TASK-002: Bioequivalence of Bedaquiline 400mg Administered in Crushed Form Compared to Tablet Form in Healthy Male and Female Adults Under Fed Conditions (BDQ Crush Study)
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Bioequivalence of bedaquiline 4 x 100mg given to healthy adult males and females orally in tablet form compared to crushed form
研究概览
简要总结
This is a randomized, open-label, cross-over study comparing the bioequivalence of bedaquiline administered in whole tablet form versus bedaquiline administered in crushed (experimental) form in healthy adult volunteers.
详细描述
This is a randomized, open-label, cross-over, bioequivalence study with two single treatment periods, separated by a 14-day wash-out period, conducted among 24 healthy adult males and females, who receive 400mg (4 x 100mg) bedaquiline orally in one of two sequences: either first in whole tablet form and second in crushed (experimental) form, or vice versa under fed conditions. The bioequivalence evaluation will be based on primary pharmacokinetic (pk) parameters affecting the extent of absorption, i.e., the bioavailability. If bioequivalence is not shown, the knowledge about the differences in bioavailability between whole and crushed tablets will be used for assessing the need of dose adjustment in children receiving the crushed form.
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
- •Written informed consent, including HIV testing
- •Male or female between 18 and 55 years of age inclusive
- •Body weight (in light clothing and with no shoes) between 40 and 90 kg, inclusive
- •In the opinion of the investigator, able to comply with the requirements of the protocol e.g. able to attend all visits for PK analysis
- •Be of non-childbearing potential or using effective methods of birth control
排除标准
- •Known or suspected hypersensitivity or intolerance to bedaquiline or any other constituents of the study drug, i.e. lactose
- •A history or clinical evidence of any clinically significant cardiac condition including but not limited to congenital long QT syndrome, Torsades de Pointes, bradyarrhythmias
- •Uncontrolled cardiac dysrhythmias
- •Severe hepatic impairment (Child Pugh C)
- •History, symptoms or signs of heart failure
- •History, symptoms or signs of hypothyroidism, whether currently controlled or uncontrolled
- •Any other serious uncontrolled medical condition or clinically significant abnormality, which, in the opinion of the investigator, might compromise the safety of the subject or which might interfere with the study.
- •Evidence of clinically significant (as judged by the investigator), metabolic, gastrointestinal, cardiovascular, musculoskeletal, ophthalmological, pulmonary, neurological, psychiatric or endocrine diseases, malignancy, or other abnormalities.
- •Concomitant use of medicines known to prolong the QTc interval, or use of CYP3A4 inducers/inhibitors including but not limited to, carbamazepine, phenytoin, St. John's wort, ciprofloxacin, erythromycin, clarithromycin, fluconazole, ketoconazole, ritonavir or other anti-retroviral medications, fluoroquinolones and clofazamine.
- •HIV positive, already known or as per HIV test done at screening.
- •Hepatitis B or C positive
- •QTc prolongation as per ECG with a QTcF of >450msec or any other significant finding on the ECG as per the investigator
- •Receipt of any study drug within the past 3 months.
- •Scheduled to receive any other investigational drug during the course of the study.
- •Known or suspected, current or history of within the past 2 years, alcohol or drug abuse, that is, in the opinion of the Investigator, sufficient to compromise the safety or cooperation of the volunteer.
- •Evidence or suspicion of active TB or documented recent (within the last year) household contact with an infectious TB case.
- •The following toxicities at screening as defined by the DAIDS toxicity table (November 2014)
- •aspartate aminotransferase (AST) grade 3 (≥3.0 x ULN)
- •alanine aminotransferase (ALT) grade 3 (≥3.0 x ULN)
研究组 & 干预措施
Sequence 1
Bedaquiline 4 x 100mg administered in a whole tablet form, followed by bedaquiline 4 x 100mg administered in crushed form as a once only oral dose
干预措施: bedaquiline (Drug)
Sequence 2
Bedaquiline 4x 100mg administered in crushed form, followed by bedaquiline 4 x 100mg administered in a whole tablet form, as a once only oral dose
干预措施: bedaquiline (Drug)
结局指标
主要结局
Bioequivalence of bedaquiline 4 x 100mg given to healthy adult males and females orally in tablet form compared to crushed form
时间窗: Two single treatment sequences, separated by a 14-day wash-out period
The bioequivalence evaluation will be based on primary PK parameters affecting the extent of absorption, i.e. the bioavailability.
次要结局
未报告次要终点