A Study to Investigate the Regional Brain Kinetics of Brain Drug Transporters Using P-glycoprotein and Breast Cancer Resistance Protein Substrates and by Using the Positron Emission Tomography Ligand 11C-JNJ-63779586 in the Human Brain

Alzheimer Disease Clinical Trial

Official title:

An Open-Label Microdosing Study to Investigate the Regional Brain Kinetics of Brain Drug Transporters Using P-glycoprotein and Breast Cancer Resistance Protein Substrates and by Using the Positron Emission Tomography Ligand 11C-JNJ-63779586 in the Human Brain

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03089918
• Other study ID #: CR108288
• Secondary ID: 63779586NAP10012
• Status: Completed
• Phase: Phase 1
• Start date: May 17, 2017
• Est. completion date: August 24, 2018

Study information

• Verified date: December 2021
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to investigate the total body biodistribution and radiation dosimetry of 11C-JNJ-63779586 by Positron Emission Tomography (PET) in healthy young adult males (Part A); to estimate and compare the uptake, distribution, and clearance of 11C-JNJ-63779586 in the brain by PET between mild Alzheimer Disease (AD) participants (males/females) and age- and gender-matched control participants (Part B), corrected for regional cerebral blood flow differences; and to model the tissue specific kinetics of 11C-JNJ-63779586 in human brain with the appropriate input function (IF) (Part B).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: August 24, 2018
• Est. primary completion date: August 24, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

Part A

• Healthy men between 18 and 55 years of age, inclusive

• Body mass index (BMI) between 18 and 30 kilogram per meter square (kg/m^2) ², inclusive, and a body weight of not less than 50 kilogram (kg) Part B

• Men or women with mild Alzheimer's Disease (AD), age- and gender-matched control participants, between 55 and 85 years of age, inclusive

• BMI between 18 and 35 kg/m^2, inclusive, and a body weight of not less than 50 kg

• Mild AD participants will be amyloid positive and have a mini-mental state examination (MMSE) greater than or equal to (>=) 20. The matched control participants will be amyloid negative and have a MMSE >= 26, respectively

Exclusion Criteria:

• History of or current clinically significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic disease, coagulation disorders (including any abnormal bleeding or blood dyscrasias), lipid abnormalities, significant pulmonary disease, including bronchospastic respiratory disease, diabetes mellitus, hepatic or renal insufficiency (estimated glomerular filtration rate [eGFR] within the screening period of less than 60 milliLitre per minute per 1.73 meter square [mL/min/1.73 m^2], thyroid disease, neurologic or psychiatric disease, infection, or any other illness that the investigator considers should exclude the participant or that could interfere with the interpretation of the study results

• Clinically significant abnormal values for hematology, clinical chemistry, or urinalysis at screening or at admission to the study center as deemed appropriate by the investigator

• Participant has a clinically relevant abnormal physical- or neurological examination, vital signs or 12-lead electrocardiogram (ECG)

• Participant has a history of epilepsy or fits or unexplained black-outs other than vasovagal collapse within 10 years before screening

• Participant has past or planned exposure to ionizing radiation that in combination with the planned administration with the study Positron Emission Tomography (PET) ligand and Computerized Tomography (CT) scan would result in a cumulative exposure that exceeds local recommended exposure limits

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Drug:
• 11C-JNJ-63779586
Participants will receive IV injection with 11C-JNJ-63779586 in Part A and Part B.

Locations

Country	Name	City	State
Belgium	UZ Leuven	Leuven
Belgium	University of Antwerpen	Wilrijk

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effective Radiation Dose Following Injection of 11C-JNJ-63779586 (Part A)	Whole body and organ specific dosimetry for the tracer will be estimated using specific software for calculation of the absorbed radiation dose. Afterwards, dosimetry will be compared with other carbon-11 labeled radiotracers. According to these results, the same or lower dose might be used for Part B, to prevent high radiation doses to certain organs.	Day 1
Primary	Total and Regional Brain Compartmental Kinetics for Volume of Distribution of 11C-JNJ-63779586 (Part B)	Regional brain uptake will be determined using a Volume of interest (VOI) based analysis. Differences in regional brain uptake between Alzheimer Disease (AD) and control participants will be determined using statistical parametric mapping. Regional uptake of 11C-JNJ-63779586 into brain (K1) will be assessed and compared between participants with AD and control participants, corrected for regional blood flow.	Day 1
Primary	Percent Intact Tracer of 11C-JNJ-63779586 in Blood Samples (Part B)	Sequential arterial blood samples will be taken post tracer injection to model an arterial input function (IF) of the tracer and allow analysis of radio metabolites (percent intact tracer).	Day 1
Primary	Radiometabolite Fraction of 11C-JNJ-63779586 in Blood Samples (Part B)	Sequential arterial blood samples will be taken post tracer injection to model an arterial input function (IF) of the tracer and allow analysis of radio metabolites (percent intact tracer).	Day 1
Secondary	Number of Participants with Adverse Events as a Measure of Safety and Tolerability (Part A and Part B)	An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	Up to 29 days (Part A) and Up to 105 days (Part B)