Safety and Pharmacokinetics (PK) of Raltegravir in HIV (Human Immunodeficiency Virus)-Infected Children and Adolescents

• Status: Completed
• Trial end date: 2017-05-18
• Target enrollment: 0
• Participant gender: All

Summary

Integrase is 1 of 3 HIV (Human Immunodeficiency Virus)-1 enzymes required for viral replication. Raltegravir is a drug that prevents integrase from working properly. This drug has been tested for safety and efficacy in adults, but this is the first study to examine raltegravir in children and adolescents. The purpose of this study was to determine the appropriate dose for raltegravir across the pediatric age range from 4 weeks to 18 years of age, by acquiring short and long term safety data, intensive and population pharmacokinetic (PK) data, and efficacy experience with raltegravir in HIV-infected children and adolescents.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Treatments: Raltegravir Potassium

Criteria

Inclusion Criteria for All Participants:

• Documentation of HIV-1 infection, defined as positive results from two samples collected at different time points. More information on this criterion can be found in the protocol.

• For participants in Cohorts I, IIA, IIB, and III: On unchanged therapeutic regimen for at least 12 weeks, or treatment experienced (not including therapy to interrupt maternal-to-child-transmission (MTCT)) but on no treatment for 4 or more weeks prior to study entry. More information on this criterion can be found in the protocol.

• Participants in Cohorts IV must have received therapy to either interrupt MTCT and/or to treat HIV infection and participants in Cohort V must have received therapy to interrupt MTCT but have not received other anti-HIV therapies.

• HIV RNA (ribonucleic acid) of 1,000 copies/mL or greater at screening

• Demonstrated ability or willingness to take assigned raltegravir preparation

• Parent or legal guardian or participant able and willing to provide signed informed consent when applicable

• Female participants who are sexually active and potentially able to become pregnant must use two methods of birth control while on study and for 3 months after stopping study drug. More information on this criterion can be found in the protocol. Male participants must not participate in sperm donation programs. Male participants engaging in sexual activity that could lead to pregnancy must use a condom.

• Willing to be re-registered within same cohort if a dose change is recommended

Exclusion Criteria for All Participants:

• Known Grade 3 or higher of any of the following laboratory tests within 30 days prior to study entry: neutrophil count, hemoglobin, platelets, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lipase, serum creatinine

• Clinical evidence of pancreatitis

• Treatment for active tuberculosis (TB) infection or disease.

• History of lactic acidosis in 3 months prior to study entry. More information on this criterion can be found in the protocol.

• Diagnosis of new Centers for Disease Control Stage C criteria or opportunistic or bacterial infection diagnosed within 30 days prior to study screening and not considered clinically stable

• Prior treatment with another experimental HIV integrase inhibitor

• Immunosuppressive therapy within 30 days prior to beginning raltegravir study treatment. Participants taking short courses of corticosteroids are not excluded.

• Current or anticipated use of any disallowed medications, listed in the protocol.

• Any history of malignancy

• Participants who are unlikely to adhere to the study procedures or keep appointments

• Participants who are planning to relocate during study

• Any clinically significant diseases (other than HIV) or findings during the screening medical history or physical examination that, in the opinion of the investigator, would compromise the outcome of the study

• Current or past participation in an investigational study with a compound or device that is not commercially available within 30 days of signing informed consent

• Participants who are pregnant or breastfeeding. Infants who are receiving breastmilk are allowed to enroll.

• For participants in Cohorts IV and V, participant's caregiver is unable to access clean water supply (as defined by local standards) to re-suspend raltegravir oral granules

Exclusion Criteria for Stage I Participants:

• Stage I mini cohort (initial 4 participants) only: current or anticipated use of antiretroviral regimen that includes atazanavir, tenofovir, or tipranavir during Stage I. Any other commercially available antiretroviral drugs are acceptable.

• Stage I participants enrolling after initial 4 participants: use of atazanavir, tenofovir, or tipranavir prior to the intensive PK testing. More information on this criterion can be found in the protocol.

Exclusion Criteria for Stage II Participants Taking Atazanavir as Part of Their Background Regimen:

• Total bilirubin of Grade 4 or higher within 30 days of study entry

• Total bilirubin value lower than Grade 4 but direct bilirubin or concurrent transaminase greater than 1.5 times the upper limit of normal and participant is symptomatic, within 30 days prior to study entry