Clinical trial NCT02023255: A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of JNJ-39393406 in Healthy Participants
Official title: A Double-Blind, Placebo-Controlled, Randomized, Multiple Ascending Dose Study to Investigate the Safety, Tolerability and Pharmacokinetics of JNJ-39393406 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy
JNJ-39393406
Safety
Tolerability
Pharmacokinetics
Lead sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Sponsor class: INDUSTRY
First posted: 2013-12-30
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to evaluate the safety and tolerability of multiple dose administration of JNJ-39393406 in young healthy participants, and subsequently in healthy elderly participants.

Detailed description: This is a double-blind (neither physician nor participant knows the treatment that the participant receives), placebo-controlled (study in which an inactive substance is given to one group of participants, while the study medication is given to another group), randomized (the study medication is assigned by chance), and multiple ascending dose (participants will receive multiple doses of study medication and the dose level is subsequently escalated in further groups) study. This study will consist of screening phase (between 21 and 2 days prior to dose administration), a double-blind treatment phase (Part A - 7 days and Part B - 13 days), and a follow-up phase (within 7 to 14 days after last dose administration). In Part A of the multiple ascending dose study approximately 40 young healthy male participants will be randomly allocated to 5 cohorts (group of individuals with similar characteristics) to receive single daily doses of either JNJ-39393406 or placebo for 7 consecutive days. After each dose level, safety, tolerability, and pharmacokinetic (PK) profile (explores what the body does to a medication) of the dose level will be evaluated and the next dose level will be escalated considering the safety and tolerability data. In Part B of the study approximately 48 elderly healthy male and female participants will be randomly allocated to A, B, and C cohorts to receive single daily doses of either JNJ-39393406 or placebo for 13 consecutive days. Dose levels in Part B will be selected based on the PK data from Part A. In both Part A and Part B of the study the dose levels will be increased only after acceptable safety and tolerability data will be obtained. Safety evaluations will include assessments of adverse events, clinical laboratory tests, 24-hour creatinine clearance, Holter monitoring, telemetry, electrocardiogram, vital signs, physical examination, and neurological examination. The study duration for each participant will be approximately 8 weeks.

Eligibility criteria: Inclusion Criteria:

* Willing to adhere to the prohibitions and restrictions specified in the protocol
* Part A: Body mass index (BMI) between 18 and 30 kg/m2, inclusive (BMI = weight/height2)
* Part B: Female participants must be postmenopausal (for at least 12 months)
* BMI between 18 and 33 kg/m2, inclusive

Exclusion Criteria:

* Clinically significant abnormal values for clinical chemistry, hematology or urinalysis at screening or admission. It is expected that laboratory values will generally be within the normal range for the laboratory, though minor deviations, which are not considered to be of clinical significance to the investigator, are acceptable
* Clinically significant abnormal physical examination, vital signs or 12 lead electrocardiogram (ECG) at screening. Minor deviations in ECG, which are not considered to be of clinical significance to the investigator, are acceptable
* Clinically significant abnormal 24 hour Holter monitoring at screening in the opinion of the investigator
* Significant history of or current psychiatric or neurological illness
* Serology positive for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus antibodies at screening

Primary outcomes:
measure: Number of participants with adverse events
timeFrame: Up to Day 56
measure: Maximum Observed Plasma Concentration (Cmax) of JNJ-39393406 in Part A of the study
timeFrame: Days 1 and 7 (predose, 10, 20, 30, 45 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18 hours), Days 2 to 6 (predose), Day 8 (24 hours), and Days 9, 10 (48/72 hours)
measure: Maximum Observed Plasma Concentration (Cmax) of JNJ-39393406 in Part B of the study
timeFrame: Days 1 and 7 (predose, 10, 20, 30, 45 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18 hours), Days 2, 3, 4, 5, 6, 8, 9, 10, 11, 13 (predose), Day 12 (predose, 1, 2, 4, 6, 8 hours), Day 14 (24 hours), and Days 15, 16 (48/72 hours)
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ-39393406 in Part A of the study
timeFrame: Days 1 and 7 (predose, 10, 20, 30, 45 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18 hours), Days 2 to 6 (predose), Day 8 (24 hours), and Days 9, 10 (48/72 hours)
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ-39393406 in Part B of the study
timeFrame: Days 1 and 7 (predose, 10, 20, 30, 45 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18 hours), Days 2, 3, 4, 5, 6, 8, 9, 10, 11, 13 (predose), Day 12 (predose, 1, 2, 4, 6, 8 hours), Day 14 (24 hours), and Days 15, 16 (48/72 hours)
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Time at Last Observed Quantifiable Concentration (AUC[t]) of JNJ-39393406 in Part A of the study
timeFrame: Days 1 and 7 (predose, 10, 20, 30, 45 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18 hours), Days 2 to 6 (predose), Day 8 (24 hours), and Days 9, 10 (48/72 hours)
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Time at Last Observed Quantifiable Concentration (AUC[t]) of JNJ-39393406 in Part B of the study
timeFrame: Days 1 and 7 (predose, 10, 20, 30, 45 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18 hours), Days 2, 3, 4, 5, 6, 8, 9, 10, 11, 13 (predose), Day 12 (predose, 1, 2, 4, 6, 8 hours), Day 14 (24 hours), and Days 15, 16 (48/72 hours)
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[infinity]) of JNJ-39393406 in Part A of the study
timeFrame: Days 1 and 7 (predose, 10, 20, 30, 45 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18 hours), Days 2 to 6 (predose), Day 8 (24 hours), and Days 9, 10 (48/72 hours)
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[infinity]) of JNJ-39393406 in Part B of the study
timeFrame: Days 1 and 7 (predose, 10, 20, 30, 45 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18 hours), Days 2, 3, 4, 5, 6, 8, 9, 10, 11, 13 (predose), Day 12 (predose, 1, 2, 4, 6, 8 hours), Day 14 (24 hours), and Days 15, 16 (48/72 hours)
measure: Terminal Rate Constant (Lambda[z]) of JNJ-39393406 in Part A of the study
timeFrame: Days 1 and 7 (predose, 10, 20, 30, 45 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18 hours), Days 2 to 6 (predose), Day 8 (24 hours), and Days 9, 10 (48/72 hours)
measure: Terminal Rate Constant (Lambda[z]) of JNJ-39393406 in Part B of the study
timeFrame: Days 1 and 7 (predose, 10, 20, 30, 45 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18 hours), Days 2, 3, 4, 5, 6, 8, 9, 10, 11, 13 (predose), Day 12 (predose, 1, 2, 4, 6, 8 hours), Day 14 (24 hours), and Days 15, 16 (48/72 hours)
measure: Plasma Decay Half-Life (t1/2) of JNJ-39393406 in Part A of the study
timeFrame: Days 1 and 7 (predose, 10, 20, 30, 45 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18 hours), Days 2 to 6 (predose), Day 8 (24 hours), and Days 9, 10 (48/72 hours)
measure: Plasma Decay Half-Life (t1/2) of JNJ-39393406 in Part B of the study
timeFrame: Days 1 and 7 (predose, 10, 20, 30, 45 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18 hours), Days 2, 3, 4, 5, 6, 8, 9, 10, 11, 13 (predose), Day 12 (predose, 1, 2, 4, 6, 8 hours), Day 14 (24 hours), and Days 15, 16 (48/72 hours)
measure: Change from baseline in cognition in elderly and young healthy participants in Part A of the study
timeFrame: Baseline to Day 6
measure: Change from baseline in cognition in elderly and young healthy participants in Part B of the study
timeFrame: Baseline to Day 13
Secondary outcomes:
Other outcomes:
Locations:
city: Antwerpen
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: