Drug Interactions Between Voriconazole and Atazanavir Coadministered as Atazanavir/Ritonavir in Healthy Participants

NCT00833482 | Completed Phase 1 Results

• 2 other identifiers: AI424-3832009-009095-13
• Study Type: interventional
• Target: 185
• Locations: 2 countries
• Sites: 2

Brief Summary

This study assesses the effects of voriconazole, 200 mg, administered twice daily (BID), on the steady-state pharmacokinetics of atazanavir administered as atazanavir/ritonavir, 300/100 mg once daily (QD), in healthy participants with functional CYP2C19 alleles. The study also reviews the effects of atazanavir/ritonavir, 300/100 mg QD, on the pharmacokinetics of voriconazole, 200 mg, BID in healthy participants with functional CYP2C19 alleles.

Conditions

Human Immunodeficiency Virus Type 1 (HIV-1); HIV Infections

Outcome Measures

Primary Outcomes (6)

• Maximum Observed Plasma Concentration (Cmax) and Minimum Observed Plasma Concentration (Cmin) of Atazanavir, Administered as Atazanavir/Ritonavir With and Without Voriconazole, in Participants Who Are Extensive Metabolizers (EM)

  EM participants are those with functional CYP2C19 alleles.

  Predose and at 1, 2, 3, 4, 5, 7, 9,13, and 24 hours postdose on Days 20 and 30 of a 30-day cycle

• Time to Maximum Concentration (Tmax) of Atazanavir, Administered as Atazanavir/Ritonavir With and Without Voriconazole, in EM Participants

  EM=extensive metabolizers, or participants with functional CYP2C19 alleles.

  Predose and at 1, 2, 3, 4, 5, 7, 9,13, and 24 hours postdose on Days 20 and 30 of a 30-day cycle

• Area Under the Plasma Concentration-time Curve in 1 Dosing Interval [AUC(TAU)] of Atazanavir Administered as Atazanavir/Ritonavir With and Without Voriconazole, in EM Participants

  EM=extensive metabolizers, or participants with functional CYP2C19 alleles.

  Predose and at 1, 2, 3, 4, 5, 7, 9,13, and 24 hours postdose on Days 20 and 30 of a 30-day cycle

• Tmax of Voriconazole, Administered With and Without Atazanavir/Ritonavir, in EM Participants

  Tmax=time to maximum concentration; EM=extensive metabolizers, or participants with functional CYP2C19 alleles.

  Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdoseDays 3 and 30 of a 30-day cycle

• Cmax and Cmin of Voriconazole, Administered With and Without Atazanavir/Ritonavir, in EM Participants

  Cmax=maximum observed plasma concentration; Cmin=minimum observed plasma concentration; EM=extensive metabolizers, or participants with functional CYP2C19 alleles.

  Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdoseDays 3 and 30 of a 30-day cycle

• AUC(TAU)of Voriconazole, Administered With and Without Atazanavir/Ritonavir, in EM Participants

  AUC(TAU)=area under the plasma concentration-time curve in 1 dosing interval; EM=extensive metabolizers, or participants with functional CYP2C19 alleles.

  Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdoseDays 3 and 30 of a 30-day cycle

Secondary Outcomes (8)

• Cmax and Cmin of Ritonavir, Administered As Atazanavir/Ritonavir With and Without Voriconazole, in EM Participants

  Predose and at 1, 2, 3, 4, 5, 7, 9,13, and 24 hours postdose on Days 20 and 30 of a 30-day cycle

• Tmax of Ritonavir, Administered As Atazanavir/Ritonavir With and Without Voriconazole, in EM Participants

  Predose and at 1, 2, 3, 4, 5, 7, 9,13, and 24 hours postdose on Days 20 and 30 of a 30-day cycle

• AUC(TAU) of Ritonavir, Administered As Atazanavir/Ritonavir With and Without Voriconazole, in EM Participants

  Predose and at 1, 2, 3, 4, 5, 7, 9,13, and 24 hours postdose on Days 20 and 30 of a 30-day cycle

• Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Any AE

  Days 1 to 31 (discharge), continuously

• Number of Participants With Marked Abnormalities in Serum Chemistry Test Results

  Within 21 days of Day 1 and on Days 3, 10, 20, 26, and 31 (at discharge)

Study Arms (5)

Voriconazole, 200 mg BID (EM)

ACTIVE COMPARATOR

Drug: Voriconazole

Atazanavir/Ritonavir, 300/100 QD (EM & PM)

ACTIVE COMPARATOR

Drug: Atazanavir; Drug: Ritonavir

Atazanavir/Ritonavir, 300/100mgQD + Voriconazole, 200mgBID(EM)

ACTIVE COMPARATOR

Drug: Voriconazole; Drug: Atazanavir; Drug: Ritonavir

Voriconazole, 50 mg BID (PM)

ACTIVE COMPARATOR

Drug: Voriconazole

Atazanavir/ritonavir, 300/100mgQD+voriconazole, 50mgBID (PM)

ACTIVE COMPARATOR

Drug: Voriconazole; Drug: Atazanavir; Drug: Ritonavir

Interventions

Voriconazole DRUG

Treatment A: Participants with functional CYP2C19 alleles (EM) received oral tablets of voriconazole, 400 mg, twice daily (BID), on Day 1, then 200 mg BID on Days 2 and 3. Voriconazole dose was given at least 1 hour after a light meal. Treatment C: EM participants received atazanavir/ritonavir, 300/100 mg once daily (QD), plus voriconazole, 400 mg BID on Day 21 then 200 mg BID on Days 22-30. Atazanavir/ritonavir dose was administered in the morning within 5 minutes of completing a light meal, and 1 hour before voriconazole morning dose. Treatment E: PM participants received atazanavir/ritonavir, 300/100 mg QD plus voriconazole, 100 mg BID, on Day 21, then 50 mg BID on Days 22-30.

Atazanavir/Ritonavir, 300/100mgQD + Voriconazole, 200mgBID(EM); Atazanavir/ritonavir, 300/100mgQD+voriconazole, 50mgBID (PM); Voriconazole, 200 mg BID (EM); Voriconazole, 50 mg BID (PM)

Atazanavir DRUG

Treatment B in EM participants: EM participants received atazanavir/ritonavir, 300/100 mg once daily (QD), on Days 11 through 20. Treatment B in participants who were poor metabolizers of CYP2C19 (PMs): PM participants received oral tablets of atazanavir/ritonavir, 300/100 mg QD, on Days 11 through 20. Treatment C: EM participants received atazanavir/ritonavir, 300/100 mg QD, plus voriconazole, 400 mg BID on Day 21 then 200 mg BID on Days 22-30. Treatment E: PM participants received atazanavir/ritonavir, 300/100 mg QD plus voriconazole, 100 mg BID, on Day 21, then 50 mg BID on Days 22-30.

Also known as: Reyataz, BMS-232632

Atazanavir/Ritonavir, 300/100 QD (EM & PM); Atazanavir/Ritonavir, 300/100mgQD + Voriconazole, 200mgBID(EM); Atazanavir/ritonavir, 300/100mgQD+voriconazole, 50mgBID (PM)

Ritonavir DRUG

Treatment B: EM participants received atazanavir/ritonavir, 300/100 mg once daily (QD), on Days 11 through 20. Atazanavir/ritonavir dose was administered in the morning within 5 minutes of completing a light meal. Treatment C: EM participants received atazanavir/ritonavir, 300/100 mg QD, plus voriconazole, 400 mg BID on Day 21 then 200 mg BID on Days 22-30. Atazanavir/ritonavir dose was administered in the morning within 5 minutes of completing a light meal, and 1 hour before voriconazole morning dose.Treatment E: PM participants received atazanavir/ritonavir, 300/100 mg QD plus voriconazole, 100 mg BID, on Day 21, then 50 mg BID on Days 22-30. Treatment B in PM participants: PM participants received atazanavir/ritonavir, 300/100 mg QD, on Days 11 through 20. Atazanavir/ritonavir dose was administered in the morning within 5 minutes of completing a light meal.

Atazanavir/Ritonavir, 300/100 QD (EM & PM); Atazanavir/Ritonavir, 300/100mgQD + Voriconazole, 200mgBID(EM); Atazanavir/ritonavir, 300/100mgQD+voriconazole, 50mgBID (PM)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy participants as determined by no clinically significant deviation from normal
• Body Mass Index (BMI) of 18 to 32 kg/m\^2, inclusive. BMI=weight(kg)/height (m)\^2
• Women who are not of childbearing potential (WOCBP)(ie, who are postmenopausal or surgically sterile) and men, ages 18 to 45 years, inclusive

You may not qualify if:

• WOCBP
• Sexually active fertile men not using effective birth control if their partners are WOCBP
• Proven or suspected acute hepatitis (within 12 months prior to the 1st dose)
• Any significant acute or chronic medical illness
• Any gastrointestinal surgery that could impact on the absorption of study drug
• Smoking more than 5 cigarettes per day
• History of any hemolytic disorders (including drug-induced hemolysis)
• History of acute or chronic pancreatitis
• History of hypochlorhydria or achlorhydria
• Men and women weighing \<40 kg
• Positive blood screen for hepatitis C antibody, hepatitis B surface antigen, or HIV-1 or HIV-2 antibody
• Patients with galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (2)

West Coast Clinical Trials, Llc

Cypress, California, 90630, United States

Location

Local Institution

Nijmegen, 6425 GA, Netherlands

Location

Related Links

• Investigator Inquiry form

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; HIV Infections

Interventions

Voriconazole; Atazanavir Sulfate; Ritonavir

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; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyridines; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Thiazoles; Sulfur Compounds; Organic Chemicals

Results Point of Contact

• Title: BMS Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  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
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2009
• First Posted: February 2, 2009
• Study Start: September 1, 2009
• Primary Completion: July 1, 2010
• Study Completion: February 1, 2011
• Last Updated: October 25, 2012
• Results First Posted: October 25, 2012

Record last verified: 2012-09

Locations

NL (1); US (1)