HIVPhase 2/3NCT01172535
A Phase II/III Trial of Lopinavir/Ritonavir Dosed According to the WHO Pediatric Weight Band Dosing Guidelines
A Phase 2/3 study testing Lopinavir/ritonavir in people with HIV, run by National Institute of Allergy and Infectious Diseases (NIAID) at 19 sites in 4 countries.
Trial summary
Treatment of children and infants with HIV requires modification of medication dosing according to a child's specific weight. For lopinavir/ritonavir (LPV/r), a second line treatment option that is increasingly necessary due to infant drug resistance, this dosing is often complicated and impractical in busy clinical… Read more about this study
- Who is it for?
- Ages 4 weeks and older
- Conditions the study is for
- HIV
- What is being tested?
- Lopinavir/ritonavir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 97 participants
- Where
- 19 sitesin 4 countries
- Study dates
- Nov 2010to Dec 2013
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 weeks and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Weight equal to or greater than 3 kg, but less than 25 kg, at the time of enrollment
- Confirmed diagnosis of HIV-1 infection
- Lopinavir/ritonavir (LPV/r)-treatment naïve and LPV/r-treatment eligible as defined by country-specific guidelines or the WHO pediatric treatment guidelines and confirmed by investigator
- Willingness to take two nucleoside reverse transcriptase inhibitos (NRTIs), in accordance with appropriate national or international treatment guidelines
- Demonstrated ability and willingness to swallow tablets for children larger than 10 kg. This can be assessed before inclusion (for example, a test trial with similar size solid tablet such as tic-tac).
- Participants in the weight band between 10 and 16.9 kg that are unable to swallow tablets will receive liquid formulation
- Parent or legal guardian able and willing to provide written informed consent
Who cannot join
- Planned concurrent use of non-nucleoside reverse transcriptase inhibitors (NNRTIs), integrase inhibitors, or an entry inhibitor
- Planned concurrent protease inhibitor (PI) use, other than LPV/r
- Prior treatment with LPV/r. Prior treatment with other PIs is allowed.
- Results of certain laboratory tests indicating adverse events of Grade 3 or greater
- Results of a lipase test indicating adverse event of Grade 2 or greater or clinical evidence of pancreatitis within 30 days prior to study entry
- Tuberculosis co-treatment with rifampicin-containing regimen
Show all 13Show fewer
- Treatment with any enzyme-inducing antiepileptic drugs, such as henobarbital, phenytoin or carbamazepine
- Clinical condition requiring the use of a prohibited medication (see protocol for more details)
- Clinically unstable child requiring acute treatment for a serious opportunistic infection
- Chemotherapy for active malignancy
- Any clinically significant diseases (other than HIV-1 infection) or clinically significant findings during the screening medical history or physical examination that, in the investigator's opinion, would compromise participation in this study
- Treatment with experimental drugs for any indication within 30 days prior to study entry
- Known history of cardiac conduction abnormality and/or underlying structural heart disease, including congenital long QT
Trial locations and contacts
19 sites in 4 countries.
19 sites in 4 countries
Brazil7 sites
SOM Federal University Minas Gerais Brazil NICHD CRS
Belo Horizonte, Minas Gerais, 30130-100
Hosp. Santa Casa Porto Alegre Brazil NICHD CRS
Porto Alegre, Rio Grande do Sul, 90020-090
Hospital Federal dos Servidores do Estado NICHD CRS
Rio de Janeiro, 20221-903
Instituto de Puericultura e Pediatria Martagao Gesteira - UFRJ NICHD CRS
Rio de Janeiro, 21941-612
Hosp. Geral De Nova Igaucu Brazil NICHD CRS
Rio de Janeiro, 26030
Inst de Infectologia Emilio Ribas Sao Paulo Brazil NICHD CRS
São Paulo, 01246-900
Univ. of Sao Paulo Brazil NICHD CRS
São Paulo, 14049-900
Thailand7 sites
Siriraj Hospital Mahidol University CRS
Bangkok, Bangkoknoi, 10700
Prapokklao Hosp. CRS
Chanthaburi, 22000
Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS
Chiang Mai, 50200
Chiangrai Prachanukroh Hospital CRS
Chiangrai, 57000
Chonburi Hosp. CRS
Chon Buri, 2000
Phayao Provincial Hosp. CRS
Phayao, 56000
Bhumibol Adulyadej Hosp. CRS
Saimai, Bangkok, 10220
United States3 sites
Univ. of Colorado Denver NICHD CRS
Aurora, Colorado, 80045
Boston Medical Center Ped. HIV Program NICHD CRS
Boston, Massachusetts, 02118
University of California, UC San Diego CRS
La Jolla, California, 92093-0672
South Africa2 sites
Shandukani CRS
Johannesburg, Gauteng, 2001
Family Clinical Research Unit (FAM-CRU) CRS
Tygerberg, Western Cape, 7505
About this study
Treatment of children and infants with HIV requires modification of medication dosing according to a child's specific weight. For lopinavir/ritonavir (LPV/r), a second line treatment option that is increasingly necessary due to infant drug resistance, this dosing is often complicated and impractical in busy clinical settings. To address this, the World Health Organization (WHO) has released a simplified dosing table based on infant weight bands. This study will evaluate the absorption, safety, and tolerance of LPV/r in infants when dosed according to the new WHO guidelines.
Read the detailed description
Because of previous exposure to nevirapine or other non-nucleoside reverse transcriptase inhibitors (NNRTIs), either by direct treatment or through their mothers in pregnancy, infants must often receive an alternate antiretroviral regimen that includes LPV/r. Dosing of LPV/r is currently based on a child's specific weight, and calculations of proper dosages are often too complicated to be practical in busy clinics, particularly those in limited resource settings. In order to simplify medication delivery and reduce prescribing errors, the WHO has released a dosing schedule for LPV/r based on groupings of infants and children by weight. This study will evaluate the pharmacokinetics, safety, and tolerance of LPV/r dosed according to these guidelines. The following strata were used to guide accrual:
Number of Participants to be Enrolled by Weight Band:
3-4.9 kg: 11 liquid
5-6.9 kg: 11 liquid
7-9.9 kg: 17 liquid
10-16.9 kg: 11 liquid, 22 tablet
17-19.9 kg: 11 tablet
20-24.9 kg: 11 tablet
Participation in this study will last 6 months. Infant participants and their caretakers will need to attend study visits at entry and Weeks 2, 4, 12, and 24. At entry, participants will be given LPV/r either in liquid or tablet form, depending on whether they can swallow pills. Dosing will be calculated using the WHO schedule. At all study visits, participants will undergo a physical exam and caretakers will be asked about how well the child is taking the study medications. In addition, at Weeks 4, 12, and 24, blood samples will be taken from the participant to determine health and levels of the medication in the body. The visit on Week 4 will also require pharmacokinetic testing, which means the child will need to be monitored at the hospital for 12 hours and complete six additional blood drawls. All other study visits will last 1 to 2 hours.
- Conditions
- HIV
- Being tested
- Lopinavir/ritonavir
- Keywords
- Lopinavir/ritonavir, Pediatric dosing, World Health Organization
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lopinavir/ritonavirDrug
Also called Kaletra, LPV/r
Heat-stable tablets of 100 mg lopinavir, 25 mg ritonavir, or liquid formulation of 80 mg lopinavir, 20 mg ritonavir, dosed according to World Health Organization (WHO) pediatric weight band dosing guidelines
| Study group | Role | What they receive |
|---|---|---|
| Lopinavir/ritonavir | Experimental | Participants will receive lopinavir/ritonavir in addition to two nucleoside reverse transcriptase inhibitors (NRTIs) chosen by their doctors. Receives: Drug: Lopinavir/ritonavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Lopinovir/Ritonavir Area Under the Concentration-time Curve (AUC0-24)
Area under the curve over 24 hours (AUC0-24), as determined by a non-compartmental analysis of 12-hour pharmacokinetic sampling for lopinavir/ritonavir
Measured: Measured at 4 weeks of treatment prior to the observed dose and at 2, 4, 6, 8, and 12 hours post-dose
Maximum Concentration of Lopinavir/Ritonavir (Cmax)
Maximum concentration of lopinavir/ritonavir, as determined by analysis of 12-hour pharmacokinetic sampling
Measured: Measured at 4 weeks of treatment prior to the observed dose and at 2, 4, 6, 8, and 12 hours post-dose
Minimum Concentration of Lopinavir/Ritonavir (Cmin)
Minimum concentration of lopinavir/ritonavir, as determined by analysis of 12-hour pharmacokinetic sampling
Measured: Measured at 4 weeks of treatment prior to the observed dose and at 2, 4, 6, 8, and 12 hours post-dose
Clearance of Lopinavir/Ritonavir (CL/F)
Clearance of lopinavir/ritonavir, as determined by analysis of 12-hour pharmacokinetic sampling
Measured: Measured at 4 weeks of treatment prior to the observed dose and at 2, 4, 6, 8, and 12 hours post-dose
Proportion of Participants With an AUC of Less Than 10% of Adults
Proportion of participants with an AUC less that 10% of adults (AUC0-24 <104 mcg*hr/mL)
Measured: Measured at 4 weeks of treatment prior to the observed dose and at 2, 4, 6, 8, and 12 hours post-dose
Number of Participants Experiencing Adverse Events of Grade 3 or 4
Adverse events were graded by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, dated December, 2004, Clarification August 2009, which is available on the RSC web site (http://rsc.tech-res.com/safetyandpharmacovigilance/). Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = potentially life-threatening, Grade 5 = death
Measured: Measured at study visits through end of study (weeks 2, 4, 12, 24)
Proportion of Participants Tolerating LPV/r
Participants were considered to have tolerated medication if they did not stop treatment before the 24 week PK visit for any reason other than completing treatment or death not related to treatment.
Measured: Measured at study completion (week 24)
Secondary outcomes (3)
Adherence
Adherence, defined as proportion of doses taken (note: proportion could be greater than 1.0 for reasons such as tablets having to be taken twice due to first one being spit out or imprecise measurement of liquid doses)
Measured: Measured at week 4, week 12, and study completion (week 24)
Treatment Efficacy (HIV Viral Load)
Having HIV viral load <400 copies/mL at the week 24 visit
Measured: Measured at entry and study completion (week 24)
Treatment Efficacy (CD4%)
Having CD4%≥25 at the week 24 visit.
Measured: Measured at entry and study completion (week 24)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2010 (estimated)
- Study startNov 2010
- Primary completionDec 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HIVStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 97 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Jorge A. Pinto, MD, Study chair, Federal University of Minas Gerais
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01172535
- Sponsor's protocol ID
- P1083
- Other IDs
- 10787, IMPAACT P1083
- Status last verified
- Nov 2015
- First submitted
- 28 Jul 2010
- Last updated
- 5 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II/III Trial of Lopinavir/Ritonavir Dosed According to the WHO Pediatric Weight Band Dosing Guidelines
- ClinicalTrials.gov ID
- NCT01172535
- Acronym / sponsor ID
- P1083
- Conditions
- HIV
- Keywords
- Lopinavir/ritonavir, Pediatric dosing, World Health Organization
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 97 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Nov 2010
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 29 Jul 2010 (estimated)
- Results
- Posted 21 Dec 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Treatment of children and infants with HIV requires modification of medication dosing according to a child's specific weight. For lopinavir/ritonavir (LPV/r), a second line treatment option that is increasingly necessary due to infant drug resistance, this dosing is often complicated and impractical in busy clinical settings. To address this, the World Health Organization (WHO) has released a simplified dosing table based on infant weight bands. This study will evaluate the absorption, safety, and tolerance of LPV/r in infants when dosed according to the new WHO guidelines.
Detailed description
Because of previous exposure to nevirapine or other non-nucleoside reverse transcriptase inhibitors (NNRTIs), either by direct treatment or through their mothers in pregnancy, infants must often receive an alternate antiretroviral regimen that includes LPV/r. Dosing of LPV/r is currently based on a child's specific weight, and calculations of proper dosages are often too complicated to be practical in busy clinics, particularly those in limited resource settings. In order to simplify medication delivery and reduce prescribing errors, the WHO has released a dosing schedule for LPV/r based on groupings of infants and children by weight. This study will evaluate the pharmacokinetics, safety, and tolerance of LPV/r dosed according to these guidelines. The following strata were used to guide accrual:
Number of Participants to be Enrolled by Weight Band:
3-4.9 kg: 11 liquid
5-6.9 kg: 11 liquid
7-9.9 kg: 17 liquid
10-16.9 kg: 11 liquid, 22 tablet
17-19.9 kg: 11 tablet
20-24.9 kg: 11 tablet
Participation in this study will last 6 months. Infant participants and their caretakers will need to attend study visits at entry and Weeks 2, 4, 12, and 24. At entry, participants will be given LPV/r either in liquid or tablet form, depending on whether they can swallow pills. Dosing will be calculated using the WHO schedule. At all study visits, participants will undergo a physical exam and caretakers will be asked about how well the child is taking the study medications. In addition, at Weeks 4, 12, and 24, blood samples will be taken from the participant to determine health and levels of the medication in the body. The visit on Week 4 will also require pharmacokinetic testing, which means the child will need to be monitored at the hospital for 12 hours and complete six additional blood drawls. All other study visits will last 1 to 2 hours.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lopinavir/ritonavir | Experimental | Drug: Lopinavir/ritonavirParticipants will receive lopinavir/ritonavir in addition to two nucleoside reverse transcriptase inhibitors (NRTIs) chosen by their doctors. |
Who may qualify
- Ages
- 4 weeks and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Weight equal to or greater than 3 kg, but less than 25 kg, at the time of enrollment
- Confirmed diagnosis of HIV-1 infection
- Lopinavir/ritonavir (LPV/r)-treatment naïve and LPV/r-treatment eligible as defined by country-specific guidelines or the WHO pediatric treatment guidelines and confirmed by investigator
- Willingness to take two nucleoside reverse transcriptase inhibitos (NRTIs), in accordance with appropriate national or international treatment guidelines
- Demonstrated ability and willingness to swallow tablets for children larger than 10 kg. This can be assessed before inclusion (for example, a test trial with similar size solid tablet such as tic-tac).
Key exclusion criteria (13 listed)
- Planned concurrent use of non-nucleoside reverse transcriptase inhibitors (NNRTIs), integrase inhibitors, or an entry inhibitor
- Planned concurrent protease inhibitor (PI) use, other than LPV/r
- Prior treatment with LPV/r. Prior treatment with other PIs is allowed.
- Results of certain laboratory tests indicating adverse events of Grade 3 or greater
- Results of a lipase test indicating adverse event of Grade 2 or greater or clinical evidence of pancreatitis within 30 days prior to study entry
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lopinavir/ritonavirAlso: Kaletra, LPV/rHeat-stable tablets of 100 mg lopinavir, 25 mg ritonavir, or liquid formulation of 80 mg lopinavir, 20 mg ritonavir, dosed according to World Health Organization (WHO) pediatric weight band dosing guidelines | Drug | Lopinavir/ritonavir |
Primary outcome
Lopinovir/Ritonavir Area Under the Concentration-time Curve (AUC0-24)
Time frame: Measured at 4 weeks of treatment prior to the observed dose and at 2, 4, 6, 8, and 12 hours post-dose
Area under the curve over 24 hours (AUC0-24), as determined by a non-compartmental analysis of 12-hour pharmacokinetic sampling for lopinavir/ritonavir
Maximum Concentration of Lopinavir/Ritonavir (Cmax)
Time frame: Measured at 4 weeks of treatment prior to the observed dose and at 2, 4, 6, 8, and 12 hours post-dose
Maximum concentration of lopinavir/ritonavir, as determined by analysis of 12-hour pharmacokinetic sampling
Minimum Concentration of Lopinavir/Ritonavir (Cmin)
Time frame: Measured at 4 weeks of treatment prior to the observed dose and at 2, 4, 6, 8, and 12 hours post-dose
Minimum concentration of lopinavir/ritonavir, as determined by analysis of 12-hour pharmacokinetic sampling
Clearance of Lopinavir/Ritonavir (CL/F)
Time frame: Measured at 4 weeks of treatment prior to the observed dose and at 2, 4, 6, 8, and 12 hours post-dose
Clearance of lopinavir/ritonavir, as determined by analysis of 12-hour pharmacokinetic sampling
Proportion of Participants With an AUC of Less Than 10% of Adults
Time frame: Measured at 4 weeks of treatment prior to the observed dose and at 2, 4, 6, 8, and 12 hours post-dose
Proportion of participants with an AUC less that 10% of adults (AUC0-24 <104 mcg*hr/mL)
Number of Participants Experiencing Adverse Events of Grade 3 or 4
Time frame: Measured at study visits through end of study (weeks 2, 4, 12, 24)
Adverse events were graded by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, dated December, 2004, Clarification August 2009, which is available on the RSC web site (http://rsc.tech-res.com/safetyandpharmacovigilance/). Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = potentially life-threatening, Grade 5 = death
Proportion of Participants Tolerating LPV/r
Time frame: Measured at study completion (week 24)
Participants were considered to have tolerated medication if they did not stop treatment before the 24 week PK visit for any reason other than completing treatment or death not related to treatment.
3 secondary outcomes
Adherence
Time frame: Measured at week 4, week 12, and study completion (week 24)
Treatment Efficacy (HIV Viral Load)
Time frame: Measured at entry and study completion (week 24)
Treatment Efficacy (CD4%)
Time frame: Measured at entry and study completion (week 24)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jorge A. Pinto, MD study chair
Federal University of Minas Gerais
19 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Lopinavir/ritonavir in people with HIV, run by National Institute of Allergy and Infectious Diseases (NIAID) at 19 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in Brazil, Thailand, United States, South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Dec 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Lopinovir/Ritonavir Area Under the Concentration-time Curve (AUC0-24) (time frame: Measured at 4 weeks of treatment prior to the observed dose and at 2, 4, 6, 8, and 12 hours post-dose). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2021.