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| ID | Type | Description | Link |
|---|---|---|---|
| 42847922EDI1010 | Other Identifier | Janssen Research & Development, LLC |
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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.
This is an open-label (all people know the identity of the intervention), single-center, fixed-sequence, study of JNJ-42847922 in healthy participants. The study consists of 3 Phases: Screening Phase (28 Days), open-label treatment Phase (40 Days) and follow up visit (7 to 14 Days after last study procedure). The duration of participation in the study for each participant is approximately 82 Days. Participants' safety will be monitored throughout the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| JNJ-42847922 | Drug | Participants will receive JNJ-42847922 20 milligram (mg) tablet orally once daily from Day 1 to Day 9. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Janssen Research & Development, LLC Clinical Trial | Janssen Research & Development, LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Overland Park | Kansas | United States |
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| ID | Term |
|---|---|
| C000655226 | seltorexant |
| D008874 | Midazolam |
| D014859 | Warfarin |
| ID | Term |
|---|---|
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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| Midazolam | Drug | Participants will receive midazolam 4 milligram (mg) syrup orally once on Day 1 during treatment A and on Day 7 during treatment B. |
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| Warfarin | Drug | Participants will receive warfarin 25 milligram (mg) tablet orally once on Day 3 during treatment A and on Day 9 during treatment B. |
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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 |
| Screening up to follow-up visit (7 to 14 days after last study procedure) |
| D006571 | Heterocyclic Compounds |
| D015110 | 4-Hydroxycoumarins |
| D003374 | Coumarins |
| D001578 | Benzopyrans |
| D011714 | Pyrans |
| D006573 | Heterocyclic Compounds, 1-Ring |