Effect of Ketoconazole on the Pharmacokinetics of BMS-650032 in Healthy Subjects

Recruitment & Eligibility

Status: Open to Recruitment

Sex: Not specified

Target Recruitment: 16

Inclusion Criteria

4.2.1 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, Sex, and Reproductive Status
a) Women who are not of childbearing potential (ie. who are postmenopausal or
surgically sterile) and men, ages 18 to 49, 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/m

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. 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
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 of 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 or male subject who have sex with women who are unwilling to agree to
practice double barrier contraception (ie condom with spermicide) and refrain
from donating sperm during study participation and for at least 12 weeks
following dosing.
2) Medical History and Concurrent Diseases
a) At risk for tuberculosis (TB) infection. Specifically subjects with:
i) Current clinical, radiographic or laboratory evidence of active or latent TB
ii) A history of active TB within the last 3 years, even if it was treated.
iii) A history of active TB greater than 3 years ago unless there is documentation
that the prior anti-TB treatment was appropriate in duration and type
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 10 cigarettes per day.
k) A personal history of clinically significant cardiac disease, symptomatic or
asymptomatic arrhythmias, syncopal episodes, or additional risk factors for
torsades de pointes.
l) Recent (within 6 months) drug or alcohol abuse as defined in DSM IV, Diagnostic
Criteria for Drug and Alcohol Abuse.
m) Any other sound medical, psychiatric and/or social reason as determined by the
investigator.
3) Physical and Laboratory Test Findings
a) 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.
b) Any of the following screening or Day 1 laboratory results outside of the ranges
specified below as defined by the central laboratory, confirmed by repeat analysis.
i) Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) > upper
limit of normal (ULN)
ii) Total bilirubin >ULN
iii) Hemoglobin <0.9 x LLN
iv) CK > 2 x ULN
v) Serum creatinine > ULN
c

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To assess the effects of ketoconazole on the steady state pharmacokinetics (PK) of BMS-650032 in healthy subjects.Timepoint: Serial blood samples for BMS-650032 PK will be collected pre-doses and up to<br>12 hours post AM and PM doses on Days 7 and 14. Blood samples for BMS-650032 trough concentrations<br>will be collected pre-AM doses on Days 2, 4, 6, 9, 11, and 13.

Secondary Outcome Measures

Name	Time	Method
To assess the safety and tolerability of multiple dose BMS-650032 when administered alone and with<br>ketoconazole.<br>To assess the diurnal variation of BMS-650032 PK when administered alone and with ketoconazole.<br>To characterize the PK of BMS-650032 in Indian subjects.Timepoint: Within 30 days after first dose