Phase 3
Completed N=97
A Phase II/III Trial of Lopinavir/Ritonavir Dosed According to the WHO Pediatric Weight Band Dosing Guidelines
Source: ClinicalTrials.gov NCT01172535 ↗Enrolled (actual)
97
Serious AEs
20.6%
Results posted
Dec 2015
Primary outcomePrimary: Lopinovir/Ritonavir Area Under the Concentration-time Curve (AUC0-24) — 196 mcg*hr/mL
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Lopinovir/Ritonavir Area Under the Concentration-time Curve (AUC0-24) |
196 | — |
| PRIMARY Maximum Concentration of Lopinavir/Ritonavir (Cmax) |
11.25 | — |
| PRIMARY Minimum Concentration of Lopinavir/Ritonavir (Cmin) |
2.47 | — |
| PRIMARY Clearance of Lopinavir/Ritonavir (CL/F) |
0.15 | — |
| PRIMARY Proportion of Participants With an AUC of Less Than 10% of Adults |
0.15 | — |
| PRIMARY Number of Participants Experiencing Adverse Events of Grade 3 or 4 |
32 | — |
| PRIMARY Proportion of Participants Tolerating LPV/r |
0.93 | — |
| SECONDARY Adherence |
1.00; 0.99; 1.00 | — |
| SECONDARY Treatment Efficacy (HIV Viral Load) |
0.72 | — |
| SECONDARY Treatment Efficacy (CD4%) |
0.71 | — |
Eligibility 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
Data sourced from ClinicalTrials.gov (NCT01172535). 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.