BASIC: Boosted Atazanavir or Saquinavir Induced Lipid Changes

NCT00389402 | Completed Phase 4

• 2 other identifiers: 05-IAT-0110Eudract number: 2006-000666-37
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess differences in changes in plasma lipids between patients on saquinavir/ritonavir or atazanavir/ritonavir in combination with tenofovir disoproxil fumarate and emtricitabine as a first-line regimen in patients previously naive for antiretroviral therapy. This study is an extension from the SSAR 2004/0002 which randomised patients over the same treatment arms.

Conditions

HIV Infections

Keywords

lipids; lipodystrophy; fat distribution; hiv-1; antiretroviral therapy; Treatment Naive

Outcome Measures

Primary Outcomes (1)

• To assess the differences in changes in plasma lipids after once-daily saquinavir/ritonavir (2000/100 mg) or atazanavir/ritonavir (300/100 mg) each in combination with tenofovir disoproxil fumarate (300 mg QD) and emtricitabine (200 mg QD) for 24 weeks

Secondary Outcomes (6)

• To assess the differences in changes in plasma lipids after once-daily saquinavir/ritonavir (2000/100 mg QD) or atazanavir/ritonavir (300/100 mg QD) each in combination with tenofovir disoproxil fumarate and emtricitabine for 48 weeks.

• To compare differences in changes in glucose metabolism.

• To compare changes in fat redistribution in both study arms.

• To relate differences in changes in lipids, glucose metabolism and abdominal fat distribution to the plasma exposure of the different protease inhibitors (including ritonavir) used in the trial.

• To assess the change in estimated glomerular filtration rate (GFR) by Cockcroft-Gault, MDRD and cystatin C-derived equations in both study arms.

Interventions

saquinavir/ritonavir DRUG

atazanavir/ritonavir DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Providing written informed consent
• HIV-1 infected patients.
• At least 18 years of age.
• Males or non-pregnant, non-lactating females. Women of childbearing age must have a negative urine pregnancy test at screening. All female participants must be encouraged to utilise adequate contraception for the month preceding entry and for the duration of the study.
• Anti-retroviral treatment naive.
• Indication for antiretroviral therapy according to current treatment guidelines.

You may not qualify if:

• CD4 count \> 350 cells/mm3, except in case of symptomatic HIV disease and/or an AIDS-defining illness.
• HIV-2 co infection.
• Use of co-medication with a known pharmacological interaction which precludes the appropriate use of one or more of the study drugs.
• Anticipated non-compliance with the protocol.
• Presence of a newly (within 30 days prior to the time of enrolment) diagnosed HIV-related opportunistic infection or condition which may interfere with the ability to comply with the study.
• Chronic active viral hepatitis or other chronic liver disease, which in the opinion of the investigator is a contraindication for the use of any of the study drugs. Patients who may be considered to have active HBV replication (HBV-surface antigen positive and/or HBV-DNA positive) may be excluded in case the investigator feels that the benefit of starting tenofovir/emtricitabine does not outweigh the risk of a "hepatitis flare" in case tenofovir/emtricitabine would need to be prematurely discontinued for any reason during the trial. Chronic hepatitis C is allowed, provided that treatment for hepatitis C is not anticipated during the study period.
• Women who are pregnant, or have the intention to become pregnant during the study period.
• Clinically relevant laboratory abnormalities: anaemia, thrombocytopenia, leucopenia, elevated liver transaminases, elevated bilirubin, elevated amylase, elevated lipase, which in the opinion of the investigator is a contraindication for the use of any of the study drugs, or any current known clinical or laboratory parameter of ACTG Grade 4 (see Appendix 2). However, asymptomatic Grade 4 abnormalities will be permitted at the discretion of the investigator if deemed clinically appropriate. Abnormalities deemed insignificant by the investigator must be discussed with the sponsor prior to enrolment.
• Significant renal dysfunction (creatinine clearance \[CrCl\] \<60 mL/min) and/or hepatic impairment (aspartate aminotransferase/alanine aminotransferase \[AST/ALT\] \>3 X ULN and/or documented liver cirrhosis)
• Note: The site will calculate each patient's CrCl using the Cockcroft-Gault formula as shown below:
• CrCl = \[140 - age (yr)\] × weight (kg) × constant 72 × serum creatinine (Cr) (mg/dL) where, constant = 1 for men and 0.85 for women.
• Use of nephrotoxic agents which in the opinion of the investigator are a contraindication for the use of tenofovir disoproxil fumarate and any other of the study drugs.
• Patients who have received within 4 weeks prior to entry, or who have an anticipated need for treatment with radiation therapy or cytotoxic chemotherapeutic agents during the protocol study period.
• Patients who have taken any investigational drug 30 days prior to the start of the study.

Sponsors & Collaborators

• International Antiviral Therapy Evaluation Center: lead
• Hoffmann-La Roche: collaborator
• Gilead Sciences: collaborator

Study Sites (1)

Academic Medical Centre, University of Amsterdam

Amsterdam, 1105 AZ, Netherlands

Location

Related Links

• Related Info

MeSH Terms

Conditions

HIV Infections; Lipodystrophy; Acquired Immunodeficiency Syndrome

Interventions

Saquinavir; Ritonavir; atazanavir, ritonavir drug combination

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; Skin Diseases, Metabolic; Skin Diseases; Skin and Connective Tissue Diseases; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Peter Reiss, MD, PhD

  Academic Medical Centre, University of Amsterdam, the Netherlands

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 17, 2006
• First Posted: October 18, 2006
• Study Start: July 1, 2006
• Study Completion: July 1, 2008
• Last Updated: June 11, 2010

Record last verified: 2010-06

Locations

NL (1)