A Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of JNJ-54861911 in Healthy Elderly Participants

Healthy Clinical Trial

Official title:

A Double-Blind, Placebo-Controlled, Randomized, Multiple-Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-54861911 in Healthy Elderly Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01887535
• Other study ID #: CR101620
• Secondary ID: 2013-000217-21
• Status: Completed
• Phase: Phase 1
• First received: June 5, 2013
• Last updated: January 13, 2014
• Start date: May 2013
• Est. completion date: December 2013

Study information

• Verified date: January 2014
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health Products
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple-ascending dose JNJ-54861911 which is currently being developed for the treatment of Alzheimer's disease.

Description:

This multiple ascending dose study is anticipated to enroll 5 cohorts (small groups). Cohorts 1 to 4 will be conducted as a double-blind (neither investigator nor participant knows which treatment the participant receives), randomized (participants are assigned different treatments based on chance), placebo-controlled (placebo is an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial) study. Cohort 5 will be performed as an open-label study (all people know the identity of the intervention), using a recently made available solid dose formulation of JNJ-54861911.

The study is designed to evaluate the safety (side effects), tolerability, pharmacokinetics (how the drug is absorbed in the body, distributed within the body, and how it is removed from the body over time, ie, what the body does to the drug), and pharmacodynamics (what the drug does to the body) of JNJ-54861911. The study population will consist of approximately 38 healthy elderly participants divided among approximately 5 cohorts. For all participants the study will consist of 3 phases: eligibility screening examination phase (between 28 and 2 days prior to the first dose administration), a 14-day double-blind (Cohorts 1 to 4) or open-label (Cohort 5) treatment phase, and a follow-up examination phase (within 7 to 14 days after last dose administration). Participants who successfully complete the screening examination and are considered eligible to participate will be admitted to the clinical unit on Day -1 before administration of the study drug.

Cohorts 1 to 4 will consist of 8 participants. Within these cohorts, participants will be randomly assigned to double-blind treatment with an oral suspension of JNJ-54861911 3 mg, 10 mg, 30 mg, or 80 mg (n=6/cohort) or matching placebo (n=2/cohort). Cohorts 1 to 4 will be used for dose escalations and assessing the maximal tolerated dose using an oral suspension of JNJ-54861911. Cohort 5 will consist of 6 participants who will all receive open-label treatment with a single solid dose formulation of JNJ 54861911 25 mg. Cohort 5 will assess if the recently made available solid dose formulation (strength 25 mg) has similar pharmacokinetic properties and pharmacodynamic effects as the oral suspension at a dose level in the range that has been assessed earlier (Cohorts 1 to 4) and was found to be safe and well tolerated. All cohorts (Cohorts 1 to 5) will follow the same study assessments.

Participants will be administered single doses of study medication on Days 1 to 14. Following and/or during each dose level of the study (cohort), the observed safety and tolerability profile of the ongoing cohort and previous cohort will be evaluated and doses will only be increased if the observed safety and tolerability profile is acceptable. Plasma pharmacokinetic profiles of the ongoing cohort (up to and including Day 7) and plasma and cerebrospinal fluid (CSF) pharmacokinetic profiles as well as CSF plasma amyloid beta (Aβ) profiles of the previous cohort (up to and including Day 14) if applicable, will support dose increase decisions. Actual dose levels as well as the magnitude of dose escalation will depend on the results of the ongoing single-ascending dose study (54861911ALZ1001), the observed safety and tolerability profile, as well as the observed exposures. Participants will be discharged from the clinical unit after the last study assessment on Day 16 or approximately 24 hours after the indwelling catheter has been removed, whatever occurs later. If discharged on Day 16, participants will return to the clinical unit on Day 17 (72 hours post-dose Day 14) for plasma pharmacokinetic sampling. Safety assessments will be performed throughout the study. The maximal study duration for a participant will not exceed 8 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 55 Years to 75 Years

Eligibility

Inclusion Criteria:

• Good general health

• Body mass index (BMI) between 18 and 32 kg/m2, inclusive

• Women must be postmenopausal, permanently sterilized or otherwise be incapable of pregnancy

• Must adhere to required contraception during and for 3 months after study

Exclusion Criteria:

• Clinically significant medical or psychiatric illness

• Alcohol or substance abuse; excessive nicotine or caffeine use

• Recently received an investigational drug, vaccine, or invasive medical device

• Unable to abide by protocol restrictions on use of other medications

• Relevant history of lower back pain or scoliosis and/or major (lumbar) back surgery

• Allergic to local anesthetics and/or iodine

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• JNJ-54861911 3 mg
JNJ-54861911 3 mg will be administered as an oral suspension formulation.
• JNJ-54861911 10 mg
JNJ-54861911 10 mg will be administered as an oral suspension formulation.
• JNJ-54861911 30 mg
JNJ-54861911 30 mg will be administered as an oral suspension formulation.
• JNJ-54861911 80 mg
JNJ-54861911 80 mg will be administered as an oral suspension formulation.
• JNJ-54861911 25 mg
JNJ-54861911 25 mg will be administered as a solid dose formulation.
• Placebo
Matching placebo will be administered as an oral suspension formulation.

Locations

Country	Name	City	State
n/a

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	The number of volunteers who experience adverse events as a measure of safety and tolerability of JNJ-54861911 after multiple dose administration in the target dose range and above		Up to 72 hours	Yes
Secondary	Maximal tolerated dose (MTD) or maximal feasible exposure level of JNJ-54861911 after multiple dose administration		Up to 72 hours	No
Secondary	Maximum observed plasma/cerebrospinal fluid (CSF) concentration (Cmax) of JNJ-54861911	Cmax is observed maximum plasma concentration of study drug, taken directly from the plasma concentration-time profile	Up to 72 hours	No
Secondary	Levels of amyloid beta (Aß) fragments (Aß1-37, Aß1-38, Aß1-40 and Aß1-42) in CSF after multiple dose administration		Up to 36 hours	No
Secondary	Time to reach maximum observed plasma/CSF concentration of JNJ-54861911	Time when Cmax is observed, taken directly from the plasma concentration-time profile	Up to 72 hours	No
Secondary	Area under the plasma/CSF concentration-time curve (AUC) from time 0 to t hours of JNJ-54861911	The AUC (0 to t hours) is area under the plasma concentration-time curve from time 0 to t hours after dosing; t is time of the quantifiable concentration Clast	Up to 72 hours	No
Secondary	Half-life of JNJ-54861911	Defined as 0.693/elimination rate constant	Up to 72 hours	No