Saquinavir/Ritonavir in Single Therapy as Maintenance Treatment

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.

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

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Saquinavir/Ritonavir : 2 capsules (500 mg) / 12 hours

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; 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; Other Names: Invirase
No Intervention: 2; IP o NNUCS + 2 NUCS as a HAART therapy .

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Virological response: Viral Load	weeks 24 and 48

Secondary Outcome Measures

Outcome Measure	Time Frame
CD4 and CD8 lymphocyte count.	weeks 24 and 48
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,...	weeks 24 and 48
Karnofsky Index.	weeks 24 and 48
Adverse events.	during the 48 weeks of follow-up
Trough plasma concentrations of Saquinavir.	during the 48 weeks of follow-up
Lipid study in plasma (total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides)	during the 48 weeks of follow-up
Serology for Hepatitis B and C virus.	at baseline visit
Assessment of treatment adherence.	at baseline and weeks 4, 12, 24, 36 and 48
Assessment of quality of life (by means of the MOS-HIV questionnaire).	at baseline and weeks 4, 12, 24, 36 and 48
Genotype if virological failure.	at any time of study if it is necessary

Collaborators and Investigators

• Sponsor: Germans Trias i Pujol Hospital
• Collaborators: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
• 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

Study record dates

Study Major Dates

• Study Start: June 1, 2006
• Primary Completion (Actual): May 1, 2008
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: September 20, 2006
• First Submitted That Met QC Criteria: September 20, 2006
• First Posted (Estimate): September 21, 2006

Study Record Updates

• Last Update Posted (Actual): December 4, 2019
• Last Update Submitted That Met QC Criteria: December 3, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Safety; HIV-1; Saquinavir/ritonavir; Single therapy; Virological efficacy
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir; Saquinavir
• Other Study ID Numbers: SQV/RTV-MONOTERAPIA; 2006-001136-47