Clinical trial NCT01932333: A Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-40411813 in Male and Female Elderly Patients
Official title: A Double-Blind, Placebo-Controlled, Randomized, Multiple Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-40411813 in Male and Female Elderly Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy
Safety
Tolerability
Pharmacokinetics
Pharmacodynamics
JNJ-40411813
Positive allosteric modulator
Lead sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Sponsor class: INDUSTRY
First posted: 2013-08-30
Enrollment: 36
Sex: ALL
Minimum age (years): 65
Maximum age (years): 85
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (what the body does to the study medication) and pharmacodynamics (the study of the action or effects the study medication has on the body) of single- and multiple, escalating oral doses of JNJ-40411813.

Detailed description: This is a double-blind (neither physician nor participants knows the treatment that the participant receives), randomized (study medication is assigned by chance), placebo-controlled (an inactive substance is compared with a medication to test whether the medication has a real effect in a clinical study), single- and multiple ascending dose study. This study consists of 3 phases: screening phase, treatment phase, and follow-up phase. This study will be conducted in 2 cohorts (groups) (Cohort 1: JNJ-40411813 50 mg and Cohort 2: JNJ-40411813 100 mg) and each cohort consists of 2 periods (Period 1: single dose and Period 2: multiple doses). Approximately 36 participants will be enrolled in this study (18 participants will be enrolled in each cohort) to receive JNJ-40411813 or placebo in 2:1 ratio. If safety/tolerability and pharmacokinetic results profile is favorable for single dose of JNJ-40411813, multiple dose administration will follow. Safety will be evaluated by the assessment of adverse events, vital signs, schellong test (a test for circulatory function), 12-lead electrocardiogram, physical examination, neurological examination (to measure mental status, motor examination, reflexes, sensory, gait and cranial nerves), vertigo (giddiness) symptom, and clinical laboratory tests which will be monitored throughout the study. The total duration of study participation for a participant will be 9 weeks.

Eligibility criteria: Inclusion Criteria:

* Female participants must be postmenopausal for at least 12 months
* Body mass index (BMI) between 18 and 33 kg/m2 (BMI is calculated as weight \[kilogram\] divided by square of height \[meter\])

Exclusion Criteria:

* Clinically significant abnormal values for laboratory tests and abnormal physical examination
* Significant history of or current significant unstable medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematological disease, bronchospastic respiratory disease, dyspnea (difficulty in breathing), diabetes mellitus, thyroid disease, infection
* Significant history of or current psychiatric or neurological illness
* Serology positive for hepatitis B surface antigen, hepatitis C antibodies or HIV antibodies at screening
* Positive urine screen for drugs of abuse and positive alcohol breath test at screening or administration of the study medication
* Only the use of any prescription medication that is known to be potent CYP3A4 inhibitors or inducers within 2 weeks of start of study medication

Primary outcomes:
measure: Cohort 1 and Cohort 2: Number of participants with adverse events
timeFrame: 9 weeks
measure: Peak plasma concentration of JNJ 40411813
timeFrame: Both Cohorts, Period 1: Day 1 (predose to 12 hrs), Day 2 (24 and 36 hrs), Day 3, and Day 4; Both Cohorts, Period 2: Day 1 (predose to 12 hrs); predose on Days 2, 3, 4, 5, 6, 7, 8, 9; Day 10 (predose to 12 hrs); Day 11 (0 and 12 hrs); Days 12, 13, and 14
measure: Time to reach the peak plasma concentration of JNJ 40411813
timeFrame: Both Cohorts, Period 1: Day 1 (predose to 12 hrs), Day 2 (24 and 36 hrs), Day 3, and Day 4; Both Cohorts, Period 2: Day 1 (predose to 12 hrs); predose on Days 2, 3, 4, 5, 6, 7, 8, 9; Day 10 (predose to 12 hrs); Day 11 (0 and 12 hrs); Days 12, 13, and 14
measure: Area under the plasma concentration of JNJ 40411813 - time curve from 0 to t hours post dosing
timeFrame: Both Cohorts, Period 1: Day 1 (predose to 12 hrs), Day 2 (24 and 36 hrs), Day 3, and Day 4; Both Cohorts, Period 2: Day 1 (predose to 12 hrs); predose on Days 2, 3, 4, 5, 6, 7, 8, 9; Day 10 (predose to 12 hrs); Day 11 (0 and 12 hrs); Days 12, 13, and 14
measure: Elimination rate constant of JNJ 40411813
timeFrame: Both Cohorts, Period 1: Day 1 (predose to 12 hrs), Day 2 (24 and 36 hrs), Day 3, and Day 4; Both Cohorts, Period 2: Day 1 (predose to 12 hrs); predose on Days 2, 3, 4, 5, 6, 7, 8, 9; Day 10 (predose to 12 hrs); Day 11 (0 and 12 hrs); Days 12, 13, and 14
measure: Terminal half-life of JNJ 40411813
timeFrame: Both Cohorts, Period 1: Day 1 (predose to 12 hrs), Day 2 (24 and 36 hrs), Day 3, and Day 4; Both Cohorts, Period 2: Day 1 (predose to 12 hrs); predose on Days 2, 3, 4, 5, 6, 7, 8, 9; Day 10 (predose to 12 hrs); Day 11 (0 and 12 hrs); Days 12, 13, and 14
measure: Area under the plasma concentration of JNJ 40411813 - time curve from 0 to infinity post dosing
timeFrame: Both Cohorts, Period 1: Day 1 (predose to 12 hrs), Day 2 (24 and 36 hrs), Day 3, and Day 4
measure: Predose plasma concentration of JNJ 40411813
timeFrame: Both Cohorts, Period 2: Day 1 (predose to 12 hrs); predose on Days 2, 3, 4, 5, 6, 7, 8, 9; Day 10 (predose to 12 hrs); Day 11 (0 and 12 hrs); Days 12, 13, and 14
measure: Average plasma concentration of JNJ 40411813 at steady state
timeFrame: Both Cohorts, Period 2: Day 1 (predose to 12 hrs); predose on Days 2, 3, 4, 5, 6, 7, 8, 9; Day 10 (predose to 12 hrs); Day 11 (0 and 12 hrs); Days 12, 13, and 14
measure: Cognitive test
timeFrame: Both Cohorts, Period 1: Screening; Both Cohorts, Period 2: Day -1 (1 day before study treatment) and Day 7
measure: Addiction Research Center Inventory questionnaire (ARCI-Q)
timeFrame: Both Cohorts, Period 1: Day -1 and Day 1 (3 hrs post dose); Both Cohorts, Period 2: Day 7
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 Clinical Trial
role: STUDY_DIRECTOR
References: