Phase 2
Completed N=153
Safety and Pharmacokinetics (PK) of Raltegravir in HIV (Human Immunodeficiency Virus)-Infected Children and Adolescents
Source: ClinicalTrials.gov NCT00485264 ↗Enrolled (actual)
153
Serious AEs
41.0%
Results posted
Dec 2014
Primary outcomePrimary: Percentage of Participants With Grade 3 or 4 Adverse Events (AEs) — 20.3; 25; 15.4; 30 percentage of participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Grade 3 or 4 Adverse Events (AEs) |
23.7; 25; 23.1; 40; 42.9; 33.3 | — |
| PRIMARY Number of Participants Terminated From Treatment Due to Suspected Adverse Drug Reaction (SADR) Attributable to the Study Medication |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants Who Died |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Pharmacokinetic (PK) Parameter: Area Under the Curve (AUC12h) |
10.2; 13.4; 10.5; 9.5; 9.3; 10.9 | — |
| PRIMARY PK Parameter: Maximum Plasma Concentration (Cmax) |
2813.1; 4055.7; 5314.2; 5204.8; 5683.0; 4299.0 | — |
| PRIMARY PK Parameter: Time to Half of Maximum Plasma Concentration Cmax (T1/2) |
4.9; 3.7; 4.5; 4.1; 3.0; 2.1 | — |
| PRIMARY PK Parameter: Concentration at 12 Hours Postdose (C12h) |
197.0; 399.4; 78.7; 39.5; 56.4; 99.6 | — |
| SECONDARY Percentage of Participants With Grade 3 or 4 Adverse Events (AEs) |
23.7; 25; 23.1; 40; 42.9; 33.3 | — |
| SECONDARY Number of Participants Terminated From Treatment Due to Suspected Adverse Drug Reaction (SADR) Attributable to the Study Medication |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants Who Died |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Percentage of Participants With ≥1 log10 Drop From Baseline in HIV RNA or HIV RNA <400 Copies/mL |
72.4; 50; 76.9; 70; 85.7; 100 | — |
| SECONDARY Change of CD4 Count From Baseline |
114.6; -35.8; 143.4; 147.2; 400.5; 499.2 | — |
| SECONDARY Change of CD4 Percent From Baseline |
4.1; 2.2; 0.8; 5.3; 6.2; 9.0 | — |
Eligibility 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 biliru
Data sourced from ClinicalTrials.gov (NCT00485264). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.