Clinical trial NCT01106469: Pharmacokinetics (PK) and Pharmacodynamics (PD) Study of Single and Multiple Ascending Doses of JNJ-41443532 in Healthy Male Participants
Official title: Single and Multiple Ascending Dose Study to Investigate the Safety, Tolerability, Food Effect, Pharmacokinetics, and Pharmacodynamics of JNJ-41443532 in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy Volunteers
Healthy
JNJ-41443532
Pharmacokinetics
Lead sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Sponsor class: INDUSTRY
First posted: 2010-04-20
Enrollment: 74
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to investigate the safety, tolerability, food effect as well as the pharmacokinetics (how the drug is absorbed in the body, how it is distributed within the body and how it is removed from the body over time) and pharmacodynamics (the effects of the drug) of single and multiple ascending doses of JNJ-41443532 in healthy male participants.

Detailed description: This is a randomized (study drug assigned by chance), double-blind (neither physician nor participant knows the name of the assigned drug), placebo-controlled, single and multiple ascending dose study conducted at a single study center. The study has 4 parts. Part 1 is a randomized, double-blind, alternating panel, single ascending oral dose study. Two alternating treatment panels (A and B) each with nine healthy male participants will be studied with successively increasing dose levels. Part 2 is a randomized, open-label (all people involved know the identity of the intervention), 2-period crossover study to evaluate what the effect of administering JNJ- 41443532 with food (i.e. standard high fat breakfast meal) relative to administration in the fasted state will have on pharmacokinetics/blood levels of JNJ-41443532. Part 3 is a randomized, double-blind, single oral dose study in obese, otherwise healthy male participants. Part 4 is a double-blind, randomized, placebo-controlled multiple ascending dose study in up to 5 sequential treatment groups of healthy male participants. Safety assessments include monitoring of adverse events, and evaluation of lab results, cardiac parameters, vital signs, and physical exams. In Parts 1, 2, and 3 participants receive study medication (JNJ-41443532 or placebo) orally on Day 1 after an overnight fast of at least 10 hours; planned doses are 25 to 1500 mg. In Part 4, participants receive study medication (JNJ-41443532 or placebo) orally each day for 10 consecutive days after an overnight fast of at least 10 hours; planned doses are 100 to 1000 mg.

Eligibility criteria: Inclusion Criteria:

* Males, age 18 to 45 years inclusive for Part 1 and age 18 to 55 years inclusive for Parts 2, 3, and 4
* Weight = 60 kilograms and Body Mass Index (BMI) between 18.5 and 29.9 kg/m2 (inclusive)
* BMI between 30 to 39.9 kg/m2 for obese participants
* Healthy on the basis of physical examination, medical history, vital signs, electrocardiogram (ECG), and clinical laboratory tests performed at screening
* Men must agree to use a double barrier method of birth control (e.g. condom and use of spermicide with diaphragm, hormonal contraceptives or intrauterine devices by female partner) and to not donate sperm during the study and for 3 months after receiving the last dose of study drug
* Willing to adhere to the prohibitions and restrictions specified in this protocol

Exclusion Criteria:

* History of, or currently active, significant illness or medical disorders, including (but not limited to) cardiovascular disease (including cardiac arrhythmias, myocardial infarction, stroke, peripheral vascular disease), endocrine or metabolic disease (e.g. hyper/hypo-thyroidism), hematological disease (e.g. von Willebrand's disease or other bleeding disorders), respiratory disease, hepatic or gastrointestinal disease, neurological or psychiatric disease, ophthalmologic disorders (including retinal disorders or cataracts), neoplastic disease, skin disorder, or any other illness that the Investigator considers should exclude the participant
* Participants at risk for QTc prolongation (specific heart rhythm irregularity)
* Within 12 months prior to screening, has had a clinically important, serious infection (e.g. hepatitis, pneumonia, or pyelonephritis), has been hospitalized for an infection or has been treated with intravenous (IV) antibiotics for an infection
* Smoker or tobacco user within the past 3 months
* History of alcohol or drug abuse
* History of clinically significant drug and/or food allergies, including allergies or intolerance (e.g. lactose intolerance)
* Donation of 1 or more units of blood or acute loss of an equivalent amount of blood within 60 days prior to study drug administration
* Received an experimental drug or used an experimental medical device within 60 days

Primary outcomes:
measure: Determine the pharmacokinetic properties of single and multiple doses JNJ-41443532 as determined by blood level concentrations.
timeFrame: Part 1 - Approximately 13 weeks; Part 2 - Approximately 7 weeks; Part 3 - Approximately 6 weeks; Part 4 - Approximately 7 weeks
Secondary outcomes:
measure: Determine the safety and tolerability of JNJ-41443532 as determined by evaluation of adverse events, lab results, cardiac monitoring, vital signs, and physical exams.
timeFrame: Part 1 - Approximately 13 weeks; Part 2 - Approximately 7 weeks; Part 3 - Approximately 6 weeks; Part 4 - Approximately 7 weeks
measure: To explore the relationship between JNJ-41443532 plasma concentrations and pharmacodynamic effects (concentration-effect relationships).
timeFrame: Part 1 - Approximately 13 weeks; Part 2 - Approximately 7 weeks; Part 3 - Approximately 6 weeks; Part 4 - Approximately 7 weeks
measure: To explore the pharmacodynamic (PD) effects of JNJ-41443532 and to compare the differences between treatment groups
timeFrame: Part 1 - Approximately 13 weeks; Part 2 - Approximately 7 weeks; Part 3 - Approximately 6 weeks; Part 4 - Approximately 7 weeks
Other outcomes:
Locations:
city: Merksem
country: Belgium
Study officials:
affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
name: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial
role: STUDY_DIRECTOR
References: