A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of TMC647055 in Combination With Ritonavir (Part 1) and the Co-administration of TMC435, TMC647055 and Ritonavir (Part 2) in Healthy Japanese Participants

NCT02064842 | Completed Phase 1

• 3 other identifiers: CR103540TMC435HPC10112013-004236-30
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to investigate the safety, tolerability, and pharmacokinetics of TMC647055 in combination with ritonavir (Part 1); potential pharmacokinetic drug-drug interactions between TMC435 and the combination of TMC647055 with ritonavir; and to evaluate the short-term safety and tolerability when TMC435, TMC647055 and Ritonavir are co-administered (Part 2) in healthy Japanese participants.

Conditions

Healthy

Keywords

Healthy; TMC647055; TMC435; Simeprevir; Sovriad; Ritonavir (RTV)

Outcome Measures

Primary Outcomes (11)

• Part 1: Number of participants with adverse events following the administration of TMC647055

  Assessment will be following single oral doses of TMC647055/Ritonavir 150/30 mg, 450/30 mg and 600/30 mg

  Up to Day 8

• Part 1: Maximum observed plasma concentration of TMC647055

  Assessment will be following single oral doses of TMC647055/Ritonavir 150/30 mg, 450/30 mg and 600/30 mg

  Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16 hours postdose); Day 2 (24 and 36 hours postdose); Day 3; and in case of early withdrawal (once between Day 6 to 8)

• Part 1: The actual sampling time to reach the maximum observed plasma of TMC647055

  Assessment will be following single oral doses of TMC647055/Ritonavir 150/30 mg, 450/30 mg and 600/30 mg

  Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16 hours postdose); Day 2 (24 and 36 hours postdose); Day 3; and in case of early withdrawal (once between Day 6 to 8)

• Part 1: The actual sampling time of last measurable plasma concentration of TMC647055

  Assessment will be following single oral doses of TMC647055/Ritonavir 150/30 mg, 450/30 mg and 600/30 mg

  Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16 hours postdose); Day 2 (24 and 36 hours postdose); Day 3; and in case of early withdrawal (once between Day 6 to 8)

• Part 1: Area under curve (AUC) of TMC647055

  AUC from time 0 up to 24 hours after dosing, from time 0 to the time of the last measurable concentration, and from time 0 to infinite time will be assessed. Assessment will be following single oral doses of TMC647055/Ritonavir 150/30 mg, 450/30 mg and 600/30 mg

  Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16 hours postdose); Day 2 (24 and 36 hours postdose); Day 3; and in case of early withdrawal (once between Day 6 to 8)

• Part 2: Maximum observed plasma concentration of TMC435

  Assessment will be following TMC435 75 mg co-administered with TMC647055/ritonavir 450/30 mg; TMC435 100 mg co-administered with TMC647055/ritonavir 600/30 mg; and TMC435 150 mg alone

  Day 1 (predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose); Day 2; Day 5; Day 6; Day 7 (predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose); Day 8; Day 9; Day 10; and end of treatment period or early withdrawal (once between Day 12 to 14)

• Part 2: The actual sampling time to reach the maximum observed plasma of TMC435

  Assessment will be following TMC435 75 mg co-administered with TMC647055/ritonavir 450/30 mg; TMC435 100 mg co-administered with TMC647055/ritonavir 600/30 mg; and TMC435 150 mg alone

  Day 1 (predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose); Day 2; Day 5; Day 6; Day 7 (predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose); Day 8; Day 9; Day 10; and end of treatment period or early withdrawal (once between Day 12 to 14)

• Part 2: Area under curve (AUC) of TMC435

  AUC from time 0 up to 24 hours after dosing will be assessed. Assessment will be following TMC435 75 mg co-administered with TMC647055/ritonavir 450/30 mg; TMC435 100 mg co-administered with TMC647055/ritonavir 600/30 mg; and TMC435 150 mg alone

  Day 1 (predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose); Day 2; Day 5; Day 6; Day 7 (predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose); Day 8; Day 9; Day 10; and end of treatment period or early withdrawal (once between Day 12 to 14)

• Part 2: Maximum observed plasma concentration of TMC647055

  Assessment will be following TMC647055 600 mg co-administered with TMC435 100 mg and ritonavir 30 mg; and TMC647055 450 mg co-administered with TMC435 75 mg and ritonavir 30 mg

  Day 1 (predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose); Day 2; Day 5; Day 6; Day 7 (predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose); Day 8; Day 9; Day 10; and end of treatment period or early withdrawal (once between Day 12 to 14)

• Part 2: The actual sampling time to reach the maximum observed plasma of TMC647055

  Assessment will be following TMC647055 600 mg co-administered with TMC435 100 mg and ritonavir 30 mg; and TMC647055 450 mg co-administered with TMC435 75 mg and ritonavir 30 mg

  Day 1 (predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose); Day 2; Day 5; Day 6; Day 7 (predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose); Day 8; Day 9; Day 10; and end of treatment period or early withdrawal (once between Day 12 to 14)

• Part 2: Area under curve (AUC) of TMC647055

  AUC from time 0 up to 24 hours after dosing will be assessed. Assessment will be following TMC647055 600 mg co-administered with TMC435 100 mg and ritonavir 30 mg; and TMC647055 450 mg co-administered with TMC435 75 mg and ritonavir 30 mg

  Day 1 (predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose); Day 2; Day 5; Day 6; Day 7 (predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose); Day 8; Day 9; Day 10; and end of treatment period or early withdrawal (once between Day 12 to 14)

Secondary Outcomes (4)

• Part 2: Maximum observed plasma concentration of ritonavir (RTV)

  Day 1 (predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose); Day 2; Day 5; Day 6; Day 7 (predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose); Day 8; Day 9; Day 10; and end of treatment period or early withdrawal (once between Day 12 to 14)

• Part 2: The actual sampling time to reach the maximum observed plasma of ritonavir (RTV)

  Day 1 (predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose); Day 2; Day 5; Day 6; Day 7 (predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose); Day 8; Day 9; Day 10; and end of treatment period or early withdrawal (once between Day 12 to 14)

• Part 2: Area under curve (AUC) of ritonavir (RTV)

  Day 1 (predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose); Day 2; Day 5; Day 6; Day 7 (predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose); Day 8; Day 9; Day 10; and end of treatment period or early withdrawal (once between Day 12 to 14)

• Part 2: Number of participants with adverse events following the administration of TMC435

  Up to Day 14

Study Arms (9)

TMC647055 150 mg or placebo + ritonavir (RTV)

EXPERIMENTAL

Participants in Part 1 will receive a single oral dose of 150 mg of TMC647055 or placebo with 30 mg of RTV on Day 1.

Drug: TMC647055; Drug: Placebo; Drug: Ritonavir (RTV)

TMC647055 450 mg or placebo + RTV

EXPERIMENTAL

Participants in Part 1 will receive a single oral dose of 450 mg of TMC647055 or placebo with 30 mg of RTV on Day 1.

Drug: TMC647055; Drug: Placebo; Drug: Ritonavir (RTV)

TMC647055 600 mg or placebo + RTV

EXPERIMENTAL

Participants in Part 1 will receive a single oral dose of 600 mg of TMC647055 or placebo with 30 mg of RTV on Day 1.

Drug: TMC647055; Drug: Placebo; Drug: Ritonavir (RTV)

Sequence 1 (Treatment A-B-C)

EXPERIMENTAL

Participants in Part 2 will receive Treatment ABC in the following sequence - Treatment A: TMC435 150 mg once daily on Days 1 to 7; Treatment B: TMC435 75 mg once daily + TMC647055 450 mg once daily in combination with RTV 30 mg once daily on Days 1 to 7; and Treatment C: TMC435 100 mg once daily + TMC647055 600 mg once daily in combination with RTV 30 mg once daily on Days 1 to 7 with a washout period of 7 days between consecutive treatment sessions in each individual participant.

Drug: TMC647055; Drug: TMC435; Drug: Ritonavir (RTV)

Sequence 2 (Treatment B-C-A)

EXPERIMENTAL

Participants in Part 2 will receive Treatment BCA in the following sequence - Treatment B: TMC435 75 mg once daily + TMC647055 450 mg once daily in combination with RTV 30 mg once daily on Days 1 to 7; Treatment C: TMC435 100 mg once daily + TMC647055 600 mg once daily in combination with RTV 30 mg once daily on Days 1 to 7; and Treatment A: TMC435 150 mg once daily on Days 1 to 7 with a washout period of 7 days between consecutive treatment sessions in each individual participant.

Drug: TMC647055; Drug: TMC435; Drug: Ritonavir (RTV)

Sequence 3 (Treatment C-A-B)

EXPERIMENTAL

Participants in Part 2 will receive Treatment CAB in the following sequence - Treatment C: TMC435 100 mg once daily + TMC647055 600 mg once daily in combination with RTV 30 mg once daily on Days 1 to 7; Treatment A: TMC435 150 mg once daily on Days 1 to 7; and Treatment B: TMC435 75 mg once daily + TMC647055 450 mg once daily in combination with RTV 30 mg once daily on Days 1 to 7 with a washout period of 7 days between consecutive treatment sessions in each individual participant.

Drug: TMC647055; Drug: TMC435; Drug: Ritonavir (RTV)

Sequence 4 (Treatment A-C-B)

EXPERIMENTAL

Participants in Part 2 will receive Treatment ACB in the following sequence - Treatment A: TMC435 150 mg once daily on Days 1 to 7; Treatment C: TMC435 100 mg once daily + TMC647055 600 mg once daily in combination with RTV 30 mg once daily on Days 1 to 7; and Treatment B: TMC435 75 mg once daily + TMC647055 450 mg once daily in combination with RTV 30 mg once daily on Days 1 to 7 with a washout period of 7 days between consecutive treatment sessions in each individual participant.

Drug: TMC647055; Drug: TMC435; Drug: Ritonavir (RTV)

Sequence 5 (Treatment B-A-C)

EXPERIMENTAL

Participants in Part 2 will receive Treatment BAC in the following sequence - Treatment B: TMC435 75 mg once daily + TMC647055 450 mg once daily in combination with RTV 30 mg once daily on Days 1 to 7; Treatment A: TMC435 150 mg once daily on Days 1 to 7; and Treatment C: TMC435 100 mg once daily + TMC647055 600 mg once daily in combination with RTV 30 mg once daily on Days 1 to 7 with a washout period of 7 days between consecutive treatment sessions in each individual participant.

Drug: TMC647055; Drug: TMC435; Drug: Ritonavir (RTV)

Sequence 6 (Treatment C-B-A)

EXPERIMENTAL

Participants in Part 2 will receive Treatment CBA in the following sequence - Treatment C: TMC435 100 mg once daily + TMC647055 600 mg once daily in combination with RTV 30 mg once daily on Days 1 to 7; Treatment B: TMC435 75 mg once daily + TMC647055 450 mg once daily in combination with RTV 30 mg once daily on Days 1 to 7; and Treatment A: TMC435 150 mg once daily on Days 1 to 7 with a washout period of 7 days between consecutive treatment sessions in each individual participant.

Drug: TMC647055; Drug: TMC435; Drug: Ritonavir (RTV)

Interventions

TMC647055 DRUG

TMC647055 150 mg (1 capsule), 450 mg (3 capsules), 600 mg (4 capsules) taken orally (by mouth) once daily on Day 1 in Part 1. TMC647055 450 mg (3 capsules), and 600 mg (4 capsules) taken orally once daily on Days 1 to 7 in Part 2

Sequence 1 (Treatment A-B-C); Sequence 2 (Treatment B-C-A); Sequence 3 (Treatment C-A-B); Sequence 4 (Treatment A-C-B); Sequence 5 (Treatment B-A-C); Sequence 6 (Treatment C-B-A); TMC647055 150 mg or placebo + ritonavir (RTV); TMC647055 450 mg or placebo + RTV; TMC647055 600 mg or placebo + RTV

TMC435 DRUG

TMC435 1 capsule of 75 mg, 100 mg, and 150 mg taken orally on Days 1 to 7 in Part 2

Sequence 1 (Treatment A-B-C); Sequence 2 (Treatment B-C-A); Sequence 3 (Treatment C-A-B); Sequence 4 (Treatment A-C-B); Sequence 5 (Treatment B-A-C); Sequence 6 (Treatment C-B-A)

Placebo DRUG

Placebo capsule once daily taken orally on Day 1 in Part 1

TMC647055 150 mg or placebo + ritonavir (RTV); TMC647055 450 mg or placebo + RTV; TMC647055 600 mg or placebo + RTV

Ritonavir (RTV) DRUG

RTV 30 mg (ie, 0.38 mL oral solution of RTV \[80 mg/mL strength\]) taken orally on Day 1 in Part 1 and on Days 1 to 7 in Part 2

Sequence 1 (Treatment A-B-C); Sequence 2 (Treatment B-C-A); Sequence 3 (Treatment C-A-B); Sequence 4 (Treatment A-C-B); Sequence 5 (Treatment B-A-C); Sequence 6 (Treatment C-B-A); TMC647055 150 mg or placebo + ritonavir (RTV); TMC647055 450 mg or placebo + RTV; TMC647055 600 mg or placebo + RTV

Eligibility Criteria

• Age: 20 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Man or woman of Japanese descent who has resided outside Japan for no more than 5 years and whose parents and grandparents are Japanese as determined by participant's verbal report
• Must have signed an informed consent form
• Women must be of non-child-bearing potential (postmenopausal for at least 2 years, surgically sterile, or otherwise incapable of becoming pregnant)
• Women, except for postmenopausal women, should have a negative serum b-human chorionic gonadotropin pregnancy test at screening
• Men heterosexually active with a woman of childbearing potential must agree to use two effective methods of birth control, and all men must also not donate sperm during the study and for 3 months after receiving the last dose of study medication
• Must have a body mass index between 16.0 and 30.0 kg/m2, inclusive, and body weight not less than 45 kg at screening

You may not qualify if:

• History or evidence of current use of alcohol, barbiturate, amphetamine, recreational or narcotic drug use within the past 1 year which in the Investigator's opinion would compromise participant's safety and/or compliance with the study procedures
• Participant's with Hepatitis A, B, or C infection, or human immunodeficiency virus type 1 or 2 (HIV-1 or HIV-2) infection at study screening
• Female participants who are breastfeeding at screening
• History of liver or renal impairment, significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, neoplastic, or metabolic disturbances
• History of clinically relevant skin disease or history of allergy to any medication

Sponsors & Collaborators

• Janssen R&D Ireland: lead

Study Sites (1)

Unknown Facility

Harrow, United Kingdom

Location

MeSH Terms

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; Ritonavir

Intervention Hierarchy (Ancestors)

Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Thiazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Janssen R&D Ireland Clinical Trial

  Janssen R&D Ireland

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2014
• First Posted: February 17, 2014
• Study Start: February 1, 2014
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: May 16, 2014

Record last verified: 2014-05

Locations

GB (1)