A Study to Assess Effect of JNJ-54861911 on Pharmacokinetics of Cocktail Representatives for Cytochrome P450 (CYP) 3A4, CYP2B6, CYP2C9, and CYP1A2 Substrates

November 23, 2015 updated by: Janssen Research & Development, LLC

An Open-Label, Fixed-Sequence Study in Healthy Male Subjects to Assess the Drug Interaction Potential of Multiple-Doses of JNJ-54861911 With a Drug "Cocktail" Representative for CYP3A4, CYP2B6, CYP2C9, and CYP1A2 Substrates

The purpose of this study is to assess the effects of single and multiple once daily doses of 50 milligram (mg) of JNJ-54861911 on pharmacokinetics (PK) (study of the way a drug enters and leaves the blood and tissues over time) of caffeine, midazolam, and tolbutamide in healthy male participants.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a single-center, open-label (participants and researchers are aware about the treatment, participants are receiving), fixed-sequence study in healthy male participants. The study consists of 3 phases: Screening Phase (within 21 to 2 days prior to the first dose administration on Day 1), Open Label Treatment Phase (Day 1 up to Day 9), and Follow-up Phase (7 to 14 days after discharge from the study unit on Day 10 or at early withdrawal). The maximum duration of study will be 7 weeks per participant. During the Open-Label Treatment Phase, participants will receive JNJ-54861911, 50 mg (2*25 mg tablets) orally once daily from Day 2 to Day 9 along with caffeine 100 mg (2*50 mg tablets), midazolam 2 mg (1 milliliter [mL], 2 mg/mL solution), and tolbutamide 500 mg tablet, orally on Day 1, 2, and 9. Blood samples will be collected pre-dose (Day 1) up to Day 10 to understand the PK characteristics of midazolam, 1-hydroxy midazolam (midazolam metabolite), caffeine, paraxanthine (caffeine metabolite), tolbutamide, 4-hydroxytolbutamide and carboxytolbutamide (tolbutamide metabolites). In addition, a blood sample will be collected on Day -1 from all enrolled participants to study genetic factors that may influence the PK, safety, and/or tolerability of JNJ-54861911 and co-medications. Participants' safety will be monitored throughout the study.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
16

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Signed an informed consent document indicating they understand the purpose of and procedures required for the study, and are willing to participate in the study
  • Body mass index between 18 and 30 kilogram per square meter
  • Must be healthy on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at Screening or admission (up to Day 1 pre-dose)
  • Man, who is sexually active with a woman of child-bearing potential and has not had a vasectomy, must agree to use an adequate contraception method as deemed appropriate by the Investigator, and must also agree to not donate sperm during the study and for 90 days after receiving the last dose of study drug
  • Participant must be healthy on the basis of clinical laboratory tests performed at Screening as per Investigator's judgment

Exclusion Criteria:

  • History of or current liver or renal insufficiency, closed-angle glaucoma, significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, dermatological or metabolic disturbances
  • Known allergies, hypersensitivity, or intolerance to JNJ-54861911 or its excipients, sulfonamides, midazolam, caffeine or tolbutamide.
  • History of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at Screening
  • History of drug or alcohol abuse according to current Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria within 6 months before Screening or positive test result(s) for alcohol and/or drugs of abuse (including barbiturates, opiates, cocaine, cannabinoids, amphetamines, metamphetamines, benzodiazepines and cotinine) at Screening or admission
  • Smoking of cigarettes (or equivalent) and/or used nicotine based products within 3 months prior to study drug administration

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: JNJ-54861911 + Caffeine + Midazolam +Tolbutamide
JNJ-54861911, 50 milligram (mg) (2*25 mg tablets) orally once daily from Day 2 to Day 9 along with caffeine 100 mg (2*50 mg tablets), midazolam 2 mg (1 milliliter [mL], 2 mg/mL solution), and tolbutamide 500 mg tablet, orally on Day 1, 2, and 9.
Drug: JNJ-54861911
JNJ-54861911, 50 mg (2*25 mg tablets) orally once daily from Day 2 to Day 9.
Drug: Caffeine
Single oral dose of caffeine 100 mg (2*50 mg tablets), on Day 1, 2, and 9.
Drug: Midazolam
Single oral dose of midazolam 2 mg (1 mL, 2 mg/mL solution), on Day 1, 2, and 9.
Drug: Tolbutamide
Single oral dose of Tolbutamide 500 mg tablet, on Day 1, 2, and 9.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Maximum Observed Plasma Concentration (Cmax)
Time Frame: Pre-dose on Day 1,2,3,9,10 and 0.5,1,1.5,2,2.5,3,4,6,8,10,12,16 hours post-dose on Day 1,2,9 (for Caffeine and Tolbutamide); Pre-dose on Day 1,9 and 0.5,1,1.5,2,2.5,3,4,6 hours post-dose on Day 1,2,9 (for Midazolam)
The Cmax is the maximum observed plasma concentration.
Pre-dose on Day 1,2,3,9,10 and 0.5,1,1.5,2,2.5,3,4,6,8,10,12,16 hours post-dose on Day 1,2,9 (for Caffeine and Tolbutamide); Pre-dose on Day 1,9 and 0.5,1,1.5,2,2.5,3,4,6 hours post-dose on Day 1,2,9 (for Midazolam)
Time to Reach Maximum Concentration (Tmax)
Time Frame: Pre-dose on Day 1,2,3,9,10 and 0.5,1,1.5,2,2.5,3,4,6,8,10,12,16 hours post-dose on Day 1,2,9 (for Caffeine and Tolbutamide); Pre-dose on Day 1,9 and 0.5,1,1.5,2,2.5,3,4,6 hours post-dose on Day 1,2,9 (for Midazolam)
The Tmax is time to reach the maximum observed plasma concentration.
Pre-dose on Day 1,2,3,9,10 and 0.5,1,1.5,2,2.5,3,4,6,8,10,12,16 hours post-dose on Day 1,2,9 (for Caffeine and Tolbutamide); Pre-dose on Day 1,9 and 0.5,1,1.5,2,2.5,3,4,6 hours post-dose on Day 1,2,9 (for Midazolam)
Time to Last Quantifiable Plasma Concentration (Tlast)
Time Frame: Pre-dose on Day 1,2,3,9,10 and 0.5,1,1.5,2,2.5,3,4,6,8,10,12,16 hours post-dose on Day 1,2,9 (for Caffeine and Tolbutamide); Pre-dose on Day 1,9 and 0.5,1,1.5,2,2.5,3,4,6 hours post-dose on Day 1,2,9 (for Midazolam)
The Tlast is time to last observed quantifiable plasma concentration (Clast).
Pre-dose on Day 1,2,3,9,10 and 0.5,1,1.5,2,2.5,3,4,6,8,10,12,16 hours post-dose on Day 1,2,9 (for Caffeine and Tolbutamide); Pre-dose on Day 1,9 and 0.5,1,1.5,2,2.5,3,4,6 hours post-dose on Day 1,2,9 (for Midazolam)
Area Under the Plasma Concentration-time Curve From Time Zero to Last Quantifiable Time (AUC [0-last])
Time Frame: Pre-dose on Day 1,2,3,9,10 and 0.5,1,1.5,2,2.5,3,4,6,8,10,12,16 hours post-dose on Day 1,2,9 (for Caffeine and Tolbutamide); Pre-dose on Day 1,9 and 0.5,1,1.5,2,2.5,3,4,6 hours post-dose on Day 1,2,9 (for Midazolam)
The AUC (0-last) is area under the plasma concentration-time curve from time zero to time of last quantifiable concentration.
Pre-dose on Day 1,2,3,9,10 and 0.5,1,1.5,2,2.5,3,4,6,8,10,12,16 hours post-dose on Day 1,2,9 (for Caffeine and Tolbutamide); Pre-dose on Day 1,9 and 0.5,1,1.5,2,2.5,3,4,6 hours post-dose on Day 1,2,9 (for Midazolam)
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - infinity])
Time Frame: Pre-dose on Day 1,2,3,9,10 and 0.5,1,1.5,2,2.5,3,4,6,8,10,12,16 hours post-dose on Day 1,2,9 (for Caffeine and Tolbutamide); Pre-dose on Day 1,9 and 0.5,1,1.5,2,2.5,3,4,6 hours post-dose on Day 1,2,9 (for Midazolam)
The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to extrapolated infinite time, calculated as the sum of AUC (0-last) and Clast/lambda(z), where AUC (0-last) is area under the plasma concentration-time curve from time zero to last quantifiable time; Clast is the last observed quantifiable concentration; and lambda(z) is first-order rate constant associated with the terminal portion of the semilogarithmic drug concentration-time curve.
Pre-dose on Day 1,2,3,9,10 and 0.5,1,1.5,2,2.5,3,4,6,8,10,12,16 hours post-dose on Day 1,2,9 (for Caffeine and Tolbutamide); Pre-dose on Day 1,9 and 0.5,1,1.5,2,2.5,3,4,6 hours post-dose on Day 1,2,9 (for Midazolam)
Area Under the Plasma Concentration-time Curve From Time Zero to Time 24 Hours (AUC [0-24])
Time Frame: Pre-dose on Day 1,2,3,9,10 and 0.5,1,1.5,2,2.5,3,4,6,8,10,12,16 hours post-dose on Day 1,2,9 (for Caffeine and Tolbutamide); Pre-dose on Day 1,9 and 0.5,1,1.5,2,2.5,3,4,6 hours post-dose on Day 1,2,9 (for Midazolam)
The AUC (0-24) is area under the plasma concentration-time curve from time zero to time 24 hours.
Pre-dose on Day 1,2,3,9,10 and 0.5,1,1.5,2,2.5,3,4,6,8,10,12,16 hours post-dose on Day 1,2,9 (for Caffeine and Tolbutamide); Pre-dose on Day 1,9 and 0.5,1,1.5,2,2.5,3,4,6 hours post-dose on Day 1,2,9 (for Midazolam)
Elimination Half-Life (t1/2)
Time Frame: Pre-dose on Day 1,2,3,9,10 and 0.5,1,1.5,2,2.5,3,4,6,8,10,12,16 hours post-dose on Day 1,2,9 (for Caffeine and Tolbutamide); Pre-dose on Day 1,9 and 0.5,1,1.5,2,2.5,3,4,6 hours post-dose on Day 1,2,9 (for Midazolam)
Elimination half-life associated with the terminal slope of the semilogarithmic drug concentration-time curve, is calculated as 0.693 divided by lambda(z), where lambda(z) is first-order rate constant associated with the terminal portion of the curve. The t1/2 is the measure of time, for plasma concentration to decrease by one half.
Pre-dose on Day 1,2,3,9,10 and 0.5,1,1.5,2,2.5,3,4,6,8,10,12,16 hours post-dose on Day 1,2,9 (for Caffeine and Tolbutamide); Pre-dose on Day 1,9 and 0.5,1,1.5,2,2.5,3,4,6 hours post-dose on Day 1,2,9 (for Midazolam)
Elimination Rate Constant (lambda[z])
Time Frame: Pre-dose on Day 1,2,3,9,10 and 0.5,1,1.5,2,2.5,3,4,6,8,10,12,16 hours post-dose on Day 1,2,9 (for Caffeine and Tolbutamide); Pre-dose on Day 1,9 and 0.5,1,1.5,2,2.5,3,4,6 hours post-dose on Day 1,2,9 (for Midazolam)
Lambda(z) is first-order elimination rate constant associated with the terminal portion of the semilogarithmic drug concentration-time curve.
Pre-dose on Day 1,2,3,9,10 and 0.5,1,1.5,2,2.5,3,4,6,8,10,12,16 hours post-dose on Day 1,2,9 (for Caffeine and Tolbutamide); Pre-dose on Day 1,9 and 0.5,1,1.5,2,2.5,3,4,6 hours post-dose on Day 1,2,9 (for Midazolam)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)
Time Frame: Baseline up to follow-up (7 to 14 days after discharge from the study unit on Day 10 or at early withdrawal)
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An 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.
Baseline up to follow-up (7 to 14 days after discharge from the study unit on Day 10 or at early withdrawal)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Janssen Research & Development, LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 5, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 5, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 7, 2014

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 24, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 23, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CR105152
  • 54861911ALZ1010 (Other Identifier: Janssen Research & Development, LLC)
  • 2014-001794-14 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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