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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: JNJ-40411813; Drug: JNJ-40411813

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 001; 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; 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.; Drug: 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.

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: May 19, 2011
• First Submitted That Met QC Criteria: May 19, 2011
• First Posted (Estimate): May 23, 2011

Study Record Updates

• Last Update Posted (Estimate): July 9, 2013
• Last Update Submitted That Met QC Criteria: July 8, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: Positron Emission Tomography (PET); JNJ-40411813; Serotonin-2A (5-HT2A) receptor antagonist; Male Volunteers
• Other Study ID Numbers: CR017485; 40411813EDI1008 (Other Identifier: Johnson & Johnson Pharmaceutical Research and Development, L.L.C.); 2010-022176-32 (Other Identifier: Johnson & Johnson Pharmaceutical Research and Development, L.L.C.)