Study to Assess the Pharmacokinetic Drug - Drug Interactions between Atazanavir Plus Ritonavir Coadministered with Voriconazole in Healthy Subjects.

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 24

Inclusion Criteria

1) Signed Written Informed Consent
a) The signed informed consent form.
2) Target Population
a) Healthy subjects as determined by no clinically significant deviation from normal
in medical history, physical examination, ECGs, and clinical laboratory
determinations.
b) Body Mass Index (BMI) of 18 to 32 kg/m2, inclusive. BMI = weight (kg)/
[height (m)]2.
3) Age and Sex
a) Women who are not of childbearing potential (ie, who are postmenopausal or
surgically sterile) and men, ages 18 to 45 inclusive.
Women are considered surgically sterile only if they have undergone a
hysterectomy, bilateral tubal ligation, or bilateral oophorectomy. Post menopause
is defined as:
• Amenorrhea >= 12 consecutive months without another cause or
• For women with irregular menstrual periods and on hormone replacement
therapy (HRT), a documented serum follicle stimulating hormone (FSH) level
> 35 mIU/mL

Exclusion Criteria

1) Sex and Reproductive Status
a) WOCBP
• WOCBP include any female who has experienced menarche and who has not
undergone successful surgical sterilization (hysterectomy, bilateral tubal
ligation, or bilateral oophorectomy) or is not postmenopausal. Women who
are using oral contraceptives, other hormonal contraceptives (vaginal
products, skin patches, or implanted or injectable products), or mechanical
products such as an intrauterine device or barrier methods (diaphragm,
condoms, spermicides) to prevent pregnancy, or are practicing abstinence or
where their partner is sterile (eg, vasectomy) should be considered to be of
childbearing potential.
b) Women who are pregnant or breastfeeding
c) Women with a positive pregnancy test on enrollment or prior to administration of
investigational product.
d) Sexually active fertile men not using effective birth control if their partners are
WOCBP.
2) Medical History and Concurrent Diseases
a) Proven or suspected acute hepatitis (within 12 months prior to the 1st dose)
b) Any significant acute or chronic medical illness.
c) Current or recent (within 3 months) gastrointestinal disease.
d) Any major surgery within 4 weeks prior to study drug administration.
e) Any gastrointestinal surgery that could impact upon the absorption of study drug.
f) Donation of blood or plasma to a blood bank or in a clinical study (except a
screening visit) within 4 weeks prior to study drug administration.
g) Blood transfusion within 4 weeks prior to study drug administration.
h) Inability to tolerate oral medication.
i) Inability to be venipunctured and/or tolerate venous access.
j) Smoking more than 5 cigarettes per day.
k) Recent (within 6 months) drug or alcohol abuse as defined in DSM IV, Diagnostic
Criteria for Drug and Alcohol Abuse (Appendix 2).
l) Any other sound medical, psychiatric and/or social reason as determined by the
investigator.
m) Consumption of alcohol within 3 days prior to the first dose of study drug.
n) Intractable diarrhea (>= 6 loose stools/day for at least 7 consecutive days) within
30 days prior to the first dose of study drug.
o) History of any hemolytic disorders (including drug-induced hemolysis).
p) History of acute or chronic pancreatitis.
q) History of hypochlorhydria or achlorhydria.
3) Physical and Laboratory Test Findings
a) Men and Women < 40 Kg
b) Homozygous CYP2C19 poor metabolizers
c) Evidence of organ dysfunction or any clinically significant deviation from normal
in physical examination, vital signs, ECG or clinical laboratory determinations
beyond what is consistent with the target population.
d) Positive urine screen for drugs of abuse.
e) Positive blood screen for hepatitis C antibody, hepatitis B surface antigen, or HIV
viral RNA or HIV-1, -2 antibody.
f) Liver enzymes (alkaline phosphatase, AST, ALT) above the upper limit of normal
at screening or prior to dosing.
g) QT interval >= 500 msec, QTcF interval >= 450 msec either at screening or prior to
dosing (confirmed by repeat ECG).
h) PR interval >= 210 msec, QRS interval >= 120 msec either at screening or prior to
dosing (confirmed by repeat ECG).
i) First, second- or third-degree A-V block or clinically relevant ECG abnormalities
either at screening or prior to dosing.
4) Allergies and Adverse Drug Rea

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>• Pharmacokinetic Measures: Multiple-dose pharmacokinetic parameters (Cmax,<br /><br>Tmax,<br /><br>AUC(TAU), and Ctrough) will be derived from plasma concentration versus time<br /><br>for ATV, RTV<br /><br>and VOR and the combined use of these drugs. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>• Safety Outcome Measures: Safety assessments will be based on medical review<br /><br>of adverse event<br /><br>reports and the results of vital sign measurements, ECGs, physical<br /><br>examinations, and clinical<br /><br>laboratory tests. The incidence of observed adverse events will be tabulated<br /><br>and reviewed for<br /><br>potential significance and clinical importance.</p><br>