IMPAACT P1108, Single Arm Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Bedaquiline (BDQ) in Combination with Optimized Individualized Multidrug-Resistant Tuberculosis (MDR-TB) Therapy in HIV-Infected and HIV-Uninfected Infants, Children and Adolescents with MDR-TB Disease

• Register: CTRI
• Last refreshed on: 24 November 2021
• Main ID: CTRI/2017/12/010751
• Date of registration: 05-12-2017
• Prospective Registration: Yes
• Primary sponsor: NIH DAIDS
• Public title: IMPAACT P1108, Single Arm Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Bedaquiline (BDQ) in Combination with Optimized Individualized Multidrug-Resistant Tuberculosis (MDR-TB) Therapy in HIV-Infected and HIV-Uninfected Infants, Children and Adolescents with MDR-TB Disease
• Scientific title: IMPAACT P1108 A Phase I/II, Open-Label, Single Arm Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Bedaquiline (BDQ) in Combination with Optimized Individualized Multidrug-Resistant Tuberculosis (MDR-TB) Therapy in HIV-Infected and HIV-Uninfected Infants, Children and Adolescents with MDR-TB Disease - IMPAACT 1108
• Date of first enrolment: 11-12-2017
• Target sample size: 72
• Recruitment status: Not Yet Recruiting
• URL: http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=21455
• Study type: Interventional
• Study design: Other; Method of generating randomization sequence:Not Applicable Method of allocation concealment:Not Applicable Blinding and masking:Not Applicable
• Phase: Phase 1/ Phase 2

Countries of recruitment

Haiti, India, South Africa

Contacts

• Name: Dr Nishi Suryavanshi
• Affiliation: BJMC CTU, B J Medical College

• Name: Dr Vidya Mave
• Affiliation: BJMC CTU, B J Medical College

Key inclusion & exclusion criteria

Inclusion criteria: Weight at enrollment:

ï?· Cohort 1: At least 15 kg

ï?· Cohort 2: At least 7 kg

ï?· Cohort 3: At least 3 kg

Documented HIV status Either confirmed or probable MDR-TB Initiated on an OBR MDR-TB regimen as per routine treatment decision
Exclusion criteria: Known or presumed severe extrapulmonary manifestations of TB, including Grades 2 and 3 TB meningitis,

osteo-articular TB,

Pregnant or lactating

A clinically significant active medical condition or concomitant severe (Grade 3 or higher) illness or rapidly deteriorating Known personal or family history of long QT syndromehealth condition (excluding TB),

including immune deficiency,

A significant cardiac arrhythmia that requires medication or a history of heart disease Mean QTcF interval of > 460 ms

Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Health Condition 1: null- HIV-infected and HIV-uninfected infants, children and adolescents treated for clinically diagnosed or confirmed intra-thoracic (pulmonary) MDR-TB

Intervention(s)

Intervention1: Bedaquiline given in combination with an optimized background TB treatment regimen (OBR): 400 mg once per day for two weeks
then 200 mg three times per week
for 22 weeks
200 mg once per day for two weeks
then 100 mg three times per week
for 22 weeks
Control Intervention1: Not applicable: not applicable

Primary Outcome(s)

Determine the BDQ doses that achieve similar weekly exposure (area under the curve; AUC) of BDQ compared to adults taking BDQ at the standard recommended dose.

ï?· Evaluate the safety and tolerability of BDQ over 24 weeks from the initiation of study treatment.Timepoint: 24 weeks

Secondary Outcome(s)

Evaluate the PK of BDQ over the 24-week dosing period, by HIV status.

ï?· Describe the long-term safety and tolerability of BDQ over a 120-week (30-month) total follow-up period, by HIV status.

ï?· Describe BDQ concentrations following BDQ treatment discontinuation at 24 weeks, from study Weeks 24 to 120, by HIV status.

ï?· Describe the MDR-TB treatment response up to 120 weeks from the initiation of the study, by HIV status.Timepoint: 120 weeks

Secondary ID(s)

NIL

Source(s) of Monetary Support

NIH, Maryland, USA

Secondary Sponsor(s)

B J Govt Medical College

Ethics review

Status: Approved
Approval date: 17/05/2017
Contact:

EC-B J Medical College & Sassoon General Hospitals