Clinical trial NCT01638650: A Study of Ritonavir-Boosted Invirase (Saquinavir) in Treatment-Naïve HIV-1 Infected Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2012-07-12
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Maximal increase in QTc interval (continuous Holter 12-lead ECG monitoring time points Days 1, 3, 4, 7, 10 and 14)
timeFrame: 14 days
Secondary outcomes:
measure: Pharmacokinetics: Plasma concentrations
timeFrame: Pre-dose and 2, 4, 6, 8 and 12 hours post-dose, Days 3, 4, 7, 10 and 14
measure: Pharmacodynamics: Change in HIV-RNA levels
timeFrame: from baseline to Day 14
measure: Safety: Incidence of adverse events
timeFrame: approximately 6 months
measure: Change in ECG parameters
timeFrame: from baseline to Day 14
measure: Correlation between saquinavir plasma concentration and QTc interval changes
timeFrame: approximately 6 months
Other outcomes:
Locations:
city: London
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: