NCT02211079

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
16

participants targeted

Target at below P25 for phase_1 healthy

Timeline
Completed

Started Sep 2014

Shorter than P25 for phase_1 healthy

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 5, 2014

Completed
2 days until next milestone

First Posted

Study publicly available on registry

August 7, 2014

Completed
25 days until next milestone

Study Start

First participant enrolled

September 1, 2014

Completed
2 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2014

Completed
Last Updated

November 24, 2015

Status Verified

November 1, 2015

Enrollment Period

2 months

First QC Date

August 5, 2014

Last Update Submit

November 23, 2015

Conditions

Healthy

Keywords

HealthyJNJ-54861911CaffeineMidazolamTolbutamideCytochrome P450 3A4Cytochrome P450 2C9Cytochrome P450 1A2Alzheimer's disease

Outcome Measures

Primary Outcomes (8)

  • Maximum Observed Plasma Concentration (Cmax)

    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)

    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)

    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])

    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])

    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])

    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)

    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])

    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 Outcomes (1)

  • Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)

    Baseline up to follow-up (7 to 14 days after discharge from the study unit on Day 10 or at early withdrawal)

Study Arms (1)

JNJ-54861911 + Caffeine + Midazolam +Tolbutamide

EXPERIMENTAL

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-54861911Drug: CaffeineDrug: MidazolamDrug: Tolbutamide

Interventions

JNJ-54861911DRUG

JNJ-54861911, 50 mg (2\*25 mg tablets) orally once daily from Day 2 to Day 9.

JNJ-54861911 + Caffeine + Midazolam +Tolbutamide
CaffeineDRUG

Single oral dose of caffeine 100 mg (2\*50 mg tablets), on Day 1, 2, and 9.

JNJ-54861911 + Caffeine + Midazolam +Tolbutamide
MidazolamDRUG

Single oral dose of midazolam 2 mg (1 mL, 2 mg/mL solution), on Day 1, 2, and 9.

JNJ-54861911 + Caffeine + Midazolam +Tolbutamide
TolbutamideDRUG

Single oral dose of Tolbutamide 500 mg tablet, on Day 1, 2, and 9.

JNJ-54861911 + Caffeine + Midazolam +Tolbutamide

Eligibility Criteria

Age18 Years - 55 Years
Sexmale
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Unknown Facility

Groningen, Netherlands

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

atabecestatCaffeineMidazolamTolbutamide

Condition Hierarchy (Ancestors)

DementiaBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesTauopathiesNeurodegenerative DiseasesNeurocognitive DisordersMental Disorders

Intervention Hierarchy (Ancestors)

XanthinesAlkaloidsHeterocyclic CompoundsPurinonesPurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingBenzodiazepinesBenzazepinesBenzenesulfonamidesSulfonamidesAmidesOrganic ChemicalsSulfonylurea CompoundsUreaBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsSulfonesSulfur Compounds

Study Officials

  • Janssen Research & Development, LLC Clinical Trial

    Janssen Research & Development, LLC

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 5, 2014

First Posted

August 7, 2014

Study Start

September 1, 2014

Primary Completion

November 1, 2014

Study Completion

November 1, 2014

Last Updated

November 24, 2015

Record last verified: 2015-11

Locations

NL(1)