A 2-Part, Phase I, Single-Dose, 3-Period Crossover Relative Bioavailability Study of a Pediatric TRIUMEQ Dispersible Tablet and Pediatric Dolutegravir and Lamivudine (DTG/3TC) Fixed Dose Combination Dispersible Tablet Formulations as Compared With Adult Tablets in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Area Under the Plasma Concentration-time Curve (AUC) From Time of Dose Extrapolated to Infinity (AUC[0-inf]) in Part 1 of DTG
研究概览
简要总结
This is a 2-part, single-dose, open label, randomized 3-way cross-over study to compare BA of pediatric study drugs TRIUMEQ and (DTG/3TC) in healthy volunteers under fasted conditions. Study will be conducted in 2-parts. Each part 1 and part 2 will comprise of 3-treatment periods (TP) where Part 1, will assess BA, of pediatric TRIUMEQ dispersible tablets with an adult TRIUMEQ conventional tablet formulation and Part 2, will assess BA, of pediatric DTG/3TC dispersible tablets with adult DTG and 3TC conventional tablets formulation. Total duration of study is 9-weeks and will be conducted in approximately 36 subjects. The 2-parts, may be run in parallel as they are independent of each other. TRIUMEQ is a registered trademark of GlaxoSmithKline group of companies.
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
盲法说明
This is an open-label study in healthy volunteers.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Between 18 and 65 years of age, inclusive, at the time of signing the informed consent.
- •Healthy subjects as determined by the investigator or medically qualified designee based on a medical evaluation, including medical history, physical examination, laboratory tests, and cardiac evaluation (history and ECG).
- •Body weight >=50 kilogram (kg) for males and >=45 kg for females and body mass index (BMI) within the range 18.5 - 31.0 kilogram per square meter (kg/m^2) (inclusive).
- •Male and female subjects where the male subjects must agree to use contraception during the TP and for at least 2 weeks plus an additional 90 days (a spermatogenesis cycle) after the last dose of study treatment and refrain from donating sperm during this period. For the female subjects, female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin [hCG] test), not lactating, and at least 1 of the following conditions applies: Female with non-reproductive potential, defined as Premenopausal females with one of the following like documented tubal ligation, documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, documented hysterectomy, documented bilateral oophorectomy, the Postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone and estradiol levels consistent with menopause. Females on hormone replacement therapy (HRT), and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment; Females with reproductive potential and agrees to follow one of the options for avoiding pregnancy in females of reproductive potential, from 30 days prior to the first dose of study medication and until 2 weeks after dosing with study medication and completion of the follow-up visit; the investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception; All female subjects participating in the study should be counselled on safer sexual practices including the use and benefit/risk of effective barrier methods (e.g., male condom) and on the risk of human immune virus (HIV) transmission to an uninfected partner.
- •Subjects capable of giving signed informed consent.
- •For participation in Part 1, documentation that the subject is negative for the human leukocyte antigen (HLA)-B*5701 allele.
排除标准
- •The medical conditions included where ALT and bilirubin >1.5 × upper limit of normal (ULN) (isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin < =35%).
- •Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- •Exclusion criteria for screening ECG (a single repeat is allowed for eligibility determination) where the heart rate for the male subjects be <45 and >100 beats per minute (bpm) and that for females be < 50 and > 100 bpm; the PR interval for both be < 120 and > 220 millisecond (msec); the QRS interval be < 70 and > 120 msec and the corrected Q-T interval (QTc) obtained using the Fridericia's formula (QTcF) be >450 msec ; ECG with evidence of previous myocardial infarction (does not include ST segment changes associated with repolarization; any conduction abnormality (including but not specific to left or right complete bundle branch block, atrioventricular block [2nd degree or higher], Wolf-Parkinson-White syndrome); Sinus pauses > 3 seconds; any significant arrhythmia which, in the opinion of the principal investigator or ViiV/GlaxoSmithKline (GSK) medical monitor, will interfere with the safety of the individual subject; non-sustained or sustained ventricular tachycardia (3 consecutive ventricular ectopic beats).
- •Subjects with use of prior or concomitant therapy who are unable to refrain from the use of prescription (e.g., dofetilide) or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and ViiV Healthcare Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
- •History of regular alcohol consumption within 6 months of the study, defined as an average weekly intake of >14 drinks for males or > 7 drinks for females. One drink is equivalent to 12 gram of alcohol: 12 ounces (360 milliliter [mL]) of beer, 5 ounces (150 mL) of wine, or 1.5 ounces (45 mL) of 80 proof distilled spirits.
- •Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 1 month prior to screening.
- •Contraindications like history of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates their participation. The subject has participated in a clinical trial and has received an investigational product (IP) within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the IP (whichever is longer).
- •The subject has participated in a clinical trial and has received an IP within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the IP (whichever is longer).
- •Creatinine clearance (CrCL) < 90 mL per minute.
- •Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
- •A positive pre-study drug/alcohol/cotinine screen.
- •A positive test for HIV antibody.
- •Where participation in the study would result in donation of blood or blood product in excess of 500 mL within 60 days.
- •Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
研究组 & 干预措施
Subjects with treatment sequence ABC
The subjects in Part 1 of the study, will receive a single dose of treatment A= adult TRIUMEQ (DTG 50 mg/ABC 600 mg/3TC 300 mg, 1 conventional tablet) administered as direct-to-mouth, in TP1; treatment B=Pediatric TRIUMEQ (DTG 5 mg/ABC 60 mg/3TC 30 mg, 10 dispersible tablets) administered as a dispersion and taken immediately in TP2; and treatment C=Pediatric TRIUMEQ (DTG 5 mg/ABC 60 mg/3TC 30 mg, 10 dispersible tablets) administered as direct-to-mouth in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.
干预措施: Treatment A (Drug)
Subjects with treatment sequence ABC
The subjects in Part 1 of the study, will receive a single dose of treatment A= adult TRIUMEQ (DTG 50 mg/ABC 600 mg/3TC 300 mg, 1 conventional tablet) administered as direct-to-mouth, in TP1; treatment B=Pediatric TRIUMEQ (DTG 5 mg/ABC 60 mg/3TC 30 mg, 10 dispersible tablets) administered as a dispersion and taken immediately in TP2; and treatment C=Pediatric TRIUMEQ (DTG 5 mg/ABC 60 mg/3TC 30 mg, 10 dispersible tablets) administered as direct-to-mouth in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.
干预措施: Treatment B (Drug)
Subjects with treatment sequence ABC
The subjects in Part 1 of the study, will receive a single dose of treatment A= adult TRIUMEQ (DTG 50 mg/ABC 600 mg/3TC 300 mg, 1 conventional tablet) administered as direct-to-mouth, in TP1; treatment B=Pediatric TRIUMEQ (DTG 5 mg/ABC 60 mg/3TC 30 mg, 10 dispersible tablets) administered as a dispersion and taken immediately in TP2; and treatment C=Pediatric TRIUMEQ (DTG 5 mg/ABC 60 mg/3TC 30 mg, 10 dispersible tablets) administered as direct-to-mouth in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.
干预措施: Treatment C (Drug)
Subjects with treatment sequence BCA
The subjects in Part 1 of the study, will receive treatment B in TP1, treatment C in TP2 and treatment A in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.
干预措施: Treatment A (Drug)
Subjects with treatment sequence BCA
The subjects in Part 1 of the study, will receive treatment B in TP1, treatment C in TP2 and treatment A in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.
干预措施: Treatment B (Drug)
Subjects with treatment sequence BCA
The subjects in Part 1 of the study, will receive treatment B in TP1, treatment C in TP2 and treatment A in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.
干预措施: Treatment C (Drug)
Subjects with treatment sequence CAB
The subjects in Part 1 of the study will receive a single dose each of, treatment C in TP1, treatment A in TP2 and treatment B in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.
干预措施: Treatment A (Drug)
Subjects with treatment sequence CAB
The subjects in Part 1 of the study will receive a single dose each of, treatment C in TP1, treatment A in TP2 and treatment B in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.
干预措施: Treatment B (Drug)
Subjects with treatment sequence CAB
The subjects in Part 1 of the study will receive a single dose each of, treatment C in TP1, treatment A in TP2 and treatment B in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.
干预措施: Treatment C (Drug)
Subjects with treatment sequence ACB
The subjects in Part 1 of the study will receive, treatment A in TP1, treatment C in TP2 and treatment B in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.
干预措施: Treatment A (Drug)
Subjects with treatment sequence ACB
The subjects in Part 1 of the study will receive, treatment A in TP1, treatment C in TP2 and treatment B in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.
干预措施: Treatment B (Drug)
Subjects with treatment sequence ACB
The subjects in Part 1 of the study will receive, treatment A in TP1, treatment C in TP2 and treatment B in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.
干预措施: Treatment C (Drug)
Subjects with treatment sequence BAC
The subjects in Part 1 of the study will receive a single dose each of, treatment B in TP1, treatment A in TP2 and treatment C in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.
干预措施: Treatment A (Drug)
Subjects with treatment sequence BAC
The subjects in Part 1 of the study will receive a single dose each of, treatment B in TP1, treatment A in TP2 and treatment C in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.
干预措施: Treatment B (Drug)
Subjects with treatment sequence BAC
The subjects in Part 1 of the study will receive a single dose each of, treatment B in TP1, treatment A in TP2 and treatment C in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.
干预措施: Treatment C (Drug)
Subjects with treatment sequence CBA
The subjects in Part 1 of the study will receive a single dose each of, treatment C in TP1, treatment B in TP2 and treatment A in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.
干预措施: Treatment A (Drug)
Subjects with treatment sequence CBA
The subjects in Part 1 of the study will receive a single dose each of, treatment C in TP1, treatment B in TP2 and treatment A in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.
干预措施: Treatment B (Drug)
Subjects with treatment sequence CBA
The subjects in Part 1 of the study will receive a single dose each of, treatment C in TP1, treatment B in TP2 and treatment A in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.
干预措施: Treatment C (Drug)
Subjects with treatment sequence DEF
The subjects in Part 2 of the study, will receive a single dose of treatment D= Adult DTG (50 mg, 1 conventional tablet) and adult 3TC (300 mg, 1 conventional tablet) administered as direct-to-mouth, in TP1; treatment E= Pediatric DTG/3TC (DTG 5 mg/3TC 30 mg, 10 dispersible tablets) administered as a dispersion and taken immediately in TP2; and treatment F= Pediatric DTG/3TC (DTG 5 mg/3TC 30 mg, 10 dispersible tablets) administered as direct-to-mouth in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.
干预措施: Treatment D (Drug)
Subjects with treatment sequence DEF
The subjects in Part 2 of the study, will receive a single dose of treatment D= Adult DTG (50 mg, 1 conventional tablet) and adult 3TC (300 mg, 1 conventional tablet) administered as direct-to-mouth, in TP1; treatment E= Pediatric DTG/3TC (DTG 5 mg/3TC 30 mg, 10 dispersible tablets) administered as a dispersion and taken immediately in TP2; and treatment F= Pediatric DTG/3TC (DTG 5 mg/3TC 30 mg, 10 dispersible tablets) administered as direct-to-mouth in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.
干预措施: Treatment E (Drug)
Subjects with treatment sequence DEF
The subjects in Part 2 of the study, will receive a single dose of treatment D= Adult DTG (50 mg, 1 conventional tablet) and adult 3TC (300 mg, 1 conventional tablet) administered as direct-to-mouth, in TP1; treatment E= Pediatric DTG/3TC (DTG 5 mg/3TC 30 mg, 10 dispersible tablets) administered as a dispersion and taken immediately in TP2; and treatment F= Pediatric DTG/3TC (DTG 5 mg/3TC 30 mg, 10 dispersible tablets) administered as direct-to-mouth in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.
干预措施: Treatment F (Drug)
Subjects with treatment sequence EFD
The subjects in Part 2 of the study, will receive a single dose respectively of treatment E in TP1, treatment F in TP2 and treatment D in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.
干预措施: Treatment D (Drug)
Subjects with treatment sequence EFD
The subjects in Part 2 of the study, will receive a single dose respectively of treatment E in TP1, treatment F in TP2 and treatment D in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.
干预措施: Treatment E (Drug)
Subjects with treatment sequence EFD
The subjects in Part 2 of the study, will receive a single dose respectively of treatment E in TP1, treatment F in TP2 and treatment D in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.
干预措施: Treatment F (Drug)
Subjects with treatment sequence FDE
The subjects in Part 2 of the study, will receive a single dose of treatment F in TP1, treatment D in TP2 and treatment E in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.
干预措施: Treatment D (Drug)
Subjects with treatment sequence FDE
The subjects in Part 2 of the study, will receive a single dose of treatment F in TP1, treatment D in TP2 and treatment E in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.
干预措施: Treatment E (Drug)
Subjects with treatment sequence FDE
The subjects in Part 2 of the study, will receive a single dose of treatment F in TP1, treatment D in TP2 and treatment E in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.
干预措施: Treatment F (Drug)
Subjects with treatment sequence DFE
The subjects in Part 2 of the study, will receive a single dose of treatment D in TP1, treatment F in TP2 and treatment E in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.
干预措施: Treatment D (Drug)
Subjects with treatment sequence DFE
The subjects in Part 2 of the study, will receive a single dose of treatment D in TP1, treatment F in TP2 and treatment E in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.
干预措施: Treatment E (Drug)
Subjects with treatment sequence DFE
The subjects in Part 2 of the study, will receive a single dose of treatment D in TP1, treatment F in TP2 and treatment E in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.
干预措施: Treatment F (Drug)
Subjects with treatment sequence EDF
The subjects in Part 2 of the study, will receive a single dose of treatment E in TP1, treatment D in TP2 and treatment F in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.
干预措施: Treatment D (Drug)
Subjects with treatment sequence FED
The subjects in Part 2 of the study, will receive a single dose of treatment F in TP1, treatment E in TP2 and treatment D in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.
干预措施: Treatment F (Drug)
Subjects with treatment sequence EDF
The subjects in Part 2 of the study, will receive a single dose of treatment E in TP1, treatment D in TP2 and treatment F in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.
干预措施: Treatment E (Drug)
Subjects with treatment sequence EDF
The subjects in Part 2 of the study, will receive a single dose of treatment E in TP1, treatment D in TP2 and treatment F in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.
干预措施: Treatment F (Drug)
Subjects with treatment sequence FED
The subjects in Part 2 of the study, will receive a single dose of treatment F in TP1, treatment E in TP2 and treatment D in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours.
干预措施: Treatment D (Drug)
结局指标
主要结局
Area Under the Plasma Concentration-time Curve (AUC) From Time of Dose Extrapolated to Infinity (AUC[0-inf]) in Part 1 of DTG
时间窗: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate pharmacokinetic (PK) parameters of DTG in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. PK population comprised of participants in the all participants population (participants who took at least 1 dose of study medication) for whom PK sample was obtained and who had evaluable PK assay results. Statistics has been presented on geometric least square (LS) means.
AUC From Time of Dose to Last Measurable Concentration (AUC[0-t]) in Part 1 of DTG
时间窗: Pre-dose,15 and 30 minutes,1 ,1.5 ,2 ,2.5 ,3 ,4 ,5 ,6 ,8 ,12 ,16 ,24 ,48 and 72 hours post-dose of each treatment period
Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of DTG in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Statistics has been presented on geometric LS means.
Maximum Observed Concentration (Cmax) in Part 1 of DTG in Plasma
时间窗: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of DTG in Part 1. PK analysis was conducted using standard non-compartmental methods. Statistics has been presented on geometric LS means.
AUC(0-inf) in Part 1 of ABC
时间窗: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of ABC in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Statistics has been presented on geometric LS means.
AUC(0-t) in Part 1 of ABC
时间窗: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of ABC in Part 1. PK analysis was conducted using standard non-compartmental methods. Statistics has been presented on geometric LS means.
Cmax in Part 1 of ABC in Plasma
时间窗: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of ABC in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Statistics has been presented on geometric LS means.
AUC(0-inf) in Part 1 of 3TC
时间窗: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of 3TC in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Statistics has been presented on geometric LS means.
AUC (0-t) in Part 1 of 3TC
时间窗: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of 3TC in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Statistics has been presented on geometric LS means.
Cmax in Part 1 of 3TC
时间窗: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of 3TC in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Statistics has been presented on geometric LS means
AUC(0-inf) in Part 2 of DTG in Plasma
时间窗: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of DTG in Part 2. PK analysis was conducted using standard non-compartmental methods. Statistics has been presented on geometric LS means.
AUC(0-t) in Part 2 of DTG
时间窗: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of DTG in Part 2. PK analysis was conducted using standard non-compartmental methods. Statistics has been presented on geometric LS means.
Cmax in Part 2 of DTG in Plasma
时间窗: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of DTG in Part 1. PK analysis was conducted using standard non-compartmental methods. Statistics has been presented on geometric LS means.
AUC(0-inf) in Part 2 of 3TC
时间窗: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of 3TC in Part 2. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Statistics has been presented on geometric LS means.
AUC(0-t) in Part 2 of 3TC
时间窗: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of 3TC in Part 2. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Statistics has been presented on geometric LS means.
Cmax in Part 2 of 3TC
时间窗: Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period
Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of 3TC in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Statistics has been presented on geometric LS means.
次要结局
- AUC From Time of Dose to 24 Hours (AUC[0-24]) of DTG in Part 1(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 and 24 hours post-dose of each treatment period)
- Time to Maximum Concentration (Tmax) of DTG in Plasma in Part 1(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period)
- Time of Last Quantifiable Concentration (Tlast) of DTG in Part 1(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period)
- Apparent Oral Clearance (CL/F) of DTG in Plasma in Part 1(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period)
- Apparent Volume of Distribution (Vz/F) of DTG in Part 1(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period)
- Observed Concentration at 24 Hours Postdose (C24) of DTG in Plasma in Part 1(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 and 24 hours post-dose of each treatment period)
- Last Observed Quantifiable Concentration (Ct) of DTG in Plasma in Part 1(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period)
- Terminal Elimination Phase Half-life (t½) of DTG in Plasma in Part 1(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period)
- Lag Time for Absorption (Tlag) of DTG in Part 1(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period)
- AUC(0-24) of ABC in Plasma in Part 1(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 and 24 hours post-dose of each treatment period)
- Tmax of ABC in Plasma in Part 1(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period)
- Tlast of ABC in Part 1(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period)
- CL/F of ABC in Plasma in Part 1(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period)
- Vz/F of ABC in Part 1(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period)
- C24 of ABC in Plasma in Part 1(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 and 24 hours post-dose of each treatment period)
- Ct of ABC in Plasma in Part 1(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period)
- T½ of ABC in Plasma in Part 1(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period)
- AUC(0-24) of 3TC in Plasma in Part 1(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 and 24 hours post-dose of each treatment period)
- Tmax of 3TC in Part 1(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period)
- Tlast of 3TC in Plasma in Part 1(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period)
- CL/F of 3TC in Plasma in Part 1(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period)
- Vz/F of 3TC in Plasma in Part 1(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period)
- C24 of 3TC in Plasma in Part 1(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 and 24 hours post-dose of each treatment period)
- Ct of 3TC in Plasma in Part 1(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period)
- T½ of 3TC in Plasma in Part 1(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period)
- AUC (0-24) of DTG in Plasma in Part 2(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 and 24 hours post-dose of each treatment period)
- Tmax of DTG in Plasma in Part 2(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period)
- Tlast of DTG in Plasma in Part 2(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period)
- CL/F of DTG in Plasma in Part 2(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period)
- Vz/F of DTG in Plasma in Part 2(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period)
- C24 of DTG in Plasma in Part 2(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 and 24 hours post-dose of each treatment period)
- Ct of DTG in Plasma in Part 2(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period)
- T½ of DTG in Plasma in Part 2(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period)
- Tlag of DTG in Plasma in Part 2(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period)
- AUC (0-24) of 3TC in Plasma in Part 2(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 and 24 hours post-dose of each treatment period)
- Tmax of 3TC in Plasma in Part 2(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period)
- Tlast of 3TC in Plasma in Part 2(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period)
- CL/F of 3TC in Plasma in Part 2(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period)
- Vz/F of 3TC in Plasma in Part 2(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period)
- C24 of 3TC in Plasma in Part 2(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 and 24 hours post-dose of each treatment period)
- Ct of 3TC in Plasma in Part 2(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period)
- T½ of 3TC in Plasma in Part 2(Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period)
- Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) in Part 1(Up to Day 33)
- Number of Participants With AEs and Serious Adverse Events SAEs in Part 2(Up to Day 33)
- Absolute Values for Clinical Chemistry Parameters Measured in Part 1: Glucose, Calcium, Potassium, Sodium and Urea(Day 2 of each treatment period)
- Absolute Values for Clinical Chemistry Parameters Measured in Part 1: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotranferase (AST) and Creatinine Phosphokinase (CPK)(Day 2 of each treatment period)
- Absolute Values for Clinical Chemistry Parameters Measured in Part 1: Albumin and Protein(Day 2 of each treatment period)
- Absolute Values for Clinical Chemistry Parameters Measured in Part 1: Bilirubin, Creatinine and Direct Bilirubin(Day 2 of each treatment period)
- Absolute Values for Clinical Chemistry Parameters Measured in Part 2: Glucose, Calcium, Potassium, Sodium and Urea(Day 2 of each treatment period)
- Absolute Values for Clinical Chemistry Parameters Measured in Part 2: ALT, ALP, AST and CPK(Day 2 of each treatment period)
- Absolute Values for Clinical Chemistry Parameters Measured in Part 2: Albumin and Protein(Day 2 of each treatment period)
- Absolute Values for Clinical Chemistry Parameters Measured in Part 2: Bilirubin, Creatinine and Direct Bilirubin(Day 2 of each treatment period)
- Change From Baseline in Clinical Chemistry Parameters Measured in Part 1: Glucose, Calcium, Potassium, Sodium and Urea(Baseline (Day -1) and Day 2)
- Change From Baseline in Clinical Chemistry Parameters Measured in Part 1: ALT, ALP, AST and CPK(Baseline (Day -1) and Day 2)
- Change From Baseline in Clinical Chemistry Parameters Measured in Part 1: Albumin and Protein(Baseline (Day -1) and Day 2)
- Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes and Platelets in Part 1(Day 2 of each treatment period)
- Absolute Values for Erythrocyte Mean Corpuscular Hemoglobin in Part 2(Day 2 of each treatment period)
- Absolute Values for Erythrocyte Mean Corpuscular Volume in Part 2(Day 2 of each treatment period)
- Absolute Values for Erythrocytes in Part 2(Day 2 of each treatment period)
- Absolute Values for Hemocrit in Part 2(Day 2 of each treatment period)
- Change From Baseline in Clinical Chemistry Parameters Measured in Part 1: Bilirubin, Creatinine and Direct Bilirubin(Baseline (Day -1) and Day 2)
- Change From Baseline in Clinical Chemistry Parameters Measured in Part 2: ALT, ALP, AST and CPK(Baseline (Day -1) and Day 2)
- Change From Baseline in Clinical Chemistry Parameters Measured in Part 2: Bilirubin, Creatinine and Direct Bilirubin(Baseline (Day -1) and Day 2)
- Absolute Values for Erythrocytes in Part 1(Day 2 of each treatment period)
- Absolute Values for Hemoglobin in Part 1(Day 2 of each treatment period)
- Change From Baseline in Clinical Chemistry Parameters Measured in Part 2: Glucose, Calcium, Potassium, Sodium and Urea(Baseline (Day -1) and Day 2)
- Absolute Values for Erythrocyte Mean Corpuscular Hemoglobin in Part 1(Day 2 of each treatment period)
- Change From Baseline in Clinical Chemistry Parameters Measured in Part 2: Albumin and Protein(Baseline (Day -1) and Day 2)
- Absolute Values for Hematology Parameters Including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes and Platelets in Part 2(Day 2 of each treatment period)
- Absolute Values for Hemocrit in Part 1(Day 2 of each treatment period)
- Absolute Values for Hemoglobin in Part 2(Day 2 of each treatment period)
- Change From Baseline Values for Hematology Parameters Including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes and Platelets in Part 1(Baseline (Day -1) and Day 2)
- Change From Baseline Values for Erythrocyte Mean Corpuscular Hemoglobin in Part 1(Baseline (Day -1) and Day 2)
- Change From Baseline Values for Erythrocyte Mean Corpuscular Volume in Part 1(Baseline (Day -1) and Day 2)
- Change From Baseline Values for Erythrocytes in Part 1(Baseline (Day -1) and Day 2)
- Change From Baseline Values for Hemocrit in Part 1(Baseline (Day -1) and Day 2)
- Change From Baseline Values for Hemoglobin in Part 1(Baseline (Day -1) and Day 2)
- Change From Baseline Values for Hematology Parameters Including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes and Platelets in Part 2(Baseline (Day -1) and Day 2)
- Change From Baseline Values for Erythrocyte Mean Corpuscular Hemoglobin in Part 2(Baseline (Day -1) and Day 2)
- Change From Baseline Values for Erythrocyte Mean Corpuscular Volume in Part 2(Baseline (Day -1) and Day 2)
- Change From Baseline Values for Erythrocytes in Part 2(Baseline (Day -1) and Day 2)
- Change From Baseline Values for Hemocrit in Part 2(Baseline (Day -1) and Day 2)
- Change From Baseline Values for Hemoglobin in Part 2(Baseline (Day -1) and Day 2)
- Number of Participants With Abnormal Urinalysis Parameter in Part 1(Up to Day 33)
- Number of Participants With Urine Potential of Hydrogen (pH)-Part 1(Up to Day 33)
- Number of Participants With Abnormal Urinalysis Parameter in Part 2(Up to Day 33)
- Number of Participants With Urine Potential of Hydrogen (pH)-Part 2(Up to Day 33)
- Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Part 1(Baseline (Day -1))
- Number of Participants With Abnormal ECG Findings in Part 2(Baseline (Day -1))
- Absolute Values for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) of Part 1(Day 1 at 4 hours post intervention and Day 2 of each treatment period)
- Absolute Values for Pulse Rate in Part 1(Day 1 at 4 hours post intervention and Day 2 of each treatment period)
- Absolute Values for Temperature in Part 1(Day 1 at 4 hours post intervention dose and Day 2 of each treatment period)
- Absolute Values for SBP and DBP of Part 2(Day 1 at 4 hours post intervention dose and Day 2 of each treatment period)
- Absolute Values for Pulse Rate in Part 2(Day 1 at 4 hours post intervention dose and Day 2 of each treatment period)
- Absolute Values for Temperature in Part 2(Day 1 at 4 hours post intervention dose and Day 2 of each treatment period)
- Change From Baseline in SBP and DBP of Part 1(Baseline (Day 1, pre-dose), Day 1- 4 hours and Day 2)
- Change From Baseline in Pulse Rate of Part 1(Baseline (Day 1, pre-dose), Day 1- 4 hours and Day 2)
- Change From Baseline in Temperature of Part 1(Baseline (Day 1, pre-dose), Day 1- 4 hours and Day 2)
- Change From Baseline in SBP and DBP of Part 2(Baseline (Day 1, pre-dose), Day 1- 4 hours and Day 2)
- Change From Baseline in Pulse Rate in Part 2(Baseline (Day 1, pre-dose), Day 1- 4 hours and Day 2)
- Change From Baseline in Temperature in Part 2(Baseline (Day 1, pre-dose), Day 1- 4 hours and Day 2)