Hepatitis C VirusPhase 1NCT01479881
A Study in Healthy Participants Investigating the Effect of TMC435 on the Pharmacokinetics of Immunosuppressants Cyclosporine and Tacrolimus
A Phase 1 study testing tacrolimus, TMC435 and cyclosporine in people with Hepatitis C Virus, run by Tibotec Pharmaceuticals, Ireland at 1 site in Belgium.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatitis C Virus
- What is being tested?
- tacrolimus, TMC435 and cyclosporine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteBelgium
- Study dates
- Oct 2011to Dec 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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).
Who cannot join
- A positive Human Immunodeficiency Virus (HIV)-1 or HIV-2 test at screening;
- A positive Hepatitis A, B and C test at screening
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Hepatitis C Virus
- Being tested
- tacrolimus, TMC435, cyclosporine
- Keywords
- Hepatitis C Virus, TMC435, TMC435-TiDP16-C120, TMC435-C120, HCV, Hepatitis C, Hep C, Healthy participants
- Medical subject headings
- Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tacrolimusDrug
a single 2-mg dose of tacrolimus (on Day 1 in treatment C and on Day 7 in treatment D).
TMC435Drug
TMC435, 150 mg daily for 12 days (Days 1 to 12 in treatment D).
cyclosporineDrug
A single 100-mg dose of cyclosporine (on Day 1 of treatment A and on Day 7 of treatment B).
TMC435Drug
TMC435, 150 mg daily for 10 days (Day 1 - 10 in treatment B).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: tacrolimus; Drug: TMC435 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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: 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.
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.
Measured: Up to Day 50.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Nov 2011 (estimated)
- Study startOct 2011
- Primary completionDec 2011
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatitis C VirusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tibotec Pharmaceuticals, Ireland
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Tibotec Pharmaceuticals, Ireland Clinical Trial, Study director, Tibotec Pharmaceuticals, Ireland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01479881
- Sponsor's protocol ID
- CR100686
- Other IDs
- TMC435-TIDP16-C120, 2011-003021-96
- Status last verified
- Oct 2012
- First submitted
- 20 Oct 2011
- Last updated
- 1 Nov 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01479881
- Acronym / sponsor ID
- CR100686
- Conditions
- Hepatitis C Virus
- Keywords
- Hepatitis C Virus, TMC435, TMC435-TiDP16-C120, TMC435-C120, HCV, Hepatitis C, Hep C, Healthy participants
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Tibotec Pharmaceuticals, IrelandIndustry (pharma, biotech, devices)
- Study start
- Oct 2011
- Primary completion
- Dec 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 28 Nov 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 001 | Experimental | Drug: cyclosporine, Drug: TMC435a 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. |
| 002 | Experimental | Drug: cyclosporine, Drug: TMC435TMC435 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. |
| 003 | Experimental | Drug: tacrolimus, Drug: TMC435a 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. |
| 004 | Experimental | Drug: tacrolimus, Drug: TMC435TMC435 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. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- 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).
Key exclusion criteria (2 listed)
- A positive Human Immunodeficiency Virus (HIV)-1 or HIV-2 test at screening;
- A positive Hepatitis A, B and C test at screening
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| tacrolimusa single 2-mg dose of tacrolimus (on Day 1 in treatment C and on Day 7 in treatment D). | Drug | 003, 004 |
| TMC435TMC435, 150 mg daily for 12 days (Days 1 to 12 in treatment D). | Drug | 003, 004 |
| cyclosporineA single 100-mg dose of cyclosporine (on Day 1 of treatment A and on Day 7 of treatment B). | Drug | 001, 002 |
| TMC435TMC435, 150 mg daily for 10 days (Day 1 - 10 in treatment B). | Drug | 001, 002 |
Primary outcome
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.
1 secondary outcome
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2012.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tibotec Pharmaceuticals, Ireland Clinical Trial study director
Tibotec Pharmaceuticals, Ireland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing tacrolimus, TMC435 and cyclosporine in people with Hepatitis C Virus, run by Tibotec Pharmaceuticals, Ireland at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Nov 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2012.