Effect of Ketoconazole on the Pharmacokinetics of JNJ-38518168 in Healthy Volunteers

This is an open-label (all people know the identity of the intervention), single-sequence,
randomized (dose of JNJ-38518168 (3 mg or 30 mg) is assigned by chance), single-center,
multiple-dose study designed to assess the potential effects of multiple oral administration
of ketoconazole (KTZ) on the steady-state (a situation where the overall intake of a drug is
in equilibrium with its elimination) pharmacokinetics of JNJ-38518168. Pharmacokinetics (PK)
explores how the drug is absorbed in the body, distributed within the body, and how it is
removed from the body over time. The study consists of 3 phases: a Screening Phase of
approximately 3 weeks (Days -22 to -2); an Open-Label Phase (Days -1 to 26); and a Follow-up
Phase occurring from 7 to 10 days after the last dose of study drug. Participants will be
randomly assigned to receive either a daily dose of 3 mg JNJ-38518168 (Group 1) or a daily
dose of 30 mg JNJ-38518168 (Group 2) orally administered for 25 days. All participants will
receive multiple oral doses of KTZ (200 mg every 12 hours for both Groups 1 and 2) from Day
22 through Day 25. An optional group of participants receiving 10 mg once daily of
JNJ-38518168 (Group 3) may be evaluated if the data from Groups 1 and 2 do not allow the
sponsor to estimate sufficiently the interaction between KTZ and daily dose of 10 mg
JNJ-38518168. The participants will receive an oral dose of the study drugs in the morning
of specified days, after an overnight fast for at least 10 hours. Blood samples will be
collected at various times throughout the study for evaluation of drug concentrations in
plasma. Safety will be assessed by reporting of adverse events, vital signs, physical
examination results, weight, and electrocardiogram (ECG) evaluations. Participants will
leave the study center on Day 26 after the collection of the last scheduled PK blood sample.
For each participant, a follow-up visit will occur 7 to 10 days after the last dose of study
drug. For each participant, the total duration of the study is approximately 8 weeks.

Inclusion Criteria:

- Signed informed consent document indicating that the participant understands the
purpose of and procedures required for the study and is willing to participate in the
study

- If a woman, must be postmenopausal, surgically sterile, abstinent, or, if sexually
active, be practicing an effective method of birth control before, throughout, and
for 3 months after the study

- If a man, must agree to use an adequate contraception method, or partner using
effective contraception, and to not donate sperm during the study and for 3 months
after the study

- Body mass index (BMI; weight [kg]/height2 [m]2) between 18 and 30 kg/m2 (inclusive),
and body weight not less than 50 kg

- Blood pressure between 90 and 140 mmHg systolic, inclusive, and no higher than 90
mmHg diastolic

- Non-smoker

Exclusion Criteria:

- History of or current clinically significant medical illness, condition or disease
that the investigator considers should exclude the participant or that could
interfere with the interpretation of the study results

- Clinically significant abnormal lab results at screening or at admission to the study
center

- Clinically significant abnormal physical examination or electrocardiogram (ECG) at
screening or at admission to the study center

- Use of any prescription or nonprescription medication (including vitamins and herbal
supplements), except for acetaminophen and oral contraceptives and hormonal
replacement therapy within 14 days before the first dose of study drug is scheduled

- Has a history of malignancy (the tendency of a medical condition, especially tumors,
to become progressively worse) within the previous 5 years before screening (certain
less serious malignancies during the previous 5 years, such as basal cell carcinoma
of the skin which has been adequately treated, may be allowed by the study doctor)

- Donated blood or had a substantial loss of blood within 3 months before first
administration of study drug

- Pregnant or currently breast-feeding

- Smoking or using nicotine-containing products within 3 months of screening