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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Nucleoside Reverse Transcriptase Inhibitor (NRTIs)
* Drug: ritonavir
* Drug: saquinavir [Invirase]


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Safety: Incidence of adverse events |  | approximately 6 months | 
| Change in ECG parameters |  | from baseline to Day 14 | 
| Correlation between saquinavir plasma concentration and QTc interval changes |  | approximately 6 months |