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

Tuberculosis Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02348177
• Other study ID #: DNDiHIVPed001
• Status: Completed
• Phase: Phase 4
• First received: December 3, 2014
• Last updated: May 10, 2017
• Start date: January 2013
• Est. completion date: December 2016

Study information

• Verified date: May 2017
• Source: Drugs for Neglected Diseases
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 96
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Immunologic Deficiency Syndromes
• Tuberculosis

Intervention

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
• 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

Locations

Country	Name	City	State
South Africa	The Children's Infectious Disease Clinical Research Unit; University of Stellenbosch	Cape Town	Western Cape
South Africa	Enhancing Care Foundation; Wendworth Hospital	Durban
South Africa	Empilweni Services and Research Unit	Johannesburg
South Africa	Perinatal HIV Research Unit	Johannesburg
South Africa	Shandukani Research WRHI	Johannesburg

Sponsors (5)

Lead Sponsor	Collaborator
Drugs for Neglected Diseases	French Development Agency, Medecins Sans Frontieres, Netherlands, UBS Optimus Foundation, University of Cape Town

Country where clinical trial is conducted

South Africa, 

References & Publications (46)

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* Note: There are 46 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Modelled C0/morning trough	Proportions of children treated with modelled lopinavir morning C0/morning trough <1mg/L at each of the intensive PK evaluations.	Predose
Secondary	C0/morning trough	Proportions of children with observed lopinavir morning trough, C0/morning trough <1mg/L at each of the intensive PK evaluations	Predose
Secondary	ALT	Safety and tolerability of superboosting focusing on liver functions through clinical and biochemical monitoring.	baseline, PK1, PK2, PK3
Secondary	ECG	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

External Links

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