Clinical trial NCT00623597: A Study of Invirase (Saquinavir)/Ritonavir in HIV-Infected Infants and Children.
Official title: A Phase I/II Study of Invirase® Boosted With Ritonavir in HIV Infected Infants and Children 4 Months to Less Than 6 Years Old
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2008-02-26
Enrollment: 18
Sex: ALL
Minimum age (years): 4
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This single arm study will assess the pharmacokinetics, safety and activity of saquinavir (Invirase hard gel capsules, film coated tablets or opened capsules) boosted by combination with ritonavir, in HIV-1 infected infants and children between the ages of 4 months and 6 years. Patients will commence treatment with saquinavir 50mg/kg bid plus ritonavir 2.5mg/kg or 3.0mg/kg (dependent on body weight), and a background antiretroviral regimen. If drug exposures are found to be dissimilar to those previously seen in older children and adults, or are associated with toxicities, subsequent dose adjustments will be made. The anticipated time on study treatment is 3-12 months, and the target sample size is \<100 individuals.


Eligibility criteria: Inclusion Criteria:

* infants and children, 4 months to \<6 years;
* confirmed HIV-1 infection;
* patients for whom saquinavir/ritonavir together with \>=2 background ARVs is considered appropriate.

Exclusion Criteria:

* body weight \>4kg/8.8 pounds;
* use of any concomitant medications that may interfere with the pharmacokinetics of saquinavir or ritonavir;
* malabsorption, severe chronic diarrhea or vomiting within 28 days of the study.

Primary outcomes:
measure: Plasma Trough Concentrations (Ctrough) for Saquinavir
timeFrame: Pre-dose at Weeks 8, 12, 24.
measure: Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to Twelve Hours (AUC0-12h) for Saquinavir
timeFrame: Pre-dose and 3, 4, 8, 12 hours (post-dose) on Day 14 (± 2 days), or Day 28(+ 2 days) for patients switching from an Non-nucleoside reverse transcriptase inhibitor [NNRTI] containing regimen).
measure: Incidence of Adverse Events (AE) and Serious Adverse Events (SAE)
timeFrame: From Baseline (Day 1) till Week 48 and Follow-up (Week 52)
measure: Change In Hematocrit From Baseline
timeFrame: Baseline (Day 1), Week 24 and Week 48
measure: Change In Hemoglobin, Total Protein And Total Albumin From Baseline
timeFrame: Baseline (Day 1), Week 24 and Week 48
measure: Change In White Blood Cell (WBC), Platelet, Basophil, Lymphocyte, Monocyte, Neutrophil And Eosinophil Cell Counts From Baseline
timeFrame: Baseline (Day 1), Week 24 and Week 48
measure: Change In Red Blood Cell (RBC) Counts From Baseline
timeFrame: Baseline (Day 1), Week 24 and Week 48
measure: Change In Creatine Kinase (CK), Serum Glutamic Oxaloacetic Transaminase (SGOT), Alkaline Phosphatase (ALP), Serum Glutamic-Pyruvic Transaminase (SGPT), Gamma-Glutamyl Transferase (GGT) Counts From Baseline
timeFrame: Baseline (Day 1), Week 24 and Week 48
measure: Change In Total Bilirubin, Creatinine, Uric Acid From Baseline
timeFrame: Baseline (Day 1), Week 24 and Week 48
measure: Change In Blood Urea Nitrogen (BUN), Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL Cholesterol), Triglycerides, Calcium, Potassium, Sodium, Chloride, Phosphate, Fasting Glucose From Baseline
timeFrame: Baseline (Day 1), Week 24 and Week 48
measure: Change In Hematuria, Glycosuria And Proteinuria From Baseline
timeFrame: Baseline (Day 1), Week 24 and Week 48
Secondary outcomes:
measure: Plasma Trough Concentrations (Ctrough) for Ritonavir
timeFrame: Pre-dose at Weeks 8, 12, 24
measure: Maximum Observed Concentration (Cmax) for Saquinavir and Ritonavir
timeFrame: Pre-dose and 3, 4, 8, 12 hours (post-dose) on Day 14 (± 2 days), or Day 28(+ 2 days) for patients switching from an NNRTI containing regimen and at Week 24
measure: Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to Twelve Hours (AUC0-12h) for Ritonavir
timeFrame: Pre-dose and 3, 4, 8, 12 hours (post-dose) on Day 14 (± 2 days), or Day 28(+ 2 days) for patients switching from an NNRTI containing regimen).
measure: Change From Baseline in Mean Human Immunodeficiency Virus Viral Load
timeFrame: Baseline (Day 1), Weeks 8, 12, 24, 36, and 48 (or upon premature discontinuation); a baseline collection was made if there was not already a value available taken within the previous 4 weeks.
measure: Number of Participants With Human Immunodeficiency Virus (HIV) -Ribonucleic Acid (RNA) <400 Copies/mL
timeFrame: Baseline (Day 1), Weeks 8, 12, 24, 36, and 48 (or upon premature discontinuation); a baseline collection was made if there was not already a value available taken within the previous 4 weeks.
measure: Number of Participants With Human Immunodeficiency Virus (HIV) -Ribonucleic Acid (RNA) <50 Copies/mL
timeFrame: Baseline (Day 1), Weeks 8, 12, 24, 36, and 48 (or upon premature discontinuation); a baseline collection was made if there was not already a value available taken within the previous 4 weeks.
measure: Number of Participants With >1 Log Decrease From Baseline in Human Immunodeficiency Virus (HIV) -Ribonucleic Acid (RNA )
timeFrame: From Week 8 till Week 48
measure: Number of Participants With Virological Failure
timeFrame: From Week 12 till Week 48
measure: Change From Baseline in Cluster Differentiation Antigen 4 (CD4) Lymphocyte Count
timeFrame: Baseline (Day 1), Weeks 8, 12, 24, 36, and 48 or upon premature discontinuation
measure: Change From Baseline in Cluster Differentiation Antigen 8 (CD8) Lymphocyte Count
timeFrame: Baseline (Day 1), Weeks 8, 12, 24, 36, and 48 or upon premature discontinuation
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
city: Buenos Aires
country: Argentina
city: Santa Fe
country: Argentina
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Valencia
country: Spain
city: Bangkok
country: Thailand
city: Khon Kaen
country: Thailand
city: Pathumwan
country: Thailand
city: Payathai
country: Thailand
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: