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

NCT01172535 | Completed Phase 2 Results DMC

• 3 other identifiers: P108310787IMPAACT P1083
• Study Type: interventional
• Target: 97
• Locations: 4 countries
• Sites: 19

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.

Conditions

HIV

Keywords

Lopinavir/ritonavir; Pediatric dosing; World Health Organization

Outcome Measures

Primary Outcomes (7)

• 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 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 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 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 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 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 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 at study completion (week 24)

Secondary Outcomes (3)

• Adherence

  Measured at week 4, week 12, and study completion (week 24)

• Treatment Efficacy (HIV Viral Load)

  Measured at entry and study completion (week 24)

• Treatment Efficacy (CD4%)

  Measured at entry and study completion (week 24)

Study Arms (1)

Lopinavir/ritonavir

EXPERIMENTAL

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

Drug: Lopinavir/ritonavir

Interventions

Lopinavir/ritonavir 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

Also known as: Kaletra, LPV/r

Lopinavir/ritonavir

Eligibility Criteria

• Age: 4 Weeks+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (19)

University of California, UC San Diego CRS

La Jolla, California, 92093-0672, United States

Location

Univ. of Colorado Denver NICHD CRS

Aurora, Colorado, 80045, United States

Location

Boston Medical Center Ped. HIV Program NICHD CRS

Boston, Massachusetts, 02118, United States

Location

SOM Federal University Minas Gerais Brazil NICHD CRS

Belo Horizonte, Minas Gerais, 30130-100, Brazil

Location

Hosp. Santa Casa Porto Alegre Brazil NICHD CRS

Porto Alegre, Rio Grande do Sul, 90020-090, Brazil

Location

Hospital Federal dos Servidores do Estado NICHD CRS

Rio de Janeiro, 20221-903, Brazil

Location

Instituto de Puericultura e Pediatria Martagao Gesteira - UFRJ NICHD CRS

Rio de Janeiro, 21941-612, Brazil

Location

Hosp. Geral De Nova Igaucu Brazil NICHD CRS

Rio de Janeiro, 26030, Brazil

Location

Inst de Infectologia Emilio Ribas Sao Paulo Brazil NICHD CRS

São Paulo, 01246-900, Brazil

Location

Univ. of Sao Paulo Brazil NICHD CRS

São Paulo, 14049-900, Brazil

Location

Shandukani CRS

Johannesburg, Gauteng, 2001, South Africa

Location

Family Clinical Research Unit (FAM-CRU) CRS

Tygerberg, Western Cape, 7505, South Africa

Location

Bhumibol Adulyadej Hosp. CRS

Saimai, Bangkok, 10220, Thailand

Location

Siriraj Hospital Mahidol University CRS

Bangkok, Bangkoknoi, 10700, Thailand

Location

Prapokklao Hosp. CRS

Chanthaburi, 22000, Thailand

Location

Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS

Chiang Mai, 50200, Thailand

Location

Chiangrai Prachanukroh Hospital CRS

Chiangrai, 57000, Thailand

Location

Chonburi Hosp. CRS

Chon Buri, 2000, Thailand

Location

Phayao Provincial Hosp. CRS

Phayao, 56000, Thailand

Location

MeSH Terms

Interventions

Lopinavir; lopinavir-ritonavir drug combination

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Melissa Allen, Director, IMPAACT Operations Center
• Organization: Family Health International (FHI 360)

mallen@fhi360.org

(919) 405-1429

Study Officials

• Jorge A. Pinto, MD

  Federal University of Minas Gerais

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2010
• First Posted: July 29, 2010
• Study Start: November 1, 2010
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: November 5, 2021
• Results First Posted: December 21, 2015

Record last verified: 2015-11

Locations

TH (7); ZA (2); BR (7); US (3)