Clinical trial NCT03494907: A Study to Evaluate the Effects of Single-dose Seltorexant on Electrocardiogram Intervals in Healthy Adult Participants
Official title: A Randomized, Double-blind, Placebo- and Positive-controlled, Single-dose, 4-way Crossover Study to Evaluate the Effects of Seltorexant (JNJ-42847922) on Electrocardiogram Intervals in Healthy Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2018-04-11
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: The purpose of this study is to assess the effects of single dose seltorexant on QT/QTc intervals and electrocardiogram (ECG) morphology at therapeutic and supratherapeutic exposures in healthy adult participants.


Eligibility criteria: Inclusion Criteria:

* Have signed informed consent form (ICF) indicating they understand the purpose of and procedures required for the study, including the required pharmacogenomic component (which specifies testing of genes predisposing to long or short QT and related cardiac syndromes), and are willing to participate in the study. Consent for sample storage will be obtained in the ICF
* Be Willing to adhere to the prohibitions and restrictions specified in the protocol
* A female participant must be either not of childbearing potential (ie, postmenopausal, permanently sterile) or of childbearing potential and practicing a highly effective method of contraception (failure rate of less than \[\<\]1 percent \[%\] per year when used consistently and correctly)
* A female participant must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for at least 1 month after the last study drug administration
* A male participant, 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 (eg, 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
* Must have a blood pressure (after the participant is supine for 5 minutes) between 90 and 140 millimeter of mercury (mmHg) systolic, inclusive, and no higher than 90 mmHg diastolic. Heart rate between 45 and 100 beats per minute (bpm), inclusive

Exclusion Criteria:

* Clinically significant abnormal values for hematology, serum chemistry (including thyroid stimulating hormone \[TSH\] at screening only) or urinalysis at screening or at admission to the study site
* Clinically significant abnormal physical examination, vital signs, or 12-lead electrocardiogram (ECG) at screening or at admission to the study site as deemed appropriate by the investigator
* Received a known inhibitor of CYP3A4 or CYP2C9 activity within 14 days or a period less than 5 times the drugs' half-life; whichever is longer, before the first dose of the study drug is scheduled
* Known allergy to the study drug or any of the excipients of the formulation
* Received an experimental drug or used an experimental medical device within 1 month or within a period less than 10 times the drug's half-life, whichever is longer, before the first dose of the study drug is scheduled
* A woman who is pregnant, breast-feeding, or planning to become pregnant during the study

Primary outcomes:
measure: Change From Baseline in QT/QTc Intervals
timeFrame: Baseline up to Day 3
measure: Percentage of Participants with Change from Baseline in T-wave Morphology
timeFrame: Baseline up to Day 3
measure: Percentage of Participants with Change from Baseline in U-wave Morphology
timeFrame: Baseline up to Day 3
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Pre-dose; 0.33, 0.5, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours Post-dose
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: Pre-dose; 0.33, 0.5, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours Post-dose
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last])
timeFrame: Pre-dose; 0.33, 0.5, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours Post-dose
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity])
timeFrame: Pre-dose; 0.33, 0.5, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours Post-dose
measure: Elimination Half-Life (t1/2)
timeFrame: Pre-dose; 0.33, 0.5, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours Post-dose
measure: Total Apparent Clearance (CL/F)
timeFrame: Pre-dose; 0.33, 0.5, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours Post-dose
measure: Apparent Volume of Distribution (Vd/F)
timeFrame: Pre-dose; 0.33, 0.5, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours Post-dose
measure: Metabolite to Parent (M/P) Ratio for AUC[last]
timeFrame: Pre-dose; 0.33, 0.5, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours Post-dose
measure: Metabolite to Parent (M/P) Ratio for AUC[infinity]
timeFrame: Pre-dose; 0.33, 0.5, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours Post-dose
measure: Relationship Between the Plasma Concentrations of Seltorexant and Changes in the QT/QTc Interval
timeFrame: Up to Day 3
measure: Number of Participants with Adverse Events and Serious Edverse Events as a Measure of Safety and Tolerability
timeFrame: Approximately 11 weeks
Other outcomes:
Locations:
city: Merksem
country: Belgium
facility: Clinical Pharmacology Unit
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: