A 48-Week, Randomised, Study to Describe the Pharmacokinetic Profile and Durability of Atazanavir-Saquinavir-Ritonavir Once Daily and Describe the Pharmacokinetic Profile of Saquinavir-Ritonavir Using Saquinavir 500mg Formulation: the ASK-500 Study

This study has been completed.
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by:
Kirby Institute
ClinicalTrials.gov Identifier:
NCT00192608
First received: September 13, 2005
Last updated: June 25, 2009
Last verified: June 2009
  Purpose

Saquinavir and Atazanavir are drugs used in combination therapy to treat HIV disease. Saquinavir is currently available in a 200 milligram capsule. Most individuals currently on saquinavir require to take 5 tablets twice a day. In an attempt to reduce this number of pills, a new capsule has been developed containing 500 milligrams of saquinavir. This study will assess: i) blood drug levels in individuals taking both saquinavir formulations, ii) blood drug levels in individuals taking both saquinavir formulations when given with atazanavir, iii) 48 weeks of follow up for individuals receiving the new saquinavir formulation with atazanavir as HIV therapy.


Condition Intervention
HIV Infections
Drug: saquinavir 500 formulation
Drug: cross-over arm

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A 48-Week, Randomised, Study to Describe the Pharmacokinetic Profile and Durability of Atazanavir-Saquinavir-Ritonavir Once Daily and Describe the Pharmacokinetic Profile of Saquinavir-Ritonavir Using Saquinavir 500mg Formulation.

Resource links provided by NLM:


Further study details as provided by Kirby Institute:

Primary Outcome Measures:
  • To compare the pharmacokinectic profile of ATV-SQV-RTV using SQV 500 and 200 formulations. [ Time Frame: week 48 ] [ Designated as safety issue: No ]
  • To compare the pharmacokinetic profile of SQV/r 1000/100mg bid using SQV 500 and 200 formulations. [ Time Frame: week 48 ] [ Designated as safety issue: No ]
  • To assess the durability and safety of a once daily double boosted PI regimen comprised of ATV300 - SQV1500 - RTV100 [ Time Frame: week 48 ] [ Designated as safety issue: Yes ]
  • To assess the decay pharmacokinetics [ Time Frame: week 48 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Assessment of adherence to medications. [ Time Frame: week 48 ] [ Designated as safety issue: No ]
  • Assessment of changes to CD4 lymphocyte count [ Time Frame: week 48 ] [ Designated as safety issue: No ]
  • Assessment of changes in lipid parameters [ Time Frame: week 48 ] [ Designated as safety issue: Yes ]
  • Assessment of changes in monocyte mRNA [ Time Frame: week 48 ] [ Designated as safety issue: No ]

Enrollment: 40
Study Start Date: November 2004
Study Completion Date: May 2006
Primary Completion Date: May 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: saquinavir at baseline
patients receiving NRTIs + saquinavir + ritonavir 1000/100 mg BID at entry switch from 200 mg SQV capsules to 500 mg SQV tablets following PK at day 0. After PK at day 8 NRTIs ceased and regimen changed to ATV/SQV/RTV 300/1500/100 QD using 500 mg SQV formulation and continued to week 48
Drug: saquinavir 500 formulation
NRTIs + SQV/RTV 1000/100 mg BID using 200 mg SQV capsules switched at entry to ATV/SQV/RTV 300/1500/100 mg QD using 500 mg SQV tablet for 48 weeks with PK at days 0 and 8.
Experimental: other boosted PI at baseline
Patients receiving NRTIs + PI/RTV randomised at baseline to receive ATV/SQVRTV 300/1500/100 QD using 500 mg SQV formulation or ATV/SQV/RTV 300/1600/100 QD using 200 mg formulation. Following PK at day 7, SQV formulation switched with second PK assessment at day 15. Patients then receive ATV/SQV/RTV 300/1500/100 QD to week 48.
Drug: cross-over arm
either ATV/SQV/RTV 300/1500/100 QD (500 mg SQV tabs) for 7 days then after PK SQV changed to 1600 mg QD (200 mg caps) with PK day 15, or ATV/SQV/RTV 300/1600/100 QD for 7 days with switch to SQV 1500 mg QD. After day 15 PK both groups switch to ATV/SQV/RTV 300/1500/100 QD to week 48

Detailed Description:

BACKGROUND The development of anti-HIV therapy for the treatment of HIV disease has improved the quality of life and survival of many people with HIV. However the treatments do not always work over long periods, as medications are often difficult to take due to side effects and a large numbers of pills to be taken. This has lead researchers to look for new ways to treat HIV with medications that require fewer numbers of pills and have fewer side effects.

Atazanavir and saquinavir are two drugs used to treat HIV and come from the same class of drugs known as the protease inhibitors. Atazanavir has the advantage of being taken only once a day. Saquinavir is available in a new formulation (type of pill), which will require fewer numbers of pills to be taken daily.

AIM The purpose of this study is to investigate the use of these two drugs used together with ritonavir as a once daily HIV treatment, which will consist of 6 tablets.

Furthermore this study will look at blood drug levels in individuals on atazanavir, saquinavir and ritonavir with and without the new saquinavir formulation to ensure blood levels of these drugs are adequate.

For individuals currently on the old saquinavir formulation, this study will also look at blood drug levels before and after changing to the new formulation.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

HIV-1 infected individuals aged 18 years or over On stable antiretroviral therapy for at least three months consisting of nucleoside reverse transcriptase inhibitors and protease inhibitors OR On stable antiretroviral therapy for at least three months consisting of atazanavir-saquinavir-ritonavir Undetectable HIV RNA viral load for past three months

Exclusion Criteria:

  • Individuals receiving on non-nucleoside reverse transcriptase inhibitors within the past three months
  • Individuals currently receiving other enzyme inducing agents (as per
  • Individuals receiving ritonavir at doses greater than 100 mg bid
  • Active AIDS defining illnesses
  • Previously documented intolerance or virological failure to saquinavir
  • Previously documented intolerance or virological failure to atazanavir
  • Patients who are co-infected with Hepatitis B and are likely to require, in their clinician's opinion, HBV nucleoside therapy during the study.
  • Female patients who are pregnant, breastfeeding, or who plan to become pregnant during the study
  • Any current clinical or laboratory parameter of ACTG Grade 4 (except lipids & CK)
  • Evidence of ongoing alcohol and/or drug or substance abuse that would result in the patient being unreliable in fulfilling the conditions of this protocol
  • Prior non-adherence to antiretroviral treatment regimens that would result in the patient being unreliable in fulfilling the conditions of this protocol
  • Evidence of active opportunistic infection, intercurrent illness, drug toxicity or any other condition that would preclude the patient from taking the prescribed antiretroviral regimen
  • Conditions that might interfere with evaluation of the disease under study.
  • Conditions/allergies that may compromise the safety of the patient.
  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: NCT00192608

Locations
Australia, New South Wales
St Vincents Hospital
Sydney, New South Wales, Australia, 2010
Sponsors and Collaborators
Kirby Institute
Hoffmann-La Roche
Investigators
Principal Investigator: David A Cooper, MD Kirby Institute
  More Information

Additional Information:
Publications:
Responsible Party: The University of New South Wales, University
ClinicalTrials.gov Identifier: NCT00192608     History of Changes
Other Study ID Numbers: ASK-500 14047, ACTR012605000660684
Study First Received: September 13, 2005
Last Updated: June 25, 2009
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Kirby Institute:
Pharmacokinetics, atazanavir, saquinavir, ritonavir, HIV

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Saquinavir
Ritonavir
Atazanavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 25, 2014