A Study of Ritonavir-Boosted Invirase (Saquinavir) in Treatment-Naïve HIV-1 Infected Patients

To Determine the Effect of the Modified SQV/r (Saquinavir-boosted by Ritonavir) Regimen (500/100 mg for the 1st Week Followed by 1000/100 mg for the 2nd Week) on the QTc Interval, Pharmacokinetics, and Antiviral Activity in Treatment-naive HIV-1 Infected Patients

This open-label study will evaluate the safety, pharmacokinetics and antiviral activity of a modified Invirase (saquinavir)/ritonavir regimen in treatment-naïve HIV-1 infected patients. Patients will receive Invirase 500 mg plus ritonavir 100 mg twice daily orally for the first week, followed by Invirase 1000 mg plus ritonavir 100 mg twice daily orally for the second week. The study treatment will be given in combination with two Nucleoside Reverse Transcriptase Inhibitors (NRTIs), in accordance with the current clinical HIV treatment guidelines. Anticipated time on study treatment is 14 days.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Nucleoside Reverse Transcriptase Inhibitor (NRTIs); Drug: ritonavir; Drug: saquinavir [Invirase]

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SW10 9NH

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adult patients, >/= 18 years of age
• HIV-1 infection
• Currently treatment-naïve and eligible to initiate a ritonavir-boosted Protease Inhibitor based regimen and willing and able to initiate saquinavir/ritonavir therapy for the first 14 days; the saquinavir/ritonavir regimen will be in combination with two Nucleoside Reverse Transcriptase Inhibitors (NRTIs), in accordance with the current clinical HIV treatment guidelines
• Body mass index 18-32 kg/m2, inclusive
• Female patients of childbearing potential and male patients with female partners of childbearing potential must use 2 methods of contraception as defined by protocol during the study and for at least one month after the last dose of study drug
• Non-smoker or patients who have stopped smoking more than three months prior to Day 1 of the study

Exclusion Criteria:

• Coinfection with hepatitis B or C (acute or chronic)
• Anticipated use or need for significant concomitant medical treatment during the study period, other than background antiretroviral therapy
• Participation in a clinical study with an investigational drug or device within 3 months prior to Day 1 of the study
• Pregnant or lactating women
• Any clinically relevant history of substance abuse or addiction including alcohol and/or other drugs of abuse
• Special dietary restrictions that would prohibit consumption of standardized meal (e.g. vegetarian, vegan, gluten-free, lactose-free, kosher)
• Decompensated liver disease
• Congenital or documented acquired QT prolongation
• Electrolyte disturbances, particularly uncorrected hypokalaemia
• Clinically relevant bradycardia
• Clinically relevant heart failure with reduced left-ventricular ejection fraction
• Previous history of symptomatic arrhythmias
• History of clinically significant gastro-intestinal, renal, hepatic, bronchopulmonary, neurological, psychiatric, cardiovascular, endocrinological, , hematological, or allergic disease, metabolic disorder, cancer, or cirrhosis

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Arm	Drug: Nucleoside Reverse Transcriptase Inhibitor (NRTIs); in accordance with current clinical HIV treatment guidelines; Drug: ritonavir; 100 mg bid orally, Days 1-14; Drug: saquinavir [Invirase]; 500 mg bid orally Days 1-7, 1000 mg bid orally Days 8-14

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximal increase in QTc interval (continuous Holter 12-lead ECG monitoring time points Days 1, 3, 4, 7, 10 and 14)	14 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety: Incidence of adverse events	approximately 6 months
Pharmacokinetics: Plasma concentrations	Pre-dose and 2, 4, 6, 8 and 12 hours post-dose, Days 3, 4, 7, 10 and 14
Pharmacodynamics: Change in HIV-RNA levels	from baseline to Day 14
Change in ECG parameters	from baseline to Day 14
Correlation between saquinavir plasma concentration and QTc interval changes	approximately 6 months

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: June 6, 2012
• First Submitted That Met QC Criteria: July 9, 2012
• First Posted (Estimate): July 12, 2012

Study Record Updates

• Last Update Posted (Estimate): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• 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; Nucleic Acid Synthesis Inhibitors; 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; Reverse Transcriptase Inhibitors; Saquinavir
• Other Study ID Numbers: NP25607