Pharmacokinetic Interaction Between Nevirapine and Saquinavir-sgc in HIV-1 Infected Patients

An Investigation of the Potential Pharmacokinetic Interaction Between Nevirapine (VIRAMUNE®) and Saquinavir-sgc (Fortovase®) in HIV-1 Infected Patients

The objectives of this study are to determine the effects of nevirapine on the steady-state pharmacokinetics of saquinavir-sgc and to determine the effects of saquinavir-sgc on the steady-state pharmacokinetics of nevirapine. This study will also evaluate the pharmacokinetics of nevirapine in combination with saquinavir-sgc compared to historical controls treated with nevirapine but without saquinavir-sgc.

Study Overview

• Status: Terminated
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Nevirapine; Drug: Saquinavir-sgc

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female patients between the ages of 18 and 65 years who are seropositive for HIV-1 antibody by an ELISA test and confirmed by an alternative method, e.g. Western blot

• Patients who meet the following laboratory parameters:

  • Granulocyte count ≥ 1000 cells/mm3
  • Hemoglobin ≥ 9.0 g(dL (men and women)
  • Platelet count ≥ 75,000 cells/mm3
  • Alkaline phosphatase ≤ 3.0 times the upper limit of normal
  • Serum glutamic oxalo-acetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) ≤ 3.0 times the upper limit of normal
  • Total bilirubin ≤ 1.5 times the upper limit of normal
• Patients receiving a stable antiretroviral regimen, including saquinavir-sgc (Fortovase®) 1600 mg b.i.d. in the 28 days prior to visit 1
• Female patients of childbearing potential must be willing to use a reliable form of contraception, which should include a medically approved form of barrier contraception
• Patients able to provide written informed consent and comply with study requirements
• Patients with a viral load less than 400 copies/mL

Exclusion Criteria:

• Female patients who are pregnant or breastfeeding
• Patients requiring systemic treatment with corticosteroids or drugs known to be hepatic enzyme inducers or inhibitors in the 14 days prior to visit 1. Such substances in these categories include macrolide antibiotics (erythromycin, clarithromycin, azithromycin, dirithromycin), azole antifungals (ketoconazole, fluconazole, itraconazole), rifampin, rifabutin, and phenytoin
• Patients with previous exposure to (or are currently being treated with) non-nucleoside reverse transcriptase inhibitors (NNRTIs)
• Patients receiving a protease inhibitor other than saquinavir-sgc (Fortovase®) in the 28 days prior to visit 1
• Patients receiving any investigational drug, antineoplastic agent or radiotherapy other than local skin radiotherapy treatment in the 12 weeks prior to visit 1
• Patients with malabsorption, severe chronic diarrhea or patients unable to maintain adequate oral intake
• Patients with a current history of intravenous drug abuse, alcohol or substance abuse (within the last year)
• Patients undergoing treatment for an active infection
• Patients who are heavy smokers (≥ 20 cigarettes or cigars per day)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nevirapine + Saquinavir-sgc	Drug: Nevirapine; 200 mg q.d. days 1-14 followed by 200 mg b.i.d. days 15-28; Drug: Saquinavir-sgc; 1600 mg b.i.d. from pre trial to day 28

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum observed concentration (Cmax)	up to 12 hours post-dose on days 1 and 28
Time of maximum concentration (Tmax)	up to 12 hours post-dose on days 1 and 28
Minimum observed concentration (Cmin)	up to 12 hours post-dose on days 1 and 28
Area under the plasma concentration time profile over the steady-state dosing interval (AUCτ)	up to 12 hours post-dose on days 1 and 28
Systemic clearance (Cl/F)	up to 12 hours post-dose on days 1 and 28

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of patients with adverse events	up to 28 days
Change in HIV RNA levels	Baseline and day 28
Change in cluster differentiation 4 positive (CD4+) count	Baseline and day 28

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: May 1, 1999
• Primary Completion (Actual): February 1, 2000

Study Registration Dates

• First Submitted: July 8, 2014
• First Submitted That Met QC Criteria: July 8, 2014
• First Posted (Estimate): July 9, 2014

Study Record Updates

• Last Update Posted (Estimate): July 14, 2014
• Last Update Submitted That Met QC Criteria: July 11, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; HIV Protease Inhibitors; Viral Protease Inhibitors; Nevirapine; Saquinavir
• Other Study ID Numbers: 1100.1280