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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier:
NCT01202825
First received: September 14, 2010
Last updated: March 1, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Hepatitis C
Drug: TMC647055
Drug: Placebo
Drug: TMC435
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Tibotec Pharmaceuticals, Ireland:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]

Enrollment: 72
Study Start Date: April 2010
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.
Placebo Comparator: 002 Drug: Placebo
One single dose as oral solution, selected dose ranging between 100 and 3000 mg in session VII
Experimental: 009 Drug: TMC647055
Oral solution given in session XIII, treatment arm 1 during 10 days at a dose of 1000 mg every 12 hours.
Experimental: 003 Drug: TMC647055
One single dose as oral solution, selected dose ranging between 100 and 3000 mg in session VII
Placebo Comparator: 004 Drug: Placebo
One single dose as oral solution, selected dose ranging between 100 and 3000 mg in session VII
Experimental: 005 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.
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
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
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.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01202825

Locations
Belgium
Antwerp, Belgium
Sponsors and Collaborators
Tibotec Pharmaceuticals, Ireland
Investigators
Study Director: Tibotec Pharmaceuticals Clinical Trial Tibotec Pharmaceutical Limited
  More Information

No publications provided

Responsible Party: Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier: NCT01202825     History of Changes
Other Study ID Numbers: CR017035, TMC647055HPC1001
Study First Received: September 14, 2010
Last Updated: March 1, 2013
Health Authority: Ireland: Irish Agriculture and Food Development Authority

Keywords provided by Tibotec Pharmaceuticals, Ireland:
HCV genotype 1 infected patients
TMC647055HPC1001
TMC647055
HPC
Hepatitis C
Healthy volunteers
TMC435

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on October 20, 2014