A Study to Assess the Effect of Multiple-Dose Administration of JNJ-42847922 on Midazolam and Warfarin in Healthy Participants

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: JNJ-42847922; Drug: Warfarin; Drug: Midazolam

Study type: Interventional

Funder types: Industry

Identifiers

NCT02617810

CR108066

42847922EDI1010 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 18 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

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
• 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

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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18 participants in 1 patient group

JNJ-42847922 Plus Midazolam Plus Warfarin

Experimental group

Description:

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.

Treatment:

Drug: Warfarin

Drug: Midazolam

Drug: JNJ-42847922