Clinical trial NCT02348177: Pharmacokinetics of Lopinavir/Ritonavir Superboosting in Infants and Young Children Co-infected With HIV and TB
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Acquired Immunodeficiency Syndrome
Tuberculosis
Keywords: Human immunideficiency virus
Tuberculosis
superboosting
lopinavir/ritonavir 1:1
Pediatric TB/HIV co-infection
Lead sponsor: Drugs for Neglected Diseases
Sponsor class: OTHER
Collaborators: name: University of Cape Town
name: Medecins Sans Frontieres, Netherlands
name: French Development Agency
name: UBS Optimus Foundation
First posted: 2015-01-28
Enrollment: 96
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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 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.

Primary outcomes:
measure: Modelled C0/morning trough
timeFrame: Predose
Secondary outcomes:
measure: C0/morning trough
timeFrame: Predose
measure: ALT
timeFrame: baseline, PK1, PK2, PK3
measure: ECG
timeFrame: baseline, 2 weeks after LPV/r 1:1, PK1
Other outcomes:
Locations:
city: Cape Town
country: South Africa
facility: The Children's Infectious Disease Clinical Research Unit; University of Stellenbosch
state: Western Cape
city: Durban
country: South Africa
facility: Enhancing Care Foundation; Wendworth Hospital
city: Johannesburg
country: South Africa
facility: Perinatal HIV Research Unit
city: Johannesburg
country: South Africa
facility: Shandukani Research WRHI
city: Johannesburg
country: South Africa
facility: Empilweni Services and Research Unit
Study officials:
affiliation: University of Stellenbosch
name: Mark Cotton, Professor
role: PRINCIPAL_INVESTIGATOR
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