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

Phase 1CompletedNCT02064842

Janssen R&D Ireland24 enrolled

Overview

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.

This is a single-center study which consists of 2 parts, sequentially conducted in 2 separate panels of 24 healthy adult Japanese participants each. Part 1 is a double-blinded (neither physician nor participant knows the treatment that the participant receives), placebo-controlled (placebo is compared with the study medication to test whether the study medication has a real effect in clinical study), randomized (the study medication is assigned by chance) single ascending dose (SAD) part which will consist of a screening phase, a treatment phase, and a follow-up visit. Part 1 will have 3 cohorts (Cohort A, B, and C) with 8 participants each and they will be randomly assigned to receive either a single oral dose of TMC647055 (6 participants) or placebo (2 participants) in combination with RTV. The study duration for each participant will be approximately 5 weeks from screening to follow-up visit as maximum in Part 1. Part 2 is an open-label, randomized, 3-way crossover part which will consist of a screening phase, 3 treatment phases, and a follow-up phase. Each of the 24 participants will receive Treatment A, B, and C in 6 sequences (Treatment ABC, BCA, CAB, ACB, BAC, and CBA) with a washout period of at least 7 days between consecutive treatments. Safety evaluation will include assessment of adverse events, clinical laboratory tests, vital signs, electrocardiogram, and physical examination. The study duration for each participant will be approximately 10 weeks from screening to follow-up visit as maximum.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Interventions

TMC647055DRUG

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

TMC435DRUG

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

PlaceboDRUG

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

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

Eligibility

Sex: ALLMin age: 20 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * 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 Exclusion Criteria: * 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

Outcomes

Primary Outcomes

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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

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

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

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

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

Secondary Outcomes

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

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

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

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

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

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

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

Time frame: Up to Day 14

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes