HIV Infections
Conditions
Brief summary
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.
Interventions
DRUGNucleoside Reverse Transcriptase Inhibitor (NRTIs)
in accordance with current clinical HIV treatment guidelines
DRUGritonavir
100 mg bid orally, Days 1-14
500 mg bid orally Days 1-7, 1000 mg bid orally Days 8-14
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| 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
| Measure | 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 |
Countries
United Kingdom
Outcome results
None listed