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

NCT00623597 | Completed Phase 2 Results

• 2 other identifiers: NV209112007-004617-34
• Study Type: interventional
• Target: 18
• Locations: 3 countries
• Sites: 10

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.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (11)

• 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.

  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.

  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

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  Baseline (Day 1), Week 24 and Week 48

Secondary Outcomes (10)

• Plasma Trough Concentrations (Ctrough) for Ritonavir

  Pre-dose at Weeks 8, 12, 24

• Maximum Observed Concentration (Cmax) for Saquinavir and Ritonavir

  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

  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

  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

  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.

Study Arms (1)

1

EXPERIMENTAL

Drug: ritonavir; Drug: saquinavir [Invirase]

Interventions

ritonavir DRUG

2.5-3.0mg/kg po bid (starting dose) for 48 weeks

1

saquinavir [Invirase] DRUG

50mg/kg po bid (starting dose) for 48 weeks

1

Eligibility Criteria

• Age: 4 Months - 6 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (10)

Unknown Facility

Buenos Aires, 1202, Argentina

Location

Unknown Facility

Buenos Aires, 1425, Argentina

Location

Unknown Facility

Santa Fe, 3000, Argentina

Location

Unknown Facility

Madrid, Madrid, 28046, Spain

Location

Unknown Facility

Madrid, Madrid, 28905, Spain

Location

Unknown Facility

Valencia, Valencia, 46009, Spain

Location

Unknown Facility

Bangkok, 10400, Thailand

Location

Unknown Facility

Khon Kaen, 40002, Thailand

Location

Unknown Facility

Pathumwan, 10330, Thailand

Location

Unknown Facility

Payathai, 10400, Thailand

Location

MeSH Terms

Conditions

HIV Infections

Interventions

Ritonavir; Saquinavir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Quinolines

Results Point of Contact

• Title: Roche Trial Information Hotline
• Organization: F. Hoffmann-La Roche AG

global.trial_information@roche.com

+41 61 6878333

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2008
• First Posted: February 26, 2008
• Study Start: June 1, 2008
• Primary Completion: March 1, 2010
• Study Completion: March 1, 2010
• Last Updated: March 7, 2016
• Results First Posted: January 14, 2016

Record last verified: 2016-02

Data Sharing

• IPD Sharing: Will share

Locations

ES (3); AR (3); TH (4)