Saquinavir/Ritonavir in Single Therapy as Maintenance Treatment - Full Text View

Sponsor:	Germans Trias i Pujol Hospital
Collaborator:	FUNDACIÓ LLUITA CONTRA LA SIDA
Information provided by:	Germans Trias i Pujol Hospital
ClinicalTrials.gov Identifier:	NCT00379405

Purpose

Study the efficacy of Saquinavir/Ritonavir when given in single therapy as maintenance therapy, compared to standard HAART therapies.

Condition	Intervention	Phase
HIV Infections	Drug: Saquinavir/Ritonavir : 2 capsules (500 mg) / 12 hours	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Open-Label, Comparative and Randomised Pilot Study to Evaluate the Efficacy and Safety of Saquinavir/Ritonavir in Single Therapy vs Standard HAART Therapy as Maintenance Therapy.

Resource links provided by NLM:

MedlinePlus related topics: AIDS

Drug Information available for: Saquinavir Saquinavir mesylate Ritonavir

U.S. FDA Resources

Further study details as provided by Germans Trias i Pujol Hospital:

Primary Outcome Measures:

Virological response: Viral Load [ Time Frame: weeks 24 and 48 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

CD4 and CD8 lymphocyte count. [ Time Frame: weeks 24 and 48 ] [ Designated as safety issue: No ]
Physical Exploration: including weight, height, index waist/hip (the abdominal perimeter is measured between the last floating rib and the iliac crest), assessment of changes in body fat distribution,... [ Time Frame: weeks 24 and 48 ] [ Designated as safety issue: No ]
Karnofsky Index. [ Time Frame: weeks 24 and 48 ] [ Designated as safety issue: No ]
Adverse events. [ Time Frame: during the 48 weeks of follow-up ] [ Designated as safety issue: Yes ]
Trough plasma concentrations of Saquinavir. [ Time Frame: during the 48 weeks of follow-up ] [ Designated as safety issue: No ]
Lipid study in plasma (total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides) [ Time Frame: during the 48 weeks of follow-up ] [ Designated as safety issue: Yes ]
Serology for Hepatitis B and C virus. [ Time Frame: at baseline visit ] [ Designated as safety issue: No ]
Assessment of treatment adherence. [ Time Frame: at baseline and weeks 4, 12, 24, 36 and 48 ] [ Designated as safety issue: No ]
Assessment of quality of life (by means of the MOS-HIV questionnaire). [ Time Frame: at baseline and weeks 4, 12, 24, 36 and 48 ] [ Designated as safety issue: No ]
Genotype if virological failure. [ Time Frame: at any time of study if it is necessary ] [ Designated as safety issue: No ]

Enrollment:	30
Study Start Date:	June 2006
Study Completion Date:	July 2008
Primary Completion Date:	May 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental Saquinavir (Invirase): 2 capsules (500 mg) / 12 hours	Drug: Saquinavir/Ritonavir : 2 capsules (500 mg) / 12 hours Saquinavir/Ritonavir: 2 capsules (500 mg) / 12 hours
2: No Intervention IP o NNUCS + 2 NUCS as a HAART therapy .

Detailed Description:

Different therapeutic strategies have been investigated to improve adherence to treatment and reduce toxicity. Both the reduction in the number of doses and the number of daily tablets have led to an improvement in therapeutic compliance. Similarly, the administration of new treatment regimens with a reduced number of tablets a day and without NTRI may be clinically useful in improving compliance with HAART and limiting NTRI-associated toxicity. These would comprise combinations of a PI, boosted with ritonavir, plus a non-Nucleoside and single therapy with PIs boosted with ritonavir.

In this regard, the results obtained with lopinavir/ritonavir and with atazanavir/ritonavir are very promising and open up a possible channel of research with other PIs boosted with low doses of ritonavir.

There are other PIs whose antiretroviral efficacy has also been demonstrated, such as saquinavir, but whose economic cost is much lower. Furthermore, saquinavir has a low toxicity profile, and the availability of saquinavir 500 mg facilitates comfortable administration, since it makes it possible to reduce the number of daily tablets to more than half.

Moreover, it is important to take into account that the incidence of mutations that confer resistance to saquinavir on patients that fail on combinations including this PI is very low, which makes it possible to reuse the drug in future treatment regimens or salvage patients with other PI All these characteristics (high intrinsic potency, low number of tablets, low toxicity, low potential of selection of resistant viral strains in combination with ritonavir, and low economic cost) make single therapy with the new formulation of saquinavir, boosted with low doses of ritonavir, a possible therapeutic option as maintenance strategy in HIV-infected patients with maintained suppression of the viral load.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients infected by HIV-1 (at least one documented positive Western-Blot).
Age > 18 years.
Patients on antiretroviral treatment (standard HAART therapy) for at least six months.
HIV-1 plasma viral load <50 copies/mL (documented in at least two determinations performed over the six months prior to the inclusion visit).
Patients without evidence of previous virological failure to IP
Absence of opportunistic infections and/or tumours in the three months prior to inclusion.
Subject able to follow the treatment period, without any suspicion of poor adherence during previous antiretroviral treatments.
Signature of the informed consent.

Exclusion Criteria:

Suspicion of unsuitable antiretroviral treatment compliance.
Documented existence of any of the primary mutations in the protease gene or 3 or more of the following: L10F/I/R/V, K20M/R, M36I/V, I54L/T/V, L63P, A71T/V , V82A/F/T/S, I84A/V OR L90M.
Known allergic hypersensitivity to any of the investigational drugs or any similar drug.
Hepatic tests (AST, ALT, GGT) > or equal to 5 times the upper limit of normality during the three months prior to the screening visit
Presence of renal impairment (creatinine > or equal to 1.5 times the upper limit of normality).
Pregnancy or breastfeeding. Refusal to use reliable contraceptive methods during the study period.
Participation in another clinical trial wich entail the antiretroviral treatment modification.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00379405

Locations

Spain
Hospital del Sant Pau.
Barcelona, Spain, 08025
Spain, Barcelona
Germans Trias i Pujol University Hospital
Badalona, Barcelona, Spain, 08916

Sponsors and Collaborators

Germans Trias i Pujol Hospital

FUNDACIÓ LLUITA CONTRA LA SIDA

Investigators

Principal Investigator:	Clotet Bonaventura, MD,PhD	Hospital Universitari Germans Trias i Pujol. Badalona (Barcelona)
Principal Investigator:	Negredo Eugenia, MD,PhD	Hospital Universitari Germans Trias i Pujol. Badalona. (Barcelona)
Principal Investigator:	Echeverria Patricia, MD,PhD	Hospital Universitari Germans Trias i Pujol. Badalona. (Barcelona)
Principal Investigator:	Molto Jose, MD,PhD	Hospital Universitari Germans Trias i Pujol. Badalona. (Barcelona)
Principal Investigator:	Pere Domingo, MD, PhD	Hospital de Sant Pau

More Information

No publications provided

Responsible Party:	Lluita Sida Foundation ( Lluita Sida Foundation )
Study ID Numbers:	SQV/RTV-MONOTERAPIA, 2006-001136-47
Study First Received:	September 20, 2006
Last Updated:	October 10, 2008
ClinicalTrials.gov Identifier:	NCT00379405 History of Changes
Health Authority:	Spain: Ministry of Health

Keywords provided by Germans Trias i Pujol Hospital:

Saquinavir/ritonavir
Single therapy
Virological efficacy
Safety
HIV-1

Additional relevant MeSH terms:

Anti-Infective Agents
HIV Protease Inhibitors
RNA Virus Infections
Sexually Transmitted Diseases, Viral
Anti-HIV Agents
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Saquinavir
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Infection

Antiviral Agents
Pharmacologic Actions
Immunologic Deficiency Syndromes
Protease Inhibitors
Virus Diseases
Anti-Retroviral Agents
Ritonavir
HIV Infections
Therapeutic Uses
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections

ClinicalTrials.gov processed this record on November 27, 2009