NCT02617810

Brief Summary

The purpose of this study is to evaluate effect of multiple-dose administration of JNJ-42847922 on the single-dose pharmacokinetics of oral midazolam and single-dose pharmacokinetics and pharmacodynamics of (R)- and (S)-warfarin after oral administration of racemic warfarin.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
18

participants targeted

Target at below P25 for phase_1 healthy

Timeline
Completed

Started Nov 2015

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

Study Start

First participant enrolled

November 1, 2015

Completed
12 days until next milestone

First Submitted

Initial submission to the registry

November 13, 2015

Completed
18 days until next milestone

First Posted

Study publicly available on registry

December 1, 2015

Completed
2 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2016

Completed
Last Updated

February 23, 2016

Status Verified

February 1, 2016

Enrollment Period

3 months

First QC Date

November 13, 2015

Last Update Submit

February 19, 2016

Conditions

Healthy

Keywords

HealthyJNJ-42847922MidazolamWarfarinPharmacokinetics

Outcome Measures

Primary Outcomes (36)

  • Maximum Plasma Concentration (Cmax) of Midazolam

    The Cmax is the maximum observed plasma concentration of Midazolam.

    Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B

  • Maximum Plasma Concentration (Cmax) of 1-Hydroxymidazolam

    The Cmax is the maximum observed plasma concentration of 1-Hydroxymidazolam.

    Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B

  • Maximum Plasma Concentration (Cmax) of Warfarin

    The Cmax is the maximum observed plasma concentration of Warfarin.

    Predose, 0.5, 1, 2 , 4, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours postdose on Day 3 during Treatment A and on Day 9 during Treatment B

  • Time to Reach the Maximum Plasma Concentration (Tmax) of Midazolam

    The Tmax is the time to reach the maximum observed plasma concentration of Midazolam.

    Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B

  • Time to Reach the Maximum Plasma Concentration (Tmax) of 1-Hydroxymidazolam

    The Tmax is the time to reach the maximum observed plasma concentration of 1-Hydroxymidazolam.

    Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B

  • Time to Reach the Maximum Plasma Concentration (Tmax) of Warfarin

    The Tmax is the time to reach the maximum observed plasma concentration of Warfarin.

    Predose, 0.5, 1, 2 , 4, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours postdose on Day 3 during Treatment A and on Day 9 during Treatment B

  • Time of Last Measurable Plasma Concentration (Tlast) of Midazolam

    Time to last measurable plasma concentration is evaluated.

    Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B

  • Time of Last Measurable Plasma Concentration (Tlast) of 1-Hydroxymidazolam

    Time to last measurable plasma concentration is evaluated.

    Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B

  • Time of Last Measurable Plasma Concentration (Tlast) of Warfarin

    Time to last measurable plasma concentration is evaluated.

    Predose, 0.5, 1, 2 , 4, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours postdose on Day 3 during Treatment A and on Day 9 during Treatment B

  • Area Under the Plasma Concentration-Time Curve From 0 to Last Quantifiable Concentration (AUC[0-last]) Post Dose of Midazolam

    The AUC(0-last) is the area under the plasma concentration-time curve from 0 to time of the last quantifiable concentration.

    Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B

  • Area Under the Plasma Concentration-Time Curve From 0 to Last Quantifiable Concentration (AUC[0-last]) Post Dose of 1-Hydroxymidazolam

    The AUC(0-last) is the area under the plasma concentration-time curve from 0 to time of the last quantifiable concentration.

    Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B

  • Area Under the Plasma Concentration-Time Curve From 0 to Last Quantifiable Concentration (AUC[0-last]) Post Dose of Warfarin

    The AUC(0-last) is the area under the plasma concentration-time curve from 0 to time of the last quantifiable concentration.

    Predose, 0.5, 1, 2 , 4, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours postdose on Day 3 during Treatment A and on Day 9 during Treatment B

  • Area Under the Plasma Concentration-Time Curve From 0 to Infinite Time (AUC[0-infinity]) Post Dose of Midazolam

    The AUC (0-infinity) is the area under the plasma Midazolam concentration-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 Midazolam 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.

    Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B

  • Area Under the Plasma Concentration-Time Curve From 0 to Infinite Time (AUC[0-infinity]) Post Dose of 1-Hydroxymidazolam

    The AUC (0-infinity) is the area under the plasma 1-Hydroxymidazolam concentration-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 1-Hydroxymidazolam 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.

    Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B

  • Area Under the Plasma Concentration-Time Curve From 0 to Infinite Time (AUC[0-infinity]) Post Dose of Warfarin

    The AUC (0-infinity) is the area under the plasma Warfarin concentration-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 Warfarin 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.

    Predose, 0.5, 1, 2 , 4, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours postdose on Day 3 during Treatment A and on Day 9 during Treatment B

  • Terminal Half-life (t[1/2]) of Midazolam

    Elimination half-life associated with the terminal slope Lambda (z) of the semi logarithmic drug concentration-time curve, calculated as 0.693/Lambda (z).

    Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B

  • Terminal Half-life (t[1/2]) of 1-Hydroxymidazolam

    Elimination half-life associated with the terminal slope Lambda (z) of the semi logarithmic drug concentration-time curve, calculated as 0.693/Lambda (z).

    Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B

  • Terminal Half-life (t[1/2]) of Warfarin

    Elimination half-life associated with the terminal slope Lambda (z) of the semi logarithmic drug concentration-time curve, calculated as 0.693/Lambda (z).

    Predose, 0.5, 1, 2 , 4, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours postdose on Day 3 during Treatment A and on Day 9 during Treatment B

  • Total Apparent Clearance (CL/F) of Midazolam

    The CL/F is defined as Dose/AUC (0-infinity).

    Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B

  • Total Apparent Clearance (CL/F) of 1-Hydroxymidazolam

    The CL/F is defined as Dose/AUC (0-infinity).

    Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B

  • Total Apparent Clearance (CL/F) of Warfarin

    The CL/F is defined as Dose/AUC (0-infinity).

    Predose, 0.5, 1, 2 , 4, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours postdose on Day 3 during Treatment A and on Day 9 during Treatment B

  • Apparent Volume of Distribution (Vd/F) of Midazolam

    The Vd/F is defined as Dose/\[Lambda (z)\*AUC (0-infinity)\].

    Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B

  • Apparent Volume of Distribution (Vd/F) of 1-Hydroxymidazolam

    The Vd/F is defined as Dose/\[Lambda (z)\*AUC (0-infinity)\].

    Predose, 0.5, 1, 1.5, 2, 3 , 4, 6, 8, 10, 12, 16, 24, 30, 36 and 48 hours postdose on Day 1 during Treatment A and on Day 7 during Treatment B

  • Apparent Volume of Distribution (Vd/F) of Warfarin

    The Vd/F is defined as Dose/\[Lambda (z)\*AUC (0-infinity)\].

    Predose, 0.5, 1, 2 , 4, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours postdose on Day 3 during Treatment A and on Day 9 during Treatment B

  • Maximum Observed Effect (Emax) for Prothrombin Time (PT)

    The Emax for prothrombin time (PT) will be assessed.

    Predose, 2 , 6, 12, 16, 24, 30, 36, 40, 48, 54, 60, 66, 72, 96, 120, 144 and 168 hours postdose on Day 3 during Treatment A and on Day 9 during Treatment B

  • Maximum Observed Effect (Emax) for activated Partial Thromboplastin Time (aPTT)

    The Emax for activated partial thromboplastin time (aPTT) will be assessed.

    Predose, 2 , 6, 12, 16, 24, 30, 36, 40, 48, 54, 60, 66, 72, 96, 120, 144 and 168 hours postdose on Day 3 during Treatment A and on Day 9 during Treatment B

  • Maximum Observed Effect (Emax) for International Normalized Ratio (INR)

    The Emax for international normalized ratio (INR) will be assessed.

    Predose, 2 , 6, 12, 16, 24, 30, 36, 40, 48, 54, 60, 66, 72, 96, 120, 144 and 168 hours postdose on Day 3 during Treatment A and on Day 9 during Treatment B

  • Time to Reach the Maximum Plasma Concentration (Tmax) of JNJ-42847922

    The Tmax is the time to reach the maximum observed plasma concentration of JNJ-42847922.

    2 hours postdose on Day 1 to Day 6; 2 and 26 hours postdose on Day 7; 2 hours postdose on Day 9 during Treatment B

  • Area Under the Plasma Concentration-Time Curve From 0 to 168 Hours (AUC[0-168]) Post Dose of Warfarin

    The AUC(0-168hrs) is the area under the plasma concentration-time curve from 0 to 168 hours post dosing.

    Predose, 0.5, 1, 2 , 4, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144 and 168 hours postdose on Day 3 during Treatment A and on Day 9 during Treatment B

  • Area Under the Plasma Concentration-Time Curve From 0 to 168 Hours (AUC[0-168]) Post Dose of JNJ-42847922

    The AUC(0-168hrs) is the area under the plasma concentration-time curve from 0 to 168 hours post dosing.

    2 hours postdose on Day 1 to Day 6; 2 and 26 hours postdose on Day 7; 2 hours postdose on Day 9 during Treatment B

  • Pharmacodynamic Effect by Using Bond and Lader Visual Analogue Scale (B and L VAS)

    The B and L VAS will be performed to measure effects of a JNJ-42847922 on the duration of the pharmacodynamic effect of midazolam. The B and L VAS includes 16 questions with VAS scales to rate subjective feelings.

    Day -1 of Treatment A dosing

  • Pharmacodynamic Effect by Using Bond and Lader Visual Analogue Scale (B and L VAS)

    The B and L VAS will be performed to measure effects of a JNJ-42847922 on the duration of the pharmacodynamic effect of midazolam. The B and L VAS includes 16 questions with VAS scales to rate subjective feelings.

    4 hours postdose on Day 1 during Treatment A

  • Pharmacodynamic Effect by Using Bond and Lader Visual Analogue Scale (B and L VAS)

    The B and L VAS will be performed to measure effects of a JNJ-42847922 on the duration of the pharmacodynamic effect of midazolam. The B and L VAS includes 16 questions with VAS scales to rate subjective feelings.

    8 hours postdose on Day 1 during Treatment A

  • Pharmacodynamic Effect by Using Bond and Lader Visual Analogue Scale (B and L VAS)

    The B and L VAS will be performed to measure effects of a JNJ-42847922 on the duration of the pharmacodynamic effect of midazolam. The B and L VAS includes 16 questions with VAS scales to rate subjective feelings.

    Day -1 of Treatment B dosing

  • Pharmacodynamic Effect by Using Bond and Lader Visual Analogue Scale (B and L VAS)

    The B and L VAS will be performed to measure effects of a JNJ-42847922 on the duration of the pharmacodynamic effect of midazolam. The B and L VAS includes 16 questions with VAS scales to rate subjective feelings.

    4 hours postdose on Day 7 during Treatment B

  • Pharmacodynamic Effect by Using Bond and Lader Visual Analogue Scale (B and L VAS)

    The B and L VAS will be performed to measure effects of a JNJ-42847922 on the duration of the pharmacodynamic effect of midazolam. The B and L VAS includes 16 questions with VAS scales to rate subjective feelings.

    8 hours postdose on Day 7 during Treatment B

Secondary Outcomes (1)

  • Number of Participants with Adverse Events (AEs) and Serious AEs

    Screening up to follow-up visit (7 to 14 days after last study procedure)

Study Arms (1)

JNJ-42847922 Plus Midazolam Plus Warfarin

EXPERIMENTAL

Participants will receive Treatment A (midazolam 4 milligram \[mg\] syrup once on Day 1 and warfarin 25 mg tablet once on Day 3) followed by Treatment B (JNJ-42847922 20 mg once daily from Day 1 to Day 9, midazolam 4 mg syrup once on Day 7 and warfarin 25 mg tablet once on Day 9). A washout period of 14 to 21 days will be maintained between each treatment period.

Drug: JNJ-42847922Drug: MidazolamDrug: Warfarin

Interventions

JNJ-42847922DRUG

Participants will receive JNJ-42847922 20 milligram (mg) tablet orally once daily from Day 1 to Day 9.

JNJ-42847922 Plus Midazolam Plus Warfarin
MidazolamDRUG

Participants will receive midazolam 4 milligram (mg) syrup orally once on Day 1 during treatment A and on Day 7 during treatment B.

JNJ-42847922 Plus Midazolam Plus Warfarin
WarfarinDRUG

Participants will receive warfarin 25 milligram (mg) tablet orally once on Day 3 during treatment A and on Day 9 during treatment B.

JNJ-42847922 Plus Midazolam Plus Warfarin

Eligibility Criteria

Age18 Years - 60 Years
Sexall
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
  • Willing to adhere to the prohibitions and restrictions specified in protocol
  • If a woman, must be not of child-bearing potential: postmenopausal \[greater than or equal to (\>=) 45 years of age with amenorrhea for at least 2 years, or any age with amenorrhea for at least 6 months and a serum stimulating hormone (FSH) greater than (\>) 40 International units per liter (IU/L), or surgically sterile (example, hysterectomy, oophorectomy, tubal ligation or tubal occlusion)
  • If a woman, must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction for at least 3 months after the last dose of study drug
  • If a man who is sexually active with a woman of childbearing potential and has not had a vasectomy, must agree to use an adequate contraception method as deemed appropriate by the Investigator (example, vasectomy, double-barrier, partner using effective contraception) and to not donate sperm during the study and for 3 months after receiving the last dose of study drug
  • Body mass index (BMI) between 18 and 30 kilogram (kg)/meter\^2 (m\^2), and body weight not less than 50 kg

You may not qualify if:

  • History of or current clinically significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic disease, coagulation disorders (including any abnormal bleeding or blood dyscrasias), syncope, hypotension, hypertension or vascular disorders, lipid abnormalities, significant pulmonary disease, including bronchospastic respiratory disease, diabetes mellitus, hepatic or renal insufficiency, kidney or urinary tract disturbances, thyroid disease, neurologic disease, significant psychiatric disorder, epilepsy, or fits of unexplained black-outs, infection, or any other illness that the Investigator considers should exclude the participant or that could interfere with the interpretation of the study results
  • Clinically significant abnormal values for hematology, clinical chemistry, urinalysis, or thyroid stimulating hormone (TSH) at Screening or at Day -1 of the first treatment period as deemed appropriate by the Investigator. In addition, participants must have coagulation test results \[(prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (aPTT)\] within clinically acceptable limits at Screening as deemed appropriate by the Investigator
  • Clinically significant abnormal physical examination, vital signs, or 12 lead electrocardiogram (ECG) at Screening or Day -1 of the first treatment period as deemed appropriate by the Investigator
  • Participants who are homozygous or heterozygous for CYP2C9\*2 or CYP2C9\*3 alleles
  • Use of any prescription or nonprescription medication (including vitamins and herbal supplements), except for acetaminophen, within 14 days before the first dose of the study drug is scheduled until completion of the study. In addition, participants will be excluded if they have used medications known to affect coagulation or modulate CYP2C9 or VKORC1 within 28 days of study admission

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Unknown Facility

Overland Park, Kansas, United States

Location

MeSH Terms

Interventions

seltorexantMidazolamWarfarin

Intervention Hierarchy (Ancestors)

BenzodiazepinesBenzazepinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds4-HydroxycoumarinsCoumarinsBenzopyransPyransHeterocyclic Compounds, 1-Ring

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

November 13, 2015

First Posted

December 1, 2015

Study Start

November 1, 2015

Primary Completion

February 1, 2016

Study Completion

February 1, 2016

Last Updated

February 23, 2016

Record last verified: 2016-02

Locations

US(1)