Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Bedaquiline (TMC207)
Bedaquiline · 5 trials · 4 indications
Number of participants with sputum culture conversion in MGIT at Week 24 was reported. Sputum culture conversion was defined as 3 consecutive negative sputum cultures taken at least 25 days apart.
Change from baseline in the odds of M. leprae growth in mouse footpads will be evaluated. M. leprae bacilli will be inoculated in footpads of mice, according to the method of Shepard. M. leprae growth will be determined by technologists trained and experienced in mouse footpad procedures, at 1 year after infection (or at mouse death or humane endpoint, if it occurs greater than or equal to \[\>=\] 6 months after footpad inoculation). The number of footpads with positive growth (\>=10\^5 M. leprae) will be counted and used to determine the odds of bacterial growth.
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
The Cmax is the maximum plasma concentration.
The Tmax is time to reach the maximum plasma concentration.
The Cmin is the minimum plasma concentration.
AUCtime-h is the area under the plasma concentration-time curve from the time of dose administration up to X hours.
Elimination half-life (t \[1/2\]) is associated with the terminal slope (lambda \[z\]) of the semi logarithmic drug concentration-time curve, calculated as 0.693/lambda(z). Lambda(z) is first-order rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.
AUC168h is the area under the plasma concentration-time curve from the time of dose administration up to 168 Hours.
Volume of distribution is calculated as Dose divided by Lambda(z) multiplied by AUC(infinity). The AUC (infinity) is the area under the plasma concentration-time curve from time zero to infinite time.
Apparent clearance is calculated as Dose/AUC (infinity). The AUC (infinity) is the area under the plasma concentration-time curve from time zero to infinite time.
Cmax is the maximum observed analyte concentration.
AUC (0-72 hours) is area under the analyte concentration-time curve from time 0 to 72 hours, calculated by linear-linear trapezoidal summation.
AUC (0-last) is area under the analyte concentration-time curve from time zero to the time of the last measurable (non-below quantification limit) concentration, calculated by linear-linear trapezoidal summation.
AUC (0-infinity) is the area under the analyte concentration-time curve from time zero to infinity time, calculated as the sum of AUC (0-last) and C(last)/lambda(z); wherein AUC (0-last) is area under the plasma concentration-time curve from time zero to last measurable concentration, C(last) is the last observed measurable concentration, and lambda(z) is apparent terminal elimination rate constant.
Cmax is the maximum observed analyte concentration.
Cmin is the minimum observed analyte concentration.
AUC72h is the area under the analyte concentration versus time curve (AUC) from time of administration up to 72 hours post dosing, calculated by linear-linear trapezoidal summation.
AUC240h is the area under the analyte concentration-time curve from time 0 to 240 hours, calculated by linear-linear trapezoidal summation.
| Arm | Type | Description |
|---|---|---|
| Group A: Bedaquiline (BDQ) + Clarithromycin (CAM) + Ethambutol (EB) | EXPERIMENTAL | Participants will receive BDQ 400 milligrams (mg) (4\*100 mg tablets) once daily (qd) from Week 1-2 (loading phase), BDQ 200 mg (2\*100mg tablets) bi-weekly (biw) from Week 3 to 48 (maintenance phase) and CAM 400 mg or 500 mg twice daily (2\*200 mg tablets) along with EB 500-750 mg or 15 mg/kg once a day or maximum daily dose of 1.0 gram for up to Week 48. |
| Group B: Rifampicin (RFP) or Rifabutin (RBT) + CAM + EB | ACTIVE_COMPARATOR | Participants will receive maximum of 4 capsules of RFP 450 mg daily (or maximum daily dose of 600 mg), CAM 400 mg or 500 mg (2\*200 mg tablets) twice a day along with EB 500-750 mg daily or 15 mg/kg once a day or maximum daily dose of 1.0 gram for up to Week 48, followed by 2 capsules of RBT 300 mg or 150 mg once a day. |
| Bedaquiline | EXPERIMENTAL | Participants will receive bedaquiline 200 (milligram) mg (2\*100 mg tablets) once daily for 2 weeks followed by 100 mg tablet three times a week (tiw) for 6 weeks with at least 48 hours between doses. |
| Bedaquiline (TMC207)/Background Regimen (BR) | EXPERIMENTAL | There will be 4 age-based cohorts. Participants will be enrolled concurrently in Cohorts 1 and 2 followed by sequential enrollment of Cohorts 3, 4. Cohort 1: \>= 12 to \< 18 years: bedaquiline (TMC207) tablet orally as 400 mg, once daily(qd),for first 2 weeks, followed by bedaquiline (TMC207), 200 mg 3 times per week (tiw) for 22 weeks; Cohort 2: \>=5 to \<12 years: bedaquiline (TMC207) tablet given orally as 200 mg, qd, for first 2 weeks, followed by bedaquiline (TMC207) 100 mg, tiw for 22 weeks. Cohort 3: \>=2 to \<5 years: bedaquiline (TMC207) 8 milligram per kilogram (mg/kg) qd for the first 2 weeks, followed by bedaquiline (TMC207) 4 mg/kg tiw for 22 weeks. Cohort 4: 0 months to \<2 years: bedaquiline (TMC207) doses will be selected as per weight band and age group. Bedaquiline (TMC207) will be given in combination with Background Regimen for Multidrug Resistant Tuberculosis (MDR-TB) according to WHO/national tuberculosis program (NTP) guidelines/current standard of care. |
| Treatment Sequence BAE | EXPERIMENTAL | Participants will receive a single dose of bedaquiline in 3 subsequent sessions as bedaquiline oral test tablet 1 under fasted condition (Treatment B) in period 1, followed by bedaquiline oral reference tablet under fasted condition (Treatment A) in period 2, thereafter will receive bedaquiline oral test tablet 1 under fed condition (Treatment E) in period 3. Each treatment period will be separated with a washout period of at least 28 days. |
| Treatment Sequence CAF | EXPERIMENTAL | Participants will receive a single dose of bedaquiline in 3 subsequent sessions as bedaquiline oral test tablet 2 under fasted condition (Treatment C) in period 1, followed by bedaquiline oral reference tablet under fasted condition (Treatment A) in period 2, thereafter will receive bedaquiline oral test tablet II under fed condition (Treatment F) in period 3. Each treatment period will be separated with a washout period of at least 28 days. |
| Treatment Sequence DAG | EXPERIMENTAL | Participants will receive a single dose of bedaquiline in 3 subsequent sessions as bedaquiline oral test tablet 3 under fasted condition (Treatment D) in period 1, followed by bedaquiline oral reference tablet under fasted condition (Treatment A) in period 2, thereafter will receive bedaquiline oral test tablet 3 under fed condition (Treatment G) in period 3. Each treatment period will be separated with a washout period of at least 28 days. |
| Treatment Sequence ABE | EXPERIMENTAL | Participants will receive a single dose of bedaquiline in 3 subsequent sessions as bedaquiline oral reference tablet under fasted condition (Treatment A) in period 1, followed by bedaquiline oral test tablet 1 under fasted condition (Treatment B) in period 2, thereafter will receive bedaquiline oral test tablet 1 under fed condition (Treatment E) in period 3. Each treatment period will be separated with a washout period of at least 28 days. |
| Treatment Sequence ACF | EXPERIMENTAL | Participants will receive a single dose of bedaquiline in 3 subsequent sessions as bedaquiline oral reference tablet under fasted condition (Treatment A) in period 1, followed by bedaquiline oral test tablet 2 under fasted condition (Treatment C) in period 2, thereafter will receive bedaquiline oral test tablet 2 under fed condition (Treatment F) in period 3. Each treatment period will be separated with a washout period of at least 28 days. |
| Treatment Sequence ADG | EXPERIMENTAL | Participants will receive a single dose of bedaquiline in 3 subsequent sessions as bedaquiline oral reference tablet under fasted condition (Treatment A) in period 1, followed by bedaquiline oral test tablet 3 under fasted condition (Treatment D) in period 2, thereafter will receive bedaquiline oral test tablet 3 under fed condition (Treatment G) in period 3. Each treatment period will be separated with a washout period of at least 28 days. |
| Treatment Sequence 1: Bedaquiline and Clarithromycin | EXPERIMENTAL | Participants will receive bedaquiline on Day 1 in Period 1, followed by clarithromycin on Days 1-14 and bedaquiline on Day 5 in Period 2. There will be washout period of at least 28 days starting on Day 1. |
| Treatment Sequence 2: Clarithromycin and Bedaquiline | EXPERIMENTAL | Participants will receive clarithromycin on Days 1-14 and bedaquiline on Day 5 in Period 1, followed by bedaquiline on Day 1 in Period 2. There will be a washout period of at least 28 days starting after bedaquiline administration on Day 5. |
| Name | Type | Description |
|---|---|---|
| Bedaquiline | DRUG | Participants will receive BDQ tablets only/ |
| Clarithromycin | DRUG | Participants will receive CAM 400 or 500 mg twice a day. |
| Ethambutol | DRUG | Participants will receive 500 to 750 mg daily (maximum daily dose of 1.0 gram \[g\]) or 15 mg/kg once a day. |
| Rifampicin | DRUG | Participants will receive daily dose is 450 mg (maximum 600 mg) RFP capsule once a day. |
| Rifabutin | DRUG | Participants will receive daily dose of RBT 300 mg or 150 mg capsules once a day. |
| Bedaquiline 200 mg | DRUG | Participants will receive bedaquiline 200 mg (2\*100 mg tablets) once daily for 2 weeks followed by 100 mg tablet tiw for 6 weeks with at least 48 hours between doses. |
| Bedaquiline (TMC207) | DRUG | Bedaquiline (TMC207) oral tablet adult formulation (containing 100 mg bedaquiline (TMC207) per tablet) administered as 400 milligram (mg), once daily, for the first 2 weeks, followed by bedaquiline 200 mg 3 times per week with intakes at least 2 days (48 hours) apart for 22 weeks in cohort 1. Cohort 2, 3 and 4 will receive an age appropriate oral tablet formulation containing 20mg bedaquiline . Bedaquiline tablet administered orally as 200 mg, once daily, for the first 2 weeks, followed by bedaquiline 100 mg 3 times per week with intakes at least 2 days (48 hours) apart for 22 weeks in cohort 2. In Cohort 3, dose of bedaquiline 8 mg/kg qd for the first 2 weeks, followed by bedaquiline 4 mg/kg times weekly (TIW) with intakes at least 2 days (48 hours) apart for 22 weeks will be administered. In cohort 4, bedaquiline (TMC207) qd for the first 2 weeks, followed by bedaquiline TIW with intakes at least 2 days (48 hours) apart for 22 weeks. |
| Background Regimen (BR) | DRUG | Background Regimen (BR) of Multidrug Resistant Tuberculosis (MDR-TB) medications will be dosed according to World Health Organization (WHO) guidelines, National Tuberculosis Program (NTP) guidelines and current standard of care at the site. |
| Bedaquiline (Test formulation) | DRUG | Participants will receive bedaquiline orally. |
| Bedaquiline (Reference formulation) | DRUG | Participants will receive bedaquiline orally. |
Inclusion Criteria: * Has body weight greater than or equal to (\>=) 40 kilograms (kg) at screening and on Day 1 * Has radiological evidence consistent with nontuberculous mycobacterial lung disease (NTM-LD) based on a chest Computed Tomography (CT) scan taken within 6 months prior to screening or ...
Bedaquiline is an investigational small molecule being studied for tuberculosis, multidrug-resistant tuberculosis, multibacillary leprosy, and treatment-refractory Mycobacterium Avium Complex-lung disease (MAC-LD). It has also been evaluated in healthy adult participants in clinical pharmacology studies.
Bedaquiline is being developed by Johnson & Johnson, a company traded on the New York Stock Exchange under the ticker JNJ.
Bedaquiline is in clinical development. It has been studied in Phase 1 and Phase 2 trials, including completed studies in multibacillary leprosy, healthy participants, and treatment-refractory MAC-LD. It remains an investigational drug and is not approved for these uses.
Bedaquiline has been studied in several clinical trials. NCT03384641 evaluated its efficacy and safety in participants with multibacillary leprosy in Brazil. NCT03800550 and NCT04087759 assessed drug-drug interactions and tablet formulations in healthy adults in Belgium. NCT04630145 studied it with clarithromycin and ethambutol in patients with treatment-refractory MAC-LD in Japan, South Korea, and Taiwan.
Yes, Bedaquiline is also known as TMC207. Both names refer to the same drug candidate being developed by Johnson & Johnson.
Bedaquiline is listed as being studied for multidrug-resistant tuberculosis, but no specific clinical trial data for that indication has been reported. The drug remains investigational and is in clinical development across multiple indications.