Pharmacology of Antimalarial Therapy With or Without Antiretroviral Therapy

NCT01728961 | Terminated Phase 4

• 2 other identifiers: IMPAACT P1079U01AI068632
• Study Type: interventional
• Target: 19
• Locations: 2 countries
• Sites: 3

Brief Summary

The purpose of this study is to see if taking nevirapine (NVP) for HIV changes the way artemether/lumefantrine (AL) works in children who are co-infected with both HIV and malaria. The brand of AL used in this study is Coartem® Dispersible. This study will compare the blood levels of AL in co-infected children who already take NVP prescribed by their doctor with the co-infected children who do not take anti HIV medicines because they do not meet national guidelines to start them. The study will also assess the safety of using both medications (AL and NVP) in children.

Conditions

HIV Infection; Malaria

Keywords

HIV 1; NVP; malaria; Children; Youth; nevirapine; Coartem Dispersible; Artemether; Lumefantrine; Pharmacokinetics

Outcome Measures

Primary Outcomes (5)

• Area under the curve from time zero to last quantifiable concentration (AUC)

  Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration

  NVP PK: At study entry and study day 3, AL PK: At study days 3, 4, 8, and 14

• Toxicity

  Number of subjects with adverse events of Grade 3 or higher will be recorded

  At study entry and study days 28 and 42

• Maximum observed plasma concentration (Cmax)

  Maximum observed plasma concentration computed for each individual and then summarized for the strata

  NVP PK: At study entry and study day 3, AL PK: At study days 3, 4, 8, and 14

• Minimum observed plasma concentration (Cmin)

  Minimum observed plasma concentration computed for each individual and then summarized for the strata

  NVP PK: At study entry and study day 3, AL PK: At study days 3, 4, 8, and 14

• Toxicity

  Percentage of subjects with adverse events of Grade 3 or higher will be recorded Safety Issue: Yes

  At study days 28 and 42

Secondary Outcomes (2)

• HIV-1 Viral Load

  At study entry and study days 8, 14, and 42

• NVP resistance

  At study entry and study day 42

Study Arms (2)

ARM A: AL + NVP -based ARV treatment

ACTIVE COMPARATOR

AL given to children who test positive for malaria and are already taking NVP as prescribed by their healthcare provider

Drug: Artemether/Lumefantrine (AL)

ARM B: AL with No ARV treatment

ACTIVE COMPARATOR

AL given to children who do not meet national guidelines for beginning ARV treatment

Drug: Artemether/Lumefantrine (AL)

Interventions

Artemether/Lumefantrine (AL) DRUG

Also known as: Coartem Dispersible

ARM A: AL + NVP -based ARV treatment; ARM B: AL with No ARV treatment

Eligibility Criteria

• Age: 3 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age ≥3 to ≤12 years at entry.
• Documentation of HIV-1 infection defined as positive results from two samples collected at different time points. The same method may be used at both time points. All samples tested must be whole blood, serum or plasma.
• Subjects ≤ 18 months of age
• The first test may be any of the following:
• One HIV DNA Polymerase chain reaction (PCR)
• One HIV RNA (quantitative \>5,000 copies/mL or qualitative)
• One HIV culture (prior to August 2009)
• One total HIV nucleic acid
• If the first test(s) is positive, a second sample collected and tested using any of the tests listed above (except for qualitative RNA assays) in a laboratory participating in an appropriate external quality assurance program and NIH-approved.
• Subjects \> 18 months of age
• The first test may be any of the following:
• Two rapid antibody tests from different manufacturers or based on different principles and epitopes
• One rapid antibody test AND one \[enzyme immunoassay (EIA) OR Western blot (WB) OR immunofluorescence OR chemiluminescence\]
• One EIA AND one \[WB OR immunofluorescence OR chemiluminescence\]
• One HIV DNA PCR

You may not qualify if:

• Subjects with ≥ Grade 3 hemoglobin abnormalities (toxicities will be graded by the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, dated December 2004, Clarification August 2009, must be used and is available on the Regulatory Support Center (RSC) web site (http://rsc.tech-res.com/safetyandpharmacovigilance/).
• Severe malnutrition will be defined as (i) body mass index (BMI) Z-score\< -3 Standard Deviations for children ≥5 years old or (ii) Weight-for-Height \<-3 Standard Deviations for children \<5 years old. (See Appendix IV).
• Note: Children will be evaluated for malnutrition at the time they present for study enrollment when screening evaluations are performed.
• Receipt of a protease inhibitor or efavirenz (EFV) within 4 weeks prior to study entry.
• Subjects not on ART, but who qualify for ART, according to national guidelines (based on all data available at time of enrollment).
• Use of AL for prior episode of malaria within 6 weeks of study entry.
• Currently receiving an antimalarial drug other than AL.
• Pregnancy or breastfeeding
• Signs or evidence of severe malaria. Severe malaria is defined as:
• Unarousable coma (if after convulsion, \> 30 minutes)
• OR ANY TWO OF THE FOLLOWING SYMPTOMS:
• Recent febrile convulsions (within 24 hours)
• Altered consciousness (confusion, delirium, psychosis, coma)
• Lethargy
• Unable to drink

Sponsors & Collaborators

• International Maternal Pediatric Adolescent AIDS Clinical Trials Group: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (3)

College of Med. JHU CRS (30301)

Blantyre, Blantyre, Malawi

Location

University of North Carolina Lilongwe (12001)

Lilongwe, Malawi

Location

Makerere University - JHU Research Collaboration (30293)

Kampala, Uganda

Location

MeSH Terms

Conditions

HIV Infections; Malaria

Interventions

Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Protozoan Infections; Parasitic Diseases; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Francesca Aweeka, Pharm.D.

  IMPAACT/UCSF

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2012
• First Posted: November 20, 2012
• Study Start: February 1, 2012
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: May 19, 2014

Record last verified: 2014-05

Locations

UG (1); MA (2)