A Phase II/III Trial of Lopinavir/Ritonavir Dosed According to the WHO Pediatric Weight Band Dosing Guidelines
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV
Intervention: Lopinavir/ritonavir (Drug)
Phase: Phase 2/Phase 3
Status: Completed
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID) Official(s) and/or principal investigator(s): Jorge A. Pinto, MD, Study Chair, Affiliation: Federal University of Minas Gerais
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.
Clinical Details
Official title: A Phase II/III Trial of Lopinavir/Ritonavir Dosed According to the WHO Pediatric Weight Band Dosing Guidelines
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Safety, as determined by non-occurrence of any recurring Grade 3 or non-life-threatening Grade 4 toxicity, or a single life-threatening Grade 4 toxicityArea under the curve (AUC), as determined by a non-compartmental analysis of 12-hour pharmacokinetic sampling for lopinavir/ritonavir Maximum and minimum concentrations and half-life of lopinavir/ritonavir Proportion of participants with an AUC of less than 10% of adults Number and percent of participants experiencing adverse events of Grade 3 or greater Adherence, defined as proportion of doses taken
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 by weight.
This study will evaluate the pharmacokinetics, safety, and tolerance of LPV/r dosed
according to these guidelines.
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 the infant can
swallow pills. Dosing will be calculated using the WHO schedule. At all study visits, infant
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 infant 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.
Eligibility
Minimum age: N/A.
Maximum age: N/A.
Gender(s): Both.
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
Locations and Contacts
Hosp. Geral De Nova Igaucu Brazil NICHD CRS, Rio de Janeiro 26030, Brazil
Hospital Federal dos Servidores do Estado NICHD CRS, Rio de Janeiro 20221-903, Brazil
Inst of Pediatrics Fed Univ Rio de Janeiro NICHD CRS, Rio de Janeiro 21941-590, Brazil
Inst de Infectologia Emilio Ribas Sao Paulo Brazil NICHD CRS, Sao Paulo 01246-900, Brazil
Univ. of Sao Paulo Brazil NICHD CRS, Sao Paulo 14049-900, Brazil
Prapokklao Hosp. CRS, Chantaburi 22000, Thailand
Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS, Chiang Mai 50200, Thailand
Chiangrai Prachanukroh Hospital CRS, Chiangrai 57000, Thailand
Chonburi Hosp. CRS, Chonburi 2000, Thailand
Phayao Provincial Hosp. CRS, Phayao 56000, Thailand
Bhumibol Adulyadej Hosp. CRS, Saimai, Bangkok 10220, Thailand
Siriraj Hospital Mahidol University CRS, Bangkok, Bangkoknoi 10700, Thailand
University of California, UC San Diego CRS, La Jolla,, California 92093-0672, United States
Univ. of Colorado Denver NICHD CRS, Aurora, Colorado 80045, United States
Shandukani CRS, Johannesburg, Gauteng 2001, South Africa
Boston Medical Center Ped. HIV Program NICHD CRS, Boston, Massachusetts 02118, United States
SOM Federal University Minas Gerais Brazil NICHD CRS, Belo Horizonte, Minas Gerais 30130-100, Brazil
Hosp. Santa Casa Porto Alegre Brazil NICHD CRS, Porto Alegre, Rio Grande do Sul 90020-090, Brazil
Family Clinical Research Unit (FAM-CRU) CRS, Tygerberg, Western Cape Province 7505, South Africa
Additional Information
Starting date: November 2010
Last updated: July 20, 2015
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