Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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: November 1, 2016
Last verified: November 2016
  Purpose
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.

Condition Intervention Phase
HIV Infections
Drug: Ritonavir
Drug: saquinavir [Invirase]
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effect of Moderate Liver Impairment on the Pharmacokinetics of Saquinavir After Administration of Saquinavir/Ritonavir 1000/100mg BID in HIV Patients

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 16
Study Start Date: September 2006
Study Completion Date: November 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: Ritonavir
100mg po bid
Drug: saquinavir [Invirase]
1000mg po bid
Experimental: 2 Drug: Ritonavir
100mg po bid
Drug: saquinavir [Invirase]
1000mg po bid

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00435929

Locations
United States, Illinois
Chicago, Illinois, United States, 60612
United States, New Jersey
Somers Point, New Jersey, United States, 08244
Voorhees, New Jersey, United States, 08043
United States, Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Dallas, Texas, United States, 75204
Canada, Ontario
Ottawa, Ontario, Canada, K1H 8L6
Toronto, Ontario, Canada, M5G 2C4
Puerto Rico
San Juan, Puerto Rico, 00927
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00435929     History of Changes
Other Study ID Numbers: BP17921 
Study First Received: February 15, 2007
Results First Received: December 2, 2015
Last Updated: November 1, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Hoffmann-La Roche:
Treatment Naive

Additional relevant MeSH terms:
Infection
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Ritonavir
Saquinavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors

ClinicalTrials.gov processed this record on December 07, 2016