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

Information source: Drugs for Neglected Diseases
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Acquired Immunodeficiency Syndrome; Tuberculosis

Intervention: lopinavir with ritonavir in 1:1 ratio (Drug); Lopinavir/ritonavir 4:1 (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Drugs for Neglected Diseases

Official(s) and/or principal investigator(s):
Mark Cotton, Professor, Principal Investigator, Affiliation: University of Stellenbosch

Overall contact:
Jacqueline J Crisp, Phone: +27829402178, Email: crispy@sun.ac.za

Summary

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.

Clinical Details

Official title: 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.

Study design: Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Modelled C0/morning trough

Secondary outcome:

C0/morning trough

ALT

ECG

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.

Eligibility

Minimum age: N/A. Maximum age: N/A. Gender(s): Both.

Criteria:

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.

Locations and Contacts

Jacqueline J Crisp, Phone: +27829402178, Email: crispy@sun.ac.za

Enhancing Care Foundation; Wendworth Hospital, Durban 4013, South Africa; Recruiting
Sandy Pillay, Dr., Email: pillay@ecarefoundation.com
Sandy Pillay, Principal Investigator

Empilweni Services and Research Unit, Johannesburg 2093, South Africa; Recruiting
Salome Mogogane, Email: smogogane@witshealth.co.za
Ashraf Coovadia, Professor, Principal Investigator

Perinatal HIV Research Unit, Johannesburg 1864, South Africa; Recruiting
AFAAF LIBERTY, Dr., Email: libertya@phru.co.za
Afaaf LIBERTY, Principal Investigator

Shandukani Research WRHI, Johannesburg 2001, South Africa; Recruiting
Hermien Gous, Email: hgous@wrhi.ac.za
Gurpreet Kindra, Principal Investigator

The Children's Infectious Disease Clinical Research Unit; University of Stellenbosch, Cape Town, Western Cape 7505, South Africa; Recruiting
Jacqueline J Crisp, Phone: +27 829402178, Email: crispy@sun.ac.za
Helena Rabie, Dr., Sub-Investigator

Additional Information

World Health Organization. Antiretroviral Therapy of HIV Infection in Infants and Children - Recommendations for a Public Health Approach - 2010 revision. [online] Geneva, 2010

WHO, UNAIDS, UNICEF. Global HIV/AIDS response. Epidemic update and health sector progress towards universal access: Progress report 2011. Geneva, WHO, 2011

World Health Organization. "Dosing instructions for the use of currently available fixed-dose combination TB medicines for children."

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Starting date: January 2013
Last updated: January 22, 2015

Page last updated: August 23, 2015

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