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

NCT00435929 | Completed Phase 1 Results

• 1 other identifier: BP17921
• Study Type: interventional
• Target: 16
• Locations: 3 countries
• Sites: 8

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.

Conditions

HIV Infections

Keywords

Treatment Naive

Outcome Measures

Primary Outcomes (2)

• 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)

  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.

  Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post-dose on Day 14

• Maximum Observed Plasma Concentration (Cmax) of SQV and RTV

  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.

  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 (9)

• Time of Maximum Plasma Concentration (Tmax) of SQV and RTV

  Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post-dose on Day 14

• Terminal Half-life (T1/2) of SQV and RTV

  Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post-dose on Day 14

• Minimum Observed Plasma Concentration (Cmin) of SQV and RTV

  Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post dose on Day 14

• Plasma Clearance After Oral Administration (CL/F) of SQV and RTV

  Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post dose on Day 14

• Volume of Distribution (Vd) of SQV and RTV

  Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post dose on Day 14

Study Arms (2)

1

EXPERIMENTAL

Drug: Ritonavir; Drug: saquinavir [Invirase]

2

EXPERIMENTAL

Drug: Ritonavir; Drug: saquinavir [Invirase]

Interventions

Ritonavir DRUG

100mg po bid

1; 2

saquinavir [Invirase] DRUG

1000mg po bid

1; 2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (8)

Unknown Facility

Chicago, Illinois, 60612, United States

Location

Unknown Facility

Somers Point, New Jersey, 08244, United States

Location

Unknown Facility

Voorhees Township, New Jersey, 08043, United States

Location

Unknown Facility

Philadelphia, Pennsylvania, 19104, United States

Location

Unknown Facility

Dallas, Texas, 75204, United States

Location

Unknown Facility

Ottawa, Ontario, K1H 8L6, Canada

Location

Unknown Facility

Toronto, Ontario, M5G 2C4, Canada

Location

Unknown Facility

San Juan, 00927, Puerto Rico

Location

MeSH Terms

Conditions

HIV Infections

Interventions

Ritonavir; Saquinavir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Quinolines

Results Point of Contact

• Title: F. Hoffmann-La Roche AG
• Organization: Roche Trial Information Hotline

global.trial_information@roche.com

+41 61 6878333

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2007
• First Posted: February 16, 2007
• Study Start: September 1, 2006
• Primary Completion: November 1, 2009
• Study Completion: November 1, 2009
• Last Updated: March 29, 2018
• Results First Posted: January 8, 2016

Record last verified: 2018-02

Locations

CA (2); PR (1); US (5)