A Dose-Ranging Study of JNJ-40411813 in Healthy Male Volunteers

Study Overview
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Brief Summary
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The purpose of this study is to characterize the 5-HT2A binding over the maximum feasible dose range of JNJ-40411813, to estimate the plasma concentration associated with 50% 5-HT2A binding, and to investigate the safety and tolerability of JNJ-40411813 in healthy male volunteers.

Detailed Description
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This will be an open-label (volunteers and study staff will know the identity of assigned treatment), dose-ranging study to determine 5-HT2A receptor engagement by JNJ-40411813 as a function of dose and time in healthy male volunteers. The study will consist of an eligibility screening examination, an open-label treatment period and a follow-up examination (approximately 10 days after dose administration, a follow-up examination will be performed). Initially, 4 volunteers (Cohort 1) will be included to determine 5-HT2A receptor occupancy following single dose administration of JNJ-40411813. Dependent on the results, doses for the remaining 8 volunteers (Cohort 2 and 3) will be selected to further characterize 5-HT2A receptor occupancy within the feasible dose range up to maximally 700 mg JNJ-40411813.The maximal study duration for a volunteer will be 6 weeks. In this study, [11C]-MDL 100,907 will be used as positron emission tomography (PET) ligand to investigate the concentration-related binding of 40411813 to the 5-HT2A receptor in the brain. JNJ-40411813 (200 mg to 700 mg) will be taken orally (by mouth). If multiple capsules have to be taken, the actual intake may be spread over a 15-minute period. Study drug will be administered to each volunteer just after completion of a meal and within 30 minutes after the start of the meal.

Official Title
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An Open Label Dose-Ranging Study in Healthy Male Subjects to Investigate the Binding Potential of JNJ-40411813 to Serotonin 2A Receptors in the Central Nervous System

Conditions
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Healthy

Intervention / Treatment
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* Drug: JNJ-40411813
* Drug: JNJ-40411813


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a body mass index (BMI) between 18 and 30 kg/m2, inclusive Willing to adhere to the prohibitions and restrictions specified in this protocol Volunteers must sign an informed consent to document that they understand the purpose of and procedures required for the study and are willing to participate in the study Exclusion Criteria: Have abnormal values for clinical laboratory tests, clinically significant abnormal physical examination findings, vital signs, or 12-lead Electrocardiograms (ECGs) performed at screening considered to be of clinical significance to the Investigator Have Significant history of or current significant medical illness that the Investigator considers should exclude the volunteer Have known allergies, hypersensitivity, or intolerance to JNJ-40411813, its excipients, or to the PET ligand used in the study Have significant history of psychiatric or neurological illness in first-degree relatives Been exposed to ionizing radiation as a volunteer (including diagnostic procedures) Presence of other exclusion criteria as specified in the protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 001<br>JNJ-40411813 Cohort 1: Type=2 to 3 unit=mg number=200 to 300 form=capsule route=oral use.Capsule(s) taken in the fed state Capsule(s) taken in the fed state.,JNJ-40411813 Cohort 2: Type=up to 7 unit=mg number=up to 700 mg form=capsule route=oral use. Capsule(s) taken in the fed state. | Drug: JNJ-40411813<br>* Cohort 1: Type=2 to 3, unit=mg, number=200 to 300, form=capsule, route=oral use.Capsule(s) taken in the fed state Capsule(s) taken in the fed state.<br>Drug: JNJ-40411813<br>* Cohort 2: Type=up to 7, unit=mg, number=up to 700 mg, form=capsule, route=oral use. Capsule(s) taken in the fed state.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 5-HT2A binding determined by Positron Emission Tomography (PET) scans |  | Up to 24 hours after study drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration of JNJ-40411813 |  | Up to 2 days | 
| Adverse Events Reported |  | Up to 10 days after study drug administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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JNJ-40411813, Positron Emission Tomography (PET), Serotonin-2A (5-HT2A) receptor antagonist, Male Volunteers