclosporine
- Cyclosporins
- Simeprevir
Other Study ID Numbers
- CR100686
- TMC435-TIDP16-C120 (Other Identifier: Tibotec Pharmaceuticals, Ireland)
- 2011-003021-96 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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