A Phase 2, Open-label, Randomized Controlled Trial to Assess the Safety, Bactericidal Activity, and Pharmacokinetics of Nicotinamide in Combination With Bedaquiline, Pretomanid, and Linezolid in Adults With Drug-susceptible Pulmonary Tuberculosis
试验速览
- 阶段
- 2 期
- 状态
- 暂停
- 发起方
- 入组人数
- 165
- 试验地点
- 4
- 主要终点
- Safety: TEAEs leading to NAM dose reduction
研究概览
简要总结
The purpose of this study is to determine if nicotinamide in combination with bedaquiline, pretomanid, and linezolid, is safe and effective in treating drug-susceptible pulmonary tuberculosis.
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
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-65 years at consent
- •Body weight 40-100 kg at screening
- •Written informed consent obtained
- •Newly diagnosed pulmonary TB, rifampicin- and isoniazid-sensitive
- •≥1+ AFB smear OR positive Xpert semi-quantitative result
- •Molecular confirmation of M. tuberculosis
- •Chest X-ray consistent with TB (Investigator assessment)
- •Able to spontaneously produce sputum
- •Contraception requirements met
- •Females Of Child Bearing Potential: 2 approved contraceptive methods or abstinence
- •Males: contraception or abstinence through 90 days post-dose
排除标准
- •Prior TB within 3 years, >1 prior episode, or anti-TB treatment within 60 days
- •Extrapulmonary TB (except non-significant pleural/lymph node disease)
- •Clinically significant comorbidities or substance abuse impacting safety/compliance
- •Pregnant or breastfeeding
- •HIV-positive AND any of the following:
- •Not on ART or on ART <3 months
- •CD4 <200 cells/µL
- •Viral load >200 copies/mL
- •AIDS-defining illness (other than pulmonary TB)
- •Screening lab abnormalities (protocol-defined LFTs, hematology, hepatitis B or C, HbA1c)
- •Clinically significant ECG abnormality
- •Use of prohibited concomitant medications (e.g., strong CYP3A4 modifiers, certain SSRIs)
研究组 & 干预措施
BPAL/NAM1500
Nicotinamide, bedaquiline, pretomanid, linezolid
干预措施: Bedaquiline, pretomanid, linezolid (Drug)
BPAL/NAM1500
Nicotinamide, bedaquiline, pretomanid, linezolid
干预措施: Nicotinamide (NAM) (Dietary Supplement)
BPAL/NAM2500
Nicotinamide, bedaquiline, pretomanid, linezolid
干预措施: Bedaquiline, pretomanid, linezolid (Drug)
BPAL/NAM2500
Nicotinamide, bedaquiline, pretomanid, linezolid
干预措施: Nicotinamide (NAM) (Dietary Supplement)
BPAL
Bedaquiline, pretomanid, linezolid
干预措施: Bedaquiline, pretomanid, linezolid (Drug)
结局指标
主要结局
Safety: TEAEs leading to NAM dose reduction
时间窗: From randomization through Day 64 (EOT)
Proportion of participants with this event
Bactericidal Activity
时间窗: From randomization through Day 64 (EOT)
Proportion of participants with sputum culture conversion SCC to negative for Mtb in MGIT liquid culture by Week 8 (Day 56, End of Treatment \[EOTx\]), defined as two consecutive Mtb-negative culture results, collected at least 1 day apart (i.e., not collected on the same day), occurring by Week 9 (Day 64) with no subsequent Mtb-positive cultures through Week 9 (Day 64)
Safety: SAEs
时间窗: From randomization through Day 64 (EOT)
Proportion of participants with this event
Safety: TEAEs
时间窗: From randomization through Day 64 (EOT)
Proportion of participants with this event
Safety: AESIs
时间窗: From randomization through Day 64 (EOT)
Proportion of participants with this event
Safety: TEAEs leading to treatment discontinuation
时间窗: From randomization through Day 64 (EOT)
Proportion of participants with this event
次要结局
- Bactericidal Activity(Randomization through Day 64 (EOT))
- Bactericidal activity(Randomization through Day 56 (EOTx))
- Evaluate the PK of NAM when administered with BPaL in Group 1 and 2(Day 1 and Day 14)