Randomized Single Dose Multiple Crossover Relative Bioavailability Trial of New Tablet Formulations and Suspension Formulation Compared to Current (1B) Formulation of BILR 355 BS in Healthy Male Volunteer Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 88
- 主要终点
- Cmax (maximum measured concentration of analyte in plasma)
研究概览
简要总结
- To investigate the relative bioavailability (BA) of improved tablet formulation candidates to determine which formulation will be developed for use in late Phase II and Phase III clinical trials
- To investigate the relative BA of the pediatric suspension, compared to the current 1B formulation
- To investigate the bioequivalence (BE) of BILR 355 BS in two tablet strengths; three 25mg tablets vs. one 75 mg tablet, current 1B formulation
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 60 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy HIV negative adult male volunteers
- •Age ≥18 and ≤ 60 years
- •BMI ≥18.5 and BMI ≤29.9 kg/m2
- •Ability to give signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local regulations
排除标准
- •Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
- •Surgery of gastrointestinal tract (except appendectomy)
- •Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
- •History of relevant orthostatic hypotension, fainting spells or blackouts
- •Chronic or relevant acute infections
- •History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator
- •Intake of drugs with a long half-life (>24 hours) within at least one month prior to study drug administration and during the trial
- •Use of drugs within 10 days prior to administration or during the trial which might reasonably influence the results of the trial
- •Participation in another trial with an investigational drug within two months prior to administration or during the trial
- •Current smoker
- •Alcohol abuse (more than 60 g/day)
- •Drug abuse (positive urine test for illicit prescription or non-prescription drugs or drugs of abuse).
- •Blood donation (more than 100 mL within four weeks prior to study drug administration or during the trial)
- •Excessive physical activities (within one week prior to study drug administration or during the trial)
- •Any laboratory value outside the reference range that is of clinical relevance at screening, according to the judgment of the investigator
- •Inability to comply with dietary regimen required by the protocol
- •Infected with hepatitis B or hepatitis C viruses (defined as either being hepatitis B surface antigen, or hepatitis C antibody positive
研究组 & 干预措施
Group A
randomized sequence of current low dose formulation (3 tablets) and high dose (1 tablet) BILR 355 BS 1B formulation, separated by 14-day washout
干预措施: BILR 355 BS /1B, current low dose formulation (Drug)
Group A
randomized sequence of current low dose formulation (3 tablets) and high dose (1 tablet) BILR 355 BS 1B formulation, separated by 14-day washout
干预措施: BILR 355 BS /1B, current high dose formulation (Drug)
Group A
randomized sequence of current low dose formulation (3 tablets) and high dose (1 tablet) BILR 355 BS 1B formulation, separated by 14-day washout
干预措施: Ritonavir (Drug)
Group B
randomized sequence of BILR 355 BS (JM) + SDS formulation low dose (2 tablets) ,BILR 355 BS (HM) + SDS formulation low dose (2 tablets), BILR 355 BS high dose 1B formulation (4 low dose tablets), separated by 14-day washout
干预措施: BILR 355 BS /1B, current low dose formulation (Drug)
Group B
randomized sequence of BILR 355 BS (JM) + SDS formulation low dose (2 tablets) ,BILR 355 BS (HM) + SDS formulation low dose (2 tablets), BILR 355 BS high dose 1B formulation (4 low dose tablets), separated by 14-day washout
干预措施: BILR 355 BS - Jet Milled (JM) + Sodium Dodecyl Sulfate (SDS) formulation (Drug)
Group B
randomized sequence of BILR 355 BS (JM) + SDS formulation low dose (2 tablets) ,BILR 355 BS (HM) + SDS formulation low dose (2 tablets), BILR 355 BS high dose 1B formulation (4 low dose tablets), separated by 14-day washout
干预措施: BILR 355 BS - Hammer Milled (HM) + Sodium Dodecyl Sulfate (SDS) formulation (Drug)
Group B
randomized sequence of BILR 355 BS (JM) + SDS formulation low dose (2 tablets) ,BILR 355 BS (HM) + SDS formulation low dose (2 tablets), BILR 355 BS high dose 1B formulation (4 low dose tablets), separated by 14-day washout
干预措施: Ritonavir (Drug)
Group C
randomized sequence of BILR 355 BS (JM) + SDS formulation high dose (4 tablets) , BILR 355 BS (JM) + SDS formulation mid dose (3 tablets), BILR 355 BS (HM) + SDS formulation high dose (4 tablets), separated by 14-day washout
干预措施: BILR 355 BS - Jet Milled (JM) + Sodium Dodecyl Sulfate (SDS) formulation (Drug)
Group C
randomized sequence of BILR 355 BS (JM) + SDS formulation high dose (4 tablets) , BILR 355 BS (JM) + SDS formulation mid dose (3 tablets), BILR 355 BS (HM) + SDS formulation high dose (4 tablets), separated by 14-day washout
干预措施: BILR 355 BS - Hammer Milled (HM) + Sodium Dodecyl Sulfate (SDS) formulation (Drug)
Group C
randomized sequence of BILR 355 BS (JM) + SDS formulation high dose (4 tablets) , BILR 355 BS (JM) + SDS formulation mid dose (3 tablets), BILR 355 BS (HM) + SDS formulation high dose (4 tablets), separated by 14-day washout
干预措施: Ritonavir (Drug)
Group D
randomized sequence of BILR 355 BS Suspension high dose, BILR 355 BS Suspension low dose, current low dose BILR 355 BS 1B formulation (3 tablets) separated by 14-day washout
干预措施: BILR 355 BS /1B, current low dose formulation (Drug)
Group D
randomized sequence of BILR 355 BS Suspension high dose, BILR 355 BS Suspension low dose, current low dose BILR 355 BS 1B formulation (3 tablets) separated by 14-day washout
干预措施: BILR 355 BS - Suspension low dose (Drug)
Group D
randomized sequence of BILR 355 BS Suspension high dose, BILR 355 BS Suspension low dose, current low dose BILR 355 BS 1B formulation (3 tablets) separated by 14-day washout
干预措施: BILR 355 BS - Suspension high dose (Drug)
Group D
randomized sequence of BILR 355 BS Suspension high dose, BILR 355 BS Suspension low dose, current low dose BILR 355 BS 1B formulation (3 tablets) separated by 14-day washout
干预措施: Ritonavir (Drug)
结局指标
主要结局
Cmax (maximum measured concentration of analyte in plasma)
时间窗: Up to 96 hours after drug administration
AUC0-∞ (area under the concentration time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
时间窗: Up to 96 hours after drug administration
次要结局
- Number of participants with abnormal changes in clinical laboratory parameters(Up to day 43 after first drug administration)
- Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)(Up to 96 hours after drug administration)
- Number of participants with clinically significant changes in vital signs(Up to day 43 after first drug administration)
- Number of participants with Adverse Events(Up to day 43 after first drug administration)
- AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point)(Up to 96 hours after drug administration)
- tmax (time from dosing to the maximum concentration of the analyte in plasma)(Up to 96 hours after drug administration)
- λz (terminal rate constant in plasma)(Up to 96 hours after drug administration)
- t1/2 (terminal half-life of the analyte in plasma)(Up to 96 hours after drug administration)
- MRTpo (mean residence time of the analyte in the body after po administration)(Up to 96 hours after drug administration)
- CL/F (apparent clearance of the analyte in the plasma after extravascular administration)(Up to 96 hours after drug administration)