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| ID | Type | Description | Link |
|---|---|---|---|
| 11884 | Registry Identifier | DAIDES Study ID Registry Number | |
| IMPAACT P1108 | Other Identifier | NIAID |
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| Name | Class |
|---|---|
| Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | NIH |
| National Institute of Mental Health (NIMH) | NIH |
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P1108 was a Phase I/II, open-label, single-arm, exposure-controlled dose finding study of BDQ in infants, children, and adolescents living with and without HIV, with clinically diagnosed or bacteriologically confirmed rifampin-resistant tuberculosis (RR-TB). The study was designed to evaluate the PK, safety, and tolerability of BDQ over 24 weeks.
The purpose of this study was to evaluate the pharmacokinetics (PK), safety, and tolerability of bedaquiline (BDQ) in combination with an individualized RR-TB therapy in infants, children, and adolescents with RR-TB disease, living with or without HIV.
This study was conducted among infants, children, and adolescents less than 18 years of age treated for clinically diagnosed or bacteriologically confirmed intra-thoracic (pulmonary) RR-TB and/or selected forms of extrathoracic RR-TB. Participants were assigned to cohorts based on age. Cohort 1 included children six years of age or older but less than 18 years of age; Cohort 2 included children two years of age or older but less than six years of age; and Cohort 3 included children 0 months of age and older but less than two years of age. Cohort 1 was divided into two weight bands, one for participants weighing 15 kg or more but less than 30 kg and one for participants weighing 30 kg or more. Cohort 2 included participants weighing greater than 7 kg. Cohort 3 included participants weighing at least 3 kg.
Study visits occurred at enrollment (Day 0) and at Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 32, 40, 48, 60, 72, 60, 72, and 96. Participants who exited the study before implementation of protocol Version 2.0 also had a study visit at Week 120. Participants in each cohort took BDQ once a day for approximately two weeks. For the next 22 weeks, BDQ was taken three times a week. Dosing for Cohorts 2 and 3 was based on data from Cohort 1.
Study visits included physical examinations, blood and urine collection, an electrocardiogram (ECG), medical history reviews, and other assessments.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 (>=6 to < 18 years) | Experimental | Participants ≥30 kg: 400 mg once per day through the intensive PK sampling visit, then 200 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit Participants ≥15 to <30 kg: 200 mg once per day through the intensive PK sampling visit, then 100 mg three times per week on Monday, Wednesday, and Friday through the Week 24 |
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| Cohort 2 (>=2 to < 6 years) | Experimental | Participants >7 to <30 kg: 200 mg once per day through the intensive PK sampling visit, then 100 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit |
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| Cohort 3 (>=0 to < 2 years) | Experimental | Participants >7 to <30 kg: 200 mg once per day through the intensive PK sampling visit, then 100 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit Participants ≥ 3 to ≤ 7 kg: 100 mg once per day through the intensive PK sampling visit, then 50 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bedaquiline | Drug | Participants received bedaquiline (BDQ) once per day through intensive PK sampling visit, then 3 times per week on Monday, Wednesday and Friday through the week 24 visit. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Adverse Events of ≥ Grade 3 Severity | At entry and follow-up, all lab results, signs and symptoms, and diagnoses were recorded. The core team reviewed and confirmed the sites assessment of event relatedness to study drug. An adverse event (AE) is any unfavorable and unintended sign, symptom, or diagnosis that occurs in a study participant during the conduct of the study REGARDLESS of the attribution. Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4= potentially life-threatening, 5=death. AE grading was per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table V2.1). | Measured from entry through Week 24 |
| Percentage of Participants With Adverse Events of ≥ Grade 3 Assessed by the Core Team to be at Least Possibly Related to the Study Drug | At entry and follow-up, all lab results, signs and symptoms, and diagnoses were recorded. The core team reviewed and confirmed the sites assessment of event relatedness to study drug. An adverse event (AE) is any unfavorable and unintended sign, symptom, or diagnosis that occurs in a study participant during the conduct of the study REGARDLESS of the attribution. Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4= potentially life-threatening, 5=death. AE grading was per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table V2.1. | Measured from entry through Week 24 |
| Percentage of Participants Who Were Terminated From Study Treatment Due to a Drug-related Adverse Event | At entry and follow-up, all lab results, signs and symptoms, and diagnoses were recorded. The core team reviewed and confirmed the sites assessment of event relatedness to study drug. An adverse event (AE) is any unfavorable and unintended sign, symptom, or diagnosis that occurs in a study participant during the conduct of the study REGARDLESS of the attribution. Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4= potentially life-threatening, 5=death. AE grading was per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table V2.1. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Adverse Events ≥ Grade 3 Severity | At entry and follow-up, all lab results, signs and symptoms, and diagnoses were recorded. The core team reviewed and confirmed the sites assessment of event relatedness to study drug. An adverse event (AE) is any unfavorable and unintended sign, symptom, or diagnosis that occurs in a study participant during the conduct of the study REGARDLESS of the attribution. Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4= potentially life-threatening, 5=death. AE grading was per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table V2.1). A higher grade indicates worse outcome. |
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Inclusion Criteria:
Parent/legal guardian willing and able to provide written informed consent for study participation; in addition, when applicable per local Institutional Review Board (IRB)/Ethics Committee (EC) policies and procedures, potential participant is willing and able to provide written assent for study participation.
Age at enrollment:
Weight at enrollment:
HIV status determined by testing requirements in the protocol.
Either bacteriologically confirmed intrathoracic (pulmonary) RR-TB and/or any of the following forms of extrathoracic TB:
Probable RR-TB (or clinically diagnosed RR-TB) with the inclusion of intrathoracic and/or extrathoracic TB as listed below:
More information on this criterion can be found in the protocol.
- Participant is on an RR-TB regimen as per local standard of care for at least seven days and not more than 12 weeks prior to entry, and tolerating the regimen well at entry, as determined by the site investigator based on available medical records.
Note: Participants may have received up to seven doses of non-study BDQ during the seven days prior to study enrollment. The date and dose amount of non-study BDQ doses must be available in medical records.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Anneke Hesseling, M.D., Ph.D. | Desmond Tutu TB Centre, Stellenbosch University | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Les Centres GHESKIO Clinical Research Site (GHESKIO-INLR) CRS | Port-au-Prince | HT-6110 | Haiti | |||
| Sizwe CRS |
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| Label | URL |
|---|---|
| The DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017, was used in this study | View source |
| "Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010" | View source |
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The first enrollment to the study was in September 2017 and enrollment was completed in August 2023 with a total of 54 participants who initiated study drug. There enrollments were from one site in Haiti - Les Centres Gheskio INLR CRS, and three sites from South Africa - Desmond Tutu TB Center - Stellenbosch University, Sizwe CRS, and PHRU Matlosana CRS.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1 (≥ 6 to < 18 Years) | Participants ≥30 kg: 400 mg once per day through the intensive PK sampling visit, then 200 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit Participants ≥15 to <30 kg: 200 mg once per day through the intensive PK sampling visit, then 100 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_ICF | Yes | No | Yes | Study Protocol and Informed Consent Form: Protocol and ICF | Sep 21, 2022 |
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| Measured from entry through Week 24 |
| Percentage of Participants Who Died | At entry and follow-up, all lab results, signs and symptoms, and diagnoses were recorded. The core team reviewed and confirmed the sites assessment of event relatedness to study drug. An adverse event (AE) is any unfavorable and unintended sign, symptom, or diagnosis that occurs in a study participant during the conduct of the study REGARDLESS of the attribution. Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death. AE grading was per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table V2.0. | Measured from entry through Week 24 |
| Percentage of Participants With Unstable Dysrhythmias Requiring Hospitalization and Treatment | At entry and follow-up, any participant who experienced unstable dysrhythmias that required hospitalization and treatment were considered as an adverse event. The core team reviewed and confirmed the sites assessment of event relatedness to study drug. | Measured from entry through Week 24 |
| Percentage of Participants With Absolute Corrected QT Interval by Fridericia (QTcF) ≥ 500 Msec | Evaluation of the Electrocardiogram (ECG) QTcF was performed per protocol. ECGs conducted at these visits should be performed in triplicate (if possible). Consultation with the protocol cardiologist was available and encouraged for any abnormal or equivocal ECG findings and/or questions related to cardiac toxicities and assessment. Participants were included if they had QTcF ≥ 500 msec at any study visit from entry to Week 24. | All participants had ECG performed at Screening and Entry visits and through week 24. |
| Geometric Mean of Area Under the Concentration Versus Time Curve (AUC0-24h or AUC0-168h) Bedaquiline | PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model The final population PK model was developed using a nonlinear mixed effects model (NNMEM, version 7.5).
| Intensive PK Week 1 or 2, Week 8, and Week 24, (if intensive then pre dose, and post dose at 2, 4, 6, 8 hours) and if not intensive then predose only. |
| Measured from entry through study completion, up to 120 weeks |
| Percentage of Participants With Adverse Events ≥ Grade 3 Severity Assessed by the Core Team to be at Least Possibly Related to the Study Drug. | At entry and follow-up, all lab results, signs and symptoms, and diagnoses were recorded. The core team reviewed and confirmed the sites assessment of event relatedness to study drug. An adverse event (AE) is any unfavorable and unintended sign, symptom, or diagnosis that occurs in a study participant during the conduct of the study REGARDLESS of the attribution. Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4= potentially life-threatening, 5=death. AE grading was per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table V2.1). A higher grade indicates worse outcome. | Measured from entry through study completion, up to 120 weeks |
| Percentage of Participants With Absolute Corrected QT Interval by Fridericia (QTcF) ≥ 500 Msec | Evaluation of the Electrocardiogram (ECG) QTcF was performed per protocol. ECGs conducted at these visits should be performed in triplicate (if possible). Consultation with the protocol cardiologist was available and encouraged for any abnormal or equivocal ECG findings and/or questions related to cardiac toxicities and assessment. Participants were included if they had QTcF ≥ 500 msec at any study visit from entry to Week 40. | Measured from entry through study week 40 |
| Percentage of Participants With Unstable Dysrhythmias Requiring Hospitalization and Treatment | At entry and follow-up, all lab results, signs and symptoms, and diagnoses were recorded. The core team reviewed and confirmed the sites assessment of event relatedness to study drug. An adverse event (AE) is any unfavorable and unintended sign, symptom, or diagnosis that occurs in a study participant during the conduct of the study REGARDLESS of the attribution. Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4= potentially life-threatening, 5=death. AE grading was per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table V2.1). A higher grade indicates worse outcomes. | Measured from entry through study completion, up to 120 weeks |
| Percentage of Participants Who Died | At entry and follow-up, death of all causes | Measured from entry through study completion, up to 120 weeks |
| Percentage of Participants With TB Treatment Outcomes at End of Rifampin Resistant (RR) Treatment Among Those Not Living With HIV | TB treatment outcomes were evaluated by team-identified independent endpoint reviewers through end of RR treatment and end of study. TB Treatment outcomes in children were defined as bacteriologic cure, probable cure, death, treatment failure, TB recurrence, and loss to follow-up as per protocol. | Measured from entry through end of RR treatment, up to 81 weeks |
| Percentage of Participants With TB Treatment Outcomes at End of Rifampin Resistant (RR) Treatment Among Those Living With HIV | TB treatment outcomes were evaluated by team-identified independent endpoint reviewers through end of RR treatment and end of study. TB Treatment outcomes in children were defined as bacteriologic cure, probable cure, death, treatment failure, TB recurrence, and loss to follow-up as per protocol. | Measured from entry through end of RR treatment, up to 81 weeks |
| Percentage of Participants With TB Treatment Outcomes at End of Study Among Those Not Living With HIV | TB treatment outcomes were evaluated by team-identified independent endpoint reviewers through end of study. TB Treatment outcomes in children were defined as bacteriologic cure, probable cure, death, treatment failure, TB recurrence, and loss to follow-up as per protocol. | Measured from entry through study completion, up to 120 weeks |
| Percentage of Participants With TB Treatment Outcomes at End of Study Among Those Living With HIV | TB treatment outcomes were evaluated by team-identified independent endpoint reviewers through end of study. TB Treatment outcomes in children were defined as bacteriologic cure, probable cure, death, treatment failure, TB recurrence, and loss to follow-up as per protocol. | Measured from entry through study completion, up to 120 weeks |
| Geometric Mean of Area Under the Concentration Versus Time Curve (AUC0-24h or AUC0-168h) Bedaquiline Mono-desmethyl Metabolite (M2) | PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model The final population PK model was developed using a nonlinear mixed effects model (NNMEM, version 7.5).
| Intensive PK Week 1 or 2, Week 8, and Week 24, (if intensive then pre dose, and post dose at 2, 4, 6, 8 hours) and if not intensive then predose only. |
| Geometric Mean of Maximal Concentration (Cmax) Bedaquiline | PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model The final population PK model was developed using a nonlinear mixed effects model (NNMEM, version 7.5).
| Intensive PK Week 1 or 2, Week 8, and Week 24, (if intensive then pre dose, and post dose at 2, 4, 6, 8 hours) and if not intensive then pre dose only. |
| Geometric Mean of Maximal Concentration (Cmax) Bedaquiline Mono-desmethyl Metabolite (M2) | PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model | Intensive PK Week 1 or 2, Week 8, and Week 24, (if intensive then pre dose, and post dose at 2, 4, 6, 8 hours) and if not intensive then pre dose only. |
| Geometric Mean of Trough Concentration (Ctrough) Bedaquiline | PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model. Lowest concentration at end of the dosing interval which is approximately 24h after dose at Intensive PK (Week 1 or 2) and 48-72h at Weeks 8 and 24. | Intensive PK (Week 1 or 2) 24h post dose and Weeks 8 and 24 48-72h post dose |
| Geometric Mean of Trough Concentration (Ctrough) Bedaquiline Mono-desmethyl Metabolite (M2) | PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model. Lowest concentration at end of the dosing interval which is approximately 24h after dose at Intensive PK (Week 1 or 2) and 48-72h at Weeks 8 and 24. | Intensive PK (Week 1 or 2) 24h post dose and Weeks 8 and 24 48-72h post dose |
| Median of Time of Maximal Concentration (Tmax) Bedaquiline | PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model | Intensive PK (Week 1 or 2) pre-dose and 2, 4, 6, 8 hours post dose |
| Median of Time of Maximal Concentration (Tmax) Bedaquiline Mono-desmethyl Metabolite (M2) | PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model | Intensive PK (Week 1 or 2) pre dose and 2, 4, 6, 8 hours post dose |
| Geometric Mean of Oral Clearance (CL/F) Bedaquiline | Individual clearance (CL) relative to bioavailability (F) determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model | Week 24 |
| Geometric Mean of Theoretical Steady State AUC (AUC0-168h) | Calculated PK parameter determined from weekly continuation phase dose divided by oral clearance at week 24 | Week 24 |
| Median Quantitative Post-treatment Bedaquiline Concentrations | PK assessments were performed to determine plasma concentrations of BDQ at selected time points. All concentrations reported to be below the limit of quantification were imputed to zero in these calculations | Weeks 8, 16, 24, 36, 48, 72, and 96 after BDQ discontinuation |
| Percentage of Participants With Post-treatment Bedaquiline Concentrations Below Limit of Quantifications (BLQ) | PK assessments were performed to determine plasma concentrations of BDQ at selected time points. " | Weeks 8, 16, 24, 36, 48, 72, and 96 after BDQ discontinuation |
| Johannesburg |
| Gauteng |
| South Africa |
| PHRU Matlosana CRS | Klerksdorp | North West | 2574 | South Africa |
| Desmond Tutu TB Centre - Stellenbosch University (DTTC-SU) CRS | Cape Town | Western Cape | 7505 | South Africa |
| FG001 | Cohort 2 (≥ 2 to < 6 Years) | Participants >7 to <30 kg: 200 mg once per day through the intensive PK sampling visit, then 100 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit |
| FG002 | Cohort 3 (≥ 0 to < 2 Years) | Participants >7 to <30 kg: 200 mg once per day through the intensive PK sampling visit, then 100 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit Participants ≥ 3 to ≤ 7 kg: 100 mg once per day through the intensive PK sampling visit, then 50 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit |
| COMPLETED | Through 24 weeks of study treatment |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1 (≥ 6 to < 18 Years) | Bedaquiline: Participants ≥30 kg: 400 mg once per day through the intensive PK sampling visit, then 200 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit Participants ≥ 15 to <30 kg: 200 mg once per day through the intensive PK sampling visit, then 100 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit |
| BG001 | Cohort 2 (≥ 2 to < 6 Years) | Participants >7 to <30 kg: 200 mg once per day through the intensive PK sampling visit, then 100 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit |
| BG002 | Cohort 3 (≥ 0 to < 2 Years) | Participants >7 to <30 kg: 200 mg once per day through the intensive PK sampling visit, then 100 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit Participants ≥ 3 to ≤ 7 kg: 100 mg once per day through the intensive PK sampling visit, then 50 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Continuous | Median | Inter-Quartile Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| HIV-1 status | Count of Participants | Participants |
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| Weight | Median | Inter-Quartile Range | kilogram (kg) |
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| Height | Median | Inter-Quartile Range | centimeter (cm) |
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| TB disease spectrum | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||
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| Primary | Percentage of Participants With Adverse Events of ≥ Grade 3 Severity | At entry and follow-up, all lab results, signs and symptoms, and diagnoses were recorded. The core team reviewed and confirmed the sites assessment of event relatedness to study drug. An adverse event (AE) is any unfavorable and unintended sign, symptom, or diagnosis that occurs in a study participant during the conduct of the study REGARDLESS of the attribution. Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4= potentially life-threatening, 5=death. AE grading was per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table V2.1). | All participants enrolled in the study | Posted | Number | 95% Confidence Interval | percentage of participants | Measured from entry through Week 24 |
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| Primary | Percentage of Participants With Adverse Events of ≥ Grade 3 Assessed by the Core Team to be at Least Possibly Related to the Study Drug | At entry and follow-up, all lab results, signs and symptoms, and diagnoses were recorded. The core team reviewed and confirmed the sites assessment of event relatedness to study drug. An adverse event (AE) is any unfavorable and unintended sign, symptom, or diagnosis that occurs in a study participant during the conduct of the study REGARDLESS of the attribution. Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4= potentially life-threatening, 5=death. AE grading was per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table V2.1. | All participants enrolled in the study | Posted | Number | 95% Confidence Interval | percentage of participants | Measured from entry through Week 24 |
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| Primary | Percentage of Participants Who Were Terminated From Study Treatment Due to a Drug-related Adverse Event | At entry and follow-up, all lab results, signs and symptoms, and diagnoses were recorded. The core team reviewed and confirmed the sites assessment of event relatedness to study drug. An adverse event (AE) is any unfavorable and unintended sign, symptom, or diagnosis that occurs in a study participant during the conduct of the study REGARDLESS of the attribution. Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4= potentially life-threatening, 5=death. AE grading was per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table V2.1. | All participants enrolled in the study | Posted | Number | 95% Confidence Interval | percentage of participants | Measured from entry through Week 24 |
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| Primary | Percentage of Participants Who Died | At entry and follow-up, all lab results, signs and symptoms, and diagnoses were recorded. The core team reviewed and confirmed the sites assessment of event relatedness to study drug. An adverse event (AE) is any unfavorable and unintended sign, symptom, or diagnosis that occurs in a study participant during the conduct of the study REGARDLESS of the attribution. Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death. AE grading was per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table V2.0. | All participants enrolled in the study | Posted | Number | 95% Confidence Interval | percentage of participants | Measured from entry through Week 24 |
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| Primary | Percentage of Participants With Unstable Dysrhythmias Requiring Hospitalization and Treatment | At entry and follow-up, any participant who experienced unstable dysrhythmias that required hospitalization and treatment were considered as an adverse event. The core team reviewed and confirmed the sites assessment of event relatedness to study drug. | All participants enrolled in the study | Posted | Number | 95% Confidence Interval | percentage of participants | Measured from entry through Week 24 |
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| Primary | Percentage of Participants With Absolute Corrected QT Interval by Fridericia (QTcF) ≥ 500 Msec | Evaluation of the Electrocardiogram (ECG) QTcF was performed per protocol. ECGs conducted at these visits should be performed in triplicate (if possible). Consultation with the protocol cardiologist was available and encouraged for any abnormal or equivocal ECG findings and/or questions related to cardiac toxicities and assessment. Participants were included if they had QTcF ≥ 500 msec at any study visit from entry to Week 24. | All participants enrolled in the study | Posted | Number | 95% Confidence Interval | percentage of participants | All participants had ECG performed at Screening and Entry visits and through week 24. |
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| Primary | Geometric Mean of Area Under the Concentration Versus Time Curve (AUC0-24h or AUC0-168h) Bedaquiline | PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model The final population PK model was developed using a nonlinear mixed effects model (NNMEM, version 7.5).
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| Posted | Geometric Mean | Geometric Coefficient of Variation | hour*mg/L | Intensive PK Week 1 or 2, Week 8, and Week 24, (if intensive then pre dose, and post dose at 2, 4, 6, 8 hours) and if not intensive then predose only. |
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| Secondary | Percentage of Participants With Adverse Events ≥ Grade 3 Severity | At entry and follow-up, all lab results, signs and symptoms, and diagnoses were recorded. The core team reviewed and confirmed the sites assessment of event relatedness to study drug. An adverse event (AE) is any unfavorable and unintended sign, symptom, or diagnosis that occurs in a study participant during the conduct of the study REGARDLESS of the attribution. Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4= potentially life-threatening, 5=death. AE grading was per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table V2.1). A higher grade indicates worse outcome. | All participants who enrolled on study | Posted | Number | 95% Confidence Interval | percentage of participants | Measured from entry through study completion, up to 120 weeks |
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| Secondary | Percentage of Participants With Adverse Events ≥ Grade 3 Severity Assessed by the Core Team to be at Least Possibly Related to the Study Drug. | At entry and follow-up, all lab results, signs and symptoms, and diagnoses were recorded. The core team reviewed and confirmed the sites assessment of event relatedness to study drug. An adverse event (AE) is any unfavorable and unintended sign, symptom, or diagnosis that occurs in a study participant during the conduct of the study REGARDLESS of the attribution. Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4= potentially life-threatening, 5=death. AE grading was per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table V2.1). A higher grade indicates worse outcome. | All participants who enrolled on study | Posted | Number | 95% Confidence Interval | percentage of participants | Measured from entry through study completion, up to 120 weeks |
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| Secondary | Percentage of Participants With Absolute Corrected QT Interval by Fridericia (QTcF) ≥ 500 Msec | Evaluation of the Electrocardiogram (ECG) QTcF was performed per protocol. ECGs conducted at these visits should be performed in triplicate (if possible). Consultation with the protocol cardiologist was available and encouraged for any abnormal or equivocal ECG findings and/or questions related to cardiac toxicities and assessment. Participants were included if they had QTcF ≥ 500 msec at any study visit from entry to Week 40. | All participants who enrolled on study | Posted | Number | 95% Confidence Interval | percentage of participants | Measured from entry through study week 40 |
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| Secondary | Percentage of Participants With Unstable Dysrhythmias Requiring Hospitalization and Treatment | At entry and follow-up, all lab results, signs and symptoms, and diagnoses were recorded. The core team reviewed and confirmed the sites assessment of event relatedness to study drug. An adverse event (AE) is any unfavorable and unintended sign, symptom, or diagnosis that occurs in a study participant during the conduct of the study REGARDLESS of the attribution. Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4= potentially life-threatening, 5=death. AE grading was per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table V2.1). A higher grade indicates worse outcomes. | All participants who enrolled on study | Posted | Number | 95% Confidence Interval | percentage of participants | Measured from entry through study completion, up to 120 weeks |
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| Secondary | Percentage of Participants Who Died | At entry and follow-up, death of all causes | All participants who enrolled on study | Posted | Number | 95% Confidence Interval | percentage of participants | Measured from entry through study completion, up to 120 weeks |
| |||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With TB Treatment Outcomes at End of Rifampin Resistant (RR) Treatment Among Those Not Living With HIV | TB treatment outcomes were evaluated by team-identified independent endpoint reviewers through end of RR treatment and end of study. TB Treatment outcomes in children were defined as bacteriologic cure, probable cure, death, treatment failure, TB recurrence, and loss to follow-up as per protocol. | All participants not living with HIV who enrolled on study | Posted | Number | 95% Confidence Interval | percentage of participants | Measured from entry through end of RR treatment, up to 81 weeks |
| |||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With TB Treatment Outcomes at End of Rifampin Resistant (RR) Treatment Among Those Living With HIV | TB treatment outcomes were evaluated by team-identified independent endpoint reviewers through end of RR treatment and end of study. TB Treatment outcomes in children were defined as bacteriologic cure, probable cure, death, treatment failure, TB recurrence, and loss to follow-up as per protocol. | All participants living with HIV who enrolled on study | Posted | Number | 95% Confidence Interval | percentage of participants | Measured from entry through end of RR treatment, up to 81 weeks |
| |||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With TB Treatment Outcomes at End of Study Among Those Not Living With HIV | TB treatment outcomes were evaluated by team-identified independent endpoint reviewers through end of study. TB Treatment outcomes in children were defined as bacteriologic cure, probable cure, death, treatment failure, TB recurrence, and loss to follow-up as per protocol. | All participants not living with HIV who enrolled on study | Posted | Number | 95% Confidence Interval | percentage of participants | Measured from entry through study completion, up to 120 weeks |
| |||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With TB Treatment Outcomes at End of Study Among Those Living With HIV | TB treatment outcomes were evaluated by team-identified independent endpoint reviewers through end of study. TB Treatment outcomes in children were defined as bacteriologic cure, probable cure, death, treatment failure, TB recurrence, and loss to follow-up as per protocol. | All participants living with HIV who enrolled on study | Posted | Number | 95% Confidence Interval | percentage of participants | Measured from entry through study completion, up to 120 weeks |
| |||||||||||||||||||||||||||||||||
| Secondary | Geometric Mean of Area Under the Concentration Versus Time Curve (AUC0-24h or AUC0-168h) Bedaquiline Mono-desmethyl Metabolite (M2) | PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model The final population PK model was developed using a nonlinear mixed effects model (NNMEM, version 7.5).
|
| Posted | Geometric Mean | Geometric Coefficient of Variation | hour*mg/L | Intensive PK Week 1 or 2, Week 8, and Week 24, (if intensive then pre dose, and post dose at 2, 4, 6, 8 hours) and if not intensive then predose only. |
| |||||||||||||||||||||||||||||||||
| Secondary | Geometric Mean of Maximal Concentration (Cmax) Bedaquiline | PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model The final population PK model was developed using a nonlinear mixed effects model (NNMEM, version 7.5).
|
| Posted | Geometric Mean | Geometric Coefficient of Variation | mg/L | Intensive PK Week 1 or 2, Week 8, and Week 24, (if intensive then pre dose, and post dose at 2, 4, 6, 8 hours) and if not intensive then pre dose only. |
| |||||||||||||||||||||||||||||||||
| Secondary | Geometric Mean of Maximal Concentration (Cmax) Bedaquiline Mono-desmethyl Metabolite (M2) | PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model |
| Posted | Geometric Mean | Geometric Coefficient of Variation | mg/L | Intensive PK Week 1 or 2, Week 8, and Week 24, (if intensive then pre dose, and post dose at 2, 4, 6, 8 hours) and if not intensive then pre dose only. |
| |||||||||||||||||||||||||||||||||
| Secondary | Geometric Mean of Trough Concentration (Ctrough) Bedaquiline | PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model. Lowest concentration at end of the dosing interval which is approximately 24h after dose at Intensive PK (Week 1 or 2) and 48-72h at Weeks 8 and 24. |
| Posted | Geometric Mean | Geometric Coefficient of Variation | mg/L | Intensive PK (Week 1 or 2) 24h post dose and Weeks 8 and 24 48-72h post dose |
| |||||||||||||||||||||||||||||||||
| Secondary | Geometric Mean of Trough Concentration (Ctrough) Bedaquiline Mono-desmethyl Metabolite (M2) | PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model. Lowest concentration at end of the dosing interval which is approximately 24h after dose at Intensive PK (Week 1 or 2) and 48-72h at Weeks 8 and 24. |
| Posted | Geometric Mean | Geometric Coefficient of Variation | mg/L | Intensive PK (Week 1 or 2) 24h post dose and Weeks 8 and 24 48-72h post dose |
| |||||||||||||||||||||||||||||||||
| Secondary | Median of Time of Maximal Concentration (Tmax) Bedaquiline | PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model |
| Posted | Median | Full Range | h | Intensive PK (Week 1 or 2) pre-dose and 2, 4, 6, 8 hours post dose |
| |||||||||||||||||||||||||||||||||
| Secondary | Median of Time of Maximal Concentration (Tmax) Bedaquiline Mono-desmethyl Metabolite (M2) | PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model |
| Posted | Median | Full Range | h | Intensive PK (Week 1 or 2) pre dose and 2, 4, 6, 8 hours post dose |
| |||||||||||||||||||||||||||||||||
| Secondary | Geometric Mean of Oral Clearance (CL/F) Bedaquiline | Individual clearance (CL) relative to bioavailability (F) determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model |
| Posted | Geometric Mean | Geometric Coefficient of Variation | L/h | Week 24 |
| |||||||||||||||||||||||||||||||||
| Secondary | Geometric Mean of Theoretical Steady State AUC (AUC0-168h) | Calculated PK parameter determined from weekly continuation phase dose divided by oral clearance at week 24 |
| Posted | Geometric Mean | Geometric Coefficient of Variation | hour*mg/L | Week 24 |
| |||||||||||||||||||||||||||||||||
| Secondary | Median Quantitative Post-treatment Bedaquiline Concentrations | PK assessments were performed to determine plasma concentrations of BDQ at selected time points. All concentrations reported to be below the limit of quantification were imputed to zero in these calculations | All participants that have finished 24 weeks of BDQ treatment and have at least one PK result after end of treatment | Posted | Median | Full Range | mg/L | Weeks 8, 16, 24, 36, 48, 72, and 96 after BDQ discontinuation |
| |||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Post-treatment Bedaquiline Concentrations Below Limit of Quantifications (BLQ) | PK assessments were performed to determine plasma concentrations of BDQ at selected time points. " | All participants that have finished 24 weeks of BDQ treatment and have at least one PK result after end of treatment | Posted | Number | percentage of participants | Weeks 8, 16, 24, 36, 48, 72, and 96 after BDQ discontinuation |
|
From entry through end of study follow-up with a maximum of 120 weeks
An adverse event (AE) is any unfavorable and unintended sign, symptom, or diagnosis that occurs in a study participant during the conduct of the study REGARDLESS of the attribution. Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4= potentially life-threatening, 5=death. AE grading was per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table V2.1.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1: >= 6 to < 18 Years | Participants ≥30 kg: 400 mg once per day through the intensive PK sampling visit, then 200 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit Participants ≥15 to <30 kg: 200 mg once per day through the intensive PK sampling visit, then 100 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit | 1 | 18 | 5 | 18 | 18 | 18 |
| EG001 | Cohort 2: >= 2 to < 6 Years | Participants >7 to <30 kg: 200 mg once per day through the intensive PK sampling visit, then 100 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit | 0 | 18 | 2 | 18 | 18 | 18 |
| EG002 | Cohort 3: >= 0 to < 2 Years | Participants >7 to <30 kg: 200 mg once per day through the intensive PK sampling visit, then 100 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit Participants ≥ 3 to ≤ 7 kg: 100 mg once per day through the intensive PK sampling visit, then 50 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit | 0 | 18 | 4 | 18 | 18 | 18 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Drug-induced liver injury | Hepatobiliary disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Hepatitis viral | Infections and infestations | MedDRA 28.1 | Systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | MedDRA 28.1 | Systematic Assessment |
| |
| Otitis media staphylococcal | Infections and infestations | MedDRA 28.1 | Systematic Assessment |
| |
| Tooth abscess | Infections and infestations | MedDRA 28.1 | Systematic Assessment |
| |
| Head injury | Injury, poisoning and procedural complications | MedDRA 28.1 | Systematic Assessment |
| |
| Radius fracture | Injury, poisoning and procedural complications | MedDRA 28.1 | Systematic Assessment |
| |
| Thermal burn | Injury, poisoning and procedural complications | MedDRA 28.1 | Systematic Assessment |
| |
| Blood bicarbonate decreased | Investigations | MedDRA 28.1 | Systematic Assessment |
| |
| Electrocardiogram QT prolonged | Investigations | MedDRA 28.1 | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Bipolar disorder | Psychiatric disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Childhood asthma | Respiratory, thoracic and mediastinal disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA 28.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Iron deficiency anaemia | Blood and lymphatic system disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Normochromic normocytic anaemia | Blood and lymphatic system disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Bradycardia | Cardiac disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Sinus arrhythmia | Cardiac disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Cerumen impaction | Ear and labyrinth disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Conductive deafness | Ear and labyrinth disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Ear pain | Ear and labyrinth disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Middle ear effusion | Ear and labyrinth disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Hypothyroidism | Endocrine disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Eye pain | Eye disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Ocular hyperaemia | Eye disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Lip ulceration | Gastrointestinal disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Mouth haemorrhage | Gastrointestinal disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Teething | Gastrointestinal disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Hepatomegaly | Hepatobiliary disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Hypertransaminasaemia | Hepatobiliary disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Immune reconstitution inflammatory syndrome | Immune system disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Body tinea | Infections and infestations | MedDRA 28.1 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 28.1 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 28.1 | Systematic Assessment |
| |
| Hepatitis A | Infections and infestations | MedDRA 28.1 | Systematic Assessment |
| |
| Infective exacerbation of asthma | Infections and infestations | MedDRA 28.1 | Systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | MedDRA 28.1 | Systematic Assessment |
| |
| Lower respiratory tract infection viral | Infections and infestations | MedDRA 28.1 | Systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA 28.1 | Systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA 28.1 | Systematic Assessment |
| |
| Otitis media | Infections and infestations | MedDRA 28.1 | Systematic Assessment |
| |
| Otitis media acute | Infections and infestations | MedDRA 28.1 | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA 28.1 | Systematic Assessment |
| |
| Pneumocystis jirovecii pneumonia | Infections and infestations | MedDRA 28.1 | Systematic Assessment |
| |
| Pulmonary tuberculosis | Infections and infestations | MedDRA 28.1 | Systematic Assessment |
| |
| Pustule | Infections and infestations | MedDRA 28.1 | Systematic Assessment |
| |
| Rash pustular | Infections and infestations | MedDRA 28.1 | Systematic Assessment |
| |
| Staphylococcal infection | Infections and infestations | MedDRA 28.1 | Systematic Assessment |
| |
| Tinea capitis | Infections and infestations | MedDRA 28.1 | Systematic Assessment |
| |
| Tinea versicolour | Infections and infestations | MedDRA 28.1 | Systematic Assessment |
| |
| Tonsillitis | Infections and infestations | MedDRA 28.1 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 28.1 | Systematic Assessment |
| |
| Urethritis | Infections and infestations | MedDRA 28.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 28.1 | Systematic Assessment |
| |
| Viral tonsillitis | Infections and infestations | MedDRA 28.1 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 28.1 | Systematic Assessment |
| |
| Face injury | Injury, poisoning and procedural complications | MedDRA 28.1 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 28.1 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 28.1 | Systematic Assessment |
| |
| Bilirubin conjugated increased | Investigations | MedDRA 28.1 | Systematic Assessment |
| |
| Blood albumin decreased | Investigations | MedDRA 28.1 | Systematic Assessment |
| |
| Blood bicarbonate | Investigations | MedDRA 28.1 | Systematic Assessment |
| |
| Blood bicarbonate decreased | Investigations | MedDRA 28.1 | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA 28.1 | Systematic Assessment |
| |
| Blood calcium decreased | Investigations | MedDRA 28.1 | Systematic Assessment |
| |
| Blood calcium increased | Investigations | MedDRA 28.1 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 28.1 | Systematic Assessment |
| |
| Blood lactic acid abnormal | Investigations | MedDRA 28.1 | Systematic Assessment |
| |
| Blood magnesium decreased | Investigations | MedDRA 28.1 | Systematic Assessment |
| |
| Blood phosphorus decreased | Investigations | MedDRA 28.1 | Systematic Assessment |
| |
| Blood potassium decreased | Investigations | MedDRA 28.1 | Systematic Assessment |
| |
| Blood potassium increased | Investigations | MedDRA 28.1 | Systematic Assessment |
| |
| Blood pressure diastolic increased | Investigations | MedDRA 28.1 | Systematic Assessment |
| |
| Blood pressure increased | Investigations | MedDRA 28.1 | Systematic Assessment |
| |
| Blood pressure systolic increased | Investigations | MedDRA 28.1 | Systematic Assessment |
| |
| Blood sodium decreased | Investigations | MedDRA 28.1 | Systematic Assessment |
| |
| Blood sodium increased | Investigations | MedDRA 28.1 | Systematic Assessment |
| |
| Blood uric acid increased | Investigations | MedDRA 28.1 | Systematic Assessment |
| |
| Carbon dioxide decreased | Investigations | MedDRA 28.1 | Systematic Assessment |
| |
| Haemoglobin decreased | Investigations | MedDRA 28.1 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA 28.1 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA 28.1 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 28.1 | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA 28.1 | Systematic Assessment |
| |
| Abnormal loss of weight | Metabolism and nutrition disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Underweight | Metabolism and nutrition disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Blount's disease | Musculoskeletal and connective tissue disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Juvenile idiopathic arthritis | Musculoskeletal and connective tissue disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Vulvovaginal warts | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 28.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Chronic respiratory disease | Respiratory, thoracic and mediastinal disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Oropharyngeal erythema | Respiratory, thoracic and mediastinal disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Acne | Skin and subcutaneous tissue disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Dermatitis allergic | Skin and subcutaneous tissue disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Dermatitis atopic | Skin and subcutaneous tissue disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Dermatitis diaper | Skin and subcutaneous tissue disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Eczema | Skin and subcutaneous tissue disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Hyperkeratosis | Skin and subcutaneous tissue disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Macule | Skin and subcutaneous tissue disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Papule | Skin and subcutaneous tissue disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Pityriasis alba | Skin and subcutaneous tissue disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Rash papular | Skin and subcutaneous tissue disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Skin discolouration | Skin and subcutaneous tissue disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Skin exfoliation | Skin and subcutaneous tissue disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Skin hyperpigmentation | Skin and subcutaneous tissue disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 28.1 | Systematic Assessment |
| |
| Systolic hypertension | Vascular disorders | MedDRA 28.1 | Systematic Assessment |
|
In accordance with the Clinical Trials Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| IMPAACT Clinicaltrials.gov Coordinator | Family Health International (FHI 360) | (919) 405-1429 | IMPAACT.ctgov@frontierscience.org |
| Aug 22, 2024 |
| Prot_ICF_000.pdf |
| Prot | Yes | No | No | Study Protocol: Letter of Amendment #1 | May 2, 2023 | Aug 22, 2024 | Prot_001.pdf |
| Prot | Yes | No | No | Study Protocol: Clarification Memorandum #1 | Mar 29, 2023 | Aug 22, 2024 | Prot_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 8, 2023 | Feb 4, 2025 | SAP_003.pdf |
Not provided
| ID | Term |
|---|---|
| D014376 | Tuberculosis |
| ID | Term |
|---|---|
| D009164 | Mycobacterium Infections |
| D000193 | Actinomycetales Infections |
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
Not provided
Not provided
| ID | Term |
|---|---|
| C493870 | bedaquiline |
Not provided
Not provided
Not provided
| Male |
|
| Coloured |
|
| Mixed |
|
| living with HIV |
|
| Extra Pulmonary TB (EPTB) |
|
| PTB and EPTB |
|
| OG002 | Cohort 3 (≥ 0 to < 2 Years) | Participants >7 to <30 kg: 200 mg once per day through the intensive PK sampling visit, then 100 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit Participants ≥ 3 to ≤ 7 kg: 100 mg once per day through the intensive PK sampling visit, then 50 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit |
|
|
| OG002 | Cohort 3 (≥ 0 to < 2 Years) | Participants >7 to <30 kg: 200 mg once per day through the intensive PK sampling visit, then 100 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit Participants ≥ 3 to ≤ 7 kg: 100 mg once per day through the intensive PK sampling visit, then 50 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit |
|
|
| OG002 | Cohort 3 (≥ 0 to < 2 Years) | Participants >7 to <30 kg: 200 mg once per day through the intensive PK sampling visit, then 100 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit Participants ≥ 3 to ≤ 7 kg: 100 mg once per day through the intensive PK sampling visit, then 50 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit |
|
|
|
|
| Cohort 3 (≥ 0 to < 2 Years) |
Participants >7 to <30 kg: 200 mg once per day through the intensive PK sampling visit, then 100 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit Participants ≥ 3 to ≤ 7 kg: 100 mg once per day through the intensive PK sampling visit, then 50 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit |
|
|
| OG001 | Cohort 2 (≥ 2 to < 6 Years) | Participants >7 to <30 kg: 200 mg once per day through the intensive PK sampling visit, then 100 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit |
| OG002 | Cohort 3 (≥ 0 to < 2 Years) | Participants >7 to <30 kg: 200 mg once per day through the intensive PK sampling visit, then 100 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit Participants ≥ 3 to ≤ 7 kg: 100 mg once per day through the intensive PK sampling visit, then 50 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit |
|
|
| OG002 | Cohort 3 (≥ 0 to < 2 Years) | Participants >7 to <30 kg: 200 mg once per day through the intensive PK sampling visit, then 100 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit Participants ≥ 3 to ≤ 7 kg: 100 mg once per day through the intensive PK sampling visit, then 50 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit |
|
|
| OG002 | Cohort 3 (≥ 0 to < 2 Years) | Participants >7 to <30 kg: 200 mg once per day through the intensive PK sampling visit, then 100 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit Participants ≥ 3 to ≤ 7 kg: 100 mg once per day through the intensive PK sampling visit, then 50 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit |
|
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| Cohort 3 (≥ 0 to < 2 Years) |
Participants >7 to <30 kg: 200 mg once per day through the intensive PK sampling visit, then 100 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit Participants ≥ 3 to ≤ 7 kg: 100 mg once per day through the intensive PK sampling visit, then 50 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit |
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| OG002 | Cohort 3 (≥ 0 to < 2 Years) | Participants >7 to <30 kg: 200 mg once per day through the intensive PK sampling visit, then 100 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit Participants ≥ 3 to ≤ 7 kg: 100 mg once per day through the intensive PK sampling visit, then 50 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit |
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Participants >7 to <30 kg: 200 mg once per day through the intensive PK sampling visit, then 100 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit Participants ≥ 3 to ≤ 7 kg: 100 mg once per day through the intensive PK sampling visit, then 50 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit |
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Participants >7 to <30 kg: 200 mg once per day through the intensive PK sampling visit, then 100 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit Participants ≥ 3 to ≤ 7 kg: 100 mg once per day through the intensive PK sampling visit, then 50 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit |
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Participants >7 to <30 kg:
200 mg once per day through the intensive PK sampling visit, then 100 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit
Participants ≥ 3 to ≤ 7 kg:
100 mg once per day through the intensive PK sampling visit, then 50 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit
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Participants >7 to <30 kg:
200 mg once per day through the intensive PK sampling visit, then 100 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit
Participants ≥ 3 to ≤ 7 kg:
100 mg once per day through the intensive PK sampling visit, then 50 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit
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| OG001 | Cohort 2 (≥ 2 to < 6 Years) | Participants >7 to <30 kg: 200 mg once per day through the intensive PK sampling visit, then 100 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit |
| OG002 | Cohort 3 (≥ 0 to < 2 Years) | Participants >7 to <30 kg: 200 mg once per day through the intensive PK sampling visit, then 100 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit Participants ≥ 3 to ≤ 7 kg: 100 mg once per day through the intensive PK sampling visit, then 50 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit |
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| OG001 |
| Cohort 2 (≥ 2 to < 6 Years) |
Participants >7 to <30 kg: 200 mg once per day through the intensive PK sampling visit, then 100 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit |
| OG002 | Cohort 3 (≥ 0 to < 2 Years) | Participants >7 to <30 kg: 200 mg once per day through the intensive PK sampling visit, then 100 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit Participants ≥ 3 to ≤ 7 kg: 100 mg once per day through the intensive PK sampling visit, then 50 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit |
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| OG002 |
| Cohort 3 (≥ 0 to < 2 Years) |
Participants >7 to <30 kg: 200 mg once per day through the intensive PK sampling visit, then 100 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit Participants ≥ 3 to ≤ 7 kg: 100 mg once per day through the intensive PK sampling visit, then 50 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit |
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| OG002 | Cohort 3 (≥ 0 to < 2 Years) | Participants >7 to <30 kg: 200 mg once per day through the intensive PK sampling visit, then 100 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit Participants ≥ 3 to ≤ 7 kg: 100 mg once per day through the intensive PK sampling visit, then 50 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit |
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| OG002 | Cohort 3 (≥ 0 to < 2 Years) | Participants >7 to <30 kg: 200 mg once per day through the intensive PK sampling visit, then 100 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit Participants ≥ 3 to ≤ 7 kg: 100 mg once per day through the intensive PK sampling visit, then 50 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit |
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Participants >7 to <30 kg:
200 mg once per day through the intensive PK sampling visit, then 100 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit
Participants ≥ 3 to ≤ 7 kg:
100 mg once per day through the intensive PK sampling visit, then 50 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit
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Participants >7 to <30 kg: 200 mg once per day through the intensive PK sampling visit, then 100 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit Participants ≥ 3 to ≤ 7 kg: 100 mg once per day through the intensive PK sampling visit, then 50 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit |
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Participants >7 to <30 kg: 200 mg once per day through the intensive PK sampling visit, then 100 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit Participants ≥ 3 to ≤ 7 kg: 100 mg once per day through the intensive PK sampling visit, then 50 mg three times per week on Monday, Wednesday, and Friday through the Week 24 visit |
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