A Single-Dose, Open-Label, Randomized, Replicate Crossover Pivotal Bioequivalence Study in Healthy Subjects to Assess the Bioequivalence of Darunavir 675 mg, Emtricitabine 200 mg, and Tenofovir Alafenamide 10 mg in the Presence of Cobicistat 150 mg When Administered as a Fixed Dose Combination (Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide) Compared to the Co-administration of the Separate Agents (Darunavir, Cobicistat, and Emtricitabine/Tenofovir Alafenamide), Under Fed Conditions
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Area Under the Analyte Concentration-time Curve from time Zero to Last Quantifiable time (AUC[0-last]) of Darunavir, Cobicistat, Emtricitabine and Tenofovir Alafenamide
研究概览
简要总结
The purpose of the study is to evaluate the single-dose pharmacokinetics (PK) and pivotal bioequivalence of 3 compounds Darunavir (DRV), emtricitabine (FTC), and tenofovir alafenamide (TAF) in the presence of cobicistat (COBI) when administered as an fixed dose combination (FDC) (Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide [D/C/F/TAF]) compared to the co-administration as the separate commercial formulations (DRV and F/TAF and COBI), 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
- Other
- 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
- •Must be healthy on the basis of physical examination, medical history, vital signs, and electrocardiogram (ECG) performed at screening. If there are abnormalities, 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
- •Participant must be healthy on the basis of clinical laboratory test performed at screening. 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.
- •A woman (of childbearing potential) must have a negative highly sensitive serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test, 4 days or less before dosing of the first treatment period
- •Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for participant participating in clinical studies
- •A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for at least 90 days after receiving the last dose of study drug
- •During the study and for a minimum of at least 90 days after receiving the last dose of study drug, a male participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another person (male subject should also be advised of the benefit for a female partner to use a highly effective method of contraception as condom may break or leak); must agree not to donate sperm for the purpose of reproduction.
- •Must be willing and able to adhere to the prohibitions and restrictions specified in the study protocol
排除标准
- •Has history or current clinically significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic disease, coagulation disorders (including any abnormal bleeding or blood dyscrasias), lipid abnormalities, significant pulmonary disease (including bronchospastic respiratory disease), diabetes mellitus, hepatic or renal insufficiency (for example, estimated creatinine clearance below less than [<] 90 milliliter per minute [mL/min] at screening), gastrointestinal disease (such as significant diarrhea, gastric stasis, or constipation that in the investigator's opinion could influence drug absorption or bioavailability), thyroid disease, neurologic or psychiatric disease, infection, or any other illness that the investigator considers should exclude the participant or that could interfere with the interpretation of the study results
- •Had one or more of the laboratory abnormalities at screening as outlined in the protocol by the Division of Acquired immunodeficiency syndrome (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events and in accordance with the normal ranges of the clinical laboratory
- •Clinically significant abnormalities during physical examination, vital signs, or 12 lead electrocardiogram (ECG) at screening or at admission to the study center as deemed appropriate by the investigator
- •With any history of clinically significant skin disease such as, but not limited to, dermatitis, eczema, drug rash, psoriasis, food allergy, or urticaria
- •Has a history of drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-V) criteria within 1 year before screening or positive test result(s) for alcohol and/or drugs of abuse (such as hallucinogens, barbiturates, opiates, opioids, cocaine, cannabinoids, amphetamines, methadone, benzodiazepines, methamphetamine, tetrahydrocannabinol, phencyclidine, and tricyclic antidepressants) either at screening or on Day 1 of each treatment period
研究组 & 干预措施
Treatment A
Participants will receive Treatment A (a single dose of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide [D/C/F/TAF] as one fixed dose combination [FDC] tablet under fed condition on Day 1) as per assigned treatment sequence (Treatment sequence ABBA or BAAB). A wash out period of at least 7 days will be maintained between each treatment period.
干预措施: Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide FDC (Drug)
Treatment A
Participants will receive Treatment A (a single dose of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide [D/C/F/TAF] as one fixed dose combination [FDC] tablet under fed condition on Day 1) as per assigned treatment sequence (Treatment sequence ABBA or BAAB). A wash out period of at least 7 days will be maintained between each treatment period.
干预措施: Darunavir (Drug)
Treatment A
Participants will receive Treatment A (a single dose of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide [D/C/F/TAF] as one fixed dose combination [FDC] tablet under fed condition on Day 1) as per assigned treatment sequence (Treatment sequence ABBA or BAAB). A wash out period of at least 7 days will be maintained between each treatment period.
干预措施: Emtricitabine/Tenofovir Alafenamide (Drug)
Treatment A
Participants will receive Treatment A (a single dose of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide [D/C/F/TAF] as one fixed dose combination [FDC] tablet under fed condition on Day 1) as per assigned treatment sequence (Treatment sequence ABBA or BAAB). A wash out period of at least 7 days will be maintained between each treatment period.
干预措施: Cobicistat (Drug)
Treatment B
Participants will receive Treatment B (a single dose of Darunavir [DRV], Emtricitabine/Tenofovir Alafenamide [F/TAF] and Cobicistat [COB] tablet under fed condition on Day 1) as per assigned treatment sequence (Treatment sequence ABBA or BAAB). A washout period of at least 7 days will be maintained between each treatment period.
干预措施: Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide FDC (Drug)
Treatment B
Participants will receive Treatment B (a single dose of Darunavir [DRV], Emtricitabine/Tenofovir Alafenamide [F/TAF] and Cobicistat [COB] tablet under fed condition on Day 1) as per assigned treatment sequence (Treatment sequence ABBA or BAAB). A washout period of at least 7 days will be maintained between each treatment period.
干预措施: Darunavir (Drug)
Treatment B
Participants will receive Treatment B (a single dose of Darunavir [DRV], Emtricitabine/Tenofovir Alafenamide [F/TAF] and Cobicistat [COB] tablet under fed condition on Day 1) as per assigned treatment sequence (Treatment sequence ABBA or BAAB). A washout period of at least 7 days will be maintained between each treatment period.
干预措施: Emtricitabine/Tenofovir Alafenamide (Drug)
Treatment B
Participants will receive Treatment B (a single dose of Darunavir [DRV], Emtricitabine/Tenofovir Alafenamide [F/TAF] and Cobicistat [COB] tablet under fed condition on Day 1) as per assigned treatment sequence (Treatment sequence ABBA or BAAB). A washout period of at least 7 days will be maintained between each treatment period.
干预措施: Cobicistat (Drug)
结局指标
主要结局
Area Under the Analyte Concentration-time Curve from time Zero to Last Quantifiable time (AUC[0-last]) of Darunavir, Cobicistat, Emtricitabine and Tenofovir Alafenamide
时间窗: Up to 72 hours post-dose
AUC(0-last) is the area under the analyte concentration-time curve of from time 0 to the time of the last measurable (non-below quantification limit \[non-BQL\]) concentration, calculated by linear-linear trapezoidal summation.
Maximum Observed Analyte Concentration (Cmax) of Darunavir, Cobicistat, Emtricitabine and Tenofovir Alafenamide
时间窗: Up to 72 hours post-dose
Cmax is the maximum observed analyte concentration.
次要结局
- Number of Participants with Adverse Events(From signing of the Informed consent form (ICF) till the last study-related activity (up to 10 weeks))
- Cmax of Cobicistat(Up to 72 hours post-dose)
- Area Under the Analyte Concentration-time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Darunavir, Cobicistat, Emtricitabine and Tenofovir Alafenamide(Up to 72 hours post-dose)
- AUC(0-last) of Cobicistat(Up to 72 hours post-dose)