A Study of Invirase (Saquinavir)/Ritonavir in HIV-Infected Infants and Children.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00623597
First received: February 18, 2008
Last updated: February 4, 2016
Last verified: February 2016

February 18, 2008
February 4, 2016
June 2008
March 2010   (final data collection date for primary outcome measure)
  • Plasma Trough Concentrations (Ctrough) for Saquinavir [ Time Frame: Pre-dose at Weeks 8, 12, 24. ] [ Designated as safety issue: No ]
    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.
  • Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to Twelve Hours (AUC0-12h) for Saquinavir [ 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). ] [ Designated as safety issue: No ]
    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.
  • Incidence of Adverse Events (AE) and Serious Adverse Events (SAE) [ Time Frame: From Baseline (Day 1) till Week 48 and Follow-up (Week 52) ] [ Designated as safety issue: No ]
    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
  • Change In Hematocrit From Baseline [ Time Frame: Baseline (Day 1), Week 24 and Week 48 ] [ Designated as safety issue: No ]
    Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
  • Change In Hemoglobin, Total Protein And Total Albumin From Baseline [ Time Frame: Baseline (Day 1), Week 24 and Week 48 ] [ Designated as safety issue: No ]
    Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
  • Change In White Blood Cell (WBC), Platelet, Basophil, Lymphocyte, Monocyte, Neutrophil And Eosinophil Cell Counts From Baseline [ Time Frame: Baseline (Day 1), Week 24 and Week 48 ] [ Designated as safety issue: No ]
    Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
  • Change In Red Blood Cell (RBC) Counts From Baseline [ Time Frame: Baseline (Day 1), Week 24 and Week 48 ] [ Designated as safety issue: No ]
    Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
  • 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 [ Time Frame: Baseline (Day 1), Week 24 and Week 48 ] [ Designated as safety issue: No ]
    Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
  • Change In Total Bilirubin, Creatinine, Uric Acid From Baseline [ Time Frame: Baseline (Day 1), Week 24 and Week 48 ] [ Designated as safety issue: No ]
    Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
  • 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 [ Time Frame: Baseline (Day 1), Week 24 and Week 48 ] [ Designated as safety issue: No ]
    Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
  • Change In Hematuria, Glycosuria And Proteinuria From Baseline [ Time Frame: Baseline (Day 1), Week 24 and Week 48 ] [ Designated as safety issue: No ]
    Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
  • AUC0-12h and Ctrough for saquinavir [ Time Frame: Day 14 (or Day 28 for patients switching from an NNRTI-containing regimen) ] [ Designated as safety issue: No ]
  • AEs and laboratory parameters [ Time Frame: Week 24 and Week 48 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00623597 on ClinicalTrials.gov Archive Site
  • Plasma Trough Concentrations (Ctrough) for Ritonavir [ Time Frame: Pre-dose at Weeks 8, 12, 24 ] [ Designated as safety issue: No ]
    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.
  • Maximum Observed Concentration (Cmax) for Saquinavir and 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 ] [ Designated as safety issue: No ]
    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.
  • Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to Twelve Hours (AUC0-12h) 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). ] [ Designated as safety issue: No ]
    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.
  • Change From Baseline in Mean Human Immunodeficiency Virus Viral Load [ 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. ] [ Designated as safety issue: No ]
    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)
  • Number of Participants With Human Immunodeficiency Virus (HIV) -Ribonucleic Acid (RNA) <400 Copies/mL [ 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. ] [ Designated as safety issue: No ]
    The number of participants with HIV-1 RNA results <400 copies/mL were reported
  • Number of Participants With Human Immunodeficiency Virus (HIV) -Ribonucleic Acid (RNA) <50 Copies/mL [ 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. ] [ Designated as safety issue: No ]
    The number of participants with HIV-1 RNA results <50 copies/mL were reported.
  • Number of Participants With >1 Log Decrease From Baseline in Human Immunodeficiency Virus (HIV) -Ribonucleic Acid (RNA ) [ Time Frame: From Week 8 till Week 48 ] [ Designated as safety issue: No ]
    The number of participants experiencing a greater than 1 log drop from baseline (day 1) (log 10 transformed) were reported
  • Number of Participants With Virological Failure [ Time Frame: From Week 12 till Week 48 ] [ Designated as safety issue: No ]
    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.
  • Change From Baseline in Cluster Differentiation Antigen 4 (CD4) Lymphocyte Count [ Time Frame: Baseline (Day 1), Weeks 8, 12, 24, 36, and 48 or upon premature discontinuation ] [ Designated as safety issue: No ]
    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.
  • Change From Baseline in Cluster Differentiation Antigen 8 (CD8) Lymphocyte Count [ Time Frame: Baseline (Day 1), Weeks 8, 12, 24, 36, and 48 or upon premature discontinuation ] [ Designated as safety issue: No ]
    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.
  • AUC0-12h and Ctrough for ritonavir [ Time Frame: Day 14 (or Day 28 for patients switching from an NNRTI-containing regimen) ] [ Designated as safety issue: No ]
  • Change from baseline in HIV-RNA, CD4 and CD8. [ Time Frame: Week 24 and Week 48 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Study of Invirase (Saquinavir)/Ritonavir in HIV-Infected Infants and Children.
A Phase I/II Study of Invirase® Boosted With Ritonavir in HIV Infected Infants and Children 4 Months to Less Than 6 Years Old
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.
Not Provided
Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV Infections
  • Drug: ritonavir
    2.5-3.0mg/kg po bid (starting dose) for 48 weeks
  • Drug: saquinavir [Invirase]
    50mg/kg po bid (starting dose) for 48 weeks
Experimental: 1
Interventions:
  • Drug: ritonavir
  • Drug: saquinavir [Invirase]
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
18
March 2010
March 2010   (final data collection date for primary outcome measure)

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.
Both
4 Months to 6 Years   (Child)
No
Contact information is only displayed when the study is recruiting subjects
Argentina,   Spain,   Thailand
Brazil,   United Kingdom
 
NCT00623597
NV20911, 2007-004617-34
No
Yes
Not Provided
Hoffmann-La Roche
Hoffmann-La Roche
Not Provided
Study Director: Clinical Trials Hoffmann-La Roche
Hoffmann-La Roche
February 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP