TMC647055HPC1001 - First-in-human Trial to Examine Safety, Tolerability and Pharmacokinetics (How the Drug is Absorbed Into the Bloodstream) of Increasing Single Oral Doses and of Increasing Repeated Oral Doses of TMC647055 in Healthy Volunteers and in Hepatitis C Virus Infected Patients

March 1, 2013 updated by: Tibotec Pharmaceuticals, Ireland

Phase I, First-in-human Trial in Healthy Volunteers to Examine Increasing Single and Repeated Oral Doses of TMC647055, Followed by a Repeated-dose Part in Chronic HCV-genotype 1 Infected Patients to Examine TMC647055 Given Alone or in Combination With TMC435

The purpose of this study is to assess the safety and tolerability of TMC647055 both after increasing single oral doses from 100 mg up to maximum 3000 mg in fed conditions, and after multiple oral doses in fed conditions at increasing dose levels administered for 6 days, as well as to assess the pharmacokinetics of TMC647055 after increasing single oral doses from 100 mg up to maximum 3000 mg in fed conditions, and after multiple oral doses in fed conditions at increasing dose levels administered for 6 days and to assess the effect of food on a single oral dose of TMC647055 at one dose level, all in healthy participants. In addition, the safety, tolerability, pharmacokinetics and the antiviral activity of TMC647055 will be determined after 6 days of consecutive dosing and of TMC647055 and TMC435 after 10 days of co-administration in chronic hepatitis C virus infected patients. Pharmacokinetics means how the drug is absorbed into the bloodstream, distributed in the body and eliminated from the body. TMC647055 is being investigated for the treatment of chronic hepatitis C infection.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

TMC647055 is being investigated for the treatment of chronic hepatitis C infection. This is a first-in-human, double-blind (sponsor, investigator and participant do not know which treatment is given), randomized (like flipping a coin), placebo-controlled, single centre, Phase I study in healthy volunteers to examine the safety, tolerability, and plasma pharmacokinetics of increasing single oral doses and of increasing repeated oral doses of TMC647055, followed by a double-blind repeated-dose part in chronic hepatitis C virus (HCV) infected patients. The study population will consist of 45 healthy adult volunteers between 18 and 55 years of age and 10 or 20 chronic HCV-genotype 1 infected patients between 18 and 65 years of age. The single dose escalation part of the trial will include 2 panels (Panels 1 and 2) of 9 participants each. There will be 6 sessions (Sessions I to VI): panel 1 will do sessions I, III & V; panel 2 will do sessions II, IV and VI. In each session, 6 participants will receive TMC647055 and 3 participants will receive placebo with standard meals. Over 3 sessions, each participant will receive TMC647055 twice and placebo once. The dose of TMC647055 will be consecutively increased. Planned doses will be 100 mg, 250 mg, 600 mg, 1250 mg, 2000 mg, and 3000 mg of TMC647055 or placebo, administered as a single oral administration. A wash out period of at least 10 days will be respected between 2 sessions of 1 panel. Doses may be adapted pending the safety and pharmacokinetic outcome of the previous sessions but will not exceed the limit of 3000 mg. Dose increase will only occur if the previous dose is shown to be generally safe and tolerable. For precautionary safety reasons, the dose administration in sessions IV, V and VI will be staggered: the first 4 to 5 participants of the panel will receive the dose at least 24 hours prior to the second group of 4 to 5 participants. To investigate the effect of food, one single dose will be tested in fasted conditions (Session VII). The dose of TMC647055 tested in this session will be derived from the results obtained in Sessions I to V. Participants who received TMC647055 at the selected dose with standard meals in Sessions I to V will again receive TMC647055 in fasted conditions in Session VII. Participants who received placebo will receive placebo again. The multiple-dose escalation part of the trial (sessions VIII, IX and X) will include 3 panels (Panels 3, 4, and 5) of 9 participants each: panel 3 will do session VIII, panel 4 session IX and panel 5 session X. In all panels, TMC647055 or placebo will be administered during 6 consecutive days, with on Day 6 a morning dose only. Medication is anticipated to be given either every 8 hours, every 12 hours or every 24 hours. This can be changed per dosing session following the outcome of the previous session. In each multiple dosing session, 6 participants will receive TMC647055 and 3 participants will receive placebo. The multiple dose escalation part will be started when the doses of Sessions I, II, III, and IV are found to be generally safe and tolerable based upon review of the blinded safety and pharmacokinetic data. Dose increase will only occur if the previous dose is shown to be generally safe and tolerable. The initial daily dose tested in Panel 3 will not be higher than the doses tested in Sessions I to IV. After the healthy volunteer sessions, there will be 3 sessions in chronic HCV infected patients (sessions XI, XII and XIII). Session XI will be started when the doses in healthy volunteers are found to be generally safe and tolerable and a selected dose will be given every 12 hours. The total daily dose will not exceed the highest daily dose and exposure shown to be generally safe in the multiple dose escalation in healthy volunteers. The dose for session XII will be selected based on the results from session XI and will be given every 12 hours or every 8 hours. In each session, 8 patients will receive TMC647055 and 2 patients will receive placebo. TMC647055 will be given during 6 consecutive days with on day 6 a morning dose only. Session XIII will be open-label and will consist of 2 treatment arms. In treatment arm 1, 8 patients will receive TMC647055 (1000 mg twice a day) co-administered with TMC435 (150 mg once daily) for 10 days.In treatment arm 2, 8 subjects will receive TMC435 (150 mg once daily) for 6 days. Safety and tolerability will be evaluated continuously by checking illnesses and side effects, by taking blood and urine samples, by electrocardiograms and telemetry (electrical recording of the heart, only for healthy volunteers), by taking blood pressure and heart rate and by performing physical examinations. TMC647055 or placebo will be given as an oral solution, ranging from 100 to 3000 mg in the single dose part, in the multiple dose part during 6 consecutive days either every 8 hours, 12 hours or 24 hour. In sessions XI and XII, TMC647055 or placebo will be given every 8 or 12 hours at dose and frequency determined by results of the previous sessions. In session XIII, the dose of TMC647055 will be 1000 mg twice a day and TMC435 will be given as oral capsules at 150 mg once daily.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
72

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Healthy volunteers should be healthy on the basis of physical examination, medical history, laboratory tests, triplicate electrocardiogram and vital signs, performed at screening, have 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 and be non-smoking for at least 3 months prior to selection
  • Chronic hepatitis-C infected patients should have documented chronic genotype 1a or 1b HCV infection, otherwise no clinically relevant currently active disease and a BMI of 18.0 to 35.0 kg/m2, extremes included
  • Women must be postmenopausal for at least 2 years, and/or be surgically sterile.

Exclusion Criteria:

  • All participants with a drug allergy such as, but not limited to, sulfonamides and penicillins, or with a drug allergy as witnessed in previous trials with experimental drugs
  • Use of concomitant medication, including over-the-counter products, herbal medication and dietary supplements, except for paracetamol (acetaminophen) or ibuprofen or hormone replacement therapy or for chronic hepatitis-C infected patients products that are not CYP3A4 inhibitors or inducers and stable use of methadone, in a period of 14 days before the first trial medication administration
  • Any condition that, in the opinion of the investigator, would compromise the study or the well-being of the subject or prevent the subject from meeting or performing study requirements
  • History or suspicion of current use of alcohol, barbiturate, amphetamine, recreational or narcotic drug use, which in the investigator's opinion would compromise subject's safety and/or compliance with the trial procedures
  • Participation in an investigational drug trial or having received an investigational vaccine within 30 days prior to the first intake of TMC647055 or placebo.

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: Single Group Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 001
Drug: TMC647055
One single dose as oral solution, doses from 100 mg up to a maximum of 3000 mg increasing in sessions I through VI.
Drug: TMC647055
Oral solution given in session XIII, treatment arm 1 during 10 days at a dose of 1000 mg every 12 hours.
Drug: TMC647055
In sessions VIII through X, oral solution given once daily, every 12 hours or every 8 hours on 6 consecutive days. Doses are based on outcome of previous sessions.
Drug: TMC647055
One single dose as oral solution, selected dose ranging between 100 and 3000 mg in session VII
Drug: TMC647055
Oral solution given in session XI every 12 hours, in session XII every 12 or 8 hours. Doses and regimen will be determined based on outcome of previous sessions.
Placebo Comparator: 002
Drug: Placebo
Oral solution given in session XI every 12 hours, in session XII every 12 or 8 hours. Doses and regimen will be determined based on outcome of previous sessions.
Drug: Placebo
One single dose as oral solution, selected dose ranging between 100 and 3000 mg in session VII
Drug: Placebo
In sessions VIII through X, oral solution given once daily, every 12 hours or every 8 hours on 6 consecutive days. Doses are based on outcome of previous sessions.
Experimental: 003
Drug: TMC647055
One single dose as oral solution, doses from 100 mg up to a maximum of 3000 mg increasing in sessions I through VI.
Drug: TMC647055
Oral solution given in session XIII, treatment arm 1 during 10 days at a dose of 1000 mg every 12 hours.
Drug: TMC647055
In sessions VIII through X, oral solution given once daily, every 12 hours or every 8 hours on 6 consecutive days. Doses are based on outcome of previous sessions.
Drug: TMC647055
One single dose as oral solution, selected dose ranging between 100 and 3000 mg in session VII
Drug: TMC647055
Oral solution given in session XI every 12 hours, in session XII every 12 or 8 hours. Doses and regimen will be determined based on outcome of previous sessions.
Placebo Comparator: 008
Drug: Placebo
Oral solution given in session XI every 12 hours, in session XII every 12 or 8 hours. Doses and regimen will be determined based on outcome of previous sessions.
Drug: Placebo
One single dose as oral solution, selected dose ranging between 100 and 3000 mg in session VII
Drug: Placebo
In sessions VIII through X, oral solution given once daily, every 12 hours or every 8 hours on 6 consecutive days. Doses are based on outcome of previous sessions.
Experimental: 009
Drug: TMC647055
One single dose as oral solution, doses from 100 mg up to a maximum of 3000 mg increasing in sessions I through VI.
Drug: TMC647055
Oral solution given in session XIII, treatment arm 1 during 10 days at a dose of 1000 mg every 12 hours.
Drug: TMC647055
In sessions VIII through X, oral solution given once daily, every 12 hours or every 8 hours on 6 consecutive days. Doses are based on outcome of previous sessions.
Drug: TMC647055
One single dose as oral solution, selected dose ranging between 100 and 3000 mg in session VII
Drug: TMC647055
Oral solution given in session XI every 12 hours, in session XII every 12 or 8 hours. Doses and regimen will be determined based on outcome of previous sessions.
Placebo Comparator: 004
Drug: Placebo
Oral solution given in session XI every 12 hours, in session XII every 12 or 8 hours. Doses and regimen will be determined based on outcome of previous sessions.
Drug: Placebo
One single dose as oral solution, selected dose ranging between 100 and 3000 mg in session VII
Drug: Placebo
In sessions VIII through X, oral solution given once daily, every 12 hours or every 8 hours on 6 consecutive days. Doses are based on outcome of previous sessions.
Experimental: 005
Drug: TMC647055
One single dose as oral solution, doses from 100 mg up to a maximum of 3000 mg increasing in sessions I through VI.
Drug: TMC647055
Oral solution given in session XIII, treatment arm 1 during 10 days at a dose of 1000 mg every 12 hours.
Drug: TMC647055
In sessions VIII through X, oral solution given once daily, every 12 hours or every 8 hours on 6 consecutive days. Doses are based on outcome of previous sessions.
Drug: TMC647055
One single dose as oral solution, selected dose ranging between 100 and 3000 mg in session VII
Drug: TMC647055
Oral solution given in session XI every 12 hours, in session XII every 12 or 8 hours. Doses and regimen will be determined based on outcome of previous sessions.
Experimental: 010
Drug: TMC435
Oral capsule given in session XIII, in treatment arm 1 during 10 days and in treatment arm 2 during 6 days at a dose of 150 mg once daily.
Placebo Comparator: 006
Drug: Placebo
Oral solution given in session XI every 12 hours, in session XII every 12 or 8 hours. Doses and regimen will be determined based on outcome of previous sessions.
Drug: Placebo
One single dose as oral solution, selected dose ranging between 100 and 3000 mg in session VII
Drug: Placebo
In sessions VIII through X, oral solution given once daily, every 12 hours or every 8 hours on 6 consecutive days. Doses are based on outcome of previous sessions.
Experimental: 007
Drug: TMC647055
One single dose as oral solution, doses from 100 mg up to a maximum of 3000 mg increasing in sessions I through VI.
Drug: TMC647055
Oral solution given in session XIII, treatment arm 1 during 10 days at a dose of 1000 mg every 12 hours.
Drug: TMC647055
In sessions VIII through X, oral solution given once daily, every 12 hours or every 8 hours on 6 consecutive days. Doses are based on outcome of previous sessions.
Drug: TMC647055
One single dose as oral solution, selected dose ranging between 100 and 3000 mg in session VII
Drug: TMC647055
Oral solution given in session XI every 12 hours, in session XII every 12 or 8 hours. Doses and regimen will be determined based on outcome of previous sessions.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
The number of participants with adverse events per type as a measure of safety and tolerability after increasing single and multiple oral doses in healthy volunteers.
Time Frame: Continuously from screening until the last follow-up visit 30 to 35 days after last drug intake.
Continuously from screening until the last follow-up visit 30 to 35 days after last drug intake.
Plasma and urine concentration of TMC647055 after increasing single and multiple oral doses in healthy volunteers in fed conditions.
Time Frame: For single dose sessions in plasma on days 1 (multiple times), 2 (2 times), 3 and 4 and continuous urine collection on days 1 and 2 of session IV only. For multiple dose sessions on days 1 and 6 multiple times, on day 7 2 times and on days 2-3-4-5-8-9.
For single dose sessions in plasma on days 1 (multiple times), 2 (2 times), 3 and 4 and continuous urine collection on days 1 and 2 of session IV only. For multiple dose sessions on days 1 and 6 multiple times, on day 7 2 times and on days 2-3-4-5-8-9.
Plasma concentration of TMC647055 after a single oral dose in healthy volunteers in fasted conditions as compaired to fed conditions.
Time Frame: For session 7, in plasma on days 1 (multiple timepoints), 2 (2 timepoints), 3 and 4.
For session 7, in plasma on days 1 (multiple timepoints), 2 (2 timepoints), 3 and 4.
Plasma concentration of TMC647055 after 6 days oral dosing in chronic HCV-genotype 1 infected patients.
Time Frame: On days 1 and 6 multiple times and on days 2-3-4-5-7-8-9 pre-dose.
On days 1 and 6 multiple times and on days 2-3-4-5-7-8-9 pre-dose.
The number of participants with adverse events per type as a measure of safety and tolerability after 6 days oral dosing in chronic HCV-genotype 1 infected patients.
Time Frame: Continuously from screening until the last follow-up visit 30 to 35 days after last drug intake.
Continuously from screening until the last follow-up visit 30 to 35 days after last drug intake.
Plasma concentration of TMC647055 after a single oral dose in healthy volunteers in fasted conditions as compared to fed conditions.
Time Frame: For session 7, in plasma on days 1 (multiple timepoints), 2 (2 timepoints), 3 and 4.
For session 7, in plasma on days 1 (multiple timepoints), 2 (2 timepoints), 3 and 4.
The number of participants with adverse events per type as a measure of safety and tolerability after 6 days of TMC647055, after 10 days co-administration of TMC647055 and TMC435 and after 6 days of TMC435 in chronic HCV-genotype 1 infected patients.
Time Frame: Continuously from screening until the last follow-up visit 30 to 35 days after last drug intake.
Continuously from screening until the last follow-up visit 30 to 35 days after last drug intake.
Plasma concentration of TMC647055 and TMC435, if applicable, in chronic HCV-genotype 1 infected patients.
Time Frame: Sessions XI and XII: on days 1 and 6 multiple times and on days 2-3-4-5-7-8-9 pre-dose. Session XIII: on days 1, 6 and 10 (if applicable) multiple times and on other days pre-dose.
Sessions XI and XII: on days 1 and 6 multiple times and on days 2-3-4-5-7-8-9 pre-dose. Session XIII: on days 1, 6 and 10 (if applicable) multiple times and on other days pre-dose.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
HCV RNA decrease will be measured at the tested dose(s) and regimen(s) in chronic HCV-genotype 1 infected patients.
Time Frame: At screening, day 1 through day 9 at several timepoints.
At screening, day 1 through day 9 at several timepoints.
HCV RNA will be measured in chronic HCV-genotype 1 infected patients.
Time Frame: Session XI and XII: at screening, day 1 through day 9 at several timepoints. Session XIII: at screening, day 1 through day 10 (TMC435 alone) or 14 (co-administration) at several timepoints and at the 3 follow-up visits.
Session XI and XII: at screening, day 1 through day 9 at several timepoints. Session XIII: at screening, day 1 through day 10 (TMC435 alone) or 14 (co-administration) at several timepoints and at the 3 follow-up visits.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Tibotec Pharmaceuticals, Ireland

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2010

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2011

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2011

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 14, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 14, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 16, 2010

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 4, 2013

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 1, 2013

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CR017035
  • TMC647055HPC1001 (Other Identifier: Tibotec Pharmaceuticals, Ireland)

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