Hepatitis CPhase 1NCT00938899
TMC435350-TiDP16-C101 - A Study to Examine the Safety, Tolerability and Pharmacokinetics of Increasing Oral Doses of TMC435350 After Single and Repeated Dosing
A Phase 1 study of Hepatitis C, run by Tibotec Pharmaceuticals, Ireland.
Trial summary
The purpose of this study is to examine the safety, tolerability and pharmacokinetics of increasing oral doses of TMC435350 after single and repeated dosing, followed by an open label repeated dosing session in 6 HCV genotype1 infected patients. 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
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 55 participants
- Where
- No sites listed yet
- Study dates
- Jan 2007to Sep 2007
- 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
- Healthy participants must be non-smokers, normal weight, normal ECG, healthy on the basis of a medical evaluation, physical examination, medical history, ECG, vital signs, and laboratory results
- HCV patients must be of normal weight, normal ECG, chronic genotype 1 HCV infection, non-responders or relapsers to previous treatment regimens and have a HCV viral load at least 50000 IU/mL plasma at screening.
Who cannot join
- Patients with history of cardiac disease, HIV-1 or HIV-2 test
- Women of childbearing potential
- History or evidence of abuse of alcohol, barbiturate, amphetamine, recreational or narcotic drug use, hepatitis A, B or C infection
- Positive urine drug test
- Any active or underlying disease
- History of drug allergy or hypersensitivity
Show all 18Show fewer
- Participation in an investigational trial within 30 days prior to the first intake of study medication
- Recent donation of blood
- Abnormal laboratory values
- HCV patients with cardiac disease, co-infections with HIV-1, HIV-2 or liver infection other than HCV
- Women of childbearing potential
- Participants not agreeing to use a reliable birth control method until last trial visit
- Drug abuse
- Cardiovascular, hepatic or renal disease, diabetes, epilepsy, skin or psychiatric disease
- Enrolled in another clinical trial for 90 days prior to screening
- Evidence of Child Pugh B or C liver disease
- Having received a polymerase or protease inhibitor treatment during the last 6 months
- Abnormal laboratory values
About this study
Official title: Phase I, Double Blind, Randomized, Placebo-controlled Trial in Healthy Subjects to Examine the Safety, Tolerability and Pharmacokinetics of Increasing Oral Doses of TMC435350 After Single and Repeated Dosing, Followed by an Open Label Repeated Dosing Session in 6 HCV genotype1 Infected Patients.
The purpose of this study is to examine the safety, tolerability and pharmacokinetics of increasing oral doses of TMC435350 after single and repeated dosing, followed by an open label repeated dosing session in 6 HCV genotype1 infected patients.
Read the detailed description
This trial is a randomized, double blind, placebo-controlled trial to determine the safety, tolerability and pharmacokinetics of TMC435350 after single and multiple oral doses taken by healthy non-Hepatitis C Virus infected (non-HCV) participants, followed by an open label repeated doses taken by 6 HCV-genotype 1 infected participants (non-placebo controlled). The single dose escalation part of the trial will consist of 6 sessions (Sessions Ia to VIa) and will include 2 panels of 9 healthy non-HCV infected participants each (Panels 1 and 2). The dose of the test drug will be consecutively escalated. Doses of 50 mg, 100 mg, 200 mg, 400 mg, 800 mg and 1200 mg of TMC435350 or placebo will be administered as a single oral administration alternating over the 2 panels. In each session, 6 participants will receive active treatment and 3 participants will receive placebo after a breakfast. The treatment schedule will ensure that over 3 sessions each particpant will receive active treatment twice and placebo once. There is a washout period of at least 10 days between consecutive TMC435350 or placebo dosings within each panel. Participants of Panel 1 will have an additional session to investigate food effect: a single dose of TMC435350 will be tested in fasted conditions (Session VIIa). Food effect will be investigated for the 200 mg dose in Panel 1, unless the the available concentration of the drug in the blood and safety data from previous sessions prove unnecessary. Multiple dosing will be started when Sessions Ia (single dose of 50 mg), IIa (single dose of 100 mg) and IIIa (single dose of 200 mg) are found to be safe and tolerable. The multiple dose escalation part of the trial will consist of 4 consecutive sessions (Sessions Ib to IVb) in 4 panels of 9 healthy non-HCV infected participants each (Panels 3, 4, 5 and 6). In each session, 6 participants will receive active treatment and 3 participants will receive placebo. TMC435350 or placebo will be administered during 5 consecutive days. As a potential food effect is not yet known, administration will be after a meal. Treatment is anticipated to be twice daily with doses of 50 mg, 100 mg, 200 mg and 400 mg. The available concentration of the drug in the blood will be determined up to 72 hours after the first dose, in case a single dose of TMC435350 is given (in Sessions Ia to VIIa and, if performed, Session VIIIa). In case of multiple dosing (in Sessions Ib to IVb), full pharmacokinetic profiles of TMC435350 will be determined for the first dosage interval (e.g. up to 24 hours after the first dose for a b.i.d. regimen) and up to 72 hours after the last dose. Safety and tolerability will be evaluated continuously and documented (safety report), with 24-hours interim PK data after the last dose, before stepping up to the next dose and between each session. After completion of the healthy participant sessions, an open label session (Ic) in HCV genotype 1 infected participant will be added. The trial population (Panel 7) will include 6 male or female, non-responder HCV-genotype 1 infected participants with an HCV viral load of at least 50000 IU/mL. These participants will be treated as Panel 7 with follow-up visits, after the 5 day dosing period. One dose regimen will be selected which was shown to be safe in healthy participants and as close as possible to a maximum tolerated dose, which will be administered for 5 days. In addition to drug safety and PK parameters, viral loads will be determined in plasma.
- Conditions
- Hepatitis C
- Being tested
- TMC435350; Placebo
- Keywords
- TMC435350-TiDP16-C101, TMC435350-C101, TMC435350, HCV
- Medical subject headings
- Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TMC435350; PlaceboDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the safety, tolerability and pharmacokinetics of TMC435350 after single oral doses from 50 mg up to 1200 mg and after 5 days of dosing from 50 mg up to 400 mg or up to Multiple dosing.
Measured: Pharmacokinetics and safety at time of drug intake until 72hour after the drug intake
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2009 (estimated)
- Study startJan 2007
- Primary completionSep 2007
- Study completionSep 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatitis CStudies 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
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tibotec Pharmaceuticals, Ireland
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Tibotec Pharmaceuticals Limited Clinical Trial, Study director, Tibotec Pharmaceutical Limited
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00938899
- Sponsor's protocol ID
- CR012610
- Status last verified
- Apr 2010
- First submitted
- 10 Jul 2009
- Last updated
- 19 May 2011
- Results posted
- No
Publications
Reesink HW, Fanning GC, Farha KA, Weegink C, Van Vliet A, Van 't Klooster G, Lenz O, Aharchi F, Marien K, Van Remoortere P, de Kock H, Broeckaert F, Meyvisch P, Van Beirendonck E, Simmen K, Verloes R. Rapid HCV-RNA decline with once daily TMC435: a phase I study in healthy volunteers and hepatitis C patients. Gastroenterology. 2010 Mar;138(3):913-21. doi: 10.1053/j.gastro.2009.10.033. Epub 2009 Oct 21.
PubMed 19852962
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I, Double Blind, Randomized, Placebo-controlled Trial in Healthy Subjects to Examine the Safety, Tolerability and Pharmacokinetics of Increasing Oral Doses of TMC435350 After Single and Repeated Dosing, Followed by an Open Label Repeated Dosing Session in 6 HCV genotype1 Infected Patients.
- ClinicalTrials.gov ID
- NCT00938899
- Acronym / sponsor ID
- CR012610
- Conditions
- Hepatitis C
- Keywords
- TMC435350-TiDP16-C101, TMC435350-C101, TMC435350, HCV
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- Tibotec Pharmaceuticals, IrelandIndustry (pharma, biotech, devices)
- Study start
- Jan 2007
- Primary completion
- Sep 2007 (actual)
- Study completion
- Sep 2007 (actual)
- First posted
- 14 Jul 2009 (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 examine the safety, tolerability and pharmacokinetics of increasing oral doses of TMC435350 after single and repeated dosing, followed by an open label repeated dosing session in 6 HCV genotype1 infected patients.
Detailed description
This trial is a randomized, double blind, placebo-controlled trial to determine the safety, tolerability and pharmacokinetics of TMC435350 after single and multiple oral doses taken by healthy non-Hepatitis C Virus infected (non-HCV) participants, followed by an open label repeated doses taken by 6 HCV-genotype 1 infected participants (non-placebo controlled). The single dose escalation part of the trial will consist of 6 sessions (Sessions Ia to VIa) and will include 2 panels of 9 healthy non-HCV infected participants each (Panels 1 and 2). The dose of the test drug will be consecutively escalated. Doses of 50 mg, 100 mg, 200 mg, 400 mg, 800 mg and 1200 mg of TMC435350 or placebo will be administered as a single oral administration alternating over the 2 panels. In each session, 6 participants will receive active treatment and 3 participants will receive placebo after a breakfast. The treatment schedule will ensure that over 3 sessions each particpant will receive active treatment twice and placebo once. There is a washout period of at least 10 days between consecutive TMC435350 or placebo dosings within each panel. Participants of Panel 1 will have an additional session to investigate food effect: a single dose of TMC435350 will be tested in fasted conditions (Session VIIa). Food effect will be investigated for the 200 mg dose in Panel 1, unless the the available concentration of the drug in the blood and safety data from previous sessions prove unnecessary. Multiple dosing will be started when Sessions Ia (single dose of 50 mg), IIa (single dose of 100 mg) and IIIa (single dose of 200 mg) are found to be safe and tolerable. The multiple dose escalation part of the trial will consist of 4 consecutive sessions (Sessions Ib to IVb) in 4 panels of 9 healthy non-HCV infected participants each (Panels 3, 4, 5 and 6). In each session, 6 participants will receive active treatment and 3 participants will receive placebo. TMC435350 or placebo will be administered during 5 consecutive days. As a potential food effect is not yet known, administration will be after a meal. Treatment is anticipated to be twice daily with doses of 50 mg, 100 mg, 200 mg and 400 mg. The available concentration of the drug in the blood will be determined up to 72 hours after the first dose, in case a single dose of TMC435350 is given (in Sessions Ia to VIIa and, if performed, Session VIIIa). In case of multiple dosing (in Sessions Ib to IVb), full pharmacokinetic profiles of TMC435350 will be determined for the first dosage interval (e.g. up to 24 hours after the first dose for a b.i.d. regimen) and up to 72 hours after the last dose. Safety and tolerability will be evaluated continuously and documented (safety report), with 24-hours interim PK data after the last dose, before stepping up to the next dose and between each session. After completion of the healthy participant sessions, an open label session (Ic) in HCV genotype 1 infected participant will be added. The trial population (Panel 7) will include 6 male or female, non-responder HCV-genotype 1 infected participants with an HCV viral load of at least 50000 IU/mL. These participants will be treated as Panel 7 with follow-up visits, after the 5 day dosing period. One dose regimen will be selected which was shown to be safe in healthy participants and as close as possible to a maximum tolerated dose, which will be administered for 5 days. In addition to drug safety and PK parameters, viral loads will be determined in plasma.
Study design
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Healthy participants must be non-smokers, normal weight, normal ECG, healthy on the basis of a medical evaluation, physical examination, medical history, ECG, vital signs, and laboratory results
- HCV patients must be of normal weight, normal ECG, chronic genotype 1 HCV infection, non-responders or relapsers to previous treatment regimens and have a HCV viral load at least 50000 IU/mL plasma at screening.
Key exclusion criteria (18 listed)
- Patients with history of cardiac disease, HIV-1 or HIV-2 test
- Women of childbearing potential
- History or evidence of abuse of alcohol, barbiturate, amphetamine, recreational or narcotic drug use, hepatitis A, B or C infection
- Positive urine drug test
- Any active or underlying disease
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 |
|---|---|---|
| TMC435350; Placebo | Drug | – |
Primary outcome
Determine the safety, tolerability and pharmacokinetics of TMC435350 after single oral doses from 50 mg up to 1200 mg and after 5 days of dosing from 50 mg up to 400 mg or up to Multiple dosing.
Time frame: Pharmacokinetics and safety at time of drug intake until 72hour after the drug intake
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 19 May 2011.
- Derived from this study: PubMed 19852962Reesink HW, Fanning GC, Farha KA, Weegink C, Van Vliet A, Van 't Klooster G, Lenz O, Aharchi F, Marien K, Van Remoortere P, de Kock H, Broeckaert F, Meyvisch P, Van Beirendonck E, Simmen K, Verloes R. Rapid HCV-RNA decline with once daily TMC435: a phase I study in healthy volunteers and hepatitis C patients. Gastroenterology. 2010 Mar;138(3):913-21. doi: 10.1053/j.gastro.2009.10.033. Epub 2009 Oct 21.
- Phase I, double blind, randomized, placebo-controlled trial in healthy subjects to examine safety, tolerability, PK of increasing single and repeating oral doses of TMC435, followed by an open label repeated dosing session in 6 HCV G1 infected patients.Link provided by the sponsor.
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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 Limited Clinical Trial study director
Tibotec Pharmaceutical Limited
Questions about this trial
What is this clinical trial studying?
A Phase 1 study of Hepatitis C, run by Tibotec Pharmaceuticals, Ireland.
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 2 inclusion and 18 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 19 May 2011. Status can change between updates, so confirm with the study contact before making plans.
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?
Determine the safety, tolerability and pharmacokinetics of TMC435350 after single oral doses from 50 mg up to 1200 mg and after 5 days of dosing from 50 mg up to 400 mg or up to Multiple dosing. (time frame: Pharmacokinetics and safety at time of drug intake until 72hour after the drug intake). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00938899, which also lists 1 linked publication.
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 19 May 2011.