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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
18
2.5-3.0mg/kg po bid (starting dose) for 48 weeks
50mg/kg po bid (starting dose) for 48 weeks
Unnamed facility
Buenos Aires, Argentina
Unnamed facility
Buenos Aires, Argentina
Unnamed facility
Santa Fe, Argentina
Unnamed facility
Madrid, Madrid, Spain
Unnamed facility
Madrid, Madrid, Spain
Unnamed facility
Valencia, Valencia, Spain
Unnamed facility
Bangkok, Thailand
Unnamed facility
Khon Kaen, Thailand
Unnamed facility
Pathumwan, Thailand
Unnamed facility
Payathai, Thailand
Plasma Trough Concentrations (Ctrough) for Saquinavir
Plasma trough concentration is the average steady state concentration prior to morning and evening dose. Ctrough of Saquinavir was normalized to a dose of 50 mg/kg.
Time frame: Pre-dose at Weeks 8, 12, 24.
Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to Twelve Hours (AUC0-12h) for Saquinavir
The area under the plasma concentration-time curve from time zero to twelve hours (AUC0-12h) is area under the plasma concentration-time curve from time zero through actual tlast. The area under the plasma concentration-time curve from time zero to twelve hours of saquinavir was normalized to a dose of 50 mg/kg.
Time frame: 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).
Incidence of Adverse Events (AE) and Serious Adverse Events (SAE)
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is a significant medical event in the investigator's judgment or requires intervention to prevent one or other of these outcomes
Time frame: From Baseline (Day 1) till Week 48 and Follow-up (Week 52)
Change In Hematocrit From Baseline
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline (Day 1), Week 24 and Week 48
Change In Hemoglobin, Total Protein And Total Albumin From Baseline
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline (Day 1), Week 24 and Week 48
Change In White Blood Cell (WBC), Platelet, Basophil, Lymphocyte, Monocyte, Neutrophil And Eosinophil Cell Counts From Baseline
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline (Day 1), Week 24 and Week 48
Change In Red Blood Cell (RBC) Counts From Baseline
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline (Day 1), Week 24 and Week 48
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
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline (Day 1), Week 24 and Week 48
Change In Total Bilirubin, Creatinine, Uric Acid From Baseline
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline (Day 1), Week 24 and Week 48
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
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline (Day 1), Week 24 and Week 48
Change In Hematuria, Glycosuria And Proteinuria From Baseline
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline (Day 1), Week 24 and Week 48
Plasma Trough Concentrations (Ctrough) for Ritonavir
Plasma trough concentration is the average steady state concentration prior to morning and evening dose. Ctrough of Ritonavir was normalized to a dose of 100 mg/kg.
Time frame: Pre-dose at Weeks 8, 12, 24
Maximum Observed Concentration (Cmax) for Saquinavir and Ritonavir
The Plasma Concentration (Cmax) is defined as maximum observed analyte concentration. Cmax was normalized to a dose of 50 mg/kg for Saquinavir and100 mg/kg for Ritonavir.
Time frame: 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
Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to Twelve Hours (AUC0-12h) for Ritonavir
The area under the plasma concentration-time curve from time zero to twelve hours (AUC0-12h) is area under the plasma concentration-time curve from time zero through actual tlast. The area under the plasma concentration-time curve from time zero to twelve hours of ritonasvir was normalized to a dose of 100 mg/kg.
Time frame: 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).
Change From Baseline in Mean Human Immunodeficiency Virus Viral Load
Change from baseline in plasma HIV-1 RNA was derived as Change from baseline = Log10 (HIV-1 RNA at week x) - Log10 (HIV-1 RNA at baseline)
Time frame: 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.
Number of Participants With Human Immunodeficiency Virus (HIV) -Ribonucleic Acid (RNA) <400 Copies/mL
The number of participants with HIV-1 RNA results \<400 copies/mL were reported
Time frame: 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.
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Number of Participants With Human Immunodeficiency Virus (HIV) -Ribonucleic Acid (RNA) <50 Copies/mL
The number of participants with HIV-1 RNA results \<50 copies/mL were reported.
Time frame: 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.
Number of Participants With >1 Log Decrease From Baseline in Human Immunodeficiency Virus (HIV) -Ribonucleic Acid (RNA )
The number of participants experiencing a greater than 1 log drop from baseline (day 1) (log 10 transformed) were reported
Time frame: From Week 8 till Week 48
Number of Participants With Virological Failure
Virological failure was defined as: viral load \>= 400 copies/mL on two consecutive occasions (missing visits was assumed to be above 400 copies/mL). The number of participants classified as virological failure by Age Group and viral load (≤ 10,000 copies, \>10,000 copies) were presented.
Time frame: From Week 12 till Week 48
Change From Baseline in Cluster Differentiation Antigen 4 (CD4) Lymphocyte Count
Change from Baseline in CD4+ lymphocyte count at 24 weeks and 48 weeks were presented by age group. Change from baseline in CD4+ lymphocyte count was derived as follows: Change from baseline = (CD4+ count at week 24/48) - (CD4+ count at baseline). A baseline collection was made if there was not already a value available taken within the previous 4 weeks. Baseline was on Day 1.
Time frame: Baseline (Day 1), Weeks 8, 12, 24, 36, and 48 or upon premature discontinuation
Change From Baseline in Cluster Differentiation Antigen 8 (CD8) Lymphocyte Count
Change from baseline in CD8+ lymphocyte count at 24 weeks and 48 weeks were presented by age group. Change from baseline in CD8+ lymphocyte count was derived as follows: Change from baseline = (CD8+ count at week 24/48) - (CD8+ count at baseline). A baseline collection was made if there was not already a value available taken within the previous 4 weeks. Baseline was on Day 1.
Time frame: Baseline (Day 1), Weeks 8, 12, 24, 36, and 48 or upon premature discontinuation