Pharmacokinetics of Lopinavir/Ritonavir Superboosting in Infants and Young Children Co-infected With HIV and TB

May 10, 2017 updated by: Drugs for Neglected Diseases

A Pharmacokinetics Study Comparing Lopinavir Plasma Exposure When Given as Lopinavir/Ritonavir (1:1) in the Presence of Rifampicin and Lopinavir/Ritonavir (4:1) Without Rifampicin in HIV and TB Co-infected Children in South Africa.

The purpose of this study is to determine the lopinavir levels in blood of HIV and TB infected children (3-15kg) when given lopinavir/ritonavir in a 1:1 ratio with rifampicin containing TB regimen and its safety.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a multicentre, open label, non-randomized, prospective, noninferiority study to compare the pharmacokinetics of lopinavir administered with superboosting (LPV/r 1:1) and concurrent RIF treatment or with standard boosting (LPV/r 4:1) without concurrent RIF treatment, and to assess the safety, tolerance, and virological effect of superboosting in HIV-TB co-infected infants and children weighing >3 kg and ≤15 kg.

LPV/r will be administered as the liquid 80/20 mg/mL formulation (4:1 standard boosting ratio). During anti-TB treatment, additional RTV liquid formulation will be provided to deliver a 1:1 superboosting ratio of LPV to RTV. Actual doses for antiretrovirals and anti-TB drugs will be based on the South African (SA) weight band dosing recommendations and provided as per the site standard of care.

Study Type

Interventional

Enrollment (Actual)

96

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • South Africa
      • Durban, South Africa, 4013
        • Enhancing Care Foundation; Wendworth Hospital
      • Johannesburg, South Africa, 1864
        • Perinatal HIV Research Unit
      • Johannesburg, South Africa, 2001
        • Shandukani Research WRHI
      • Johannesburg, South Africa, 2093
        • Empilweni Services and Research Unit
    • Western Cape
      • Cape Town, Western Cape, South Africa, 7505
        • The Children's Infectious Disease Clinical Research Unit; University of Stellenbosch

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 weeks and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Documentation of a confirmed diagnosis of HIV-1 infection following SA clinical guidelines
  • Weight >3kg ≤15 kg at enrolment
  • > 42 weeks gestational age
  • On LPV/r-based therapy or about to start a LPV/r-based antiretroviral combination therapy with 2 NRTIs [ABC+3TC or AZT+3TC or d4T+3TC]
  • Clinical diagnosis of TB requiring RIF-based therapy
  • Parent or legal guardian able and willing to provide written informed consent and able to attend study visits.

Exclusion Criteria:

  • For neonates, less than 42 weeks gestation and 14 days old
  • Concomitant/chronic treatment with potent enzyme-inducing/inhibiting drugs other than those in the study treatments . See Appendix E (minor inducers/inhibitors and drugs used as part of management of the condition are allowed eg. Steroids)
  • Anticipation at the start that anti-TB treatment duration will be longer than 9 months
  • Any other condition/finding that, in the investigator's opinion, would compromise the child's participation in this study eg. alanine transferase (ALT) more than 10 times upper limit of normal (ULN), or chronic renal, hepatic or gastrointestinal disease such as malabsorption.
  • Children with known malignancies and contraindications to taking LPV/r
  • Treatment with experimental drugs for any indication within 30 days prior to study entry; participation in another study may be approved by the study team.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: TB/HIV co-infection
Superboosting lopinavir with ritonavir in 1:1 ratio during TB/HIV co-infection and treatment of HIV with lopinavir/ritonavir 4:1
Drug: lopinavir with ritonavir in 1:1 ratio
During co-treatment of rifampicin containing tuberculosis treatment and lopinavir/ritonavir (4:1) based therapy, additional ritonavir is given to make lopinavir/ritonavir 1:1 ratio
Other Names:
  • Lopinavir/ritonavir
  • Ritonavir
Drug: Lopinavir/ritonavir 4:1
This is the conventional dosing of LPV/r 4:1 for HIV when TB treatment has not been started or has been stopped
Other Names:
  • Lopinavir/ritonavir

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Modelled C0/morning trough
Time Frame: Predose
Proportions of children treated with modelled lopinavir morning C0/morning trough <1mg/L at each of the intensive PK evaluations.
Predose

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
C0/morning trough
Time Frame: Predose
Proportions of children with observed lopinavir morning trough, C0/morning trough <1mg/L at each of the intensive PK evaluations
Predose
ALT
Time Frame: baseline, PK1, PK2, PK3
Safety and tolerability of superboosting focusing on liver functions through clinical and biochemical monitoring.
baseline, PK1, PK2, PK3
ECG
Time Frame: baseline, 2 weeks after LPV/r 1:1, PK1
Potential superboosting cardiac effect monitored by electrocardiogram at the beginning of anti-TB and HIV concomitant therapy
baseline, 2 weeks after LPV/r 1:1, PK1

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Drugs for Neglected Diseases

Collaborators

University of Cape Town
Medecins Sans Frontieres, Netherlands
UBS Optimus Foundation
French Development Agency

Investigators

  • Principal Investigator: Mark Cotton, Professor, University of Stellenbosch

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2013

Primary Completion (ACTUAL)

December 1, 2016

Study Completion (ACTUAL)

December 1, 2016

Study Registration Dates

First Submitted

December 3, 2014

First Submitted That Met QC Criteria

January 22, 2015

First Posted (ESTIMATE)

January 28, 2015

Study Record Updates

Last Update Posted (ACTUAL)

May 11, 2017

Last Update Submitted That Met QC Criteria

May 10, 2017

Last Verified

May 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DNDiHIVPed001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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