- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02211079
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
Completed
Conditions
Intervention / Treatment
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
Interventional
Enrollment (Actual)
16
Phase
- 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
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Groningen, Netherlands
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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
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 |
Intervention / Treatment |
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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.
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JNJ-54861911, 50 mg (2*25 mg tablets) orally once daily from Day 2 to Day 9.
Single oral dose of caffeine 100 mg (2*50 mg tablets), on Day 1, 2, and 9.
Single oral dose of midazolam 2 mg (1 mL, 2 mg/mL solution), on Day 1, 2, and 9.
Single oral dose of Tolbutamide 500 mg tablet, on Day 1, 2, and 9.
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What is the study measuring?
Primary Outcome Measures
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)
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The Cmax is the maximum observed plasma concentration.
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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)
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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)
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The Tmax is time to reach the maximum observed plasma concentration.
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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)
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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)
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The Tlast is time to last observed quantifiable plasma concentration (Clast).
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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)
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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)
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The AUC (0-last) is area under the plasma concentration-time curve from time zero to time of last quantifiable concentration.
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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)
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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)
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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.
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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)
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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)
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The AUC (0-24) is area under the plasma concentration-time curve from time zero to time 24 hours.
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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)
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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)
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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.
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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)
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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)
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Lambda(z) is first-order elimination rate constant associated with the terminal portion of the semilogarithmic drug concentration-time curve.
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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)
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Secondary Outcome Measures
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)
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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.
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Baseline up to follow-up (7 to 14 days after discharge from the study unit on Day 10 or at early withdrawal)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
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
September 1, 2014
Primary Completion (Actual)
November 1, 2014
Study Completion (Actual)
November 1, 2014
Study Registration Dates
First Submitted
August 5, 2014
First Submitted That Met QC Criteria
August 5, 2014
First Posted (Estimate)
August 7, 2014
Study Record Updates
Last Update Posted (Estimate)
November 24, 2015
Last Update Submitted That Met QC Criteria
November 23, 2015
Last Verified
November 1, 2015
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Enzyme Inhibitors
- Anesthetics, Intravenous
- Anesthetics, General
- Anesthetics
- Purinergic Antagonists
- Purinergic Agents
- Tranquilizing Agents
- Psychotropic Drugs
- Hypnotics and Sedatives
- Adjuvants, Anesthesia
- Anti-Anxiety Agents
- GABA Modulators
- GABA Agents
- Phosphodiesterase Inhibitors
- Purinergic P1 Receptor Antagonists
- Central Nervous System Stimulants
- Midazolam
- Caffeine
- Tolbutamide
Other Study ID 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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