Clinical trial NCT00435929: A Study of Saquinavir/Ritonavir in Liver-Impaired Patients With HIV Infection.
Official title: Effect of Moderate Liver Impairment on the Pharmacokinetics of Saquinavir After Administration of Saquinavir/Ritonavir 1000/100mg BID in HIV Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: Treatment Naive
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2007-02-16
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This 2 arm study will assess the effect of moderate liver impairment on the pharmacokinetics of saquinavir and ritonavir at steady state following administration of saquinavir/ritonavir 1000mg/100mg po bid in HIV patients. Saquinavir/ritonavir will be administered concomitantly with 2 to 3 active nucleoside reverse transcriptase inhibitors. The study will compare a group of HIV patients without known liver disease and a group with moderate liver disease. The anticipated time on study treatment is \<3 months, and the target sample size is \<100 individuals.


Eligibility criteria: Inclusion Criteria:

* adult patients, 18-65 years of age;
* HIV infection;
* normal liver function, or moderate liver disease (Child-Pugh grade B);
* antiretroviral therapy naive and eligible to take antiretroviral treatment as per treatment guidelines, or treatment experienced for at least 4 weeks prior to first dosing.

Exclusion Criteria:

* severe ascites at screening, or Child-Pugh grade C;
* acute infection or current malignancy requiring treatment;
* taking any inhibitor of CYP3A4 (with the exception of anti-HIV drugs) within 14 days prior to first dosing;
* taking any inducer of CYP3A4 (with the exception of anti-HIV drugs) within 4 weeks prior to pharmacokinetic evaluation (day 14 or 28);
* evidence of resistance to saquinavir.

Primary outcomes:
measure: Area Under the Plasma Concentration-Time Curve From Time of Administration to 12 Hours After Dosing (AUC 0-12h) of Saquinavir (SQV) and Ritonavir (RTV)
timeFrame: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post-dose on Day 14
measure: Maximum Observed Plasma Concentration (Cmax) of SQV and RTV
timeFrame: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post-dose on Day 14
Secondary outcomes:
measure: Time of Maximum Plasma Concentration (Tmax) of SQV and RTV
timeFrame: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post-dose on Day 14
measure: Terminal Half-life (T1/2) of SQV and RTV
timeFrame: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post-dose on Day 14
measure: Minimum Observed Plasma Concentration (Cmin) of SQV and RTV
timeFrame: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post dose on Day 14
measure: Plasma Clearance After Oral Administration (CL/F) of SQV and RTV
timeFrame: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post dose on Day 14
measure: Volume of Distribution (Vd) of SQV and RTV
timeFrame: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post dose on Day 14
measure: Cluster of Differentiation 4 (CD4 ) Count
timeFrame: Screening (Day -35 to -1), pre-dose on Day 8, Day 14 and at follow up (Day 28-Day 35)
measure: Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
timeFrame: Up to Day 35
measure: Number Participants With Abnormal Vital Signs
timeFrame: Up to Day 35
measure: Number of Participants With Abnormal Electrocardiogram (ECG) Findings
timeFrame: Up to Day 35
Other outcomes:
Locations:
city: Chicago
country: United States
state: Illinois
city: Somers Point
country: United States
state: New Jersey
city: Voorhees
country: United States
state: New Jersey
city: Philadelphia
country: United States
state: Pennsylvania
city: Dallas
country: United States
state: Texas
city: Ottawa
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: San Juan
country: Puerto Rico
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: