临床试验/NCT02064842

NCT02064842已完成1 期

A Phase 1, Double-blind, Placebo-controlled, Randomized, Single Ascending Dose Study to Investigate the Safety, Tolerability, and Pharmacokinetics of TMC647055 in Combination With a Pharmacokinetic Enhancer (Part 1) Followed by an Open-label, Randomized, 3-way Crossover Study to Evaluate Short-term Safety, Tolerability and Pharmacokinetics of the Coadministration of TMC435, TMC647055 and a Pharmacokinetic Enhancer, at Steady-state (Part 2) in Healthy Japanese Subjects.

Janssen R&D Ireland0 个研究点目标入组 24 人开始时间: 2014年2月最近更新: 2014年5月16日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方
入组人数: 24
主要终点: Part 1: Number of participants with adverse events following the administration of TMC647055

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者记录与标识符相似试验

研究概览

简要总结

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.

详细描述

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.

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Crossover
主要目的: Treatment
盲法: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

入排标准

年龄范围: 20 Years 至 55 Years（Adult）
性别: All
接受健康志愿者: 是

入选标准

•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

排除标准

•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

研究组 & 干预措施

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.

干预措施: TMC647055 (Drug)

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.

干预措施: Placebo (Drug)

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.

干预措施: Ritonavir (RTV) (Drug)

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.

干预措施: TMC647055 (Drug)

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.

干预措施: Placebo (Drug)

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.

干预措施: Ritonavir (RTV) (Drug)

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.

干预措施: TMC647055 (Drug)

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.

干预措施: Placebo (Drug)

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.

干预措施: Ritonavir (RTV) (Drug)

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.

干预措施: TMC647055 (Drug)

Sequence 1 (Treatment A-B-C)

Experimental

干预措施: TMC435 (Drug)

Sequence 1 (Treatment A-B-C)

Experimental

干预措施: Ritonavir (RTV) (Drug)

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.

干预措施: TMC647055 (Drug)

Sequence 2 (Treatment B-C-A)

Experimental

干预措施: TMC435 (Drug)

Sequence 2 (Treatment B-C-A)

Experimental

干预措施: Ritonavir (RTV) (Drug)

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.

干预措施: TMC647055 (Drug)

Sequence 3 (Treatment C-A-B)

Experimental

干预措施: TMC435 (Drug)

Sequence 3 (Treatment C-A-B)

Experimental

干预措施: Ritonavir (RTV) (Drug)

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.

干预措施: TMC647055 (Drug)

Sequence 4 (Treatment A-C-B)

Experimental

干预措施: TMC435 (Drug)

Sequence 4 (Treatment A-C-B)

Experimental

干预措施: Ritonavir (RTV) (Drug)

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.

干预措施: TMC647055 (Drug)

Sequence 5 (Treatment B-A-C)

Experimental

干预措施: TMC435 (Drug)

Sequence 5 (Treatment B-A-C)

Experimental

干预措施: Ritonavir (RTV) (Drug)

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.

干预措施: TMC647055 (Drug)

Sequence 6 (Treatment C-B-A)

Experimental

干预措施: TMC435 (Drug)

Sequence 6 (Treatment C-B-A)

Experimental

干预措施: Ritonavir (RTV) (Drug)

结局指标

主要结局

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

时间窗: Up to Day 8

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

Part 1: Maximum observed plasma concentration of TMC647055

时间窗: 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)

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

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

时间窗: 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)

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

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

时间窗: 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)

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

Part 1: Area under curve (AUC) of TMC647055

时间窗: 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)

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

Part 2: Maximum observed plasma concentration of TMC435

时间窗: 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)

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: 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

次要结局

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)

研究者

发起方

Janssen R&D Ireland

申办方类型

Industry

责任方

Sponsor

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