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
  Purpose
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.

Condition Intervention Phase
HIV Infections
Drug: ritonavir
Drug: saquinavir [Invirase]
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 18
Study Start Date: June 2008
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 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

  Eligibility

Ages Eligible for Study:   4 Months to 6 Years   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00623597

Locations
Argentina
Buenos Aires, Argentina, 1202
Buenos Aires, Argentina, 1425
Santa Fe, Argentina, 3000
Spain
Madrid, Spain, 28046
Madrid, Spain, 28905
Valencia, Spain, 46009
Thailand
Bangkok, Thailand, 10400
Khon Kaen, Thailand, 40002
Pathumwan, Thailand, 10330
Payathai, Thailand, 10400
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00623597     History of Changes
Other Study ID Numbers: NV20911  2007-004617-34 
Study First Received: February 18, 2008
Results First Received: December 10, 2015
Last Updated: February 4, 2016
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration
Individual Participant Data  
Plan to Share IPD: Yes

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Ritonavir
Saquinavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 27, 2016