IMPAACT P1106: Pharmacokinetic Characteristics of Antiretrovirals and Tuberculosis Medicines in Low Birth Weight Infants

NCT02383849 | Completed DMC

• 2 other identifiers: IMPAACT P110611882
• Study Type: observational
• Target: 124
• Locations: 1 country
• Sites: 2

Brief Summary

P1106 is Phase IV prospective pharmacokinetic (PK) study of low birth weight infants who are receiving or will be receiving as part of clinical care nevirapine (NVP) prophylaxis, tuberculosis (TB) prophylaxis or treatment and/or combination antiretroviral (ARV) treatment containing lopinavir/ritonavir (LPV/r). The study is designed to describe the pharmacokinetics and safety of NVP, INH, RIF, and LPV/r in these infants receiving the drug(s) as part of clinical care.

Conditions

Low-Birth-Weight Infant; Tuberculosis; HIV

Outcome Measures

Primary Outcomes (1)

• Clearance of NVP, INH, RIF, and LPV/r after oral dose

  Apparent clearance (CL/F) of NVP, INH, RIF, and LPV/r

  Week 24 of life

Secondary Outcomes (1)

• Primary safety endpoints

  Study duration

Study Arms (6)

Arm 1

Breastfeeding infants 7 to 14 days of age with birth weight less than 2500 grams born to HIV-infected mothers not receiving maintenance ARV therapy including NVP; Mother HIV-infected and TB negative; infant receiving NVP prophylaxis but not TB prophylaxis or treatment

Arm 2

Breastfeeding infants 7 to 84 days of age with birth weight less than or equal to 4000 grams born to HIV-infected mothers not receiving maintenance ARV therapy including NVP; Mother HIV-infected with active TB disease; infant receiving NVP prophylaxis plus isoniazid (INH) but not rifampicin (RIF) for TB prophylaxis

Arm 3

Breastfeeding infants 7 to 14 days of age with birth weight less than 2500 grams born to HIV-infected mothers not receiving maintenance ARV therapy including NVP; Mother HIV-infected with active TB disease; infant receiving NVP prophylaxis plus INH plus RIF for TB prophylaxis or treatment

Arm 4

Breast or formula feeding infants 7 to 84 days of age with birth weight less than or equal to 4000 grams born to HIV-uninfected mothers with active TB disease; infant receiving INH alone or INH plus RIF for TB prophylaxis

Arm 5

Breast or formula feeding infants newly diagnosed with HIV infection weighing less than or equal to 4000 grams at birth and are less than or equal to 12 weeks of age. Infants who were enrolled in Arms 1, 2 or 3 and later determined to be HIV infected are then are eligible to enroll in Arm 5 if started on an LPV/r regimen. Infants initiating treatment with LPV/r plus 2 NRTIs, and not receiving RIF (but may be receiving INH)

Arm 6

Breast or formula feeding infants newly diagnosed with HIV infection weighing less than 2500 grams at birth and are less than or equal to 12 weeks of age. Infants who were enrolled in Arms 1, 2 or 3 and later determined to be HIV infected are then are eligible to enroll in Arm 6 if started on an LPV/r regimen. Infants initiating treatment with LPV/r plus 2 NRTIs, and receiving RIF (and may be receiving INH)

Eligibility Criteria

• Age: 7 Days - 84 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Low birth weight (LBW) infants less than or equal to 2500 grams at birth who are receiving or will be receiving as part of clinical care nevirapine (NVP) prophylaxis, tuberculosis (TB) prophylaxis or treatment and/or combination antiretroviral (ARV) treatment containing lopinavir/ritonavir (LPV/r)

You may qualify if:

• Breastfeeding infants born to HIV-infected mothers who are receiving either no ARV therapy or ARV therapy that does not include NVP
• Age 7 to 14 days
• Birth weight less than 2500 grams
• Receiving or will be receiving prophylaxis as prescribed by clinical care provider as follows: NVP (Arm 1), NVP plus INH (Arm 2), NVP plus INH plus RIF (Arm 3)
• Parent or legal guardian able and willing to provide written informed consent. \[Note to sites: modify per locally relevant language\].
• Breastfeeding infants born to HIV-infected mothers who are receiving either no ARV therapy or ARV therapy that does not include NVP
• Age 7 to 84 days
• Birth weight less than or equal to 4000 grams
• Receiving or will be receiving prophylaxis as prescribed by clinical care provider as follows: NVP (Arm 1), NVP plus INH (Arm 2), NVP plus INH plus RIF (Arm 3)
• Parent or legal guardian able and willing to provide written informed consent. \[Note to sites: modify per locally relevant language\].
• Age 7 to 84 days
• Birth weight less than or equal to 4000 grams
• Receiving prophylaxis with INH alone or INH plus RIF as prescribed by clinical care provider
• Not receiving any therapy for HIV prophylaxis or treatment
• Parent or legal guardian able and willing to provide written informed consent. \[Note to sites: modify per locally relevant language\].

You may not qualify if:

• Any severe congenital malformation or other medical condition incompatible with life or that would interfere with study participation or interpretation, as judged by the examining clinician.

Sponsors & Collaborators

• International Maternal Pediatric Adolescent AIDS Clinical Trials Group: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (2)

Soweto IMPAACT CRS (8052)

Johannesburg, Gauteng, 1862, South Africa

Location

Family Clinical Research Unit (FAM-CRU) CRS (8950)

Cape Town, Western Cape, 7505, South Africa

Location

Related Publications (1)

• Bekker A, Yang J, Wang J, Cotton MF, Cababasay M, Wiesner L, Moye J, Browning R, Nakwa FL, Rabie H, Violari A, Mirochnick M, Cressey TR, Capparelli EV. Safety and Pharmacokinetics of Lopinavir/Ritonavir Oral Solution in Preterm and Term Infants Starting Before 3 Months of Age. Pediatr Infect Dis J. 2024 Apr 1;43(4):355-360. doi: 10.1097/INF.0000000000004243. Epub 2024 Jan 4.

  PMID: 38190642 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Cell pellets from PK sampling once will be combined and stored for a DNA extraction, amplification, and gel electrophoresis. The genotype analysis will be completed one time per study participant. All subjects receiving INH will be genotyped for NAT2. All subjects receiving NVP will be genotyped for CYP 2B6. These genotypes will be used as covariates in the population PK analyses of NVP and INH to determine their impact on CL/F (clearance \[apparent\]).

MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Mark Cotton, MD, MBChB, FCPaed, MMED

  University of Stellenbosch

  STUDY CHAIR

• Mark H Mirochnick, MD

  Boston Medical Center

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2014
• First Posted: March 9, 2015
• Study Start: August 4, 2015
• Primary Completion: February 14, 2020
• Study Completion: February 14, 2020
• Last Updated: August 6, 2021

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months following publication and available throughout period of funding of the International Maternal Pediatric Adolescent AIDS Clinical Trial (IMPAACT) Network by NIH.
• Access Criteria: * With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the IMPAACT Network. * For what types of analyses? To achieve aims in the proposal approved by the IMPAACT Network. * By what mechanism will data be made available? Researchers may submit a request for access to data using the IMPAACT "Data Request" form at: https://www.impaactnetwork.org/studies/submit-research-proposal. Researchers of approved proposals will need to sign an IMPAACT Data Use Agreement before receiving the data.

Locations

ZA (2)