A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of JNJ-39393406 in Healthy Participants

Healthy Clinical Trial

Official title:

A Double-Blind, Placebo-Controlled, Randomized, Multiple Ascending Dose Study to Investigate the Safety, Tolerability and Pharmacokinetics of JNJ-39393406 in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02023255
• Other study ID #: CR015760
• Secondary ID: 39393406EDI1002
• Status: Completed
• Phase: Phase 1
• First received: December 23, 2013
• Last updated: January 23, 2014
• Start date: January 2009
• Est. completion date: June 2009

Study information

• Verified date: January 2014
• Source: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• 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 the study is to evaluate the safety and tolerability of multiple dose administration of JNJ-39393406 in young healthy participants, and subsequently in healthy elderly participants.

Description:

This is a double-blind (neither physician nor participant knows the treatment that the participant receives), placebo-controlled (study in which an inactive substance is given to one group of participants, while the study medication is given to another group), randomized (the study medication is assigned by chance), and multiple ascending dose (participants will receive multiple doses of study medication and the dose level is subsequently escalated in further groups) study. This study will consist of screening phase (between 21 and 2 days prior to dose administration), a double-blind treatment phase (Part A - 7 days and Part B - 13 days), and a follow-up phase (within 7 to 14 days after last dose administration). In Part A of the multiple ascending dose study approximately 40 young healthy male participants will be randomly allocated to 5 cohorts (group of individuals with similar characteristics) to receive single daily doses of either JNJ-39393406 or placebo for 7 consecutive days. After each dose level, safety, tolerability, and pharmacokinetic (PK) profile (explores what the body does to a medication) of the dose level will be evaluated and the next dose level will be escalated considering the safety and tolerability data. In Part B of the study approximately 48 elderly healthy male and female participants will be randomly allocated to A, B, and C cohorts to receive single daily doses of either JNJ-39393406 or placebo for 13 consecutive days. Dose levels in Part B will be selected based on the PK data from Part A. In both Part A and Part B of the study the dose levels will be increased only after acceptable safety and tolerability data will be obtained. Safety evaluations will include assessments of adverse events, clinical laboratory tests, 24-hour creatinine clearance, Holter monitoring, telemetry, electrocardiogram, vital signs, physical examination, and neurological examination. The study duration for each participant will be approximately 8 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 88
• Est. completion date: June 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Willing to adhere to the prohibitions and restrictions specified in the protocol

• Part A: Body mass index (BMI) between 18 and 30 kg/m2, inclusive (BMI = weight/height2)

• Part B: Female participants must be postmenopausal (for at least 12 months)

• BMI between 18 and 33 kg/m2, inclusive

Exclusion Criteria:

• Clinically significant abnormal values for clinical chemistry, hematology or urinalysis at screening or admission. It is expected that laboratory values will generally be within the normal range for the laboratory, though minor deviations, which are not considered to be of clinical significance to the investigator, are acceptable

• Clinically significant abnormal physical examination, vital signs or 12 lead electrocardiogram (ECG) at screening. Minor deviations in ECG, which are not considered to be of clinical significance to the investigator, are acceptable

• Clinically significant abnormal 24 hour Holter monitoring at screening in the opinion of the investigator

• Significant history of or current psychiatric or neurological illness

• Serology positive for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus antibodies at screening

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• JNJ-39393406
In Part A of the study, participants will receive single dose of JNJ-39393406 50 mg, 150 mg, 450 mg, 1,350 mg, and 2,700 mg once daily for 7 consecutive days. In Part B of the study, participants will receive single dose of JNJ-39393406 based on the PK data from Part A of the study once daily for 13 consecutive days.

Other:
• Placebo
In Part A of the study, participants will receive placebo for 7 consecutive days and in Part B of the study, participants will receive placebo for 13 consecutive days.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with adverse events		Up to Day 56	Yes
Primary	Maximum Observed Plasma Concentration (Cmax) of JNJ-39393406 in Part A of the study	The Plasma Concentration (Cmax) is defined as maximum observed analyte concentration.	Days 1 and 7 (predose, 10, 20, 30, 45 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18 hours), Days 2 to 6 (predose), Day 8 (24 hours), and Days 9, 10 (48/72 hours)	No
Primary	Maximum Observed Plasma Concentration (Cmax) of JNJ-39393406 in Part B of the study	The Plasma Concentration (Cmax) is defined as maximum observed analyte concentration.	Days 1 and 7 (predose, 10, 20, 30, 45 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18 hours), Days 2, 3, 4, 5, 6, 8, 9, 10, 11, 13 (predose), Day 12 (predose, 1, 2, 4, 6, 8 hours), Day 14 (24 hours), and Days 15, 16 (48/72 hours)	No
Primary	Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ-39393406 in Part A of the study	The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.	Days 1 and 7 (predose, 10, 20, 30, 45 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18 hours), Days 2 to 6 (predose), Day 8 (24 hours), and Days 9, 10 (48/72 hours)	No
Primary	Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ-39393406 in Part B of the study	The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.	Days 1 and 7 (predose, 10, 20, 30, 45 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18 hours), Days 2, 3, 4, 5, 6, 8, 9, 10, 11, 13 (predose), Day 12 (predose, 1, 2, 4, 6, 8 hours), Day 14 (24 hours), and Days 15, 16 (48/72 hours)	No
Primary	Area Under the Plasma Concentration-Time Curve From Time Zero to Time at Last Observed Quantifiable Concentration (AUC[t]) of JNJ-39393406 in Part A of the study	The Area Under the Plasma Concentration-Time Curve From Time Zero to Time at Last Observed Quantifiable Concentration (AUC[t]) is area under the plasma concentration-time curve from time zero to the last quantifiable concentration.	Days 1 and 7 (predose, 10, 20, 30, 45 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18 hours), Days 2 to 6 (predose), Day 8 (24 hours), and Days 9, 10 (48/72 hours)	No
Primary	Area Under the Plasma Concentration-Time Curve From Time Zero to Time at Last Observed Quantifiable Concentration (AUC[t]) of JNJ-39393406 in Part B of the study	The Area Under the Plasma Concentration-Time Curve From Time Zero to Time at Last Observed Quantifiable Concentration (AUC[t]) is area under the plasma concentration-time curve from time zero to the last quantifiable concentration.	Days 1 and 7 (predose, 10, 20, 30, 45 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18 hours), Days 2, 3, 4, 5, 6, 8, 9, 10, 11, 13 (predose), Day 12 (predose, 1, 2, 4, 6, 8 hours), Day 14 (24 hours), and Days 15, 16 (48/72 hours)	No
Primary	Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[infinity]) of JNJ-39393406 in Part A of the study	The AUC(infinity) is area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of Area under Curve (AUC) last and C(last)/lambda(z), in which C(last) is the last observed quantifiable concentration.	Days 1 and 7 (predose, 10, 20, 30, 45 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18 hours), Days 2 to 6 (predose), Day 8 (24 hours), and Days 9, 10 (48/72 hours)	No
Primary	Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[infinity]) of JNJ-39393406 in Part B of the study	The AUC(infinity) is area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of Area under Curve (AUC) last and C(last)/lambda(z), in which C(last) is the last observed quantifiable concentration.	Days 1 and 7 (predose, 10, 20, 30, 45 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18 hours), Days 2, 3, 4, 5, 6, 8, 9, 10, 11, 13 (predose), Day 12 (predose, 1, 2, 4, 6, 8 hours), Day 14 (24 hours), and Days 15, 16 (48/72 hours)	No
Primary	Terminal Rate Constant (Lambda[z]) of JNJ-39393406 in Part A of the study	Lambda(z) is defined as terminal rate-constant which reflect the speed of drug elimination in vivo (within the living), and is estimated by log-linear regression analysis of the terminal phase of the plasma concentration versus time curve for at least 3 points.	Days 1 and 7 (predose, 10, 20, 30, 45 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18 hours), Days 2 to 6 (predose), Day 8 (24 hours), and Days 9, 10 (48/72 hours)	No
Primary	Terminal Rate Constant (Lambda[z]) of JNJ-39393406 in Part B of the study	Lambda(z) is defined as terminal rate-constant which reflect the speed of drug elimination in vivo (within the living), and is estimated by log-linear regression analysis of the terminal phase of the plasma concentration versus time curve for at least 3 points.	Days 1 and 7 (predose, 10, 20, 30, 45 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18 hours), Days 2, 3, 4, 5, 6, 8, 9, 10, 11, 13 (predose), Day 12 (predose, 1, 2, 4, 6, 8 hours), Day 14 (24 hours), and Days 15, 16 (48/72 hours)	No
Primary	Plasma Decay Half-Life (t1/2) of JNJ-39393406 in Part A of the study	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	Days 1 and 7 (predose, 10, 20, 30, 45 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18 hours), Days 2 to 6 (predose), Day 8 (24 hours), and Days 9, 10 (48/72 hours)	No
Primary	Plasma Decay Half-Life (t1/2) of JNJ-39393406 in Part B of the study	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	Days 1 and 7 (predose, 10, 20, 30, 45 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18 hours), Days 2, 3, 4, 5, 6, 8, 9, 10, 11, 13 (predose), Day 12 (predose, 1, 2, 4, 6, 8 hours), Day 14 (24 hours), and Days 15, 16 (48/72 hours)	No
Primary	Change from baseline in cognition in elderly and young healthy participants in Part A of the study	For cognitive testing a computerized test battery will be applied, focusing on memory, executive function and attention.	Baseline to Day 6	No
Primary	Change from baseline in cognition in elderly and young healthy participants in Part B of the study	For cognitive testing a computerized test battery will be applied, focusing on memory, executive function and attention.	Baseline to Day 13	No