A Crossover Study to Evaluate the Relative Oral Bioavailability and Food Effect After Single Dose Administration of JNJ-54861911 Tablet in Healthy Elderly Participants

Healthy Clinical Trial

Official title:

An Open-Label, Randomized, Three-Period Crossover Study to Evaluate the Relative Oral Bioavailability and Food Effect of JNJ-54861911 Tablet (1x25mg) After Single Dose Administration in Healthy Elderly Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02355561
• Other study ID #: CR106621
• Secondary ID: 2014-004251-3154
• Status: Completed
• Phase: Phase 1
• First received: January 30, 2015
• Last updated: March 2, 2017
• Start date: January 2015
• Est. completion date: March 2015

Study information

• Verified date: March 2017
• 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 assess the effect of a high-fat/high-caloric breakfast on the rate and extent of absorption of the single oral dose of 25 mg JNJ-54861911 test formulation in healthy elderly participants.

Description:

This is a randomized (study medication assigned to participants by chance), open-label (all people know the identity of the intervention), 3-treatment, 3-period, 6-sequence crossover (participants may receive different interventions sequentially during the trial), and single-center study of JNJ-54861911. The duration of study will be approximately of 7 weeks per participant. The study consists of 3 parts: Screening (that is, 21 days before study commences on Day 1); Open-label Treatment (consists of 3 single-dose treatments, either JNJ-54861911 formulation 1 [reference] or JNJ-54861911 formulation 2 [test] under fed or fasted condition), in subsequent 3-treatment periods, each separated with washout period of 7 days); and End-of-Study (up-to 14 days after last study drug administration). All the eligible participants will be randomly assigned to 1 of the 6 treatment sequences. In fasted conditions, study drug will be administered following a 10-hour overnight fast. In fed conditions, participants will also fast from food for 10 hours, but will consume a high fat/high calorie breakfast within a 30-minute period. Study drug will be administered 30 minutes after the start of breakfast. Participants will not be allowed to have food until 4 hours of drug administration. Blood samples will be collected for evaluation of pharmacokinetics at pre-dose and post-dose of study treatment. Relative bioavailability of two formulations of JNJ-54861911 (test and reference) will be evaluated primarily. Participants' safety will be monitored throughout the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 55 Years to 75 Years

Eligibility

Inclusion Criteria:

• Participants must have a body mass index (BMI) between 18 and 30 Kilogram (kg)/Meter (m)^2, inclusive (BMI = weight/height^2)

• Participant must be healthy for their age group with or without medication on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at Screening and admission. Minor deviations in ECG, which are not considered to be of clinical significance to the investigator, are acceptable

• Participants must be healthy on the basis of clinical laboratory tests performed at Screening. If the results of the serum chemistry panel [including liver enzymes], hematology, or urinalysis are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant. This determination must be recorded in the participant's source documents and initialed by the investigator

• Before randomization, a woman must be not of childbearing potential: postmenopausal (greater than or equal to [=] 55 years of age with amenorrhea for at least 12 months; permanently sterilized [e.g., tubal occlusion, hysterectomy, bilateral salpingectomy]); or otherwise be incapable of pregnancy. In case of questionable status qualified personal of the sponsor should be consulted to decide on the potential for inclusion of the participant

• Men who are sexually active with a woman of childbearing potential and have not had a vasectomy must agree to use a barrier method of birth control e.g., either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men must also not donate sperm during the study and for 90 days after receiving the last dose of study drug. In addition, their female partners should also use an appropriate method of birth control for at least the same duration. Effective methods of contraception include prescription oral contraceptives, contraceptive injections, intrauterine device, double barrier method, contraceptive patch

Exclusion Criteria:

• Participant has clinically significant abnormal findings in physical exam, vital signs or 12-lead ECG incl. QTcF greater than (>) 450 milliseconds (ms) for males and females, Left Bundle Branch Block, Atrioventricular (AV) Block second degree or higher, permanent pacemaker or implantable cardioverter defibrillator (ICD) at Screening or admission, which in the opinion of the investigator are not appropriate and reasonable for the population under study

• Participant has a history of or current significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematological disease, lipid abnormalities, bronchospastic respiratory disease, diabetes mellitus, thyroid disease, Parkinson's disease, infection, or any other illness that the Investigator considers should exclude the participant

• Participant has a history of or current renal [Estimated glomerular filtration rate (eGFR) less than (<) 60 based on Modification of diet in renal diseases (MDRD) formula] or hepatic insufficiency

• Participant has a history of epilepsy or fits or unexplained black-outs other than vasovagal collapse

• Participant has a history of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at Screening

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• JNJ-54861911 (Treatment A)
Participants will receive a single oral 25 mg formulation 1 of JNJ-54861911 tablet as Treatment A under fasted conditions in one of the treatment periods.
• JNJ-54861911 (Treatment B)
Participants will receive a single oral 25 mg formulation 2 of JNJ-54861911 tablet as Treatment B under fasted conditions in one of the treatment periods.
• JNJ-54861911 (Treatment C)
Participants will receive a single oral 25 mg formulation 2 of JNJ-54861911 tablet as Treatment C under fed conditions in one of the treatment periods.

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	Maximum Plasma Concentration (Cmax) of JNJ-54861911	The Cmax is the maximum observed plasma concentration of JNJ-54861911.	Pre-dose; 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post-dose on Day 1 of each period
Primary	Time to Reach the Maximum Plasma Concentration (Tmax) of JNJ-54861911	The Tmax is the time to reach the maximum observed plasma concentration of JNJ-54861911.	Pre-dose; 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post-dose on Day 1 of each period
Primary	Area Under the Plasma Concentration-Time Curve From 0 to t Hours (AUC[0-t]) Post Dose of JNJ-54861911	The AUC (0-t) calculated by trapezoidal summation [time t is the time of the last quantifiable concentration (C[last])].	Pre-dose; 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post-dose on Day 1 of each period
Primary	Area Under the Plasma Concentration-Time Curve From 0 to 24 Hours (AUC[0-24]) Post Dose of JNJ-54861911	The AUC (0-24hrs) is the area under the plasma concentration-time curve from 0 to 24 hours post dosing.	Pre-dose; 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post-dose on Day 1 of each period
Primary	Area Under the Plasma Concentration-Time Curve From 0 to Infinite Time (AUC[0-infinity]) Post Dose of JNJ-54861911	The AUC (0-infinity) is the area under the plasma JNJ-54861911concentration-time curve from time 0 to infinite time, calculated as the sum of AUC (0-last) and C(last)/lambda(z), in which AUC(0-last) is area under the plasma JNJ-54861911 concentration-time curve from time zero to time of the last quantifiable concentration, C(last) is the last observed quantifiable concentration and lambda(z) is elimination rate constant.	Pre-dose; 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post-dose on Day 1 of each period
Primary	Elimination Rate Constant (Lambda [z]) of JNJ-54861911	The Lambda (z) determined by linear regression of the terminal points of the ln-linear plasma concentration-time curve.	Pre-dose; 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post-dose on Day 1 of each period
Primary	Terminal Half-life (t[1/2]) of JNJ-54861911	The t(1/2) is defined as 0.693/Lambda (z).	Pre-dose; 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post-dose on Day 1 of each period
Primary	Relative Bioavailability (F[rel]) of JNJ-54861911	Relative bioavailability, calculated as individual Cmax and AUC treatment ratios (for the comparison of food effect).	Pre-dose; 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post-dose on Day 1 of each period
Secondary	Number of Participants with Adverse Events (AEs) and Serious AEs	An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.	Screening up to follow-up (7 to 14 days after last dose administration)