A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group Trial to Evaluate the Safety and Efficacy of Delamanid (OPC-67683) Administered Orally as 200 mg Total Daily Dose for Six Months in Patients With Pulmonary Sputum Culture-positive, Multidrug-resistant Tuberculosis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 511
- 主要终点
- Time To Sputum Culture Conversion (SCC) During 6-Month Intensive Period Using The Mycobacteria Growth Indicator Tube (MGIT) System
研究概览
简要总结
The purpose of this trial is to determine whether delamanid is effective in the treatment of multidrug-resistant tuberculosis (MDR TB) in combination with other MDR TB medications during 6 months of treatment.
详细描述
The primary objective of this trial is to evaluate the efficacy of delamanid administered orally as 100 milligrams (mg) twice daily (BID) for 2 months followed by 200 mg once daily (QD) for 4 months in combination with an optimized background treatment regimen (OBR) versus placebo with OBR during the 6-month Intensive Period of MDR TB treatment. Following the 6-month Intensive Period, OBR was administered alone during the Continuation Period for 12 to 18 months (from Month 7 up to Month 24). The trial also included a post-treatment follow-up period of 6 to 12 months (Month 19 to Month 24 to the end of Month 30). OBR given throughout the study was administered as per World Health Organization (WHO) guidelines and national treatment norms.
This trial is a multicenter, randomized, double-blind, stratified, placebo-controlled trial that was conducted globally in 2 parallel groups at 17 sites in 7 countries qualified to treat MDR TB.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 69 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provide written, informed consent
- •Current diagnosis of MDR TB
- •Chest radiograph consistent with TB
- •Able to produce sputum
- •Negative urine pregnancy test and agree to use a highly effective method of birth control and/or adequate method of contraception
排除标准
- •Allergy to any nitro-imidazoles or nitro-imidazole derivates
- •Diseases or conditions in which the use of nitro-imidazoles or nitro-imidazole derivates is contra-indicated
- •Use of disallowed medications
- •Renal impairment
- •Abnormal electrocardiogram (ECG) results
- •Cardiovascular disorders
- •Body mass index (BMI) < 16 kg/m^2
- •Karnofsky score < 50%
- •Significant metabolic, gastrointestinal, neurological, psychiatric, or endocrine diseases, active malignancy
- •Alcohol abuse
- •Pregnant, breast-feeding, or planning to conceive or father a child
- •Recent use of methadone, benzodiazepines, cocaine, amphetamine/methamphetamine, tetrahydrocannabinol, barbiturates, and opiates
- •Previous exposure to delamanid
- •Administered an investigational medicinal product (IMP) within 1 month prior to Screening (Days -21 to -2).
- •Evidence of extensively drug-resistant TB based on the definition from WHO
- •Human immunodeficiency virus (HIV) co-infection for participants screened at sites not participating in the HIV subtrial (data from the HIV subtrial will be reported separately from the Clinical Study Report for Study 242-09-213).
研究组 & 干预措施
Delamanid + OBR
In the first period of this study, known as the 6-month Intensive Period, participants were randomized to receive 100 mg delamanid orally BID (morning and evening) + OBR for 2 months, followed by 200 mg delamanid QD (every morning) + OBR for 4 months.
Following the 6-month Intensive Period, participants entered the second period of the study, known as the Continuation Period, wherein OBR was administered alone for 12 to 18 months.
OBR given throughout the study was administered as per WHO guidelines and national treatment norms.
干预措施: Delamanid + OBR (Drug)
Placebo + OBR
In the first period of this study, known as the 6-month Intensive Period, participants were randomized to receive placebo orally BID (morning and evening) + OBR for 2 months followed by placebo QD (every morning) + OBR for 4 months.
Following the 6-month Intensive Period, participants entered the second period of the study, known as the Continuation Period, wherein OBR was administered alone for 12 to 18 months.
OBR given throughout the study was administered as per WHO guidelines and national treatment norms.
干预措施: Placebo + OBR (Drug)
结局指标
主要结局
Time To Sputum Culture Conversion (SCC) During 6-Month Intensive Period Using The Mycobacteria Growth Indicator Tube (MGIT) System
时间窗: Month 6
SCC at 6 months was determined by the observation of a sputum specimen negative for growth of mycobacterium tuberculosis (MTB) using the MGIT culture system, followed by at least 1 confirmatory negative sputum culture at least 25 days after the first negative and not followed by a confirmed positive (defined as at least 2 observed positive results, not taking into account indeterminate, missing, or contaminated results). 2 specimens were collected at each visit and an algorithm in the statistical analysis plan (SAP) was used to define a single representative result. Time to SCC was then defined as the interval between the date of first dose of IMP and the date of first of 2 consecutive negative single representative time points that were at least 25 days apart. The median time in days to SCC up to Month 6 is presented.
次要结局
- Mean (Time Averaged) Area Under The Curve (AUC) Of Change From Baseline In Time To Detection (TTD) To Month 6 Using MGIT(Baseline, up to Month 6)
- Treatment Outcomes Assessed By Principal Investigators (PI)At The End Of Treatment With OBR(Month 24)
- Number of Participants Who Developed Resistance To Delamanid(Up to Month 30)
- Mean Change From Baseline In TTD Using The MGIT System(Baseline, Week 1, Week 2, Week 3, Week 24, Week 26, and Last visit (Month 18 or last visit for participants treated beyond Month 18))
- Proportion of Participants With SCC At 2 And 6 Months Using MGIT(Month 2 and Month 6)
- Proportion of Participants With Sustained SCC At Month 18, Month 24, And Month 30 Using MGIT(Month 18, Month 24, and Month 30)
- Proportion of Participants With Final Outcome At Month 30 As A Treatment Success Or Failure (Including Relapse) Using MGIT(Month 30)