A Single-dose, Open-label, Randomized, Crossover Pivotal Bioequivalence Study in Healthy Participants to Assess the Bioequivalence of Darunavir 600 mg in the Presence of Cobicistat 90 mg When Administered as a Fixed Dose Combination Tablet (Darunavir/Cobicistat) Compared to the Co-administration of the Separate Available Formulations (Darunavir 100 mg/mL Suspension at a Dose of 600 mg and Cobicistat 90 mg Tablet), Under Fed Conditions
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Area Under the DRV Concentration-time Curve From Time Zero to Last Quantifiable Time (AUC[0-last]) of DRV
研究概览
简要总结
The purpose of this study is to evaluate the single-dose pharmacokinetic (PK) and bioequivalence of Darunavir (DRV) in the presence of Cobicistat (COBI) when administered as a DRV/COBI fixed dose combination (FDC) tablet dispersed in water compared to the co-administration of the separate available formulations (DRV suspension and COBI tablet) under fed conditions in healthy participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 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
- •Healthy on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening (results must be available on Day -1 of Treatment Period 1). If there are any abnormalities (other than those listed in inclusion criterion 12 [for blood pressure]), they must be considered not clinically relevant and this determination must be recorded in the participant's source documents and initialed by the investigator
- •Healthy on the basis of clinical laboratory tests performed at screening (results must be available on Day -1 of Treatment Period 1). If the results of the serum chemistry panel, hematology, or urinalysis are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant. This determination must be recorded in the participant's source documents and initialed by the investigator
- •All women must have a negative highly sensitive serum test (beta-human chorionic gonadotropin [beta-hCG]) 4 days or less before dosing of the first treatment period
- •A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 90 days after receiving the last dose of study intervention
- •Must sign an informed consent form (ICF) indicating that the participant understands the purpose and procedures required for the study and is willing to participate in the study
- •A woman must agree not to donate eggs (ova, oocytes) or freeze for future use for the purposes of assisted reproduction during the study and for a period of 90 days after last dose
排除标准
- •History of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, which is considered cured with minimal risk of recurrence)
- •Clinically significant abnormalities during physical examination, vital signs, or 12-lead ECG at screening or at admission to the study site as deemed appropriate by the investigator
- •Known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
- •With a history of clinically significant drug allergy such as, but not limited to, sulfonamides and penicillin's, or drug allergy diagnosed in previous studies with experimental drugs
- •With a clinically significant skin disease such as, but not limited to, dermatitis, eczema, drug rash, psoriasis, food allergy, or urticaria
- •Taken any disallowed therapies, concomitant therapy before the planned first dose of study intervention
- •Pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 90 days after the last dose of study intervention
研究组 & 干预措施
Treatment Sequence AB
Participants will receive a single oral dose of darunavir (DRV) and cobicistat (COBI) as one fixed dose combination (FDC) tablet dispersed in water (Treatment A [test]) in Treatment Period 1, followed by a single dose DRV suspension and COBI tablet (Treatment B [Reference]) in Treatment Period 2 on Day 1 of each Treatment Period under fed conditions. There will be a washout period of at least 7 days from dosing on Day 1 of each Treatment Period.
干预措施: DRV/COBI FDC (Drug)
Treatment Sequence AB
Participants will receive a single oral dose of darunavir (DRV) and cobicistat (COBI) as one fixed dose combination (FDC) tablet dispersed in water (Treatment A [test]) in Treatment Period 1, followed by a single dose DRV suspension and COBI tablet (Treatment B [Reference]) in Treatment Period 2 on Day 1 of each Treatment Period under fed conditions. There will be a washout period of at least 7 days from dosing on Day 1 of each Treatment Period.
干预措施: COBI (Drug)
Treatment Sequence AB
Participants will receive a single oral dose of darunavir (DRV) and cobicistat (COBI) as one fixed dose combination (FDC) tablet dispersed in water (Treatment A [test]) in Treatment Period 1, followed by a single dose DRV suspension and COBI tablet (Treatment B [Reference]) in Treatment Period 2 on Day 1 of each Treatment Period under fed conditions. There will be a washout period of at least 7 days from dosing on Day 1 of each Treatment Period.
干预措施: DRV (Drug)
Treatment Sequence BA
Participants will receive Treatment B in Treatment Period 1, followed by Treatment A in Treatment Period 2 on Day 1 of each Treatment Period under fed conditions. There will be a washout period of at least 7 days from dosing on Day 1 of each Treatment Period
干预措施: DRV/COBI FDC (Drug)
Treatment Sequence BA
Participants will receive Treatment B in Treatment Period 1, followed by Treatment A in Treatment Period 2 on Day 1 of each Treatment Period under fed conditions. There will be a washout period of at least 7 days from dosing on Day 1 of each Treatment Period
干预措施: COBI (Drug)
Treatment Sequence BA
Participants will receive Treatment B in Treatment Period 1, followed by Treatment A in Treatment Period 2 on Day 1 of each Treatment Period under fed conditions. There will be a washout period of at least 7 days from dosing on Day 1 of each Treatment Period
干预措施: DRV (Drug)
结局指标
主要结局
Area Under the DRV Concentration-time Curve From Time Zero to Last Quantifiable Time (AUC[0-last]) of DRV
时间窗: Pre dose, up to 72 hours post dose (up to Day 4)
AUC (0-last) is the area under the DRV concentration-time curve from time zero to the time of the last measurable (non-below quantification limit \[non-BQL\]) concentration, calculated by linear-linear trapezoidal summation.
Maximum Observed Plasma Concentration (Cmax) of Darunavir (DRV)
时间窗: Pre dose, up to 72 hours post dose (up to Day 4)
Cmax is defined as the maximum observed plasma concentration of DRV.
Area Under the DRV Concentration-time Curve from Time Zero to Infinite Time (AUC[0-infinity]) of DRV
时间窗: Pre dose, up to 72 hours post dose (up to Day 4)
AUC (0-infinity) is the area under the DRV concentration-time curve from time zero to infinite time, calculated as the sum of AUC (0-last) and C(last)/lambda(z).
次要结局
- Maximum Observed Plasma Concentration (Cmax) of Cobicistat (COBI)(Pre dose, up to 72 hours post dose (up to Day 4))
- Area Under the COBI Concentration-time Curve From Time Zero to Last Quantifiable Time (AUC[0-last]) of COBI(Pre dose, up to 72 hours post dose (up to Day 4))
- Area Under the COBI Concentration-time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of COBI(Pre dose, up to 72 hours post dose (up to Day 4))
- Number of Participants With Serious Adverse Events (SAEs)(Up to 7 weeks)
- Number of Participants with Abnormalities in Physical Examinations(Up to 7 weeks)
- Number of Participants with Abnormalities in Vital Sign Measurements(Up to 7 weeks)
- Number of Participants with Abnormalities in Clinical Laboratory Tests(Up to 7 weeks)