Clinical trial NCT00833482: Drug Interactions Between Voriconazole and Atazanavir Coadministered as Atazanavir/Ritonavir in Healthy Participants
Official title: Study to Assess the Pharmacokinetic Drug - Drug Interactions Between Atazanavir Plus Ritonavir Coadministered With Voriconazole in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Human Immunodeficiency Virus Type 1 (HIV-1)
HIV Infections
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2009-02-02
Enrollment: 185
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: 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)
timeFrame: 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
measure: Time to Maximum Concentration (Tmax) of Atazanavir, Administered as Atazanavir/Ritonavir With and Without Voriconazole, in EM Participants
timeFrame: 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
measure: 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
timeFrame: 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
measure: Tmax of Voriconazole, Administered With and Without Atazanavir/Ritonavir, in EM Participants
timeFrame: 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
measure: Cmax and Cmin of Voriconazole, Administered With and Without Atazanavir/Ritonavir, in EM Participants
timeFrame: 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
measure: AUC(TAU)of Voriconazole, Administered With and Without Atazanavir/Ritonavir, in EM Participants
timeFrame: 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:
measure: Cmax and Cmin of Ritonavir, Administered As Atazanavir/Ritonavir With and Without Voriconazole, in EM Participants
timeFrame: 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
measure: Tmax of Ritonavir, Administered As Atazanavir/Ritonavir With and Without Voriconazole, in EM Participants
timeFrame: 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
measure: AUC(TAU) of Ritonavir, Administered As Atazanavir/Ritonavir With and Without Voriconazole, in EM Participants
timeFrame: 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
measure: Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Any AE
timeFrame: Days 1 to 31 (discharge), continuously
measure: Number of Participants With Marked Abnormalities in Serum Chemistry Test Results
timeFrame: Within 21 days of Day 1 and on Days 3, 10, 20, 26, and 31 (at discharge)
measure: Number of Participants With Marked Abnormalities in Hematology Laboratory Test and Urinalysis Results
timeFrame: Within 21 days of Day 1 and on Days 3, 10, 20, 26, and 31 (at discharge)
measure: Number of Participants With Investigator-identified Abnormalities in Electrocardiogram Results Not Present Prior to Administration of Study Drug and Considered Not Relevant and Not AEs by Investigator
timeFrame: Within 21 days of Day 1 and on Days -1, 21, and 31 (at discharge)
measure: Number of Participants With Abnormalities in Vital Signs
timeFrame: Within 21 days of Day 1 and on Days -1, 1, 3, 11, 21, and 31 (at discharge)
Other outcomes:
Locations:
city: Cypress
country: United States
facility: West Coast Clinical Trials, Llc
state: California
city: Nijmegen
country: Netherlands
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: