Back to resultsPharmacokinetics of Lopinavir/Ritonavir Superboosting in Infants and Young Children Co-infected With HIV and TB
Primary Purpose
Acquired Immunodeficiency Syndrome, Tuberculosis
Status
Completed
Phase
Phase 4
Locations
South Africa
Study Type
Interventional
Intervention
lopinavir with ritonavir in 1:1 ratio
Lopinavir/ritonavir 4:1
Sponsored by
About this trial
This is an interventional treatment trial for Acquired Immunodeficiency Syndrome focused on measuring Human immunideficiency virus, Tuberculosis, superboosting, lopinavir/ritonavir 1:1, Pediatric TB/HIV co-infection
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.
Sites / Locations
- The Children's Infectious Disease Clinical Research Unit; University of Stellenbosch
- Enhancing Care Foundation; Wendworth Hospital
- Perinatal HIV Research Unit
- Shandukani Research WRHI
- Empilweni Services and Research Unit
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
TB/HIV co-infection
Arm Description
Superboosting lopinavir with ritonavir in 1:1 ratio during TB/HIV co-infection and treatment of HIV with lopinavir/ritonavir 4:1
Outcomes
Primary Outcome Measures
Modelled C0/morning trough
Proportions of children treated with modelled lopinavir morning C0/morning trough <1mg/L at each of the intensive PK evaluations.
Secondary Outcome Measures
C0/morning trough
Proportions of children with observed lopinavir morning trough, C0/morning trough <1mg/L at each of the intensive PK evaluations
ALT
Safety and tolerability of superboosting focusing on liver functions through clinical and biochemical monitoring.
ECG
Potential superboosting cardiac effect monitored by electrocardiogram at the beginning of anti-TB and HIV concomitant therapy
Full Information
NCT ID
NCT02348177
First Posted
December 3, 2014
Last Updated
May 10, 2017
Sponsor
Drugs for Neglected Diseases
Collaborators
University of Cape Town, Medecins Sans Frontieres, Netherlands, French Development Agency, UBS Optimus Foundation
1. Study Identification
Unique Protocol Identification Number
NCT02348177
Brief Title
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
2. Study Status
Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
January 2013 (undefined)
Primary Completion Date
December 2016 (Actual)
Study Completion Date
December 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Drugs for Neglected Diseases
Collaborators
University of Cape Town, Medecins Sans Frontieres, Netherlands, French Development Agency, UBS Optimus Foundation
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acquired Immunodeficiency Syndrome, Tuberculosis
Keywords
Human immunideficiency virus, Tuberculosis, superboosting, lopinavir/ritonavir 1:1, Pediatric TB/HIV co-infection
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
96 (Actual)
8. Arms, Groups, and Interventions
Arm Title
TB/HIV co-infection
Arm Type
Experimental
Arm Description
Superboosting lopinavir with ritonavir in 1:1 ratio during TB/HIV co-infection and treatment of HIV with lopinavir/ritonavir 4:1
Intervention Type
Drug
Intervention Name(s)
lopinavir with ritonavir in 1:1 ratio
Other Intervention Name(s)
Lopinavir/ritonavir, Ritonavir
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Lopinavir/ritonavir 4:1
Other Intervention Name(s)
Lopinavir/ritonavir
Intervention Description
This is the conventional dosing of LPV/r 4:1 for HIV when TB treatment has not been started or has been stopped
Primary Outcome Measure Information:
Title
Modelled C0/morning trough
Description
Proportions of children treated with modelled lopinavir morning C0/morning trough <1mg/L at each of the intensive PK evaluations.
Time Frame
Predose
Secondary Outcome Measure Information:
Title
C0/morning trough
Description
Proportions of children with observed lopinavir morning trough, C0/morning trough <1mg/L at each of the intensive PK evaluations
Time Frame
Predose
Title
ALT
Description
Safety and tolerability of superboosting focusing on liver functions through clinical and biochemical monitoring.
Time Frame
baseline, PK1, PK2, PK3
Title
ECG
Description
Potential superboosting cardiac effect monitored by electrocardiogram at the beginning of anti-TB and HIV concomitant therapy
Time Frame
baseline, 2 weeks after LPV/r 1:1, PK1
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Weeks
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark Cotton, Professor
Organizational Affiliation
University of Stellenbosch
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Children's Infectious Disease Clinical Research Unit; University of Stellenbosch
City
Cape Town
State/Province
Western Cape
ZIP/Postal Code
7505
Country
South Africa
Facility Name
Enhancing Care Foundation; Wendworth Hospital
City
Durban
ZIP/Postal Code
4013
Country
South Africa
Facility Name
Perinatal HIV Research Unit
City
Johannesburg
ZIP/Postal Code
1864
Country
South Africa
Facility Name
Shandukani Research WRHI
City
Johannesburg
ZIP/Postal Code
2001
Country
South Africa
Facility Name
Empilweni Services and Research Unit
City
Johannesburg
ZIP/Postal Code
2093
Country
South Africa
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Zhang C, Denti P, Decloedt EH, Ren Y, Karlsson MO, McIlleron H. Model-based evaluation of the pharmacokinetic differences between adults and children for lopinavir and ritonavir in combination with rifampicin. Br J Clin Pharmacol. 2013 Nov;76(5):741-51. doi: 10.1111/bcp.12101.
Results Reference
background
PubMed Identifier
32071055
Citation
Rabie H, Tikiso T, Lee J, Fairlie L, Strehlau R, Bobat R, Liberty A, McIlleron H, Andrieux-Meyer I, Cotton M, Lallemant M, Denti P. Abacavir Exposure in Children Cotreated for Tuberculosis with Rifampin and Superboosted Lopinavir-Ritonavir. Antimicrob Agents Chemother. 2020 Apr 21;64(5):e01923-19. doi: 10.1128/AAC.01923-19. Print 2020 Apr 21.
Results Reference
derived
PubMed Identifier
30529029
Citation
Rabie H, Denti P, Lee J, Masango M, Coovadia A, Pillay S, Liberty A, Simon F, McIlleron H, Cotton MF, Lallemant M. Lopinavir-ritonavir super-boosting in young HIV-infected children on rifampicin-based tuberculosis therapy compared with lopinavir-ritonavir without rifampicin: a pharmacokinetic modelling and clinical study. Lancet HIV. 2018 Dec 6:S2352-3018(18)30293-5. doi: 10.1016/S2352-3018(18)30293-5. Online ahead of print.
Results Reference
derived
Learn more about this trial
Pharmacokinetics of Lopinavir/Ritonavir Superboosting in Infants and Young Children Co-infected With HIV and TB
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