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 - Full Text View

Sponsor:	The National Centre in HIV Epidemiology and Clinical Research
Collaborator:	Hoffmann-La Roche
Information provided by:	The National Centre in HIV Epidemiology and Clinical Research
ClinicalTrials.gov Identifier:	NCT00192608

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:	Treatment, Randomized, Open Label, Dose Comparison, Crossover Assignment, Pharmacokinetics Study
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:

MedlinePlus related topics: AIDS

Drug Information available for: Saquinavir Saquinavir mesylate Ritonavir BMS 232632 Atazanavir sulfate

U.S. FDA Resources

Further study details as provided by The National Centre in HIV Epidemiology and Clinical Research:

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
saquinavir at baseline: Experimental 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.
other boosted PI at baseline: Experimental 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

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

The National Centre in HIV Epidemiology and Clinical Research

Hoffmann-La Roche

Investigators

Principal Investigator:

David A Cooper, MD

The National Centre in HIV Epidemiology and Clinical Research

More Information

Additional Information:

National Centre in HIV Epidemiology and Clinical Research Homepage This link exits the ClinicalTrials.gov site

Publications:

Winston A, Mallon PW, Satchell C, MacRae K, Williams KM, Schutz M, Law M, Cooper DA, Emery S. The safety, efficacy, and pharmacokinetic profile of a switch in antiretroviral therapy to saquinavir, ritonavir, and atazanavir alone for 48 weeks and a switch in the saquinavir formulation. Clin Infect Dis. 2007 Jun 1;44(11):1475-83. Epub 2007 Apr 18.

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

Keywords provided by The National Centre in HIV Epidemiology and Clinical Research:

Pharmacokinetics, atazanavir, saquinavir, ritonavir, HIV

Additional relevant MeSH terms:

Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Saquinavir
Infection
Anti-Retroviral Agents
Therapeutic Uses
Retroviridae Infections
RNA Virus Infections
HIV Protease Inhibitors
Anti-HIV Agents
Immune System Diseases

Acquired Immunodeficiency Syndrome
Atazanavir
Enzyme Inhibitors
Antiviral Agents
Immunologic Deficiency Syndromes
Pharmacologic Actions
Protease Inhibitors
Virus Diseases
HIV Infections
Ritonavir
Sexually Transmitted Diseases
Lentivirus Infections

ClinicalTrials.gov processed this record on November 09, 2009