A Phase II/III Trial of Lopinavir/Ritonavir Dosed According to the WHO Pediatric Weight Band Dosing Guidelines

NCT ID: NCT01172535

Last Updated: 2021-11-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 97 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-11-30
• Study Completion Date: 2013-12-31

Brief 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 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.

Conditions

HIV

Keywords

Lopinavir/ritonavir; Pediatric dosing; World Health Organization

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Lopinavir/ritonavir

Participants will receive lopinavir/ritonavir in addition to two nucleoside reverse transcriptase inhibitors (NRTIs) chosen by their doctors.

Group Type: EXPERIMENTAL

Lopinavir/ritonavir

Intervention Type: DRUG

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

Interventions

Lopinavir/ritonavir

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

Intervention Type: DRUG

Other Intervention Names

Kaletra; LPV/r

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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
• 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

• Minimum Eligible Age: 4 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jorge A. Pinto, MD

Role: STUDY_CHAIR

Federal University of Minas Gerais

Locations

University of California, UC San Diego CRS

La Jolla, California, United States

Univ. of Colorado Denver NICHD CRS

Aurora, Colorado, United States

Boston Medical Center Ped. HIV Program NICHD CRS

Boston, Massachusetts, United States

SOM Federal University Minas Gerais Brazil NICHD CRS

Belo Horizonte, Minas Gerais, Brazil

Hosp. Santa Casa Porto Alegre Brazil NICHD CRS

Porto Alegre, Rio Grande do Sul, Brazil

Hospital Federal dos Servidores do Estado NICHD CRS

Rio de Janeiro, , Brazil

Instituto de Puericultura e Pediatria Martagao Gesteira - UFRJ NICHD CRS

Rio de Janeiro, , Brazil

Hosp. Geral De Nova Igaucu Brazil NICHD CRS

Rio de Janeiro, , Brazil

Inst de Infectologia Emilio Ribas Sao Paulo Brazil NICHD CRS

São Paulo, , Brazil

Univ. of Sao Paulo Brazil NICHD CRS

São Paulo, , Brazil

Shandukani CRS

Johannesburg, Gauteng, South Africa

Family Clinical Research Unit (FAM-CRU) CRS

Tygerberg, Western Cape, South Africa

Bhumibol Adulyadej Hosp. CRS

Saimai, Bangkok, Thailand

Siriraj Hospital Mahidol University CRS

Bangkok, Bangkoknoi, Thailand

Prapokklao Hosp. CRS

Chanthaburi, , Thailand

Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS

Chiang Mai, , Thailand

Chiangrai Prachanukroh Hospital CRS

Chiangrai, , Thailand

Chonburi Hosp. CRS

Chon Buri, , Thailand

Phayao Provincial Hosp. CRS

Phayao, , Thailand

Countries

Puerto Rico; United States; Brazil; South Africa; Thailand

Other Identifiers

10787

Identifier Type: REGISTRY

Identifier Source: secondary_id

IMPAACT P1083

Identifier Type: -

Identifier Source: secondary_id

P1083

Identifier Type: -

Identifier Source: org_study_id

NCT01338038

Identifier Type: -

Identifier Source: nct_alias