TuberculosisPhase 1/2NCT02906007
Evaluating the Pharmacokinetics, Safety, and Tolerability of Bedaquiline in Infants, Children, and Adolescents With Multidrug-Resistant Tuberculosis, Living With or Without HIV
A Phase 1/2 study testing Bedaquiline in people with Tuberculosis and HIV, run by National Institute of Allergy and Infectious Diseases (NIAID) at 4 sites in 2 countries.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 0 months to 17 years
- Conditions the study is for
- Tuberculosis, HIV
- What is being tested?
- Bedaquiline
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 4 sitesin 2 countries
- Study dates
- 21 Sep 2017to 2 Apr 2025
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 months to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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:
- Cohort 1: 6 years of age or older but younger than 18 years of age
- Cohort 2: 2 years of age or older but younger than 6 years of age
- Cohort 3: 0 months of age or older but younger than 2 years of age
- Weight at enrollment:
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- Cohort 1: At least 15 kg
- Cohort 2: Greater than 7 kg
- Cohort 3: At least 3 kg
- 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:
- Peripheral TB lymphadenitis
- Pleural effusion or fibrotic pleural lesions
- Stage 1 TBM or clinically stable Stage 2A TBM*
- Osteoarticular TB, including spinal TB
- Other non-disseminated forms of TB disease OR
- Probable RR-TB (or clinically diagnosed RR-TB) with the inclusion of intrathoracic and/or extrathoracic TB as listed below:
- A presumptive diagnosis of RR-TB based on well-documented clinical symptoms or signs of TB with chest radiological changes (in the case of intrathoracic TB), and/or any of the following extrathoracic disease manifestations:
- Peripheral TB lymphadenitis
- Pleural effusion or fibrotic pleural lesions
- Stage 1 TBM or clinically stable Stage 2A TBM
- Osteoarticular TB, including spinal TB
- Other non-disseminated forms of TB disease
- 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.
- For potential participants living with HIV: At least 14 days prior to entry, initiated an acceptable ART regimen defined as zidovudine/lamivudine/abacavir; NVP and two NRTIs; LPV/r and two NRTIs; an integrase class drug including dolutegravir or raltegravir with two NRTIs; or another regimen approved in advance by the Core Team.
- At entry, the participant has the following laboratory test results according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (refer to the protocol for guidance on severity grading):
- Absolute neutrophil count (normal or grade 1)
- Creatinine (normal or grade 1)
- Aspartate Amino Transferase (AST) (normal or grade 1)
- Alanine Amino Transferase (ALT) (normal or grade 1)
- Total bilirubin (normal or grade 1) Note: Laboratory tests may be repeated during the screening period, with the latest results used for eligibility determination.
- If male and engaging in sexual activity that could lead to pregnancy of the female partner: At entry, participant agrees to use a barrier method of contraception (i.e., male condom), until four weeks after discontinuation of BDQ.
- If female and of reproductive potential, defined as having reached menarche and not having undergone a documented sterilization procedure (hysterectomy, bilateral oophorectomy, or salpingotomy): Negative pregnancy test at screening within five days prior to entry.
- If female, of reproductive potential (defined in the protocol), and engaging in sexual activity that could lead to pregnancy: At entry, participant agrees to avoid pregnancy and to use at least two of the following contraception methods from entry through completion of study follow-up: condoms, diaphragm or cervical cap, intrauterine contraceptive device (IUCD), hormonal-based contraception.
- For Cohort 3 participants less than six months of age: Gestational age at birth greater than or equal to 37 weeks as determined by the site investigator based on parent/guardian report and/or available medical records.
Who cannot join
- Has any documented or suspected clinically significant medical condition or any other condition (excluding HIV and TB) that, in the opinion of the site investigator, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving study objectives.
- Known or presumed severe extrapulmonary manifestations of TB, including Stages 2B and 3 TBM as determined by the site investigator based on participant/parent/guardian report and/or available medical records.
- Participant is breastfeeding a child based on participant/parent/guardian report and/or available medical records.
- A significant cardiac arrhythmia that requires medication or a history of heart disease (heart failure, coronary artery disease) that increases the risk for Torsade de Pointes as determined by the site investigator based on participant/parent/guardian report and available medical records.
- QTcF interval greater than 460 ms (i.e., ECG mean triplicate value greater than 460 ms) at screening. Note: The centralized ECG read should be used during screening for eligibility determination.
- Clinically relevant ECG changes including but not limited to pathological Q-waves (defined as greater than 40 ms or depth greater than 0.4-0.5 mV); evidence of ventricular pre-excitation; evidence of complete or incomplete left bundle branch block or right bundle branch block; evidence of second or third degree heart block; intraventricular conduction delay with QRS duration greater than 120 ms; age-related bradycardia as defined by sinus rate less than lower limit as indicated in the protocol based on available medical records and centralized read of ECGs during screening.
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- Known personal or family history of long QT syndrome as determined by the site investigator based on participant/parent/guardian report and/or available medical records.
- Within eight weeks prior to entry, participation in other clinical studies with investigational agents or devices, unless approved in advance by the Core Team.
- Taking any prohibited medications specified in the protocol within three days prior to entry based on participant/parent/guardian report and/or available medical records.
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
South Africa3 sites
Desmond Tutu TB Centre - Stellenbosch University (DTTC-SU) CRS
Cape Town, Western Cape, 7505
Sizwe CRS
Johannesburg, Gauteng
PHRU Matlosana CRS
Klerksdorp, North West, 2574
Haiti1 site
Les Centres GHESKIO Clinical Research Site (GHESKIO-INLR) CRS
Port-au-Prince, HT-6110
About this study
Official title: A Phase I/II, Open-Label, Single Arm Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Bedaquiline (BDQ) Given in Combination With an Individualized Rifampin-Resistant Tuberculosis (RR-TB) Therapy in Infants, Children, and Adolescents With RR-TB Disease, Living With or Without HIV
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.
Read the detailed description
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.
- Conditions
- Tuberculosis, HIV
- Being tested
- Bedaquiline
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BedaquilineDrug
Also called BDQ
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Bedaquiline |
| 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 Receives: Drug: Bedaquiline |
| 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 Receives: Drug: Bedaquiline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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: 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: 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.
Measured: 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: 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: 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.
Measured: 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).
- Developed a population PK model as part of the final PK analysis
- Data used in the population PK analysis included the intensive PK visit (Week 1 or Week 2), sparse PK samples from Weeks 4, 8, 12, 16, 20, 24, etc,as available at time of final analysis (when all participants have at least Week 24 PK samples)
- Estimated individual AUC values at given time points for each participant using the developed model
Measured: 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 outcomes (20)
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.
Measured: 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: 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: 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: 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: 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: 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: 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: 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: 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).
- Developed a population PK model as part of the final PK analysis
- Data used in the population PK analysis included the intensive PK visit (Week 1 or Week 2), sparse PK samples from Weeks 4, 8, 12, 16, 20, 24, etc,as available at time of final analysis (when all participants have at least Week 24 PK samples)
- Estimated individual AUC values at given time points for each participant using the developed model
Measured: 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).
- Developed a population PK model as part of the final PK analysis
- Data used in the population PK analysis included the intensive PK visit (Week 1 or Week 2), sparse PK samples from Weeks 4, 8, 12, 16, 20, 24, etc,as available at time of final analysis (when all participants have at least Week 24 PK samples)
- Estimated individual AUC values at given time points for each participant using the developed model
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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. "
Measured: Weeks 8, 16, 24, 36, 48, 72, and 96 after BDQ discontinuation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2016 (estimated)
- Study start21 Sep 2017
- Primary completion7 Feb 2024
- Study completion2 Apr 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Anneke Hesseling, M.D., Ph.D., Study chair, Desmond Tutu TB Centre, Stellenbosch University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02906007
- Sponsor's protocol ID
- P1108
- Other IDs
- 11884, IMPAACT P1108
- Status last verified
- Jul 2026
- First submitted
- 14 Sep 2016
- Last updated
- 10 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II, Open-Label, Single Arm Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Bedaquiline (BDQ) Given in Combination With an Individualized Rifampin-Resistant Tuberculosis (RR-TB) Therapy in Infants, Children, and Adolescents With RR-TB Disease, Living With or Without HIV
- ClinicalTrials.gov ID
- NCT02906007
- Acronym / sponsor ID
- P1108
- Conditions
- Tuberculosis, HIV
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Mental Health (NIMH)
- Study start
- 21 Sep 2017 (actual)
- Primary completion
- 7 Feb 2024 (actual)
- Study completion
- 2 Apr 2025 (actual)
- First posted
- 19 Sep 2016 (estimated)
- Results
- Posted 21 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 (>=6 to < 18 years) | Experimental | Drug: BedaquilineParticipants ≥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 |
| Cohort 2 (>=2 to < 6 years) | Experimental | Drug: BedaquilineParticipants >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 |
| Cohort 3 (>=0 to < 2 years) | Experimental | Drug: BedaquilineParticipants >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 |
Who may qualify
- Ages
- 0 months to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (37 listed)
- 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:
Key exclusion criteria (9 listed)
- Has any documented or suspected clinically significant medical condition or any other condition (excluding HIV and TB) that, in the opinion of the site investigator, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving study objectives.
- Known or presumed severe extrapulmonary manifestations of TB, including Stages 2B and 3 TBM as determined by the site investigator based on participant/parent/guardian report and/or available medical records.
- Participant is breastfeeding a child based on participant/parent/guardian report and/or available medical records.
- A significant cardiac arrhythmia that requires medication or a history of heart disease (heart failure, coronary artery disease) that increases the risk for Torsade de Pointes as determined by the site investigator based on participant/parent/guardian report and available medical records.
- QTcF interval greater than 460 ms (i.e., ECG mean triplicate value greater than 460 ms) at screening. Note: The centralized ECG read should be used during screening for eligibility determination.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BedaquilineAlso: BDQParticipants 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. | Drug | Cohort 1 (>=6 to < 18 years), Cohort 2 (>=2 to < 6 years), Cohort 3 (>=0 to < 2 years) |
Primary outcome
Percentage of Participants With Adverse Events of ≥ Grade 3 Severity
Time frame: Measured from entry through Week 24
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).
Percentage of Participants With Adverse Events of ≥ Grade 3 Assessed by the Core Team to be at Least Possibly Related to the Study Drug
Time frame: Measured from entry through Week 24
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.
Percentage of Participants Who Were Terminated From Study Treatment Due to a Drug-related Adverse Event
Time frame: Measured from entry through Week 24
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.
Percentage of Participants Who Died
Time frame: Measured from entry through Week 24
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.
Percentage of Participants With Unstable Dysrhythmias Requiring Hospitalization and Treatment
Time frame: Measured from entry through Week 24
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.
Percentage of Participants With Absolute Corrected QT Interval by Fridericia (QTcF) ≥ 500 Msec
Time frame: All participants had ECG performed at Screening and Entry visits and through week 24.
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.
Geometric Mean of Area Under the Concentration Versus Time Curve (AUC0-24h or AUC0-168h) Bedaquiline
Time frame: 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.
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). * Developed a population PK model as part of the final PK analysis * Data used in the population PK analysis included the intensive PK visit (Week 1 or Week 2), sparse PK samples from Weeks 4, 8, 12, 16, 20, 24, etc,as available at time of final analysis (when all participants have at least Week 24 PK samples) * Estimated individual AUC values at given time points for each participant using the developed model
20 secondary outcomes
Percentage of Participants With Adverse Events ≥ Grade 3 Severity
Time frame: 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.
Time frame: Measured from entry through study completion, up to 120 weeks
Percentage of Participants With Absolute Corrected QT Interval by Fridericia (QTcF) ≥ 500 Msec
Time frame: Measured from entry through study week 40
Percentage of Participants With Unstable Dysrhythmias Requiring Hospitalization and Treatment
Time frame: Measured from entry through study completion, up to 120 weeks
Percentage of Participants Who Died
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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
Time frame: 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)
Time frame: 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
Time frame: 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)
Time frame: 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
Time frame: 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)
Time frame: Intensive PK (Week 1 or 2) pre dose and 2, 4, 6, 8 hours post dose
Geometric Mean of Oral Clearance (CL/F) Bedaquiline
Time frame: Week 24
Geometric Mean of Theoretical Steady State AUC (AUC0-168h)
Time frame: Week 24
Median Quantitative Post-treatment Bedaquiline Concentrations
Time frame: 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)
Time frame: Weeks 8, 16, 24, 36, 48, 72, and 96 after BDQ discontinuation
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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 studyLink provided by the sponsor.
- "Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010"Link provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anneke Hesseling, M.D., Ph.D. study chair
Desmond Tutu TB Centre, Stellenbosch University
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Bedaquiline in people with Tuberculosis and HIV, run by National Institute of Allergy and Infectious Diseases (NIAID) at 4 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 37 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in South Africa, Haiti. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Adverse Events of ≥ Grade 3 Severity (time frame: Measured from entry through Week 24). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2026.