Pharmacokinetics of Antituberculosis Drugs in Breastfeeding Women

NCT07069582 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: PRIME_V.2.0
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a sub-study of the SSTARLET trial (NCT06498414). The overall aim is to assess the pharmacokinetic profiles after taking a single dose of rifampicin, isoniazid, levofloxacin, rifapentine, and bedaquiline in breastfeeding women and the excretion of these drugs in breast milk, with the hope of including breastfeeding women in future clinical trials of TPT, including expanding the inclusion criteria of the SSTARLET trial. In this study, healthy breastfeeding women who fulfill the eligibility criteria will be enrolled from several primary health care centers in Bandung, which will be referred to the TB Research Clinic of the Universitas Padjadjaran, Bandung, Indonesia. Ten participants will be randomized to each of the following six study arms:

• Arm A: Single-dose rifampicin at 10 mg/kg body weight (RIF10).
• Arm B: Single-dose rifampicin at 20 mg/kg body weight (RIF20).
• Arm C: Single-dose isoniazid at 5 mg/kg body weight (INH5).
• Arm D: Single-dose levofloxacin at 10-15 mg/kg body weight (LFX10-15).
• Arm E: Single-dose rifapentine at 10 mg/kg body weight (RPT10).
• Arm F: Single-dose bedaquiline at 400 mg (BDQ400).

Conditions

Tuberculosis Infection; Healthy Volunteer; Breastfeeding

Keywords

Tuberculosis infection; Latent tuberculosis infection; TBI; LTBI; Breastfeeding women; Rifampicin; Levofloxacin; Rifapentine; Isoniazid; Bedaquiline

Outcome Measures

Primary Outcomes (2)

• Area under the concentration-time curve from 0 to 24 hours (AUC0-24)

  Total drug exposures in plasma and breast milk, i.e., the total area under the concentration-time curve from 0 to 24 hours (AUC0-24) after administration of rifampicin, isoniazid, levofloxacin, rifapentine, and bedaquiline.

  Day 1 following single-dose drug administration

• Peak concentration (Cmax)

  Peak concentration (Cmax) in plasma and breast milk after administration of rifampicin, isoniazid, levofloxacin, rifapentine, and bedaquiline.

  Day 1 following single-dose drug administration

Secondary Outcomes (4)

• Time to Cmax (Tmax)

  Day 1 following single-dose drug administration

• Apparent clearance (CL/F)

  Day 1 following single-dose drug administration

• Apparent volume of distribution (Vd/F)

  Day 1 following single-dose drug administration

• Half-life (t1/2)

  Day 1 following single-dose drug administration

Study Arms (6)

10 mg/kg rifampicin (RIF10)

EXPERIMENTAL

Single-dose rifampicin at 10 mg/kg body weight

Drug: Standard dose rifampicin

20 mg/kg rifampicin (RIF20)

EXPERIMENTAL

Single-dose rifampicin at 20 mg/kg body weight

Drug: High dose rifampicin

5 mg/kg isoniazid (INH5)

EXPERIMENTAL

Single-dose isoniazid at 5 mg/kg body weight

Drug: Standard dose isoniazid

10-15 mg/kg levofloxacin (LFX10-15)

EXPERIMENTAL

Single-dose levofloxacin at 10-15 mg/kg body weight

Drug: Standard dose levofloxacin

10 mg/kg rifapentine (RPT10)

EXPERIMENTAL

Single-dose rifapentine at 10 mg/kg body weight

Drug: Standard dose rifapentine

400 mg bedaquiline (BDQ400)

EXPERIMENTAL

Single-dose bedaquiline at 400 mg

Drug: Standard dose bedaquiline

Interventions

Standard dose rifampicin DRUG

Single-dose rifampicin at 10 mg/kg body weight

Also known as: RIF10

10 mg/kg rifampicin (RIF10)

High dose rifampicin DRUG

Single-dose rifampicin at 20 mg/kg body weight

Also known as: RIF20

20 mg/kg rifampicin (RIF20)

Standard dose isoniazid DRUG

Single-dose isoniazid at 5 mg/kg body weight

Also known as: INH5

5 mg/kg isoniazid (INH5)

Standard dose levofloxacin DRUG

Single-dose levofloxacin at 10-15 mg/kg body weight

Also known as: LFX10-15

10-15 mg/kg levofloxacin (LFX10-15)

Standard dose rifapentine DRUG

Single-dose rifapentine at 10 mg/kg body weight

Also known as: RPT10

10 mg/kg rifapentine (RPT10)

Standard dose bedaquiline DRUG

Single-dose bedaquiline at 400 mg

Also known as: BDQ400

400 mg bedaquiline (BDQ400)

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Breastfeeding women
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants may enter the study if all of the following apply:
• Healthy breastfeeding women aged 18 years or older, with a minimum of 3 months and a maximum of 24 months after delivery of a healthy baby, and are not currently diagnosed with either TB infection or TB disease.
• Have a body weight between 25 and 100 kg.
• Provide written informed consent.

You may not qualify if:

• Participants may not enter the study if any of the following criteria apply:
• Grade 3-4 abnormalities on baseline blood chemistry tests, including serum alanine aminotransferase (ALT), creatinine, or blood glucose.
• Grade 3-4 abnormalities on baseline hematological tests, including white blood count, platelets, or hemoglobin.
• Contraindications or history of hypersensitivity/intolerance to rifampicin, isoniazid, levofloxacin, rifapentine, or bedaquiline.
• Taking concomitant medications for TB disease, TB infection, diabetes mellitus, hypertension, HIV, cardiac disease or any other chronic diseases.
• Having a breastfed infant who was diagnosed with TB infection or TB disease and is currently on treatment.
• Pregnancy
• Have an active, acute illness at the time of study enrolment.

Sponsors & Collaborators

• McGill University Health Centre/Research Institute of the McGill University Health Centre: lead
• Faculty of Medicine Universitas Padjadjaran: collaborator

Study Sites (1)

Universitas Padjadjaran, Klinik Penelitian Tuberculosis (TB Research Clinic)

Bandung, West Java, 40161, Indonesia

Location

MeSH Terms

Conditions

Latent Tuberculosis; Breast Feeding

Interventions

Rifampin; Isoniazid; Levofloxacin; rifapentine; bedaquiline

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Latent Infection; Feeding Behavior; Behavior

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Hydrazines; Organic Chemicals; Isonicotinic Acids; Acids, Heterocyclic; Pyridines; Heterocyclic Compounds, 1-Ring; Ofloxacin; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring

Study Officials

• Dick Menzies, MD

  Research Institute of the McGill University Health Centre, Montreal, Canada

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dick Menzies, MD

CONTACT

514-934-1934; dick.menzies@mcgill.ca

Fajri Gafar, PhD

CONTACT

514-248-8108; fajri.gafar@mail.mcgill.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Simple randomization will be performed, with a ratio of 1:1:1:1:1:1 for rifampicin at 10 mg/kg (RIF10), rifampicin at 20 mg/kg (RIF20), levofloxacin at 10-15 mg/kg (LFX10-15), rifapentine at 10 mg/kg (RPT10), isoniazid at 5 mg/kg (INH5), and bedaquiline at 40 mg (BDQ400).

Study Record Dates

• First Submitted: June 12, 2025
• First Posted: July 16, 2025
• Study Start: April 1, 2026
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): October 31, 2026
• Last Updated: February 10, 2026

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Protocol and consent form will be available once approval is received from the research ethical board and will remain available.
• Access Criteria: Access criteria will be specified in the plan for data sharing, once available.

Locations

ID (1)