Phase 1
N=32
Drug Interactions Between Voriconazole and Atazanavir Coadministered as Atazanavir/Ritonavir in Healthy Participants
Human Immunodeficiency Virus Type 1 (HIV-1) · HIV Infections
Bottom Line
View on ClinicalTrials.gov: NCT00833482 ↗Enrolled (actual)
32
Serious AEs
0.0%
Results posted
Oct 2012
Primary outcome: Primary: 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) — 674; 525; 4715; 4076 ng/mL
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Voriconazole (Drug); Atazanavir (Drug); Ritonavir (Drug)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- Bristol-Myers Squibb
- Primary completion
- Jul 2010
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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) |
674; 525; 4715; 4076 | — |
| PRIMARY Time to Maximum Concentration (Tmax) of Atazanavir, Administered as Atazanavir/Ritonavir With and Without Voriconazole, in EM Participants |
3.0; 2.07 | — |
| PRIMARY 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 |
44634; 38276 | — |
| PRIMARY Tmax of Voriconazole, Administered With and Without Atazanavir/Ritonavir, in EM Participants |
1.50; 1.25 | — |
| PRIMARY Cmax and Cmin of Voriconazole, Administered With and Without Atazanavir/Ritonavir, in EM Participants |
3416; 3014; 776; 439 | — |
| PRIMARY AUC(TAU)of Voriconazole, Administered With and Without Atazanavir/Ritonavir, in EM Participants |
20284; 12944 | — |
| SECONDARY Cmax and Cmin of Ritonavir, Administered As Atazanavir/Ritonavir With and Without Voriconazole, in EM Participants |
1597; 1429; 37.1; 28.3 | — |
| SECONDARY Tmax of Ritonavir, Administered As Atazanavir/Ritonavir With and Without Voriconazole, in EM Participants |
4.0; 4.0 | — |
| SECONDARY AUC(TAU) of Ritonavir, Administered As Atazanavir/Ritonavir With and Without Voriconazole, in EM Participants |
9572; 8280 | — |
| SECONDARY Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Any AE |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Marked Abnormalities in Serum Chemistry Test Results |
0; 0; 1; 0; 0; 0 | — |
| SECONDARY Number of Participants With Marked Abnormalities in Hematology Laboratory Test and Urinalysis Results |
1; 0; 1; 0; 0; 0 | — |
| SECONDARY 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 |
0; 0; 0; 0; 2; 0 | — |
| SECONDARY Number of Participants With Abnormalities in Vital Signs |
0; 0; 0; 0; 0; 0 | — |
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
Data sourced from ClinicalTrials.gov (NCT00833482). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.