An Open-label, Randomized, 3-way Crossover Study in Healthy Adult Subjects to Assess the Relative Bioavailability of a Single Dose of JNJ-64041575 Administered as 2 Different New Concept Formulations (Oral Suspension and Tablet) Compared to Their Respective Current Formulations, and to Assess the Effect of Food on the Pharmacokinetics of the 2 New Concept Formulations
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Area Under Plasma Concentration Curve from time zero to the last quantifiable (AUC [0-last]) of ALS-008112 (JNJ-63549109)
研究概览
简要总结
The purpose of this study is to assess the rate and extent of absorption of JNJ-64041575 by measuring ALS-008112 plasma concentrations following administration of a single oral dose of JNJ-64041575 given as 2 new concept formulations (oral suspension and tablet) compared to their respective current formulations under fasted conditions and to assess the effect of food on the pharmacokinetics of the 2 new concept formulations under fed condition in healthy adult participants.
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
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participant must have a body mass index (BMI; weight in kg divided by the square of height in meters) between 18.0 and 30.0 kilogram per square meter kg/m^2, extremes included, and a body weight not less than 50.0 kg, extremes included
- •Participant must have a normal 12-lead electrocardiogram (ECG) consistent with normal cardiac conduction and function at screening, including: a) normal sinus rhythm (heart rate between 45 and 100 beats per minute [bpm], extremes included); b) QT corrected according to Fridericia's formula (QTcF) interval less than or equal to (<=)430 milliseconds (ms) for male participants and <=450 ms for female participants; c) QRS interval <=110 ms; d) PR interval <=200 ms; e) ECG morphology consistent with healthy cardiac conduction and function. Any evidence of heart block, or of left or right bundle branch block is exclusionary
- •Participants must have normal values for alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (less than or equal (<=)1.0×upper limit of laboratory normal range [ULN])
- •Contraceptive use by female participants should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies. Before randomization, a woman must be either: a) Not of childbearing potential defined as: 1) Postmenopausal: A postmenopausal state is defined as greater than (>)45 years and no menses for 12 consecutive months without an alternative medical cause and a serum follicle stimulating hormone (FSH) level in the postmenopausal range (>40 International units per liter [IU/L] or milli-international units per milliliter [mIU/mL]), OR; 2) Permanently sterile: Permanent sterilization methods include hysterectomy, bilateral salpingectomy, bilateral tubal occlusion/ligation procedures (without reversal operation), and bilateral oophorectomy b) Of childbearing potential and, if heterosexually active, 1) Practicing a highly effective method of contraception (failure rate of less than (<)1percent (%) per year when used consistently and correctly) 2) Agrees to remain on a highly effective method throughout the study and for at least 44 days after the last dose of study drug
- •A female participant, except if postmenopausal, must have a negative serum beta human chorionic gonadotropin (beta- hCG) pregnancy test at screening, and a negative urine pregnancy test on Day 1 in each treatment period
- •Participant must be able to taste and smell normally, to their own opinion. Participants who have an impaired sense of taste and/or smell due to any conditions such as allergic rhinitis, common cold, or sinusitis are not eligible to take part in the study
排除标准
- •Participant has a mouth pathology including, but not limited to, pain, ulcer, edema, mucosal erosion, gingivitis and/or (dental) abscesses, or receives treatment for oral pathologies (eg, antifungals or antibiotics) or oral treatment for any disease
- •Participant with a history of clinically significant drug allergy such as, but not limited to, sulfonamides and penicillins, or drug allergy diagnosed in previous studies with experimental drugs
- •Participant is hepatitis B surface antigen (HBsAg) positive or hepatitis C virus (HCV) antibody positive with HCV RNA positive, or has another clinically active liver disease at screening
- •Participant has a history of human immunodeficiency virus type 1 (HIV-1) or HIV 2 antibody positive, or tests positive for HIV-1 or -2 at screening
- •Participant has previously been dosed with JNJ-64041575 in more than 3 single-dose studies with JNJ-64041575 or has previously been dosed with JNJ-64041575 in a multiple-dose study with JNJ-64041575
- •Participants with 1 or more of the following laboratory abnormalities at screening as defined by the Division of Microbiology and Infectious Diseases (DMID) Adult Toxicity Table a) Serum creatinine grade 1 or greater (greater [>]1.0* upper limit of laboratory normal range [ULN]) b) Hemoglobin grade 1 or greater (<=10.5 gram per decilitre [g/dL]) c) Platelet count grade 1 or greater (<=99.999/millimeter [mm]^3) d) Reticulocyte count (absolute) below the lower limit of laboratory normal range (LLN) e) Absolute neutrophil count grade 1 or greater (<=1,500/mm^3) f) Total bilirubin grade 1 or greater (>1.0*ULN) g) Any other toxicity grade 2 or above, except for grade 2 elevations of low density lipoprotein (LDL) cholesterol and/or cholesterol
研究组 & 干预措施
Panel 1: Treatment ABC
Participants will receive 240 milligram (mg) JNJ-64041575 as 6.0 milliliter (mL) of a 40-milligram per milliliter (mg/mL) current oral suspension formulation (reference 1) under fasted conditions (Treatment A) in period 1, then 4.0 mL of a 60-mg/mL new concept oral suspension formulation (test 1) under fasted conditions (Treatment B) in period 2 followed by 4.0 mL of a 60-mg/mL new concept oral suspension formulation (test 2) under fed conditions (Treatment C) in period 3 on Day 1. There will be a washout period of at least 14 days between study drug intake in subsequent treatment periods.
干预措施: JNJ-64041575 (oral suspension formulation) (Drug)
Panel 1: Treatment BCA
Participants will receive Treatment B (test 1) in period 1, then Treatment C (test 2) in period 2 followed by Treatment A (reference 1) in period 3 on Day 1. There will be a washout period of at least 14 days between study drug intake in subsequent treatment periods.
干预措施: JNJ-64041575 (oral suspension formulation) (Drug)
Panel 1: Treatment CAB
Participants will receive Treatment C (test 2) in period 1, then Treatment A (reference 1) in period 2 followed by Treatment B (test 1) in period 3 on Day 1. There will be a washout period of at least 14 days between study drug intake in subsequent treatment periods.
干预措施: JNJ-64041575 (oral suspension formulation) (Drug)
Panel 1: Treatment ACB
Participants will receive Treatment A (reference 1) in period 1, then Treatment C (test 2) in period 2 followed by Treatment B (test 1) in period 3 on Day 1. There will be a washout period of at least 14 days between study drug intake in subsequent treatment periods.
干预措施: JNJ-64041575 (oral suspension formulation) (Drug)
Panel 1: Treatment BAC
Participants will receive Treatment B (test 1) in period 1, then Treatment A (reference 1) in period 2 followed by Treatment C (test 2) in period 3 on Day 1. There will be a washout period of at least 14 days between study drug intake in subsequent treatment periods.
干预措施: JNJ-64041575 (oral suspension formulation) (Drug)
Panel 2: Treatment FED
Participants will receive Treatment F (test 4) in period 1, then Treatment E (test 3) in period 2 followed by Treatment D (reference 2) in period 3 on Day 1. There will be a washout period of at least 14 days between study drug intake in subsequent treatment periods.
干预措施: JNJ-64041575 (oral tablet formulation ) (Drug)
Panel 1: Treatment CBA
Participants will receive Treatment C (test 2) in period 1, then Treatment B (test 1) in period 2 followed by Treatment A (reference 1) in period 3 on Day 1. There will be a washout period of at least 14 days between study drug intake in subsequent treatment periods.
干预措施: JNJ-64041575 (oral suspension formulation) (Drug)
Panel 2: Treatment DEF
Participants will receive JNJ-64041575 as 1 tablet of the 250-mg current oral tablet formulation (reference 2) under fasted conditions (Treatment D) in period 1, then 1 tablet of the 250-mg new concept oral tablet formulation (test 3) under fasted conditions (Treatment E) in period 2 followed by 1 tablet of the 250-mg new concept oral tablet formulation (test 4) under fed conditions (Treatment F) in period 3 on Day 1. There will be a washout period of at least 14 days between study drug intake in subsequent treatment periods.
干预措施: JNJ-64041575 (oral tablet formulation ) (Drug)
Panel 2: Treatment EFD
Participants will receive Treatment E (test 3) in period 1, then Treatment F (test 4) in period 2 followed by Treatment D (reference 2) in period 3 on Day 1. There will be a washout period of at least 14 days between study drug intake in subsequent treatment periods.
干预措施: JNJ-64041575 (oral tablet formulation ) (Drug)
Panel 2: Treatment FDE
Participants will receive Treatment F (test 4) in period 1, then Treatment D (reference 2) in period 2 followed by Treatment E (test 3) then in period 3 on Day 1. There will be a washout period of at least 14 days between study drug intake in subsequent treatment periods.
干预措施: JNJ-64041575 (oral tablet formulation ) (Drug)
Panel 2: Treatment DFE
Participants will receive Treatment D (reference 2) in period 1, then Treatment F (test 4) in period 2 followed by Treatment E (test 3) in period 3 on Day 1. There will be a washout period of at least 14 days between study drug intake in subsequent treatment periods.
干预措施: JNJ-64041575 (oral tablet formulation ) (Drug)
Panel 2: Treatment EDF
Participants will receive Treatment E (test 3) in period 1, then Treatment D (reference 2) in period 2 followed by Treatment F (test 4) in period 3 on Day 1. There will be a washout period of at least 14 days between study drug intake in subsequent treatment periods.
干预措施: JNJ-64041575 (oral tablet formulation ) (Drug)
结局指标
主要结局
Area Under Plasma Concentration Curve from time zero to the last quantifiable (AUC [0-last]) of ALS-008112 (JNJ-63549109)
时间窗: Up to Day 8
Area under the plasma concentration time curve (AUC) from time 0 to the time of the last measurable (non below quantification limit \[non BQL\]) concentration, calculated by linear trapezoidal summation.
Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of ALS-008112 (JNJ-63549109)
时间窗: Up to Day 8
The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time calculated as the sum of AUC (0-last) and C (0-last)/ lambda(z); wherein AUC (0-last) is area under the plasma concentration time curve from time zero to last quantifiable time, C(0-last) is the last observed quantifiable concentration, and lambda (z) is elimination rate constant.
Maximum Observed Plasma Concentration (Cmax) of ALS-008112 (JNJ-63549109)
时间窗: Up to Day 8
Cmax is the maximum observed plasma concentration.
次要结局
- Apparent Terminal Elimination Half-life (t1/2term) of ALS-008112 (JNJ-63549109)(Up to Day 8)
- Maximum Observed Plasma Concentration (Cmax) of ALS-008144 (JNJ-64167896)(Up to Day 8)
- Time to Reach Maximum Concentration (Tmax) of ALS-008144 (JNJ-64167896)(Up to Day 8)
- Area Under Plasma Concentration Curve from time zero to the last quantifiable (AUC [0-last]) of ALS-008144 (JNJ-64167896)(Up to Day 8)
- Time to Reach Maximum Concentration (Tmax) ALS-008112 (JNJ-63549109)(Up to Day 8)
- Apparent Terminal Elimination Rate Constant (lambda z) of ALS-008144 (JNJ-64167896)(Up to Day 8)
- Number of Participants With Adverse Events as a Measure of Safety and Tolerability(Screening (28 days ) to Follow up Phase (10 to 14 days after last dose))
- Taste of JNJ-64041575 following administration of different oral suspension formulations under fed and fasted conditions in healthy adult participants in Panel 1 (taste questionnaire)(Day 1)
- Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of ALS-008144 (JNJ-64167896)(Up to Day 8)
- Apparent Terminal Elimination Half-life (t1/2term) of ALS-008144 (JNJ-64167896)(Up to Day 8)
- Apparent Terminal Elimination Rate Constant (lambda z) of ALS-008112 (JNJ-63549109)(Up to Day 8)
- Taste and Swallowability of JNJ-64041575 following administration of different oral tablet formulations under fed and fasted conditions in healthy adult participants in Panel 2 (taste and swallowability questionnaire)(Day 1)