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A Study of Saquinavir/Ritonavir in Liver-Impaired Patients With HIV Infection.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00435929
First received: February 15, 2007
Last updated: September 1, 2016
Last verified: September 2016

February 15, 2007
September 1, 2016
September 2006
November 2009   (final data collection date for primary outcome 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) [ Time Frame: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post-dose on Day 14 ] [ Designated as safety issue: No ]
    Area Under the Plasma Concentration-Time Curve (AUC) is a measure of the plasma concentration of the drug over time. It is used to characterize drug absorption. The pharmacokinetic profile for following 14 days of administration with SQV/RTV 1000/100 mg BID included determining the area under the plasma concentration-time curve from 0 to 12 hours after dosing (AUC (0-12h) of SQV and RTV The AUC (0-12hours) was analyzed for SQV and RTV by non-compartmental methods, using WinNonlin.
  • Maximum Observed Plasma Concentration (Cmax) of SQV and RTV [ Time Frame: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post-dose on Day 14 ] [ Designated as safety issue: No ]
    The plasma concentration (Cmax) is defined as maximum observed analyte concentration. The pharmacokinetic profile for following 14 days of administration with SQV/RTV 1000/100 mg BID included determining the maximum observed plasma concentration (C max) of SQV and Ritonavir RTV The Cmax was analyzed for SQV and RTV by non-compartmental methods, using WinNonlin.
AUC, Cmax of saquinavir and ritonavir.
Complete list of historical versions of study NCT00435929 on ClinicalTrials.gov Archive Site
  • Time of Maximum Plasma Concentration (Tmax) of SQV and RTV [ Time Frame: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post-dose on Day 14 ] [ Designated as safety issue: No ]
    The Tmax is defined as actual sampling time to reach maximum observed analyte concentration. The Pharmacokinetic profile for following 14 days of administration with SQV/RTV 1000/100 mg BID included determining the time of maximum plasma concentration of SQV and RTV. The Tmax was analyzed for SQV and RTV by non-compartmental methods, using WinNonlin.
  • Terminal Half-life (T1/2) of SQV and RTV [ Time Frame: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post-dose on Day 14 ] [ Designated as safety issue: No ]
    Terminal half-life is the time measured for the plasma concentration to decrease by one half. The Pharmacokinetic profile for following 14 days of administration with SQV/RTV 1000/100 mg BID included determining the terminal half-life (T1/2) of SQV and RTV. The T1/2 was analyzed for SQV and RTV by non-compartmental methods, using WinNonlin.
  • Minimum Observed Plasma Concentration (Cmin) of SQV and RTV [ Time Frame: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post dose on Day 14 ] [ Designated as safety issue: No ]
    Cmin is the minimum blood plasma concentration that a drug achieves. The Pharmacokinetic profile for following 14 days of administration with SQV/RTV 1000/100 mg BID included determining the minimum observed plasma concentration (C min) of SQV and RTV The Cmin was analyzed for SQV and RTV by non-compartmental methods, using WinNonlin.
  • Plasma Clearance After Oral Administration (CL/F) of SQV and RTV [ Time Frame: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post dose on Day 14 ] [ Designated as safety issue: No ]
    The CL/F is the oral clearance; that is clearance based on oral bioavailability. The Pharmacokinetic profile for following 14 days of administration with SQV/RTV 1000/100 mg BID included determining the plasma clearance after oral administration (CL/F)of SQV and RTV The CL/F was analyzed for SQV and RTV by non-compartmental methods, using WinNonlin.
  • Volume of Distribution (Vd) of SQV and RTV [ Time Frame: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post dose on Day 14 ] [ Designated as safety issue: No ]
    Vd is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. The pharmacokinetic profile for following 14 days of administration with SQV/RTV 1000/100 mg BID included determining the Vd of SQV and RTV The Vd was analyzed for SQV and RTV by non-compartmental methods, using WinNonlin.
  • Cluster of Differentiation 4 (CD4 ) Count [ Time Frame: Screening (Day -35 to -1), pre-dose on Day 8, Day 14 and at follow up (Day 28-Day 35) ] [ Designated as safety issue: No ]
    The pharmacodynamic profile for following 14 days of administration with SQV/RTV 1000/100 mg BID included determining the cluster of differentiation 4 (CD4) count in participants in each group.
  • Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters [ Time Frame: Up to Day 35 ] [ Designated as safety issue: No ]
    Laboratory parameters specified in Clinical Operating Guidelines (COG) were summarized. AIDS Clinical Trial Group (ACTG) and American Heart Association (AHA) criteria were used to grade COG laboratory test values. Laboratory parameters for which an increase to Grade 3 (G3) or Grade 4 (G4) occurred are presented in the table below.
  • Number Participants With Abnormal Vital Signs [ Time Frame: Up to Day 35 ] [ Designated as safety issue: No ]
    Abnormal Vital signs included are high and low Pulse rate (PR), high and how Temperature (Temp), high and low Systolic Blood Pressure (SBP) and high and low Diastolic Blood Pressure (DBP). Vital signs (SBP, DBP, PR,Temp) were measured after participants were in a semi-supine position for at least 5 minutes.
  • Number of Participants With Abnormal Electrocardiogram (ECG) Findings [ Time Frame: Up to Day 35 ] [ Designated as safety issue: No ]
    Abnormal ECG findings included are high and low Heart Rate (HRT), high and low PQ/PR interval (PQ/PR), high and low QRS interval (QRS), high and low QT interval (QT), high and low QTCB interval (QTcB), high and low QTcF interval (QTcF), high and low RR interval (RR), high and low T Wave, high and low U Wave, high and low ECG. The 12 Lead ECG was recorded after participants were in a semi-supine position for at least 5 minutes. Only participants with abnormal ECG findings are presented in the table below.
Pharmacokinetics: Tmax, T1/2, CL/F, Cmin, Vd. Pharmacodynamics: HIV-1 RNA viral load, CD4, HCV-RNA viral load, HBV-DNA viral load. Safety: AEs, laboratory parameters.
Not Provided
Not Provided
 
A Study of Saquinavir/Ritonavir in Liver-Impaired Patients With HIV Infection.
Effect of Moderate Liver Impairment on the Pharmacokinetics of Saquinavir After Administration of Saquinavir/Ritonavir 1000/100mg BID in HIV Patients
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.
Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV Infections
  • Drug: Ritonavir
    100mg po bid
  • Drug: saquinavir [Invirase]
    1000mg po bid
  • Experimental: 1
    Interventions:
    • Drug: Ritonavir
    • Drug: saquinavir [Invirase]
  • Experimental: 2
    Interventions:
    • Drug: Ritonavir
    • Drug: saquinavir [Invirase]
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
16
November 2009
November 2009   (final data collection date for primary outcome measure)

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.
Both
18 Years to 65 Years   (Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada,   Puerto Rico
 
NCT00435929
BP17921
Not Provided
Not Provided
Not Provided
Hoffmann-La Roche
Hoffmann-La Roche
Not Provided
Study Director: Clinical Trials Hoffmann-La Roche
Hoffmann-La Roche
September 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP