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

NCT01202825 | Completed Phase 1

• 2 other identifiers: CR017035TMC647055HPC1001
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hepatitis C

Keywords

HCV genotype 1 infected patients; TMC647055HPC1001; TMC647055; HPC; Hepatitis C; Healthy volunteers; TMC435

Outcome Measures

Primary Outcomes (8)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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 Outcomes (2)

• HCV RNA decrease will be measured at the tested dose(s) and regimen(s) in chronic HCV-genotype 1 infected patients.

  At screening, day 1 through day 9 at several timepoints.

• HCV RNA will be measured in chronic HCV-genotype 1 infected patients.

  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.

Study Arms (10)

001

EXPERIMENTAL

Drug: TMC647055

008

PLACEBO COMPARATOR

Drug: Placebo

002

PLACEBO COMPARATOR

Drug: Placebo

009

EXPERIMENTAL

Drug: TMC647055

003

EXPERIMENTAL

Drug: TMC647055

004

PLACEBO COMPARATOR

Drug: Placebo

005

EXPERIMENTAL

Drug: TMC647055

010

EXPERIMENTAL

Drug: TMC435

006

PLACEBO COMPARATOR

Drug: Placebo

007

EXPERIMENTAL

Drug: TMC647055

Interventions

TMC647055 DRUG

One single dose as oral solution, doses from 100 mg up to a maximum of 3000 mg increasing in sessions I through VI.

001

Placebo DRUG

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.

008

TMC435 DRUG

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.

010

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tibotec Pharmaceuticals, Ireland: lead

Study Sites (1)

Unknown Facility

Antwerp, Belgium

Location

MeSH Terms

Conditions

Hepatitis C

Interventions

27-cyclohexyl-12,13,16,17-tetrahydro-22-methoxy-11,17-dimethyl-10,10-dioxide-2,19-methano-3,7:4,1-dimetheno-1H,11H-14,10,2,9,11,17-benzoxathiatetraazacyclo docosine-8,18(9H,15H)-dione; Simeprevir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Tibotec Pharmaceuticals Clinical Trial

  Tibotec Pharmaceutical Limited

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2010
• First Posted: September 16, 2010
• Study Start: April 1, 2010
• Primary Completion: November 1, 2011
• Study Completion: November 1, 2011
• Last Updated: March 4, 2013

Record last verified: 2013-03

Locations

BE (1)