- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03494907
A Study to Evaluate the Effects of Single-dose Seltorexant on Electrocardiogram Intervals in Healthy Adult Participants
September 21, 2018 updated by: Janssen Research & Development, LLC
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
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.
Study Overview
Status
Completed
Conditions
Study Type
Interventional
Enrollment (Actual)
52
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Merksem, Belgium, 2170
- Clinical Pharmacology Unit
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 55 years (ADULT)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: OTHER
- Allocation: RANDOMIZED
- Interventional Model: CROSSOVER
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Seltorexant (Low and high dose)
Participants will receive seltorexant tablets orally in 2 of 4 treatment arms (A,B,C,D) in a cross-over design, with 7 days wash-out phase between each treatment period.
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Participants will be administered oral dose of seltorexant over-encapsulated tablets on Day 1.
Other Names:
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EXPERIMENTAL: Moxifloxacin
Participants will receive moxifloxacin tablets orally in 1 of 4 treatment arms (A,B,C,D) in a cross-over design, with 7 days wash-out phase between each treatment period.
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Participants will be administered oral dose 1 of moxifloxacin on Day 1.
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EXPERIMENTAL: Placebo Matched to Seltorexant
Participants will receive seltorexant placebo tablets orally in 3 of 4 treatment arms (A,B,C,D) in a cross-over design, with 7 days wash-out phase between each treatment period.
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Participants will be administered matching placebo to seltorexant tablets on Day 1.
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EXPERIMENTAL: Placebo Matched to Moxifloxacin
Participants will receive moxifloxacin placebo tablets orally in 3 of 4 treatment arms (A,B,C,D) in a cross-over design, with 7 days wash-out phase between each treatment period.
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Participants will be administered oral dose of moxifloxacin placebo tablet on Day 1.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in QT/QTc Intervals
Time Frame: Baseline up to Day 3
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Change from baseline in QT and QTc interval will be assessed.
QT interval will be measured in triplicates from 12 lead Holter extracted triplicate ECG recordings and corrected QT (QTc) interval will be calculated based on Fridericia (QTcF), Bazett (QTcB), and/or study specific power (QTcP) equations.
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Baseline up to Day 3
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Percentage of Participants with Change from Baseline in T-wave Morphology
Time Frame: Baseline up to Day 3
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The percentage of participants in each treatment having T-wave morphology changes from baseline that represent the appearance or worsening of the morphological abnormality will be reported.
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Baseline up to Day 3
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Percentage of Participants with Change from Baseline in U-wave Morphology
Time Frame: Baseline up to Day 3
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The percentage of participants with change from baseline with abnormal U-waves morphology that represent the appearance or worsening of the morphological abnormality will be reported.
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Baseline up to Day 3
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Observed Plasma Concentration (Cmax)
Time Frame: 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
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Cmax is the maximum observed plasma concentration of seltorexant and its circulating metabolites.
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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
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Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time Frame: 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
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Tmax is the time to reach the maximum observed plasma concentration of seltorexant and its circulating metabolites.
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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
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Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last])
Time Frame: 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
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AUC(0-last) is the area under the plasma concentration-time curve from 0 to time of the last quantifiable concentration of seltorexant and its circulating metabolites.
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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
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Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity])
Time Frame: 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
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The AUC (0-infinity) is the area under the plasma 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 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.
AUC (0-infinity) will be assessed for seltorexant and its circulating metabolites.
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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
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Elimination Half-Life (t1/2)
Time Frame: 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
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Elimination half-life associated with the terminal slope Lambda (z) of the semi logarithmic drug concentration-time curve, calculated as 0.693/Lambda (z).
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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
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Total Apparent Clearance (CL/F)
Time Frame: 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
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CL/F for extravascular administration divided by the fraction of dose absorbed, calculated using the observed value of the last non-zero plasma concentration.
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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
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Apparent Volume of Distribution (Vd/F)
Time Frame: 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
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Vd/F is defined as Dose/[Lambda (z)*AUC (0-infinity)].
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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
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Metabolite to Parent (M/P) Ratio for AUC[last]
Time Frame: 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
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M/P Ratio AUC[last] is the ratio of AUC[last] of seltorexant to AUC[last] of seltorexant's metabolites.
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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
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Metabolite to Parent (M/P) Ratio for AUC[infinity]
Time Frame: 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
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M/P Ratio AUC[infinity] is the ratio of AUC[infinity] of seltorexant to AUC[infinity] of seltorexant's metabolites.
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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
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Relationship Between the Plasma Concentrations of Seltorexant and Changes in the QT/QTc Interval
Time Frame: Up to Day 3
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The relationship between change in QT/QTc interval and plasma concentrations from both doses of seltorexant at matching time points will be assessed.
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Up to Day 3
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Number of Participants with Adverse Events and Serious Edverse Events as a Measure of Safety and Tolerability
Time Frame: Approximately 11 weeks
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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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Approximately 11 weeks
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
April 9, 2018
Primary Completion (ACTUAL)
August 13, 2018
Study Completion (ACTUAL)
August 13, 2018
Study Registration Dates
First Submitted
April 5, 2018
First Submitted That Met QC Criteria
April 5, 2018
First Posted (ACTUAL)
April 11, 2018
Study Record Updates
Last Update Posted (ACTUAL)
September 25, 2018
Last Update Submitted That Met QC Criteria
September 21, 2018
Last Verified
September 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antineoplastic Agents
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Anti-Bacterial Agents
- Contraceptive Agents, Hormonal
- Contraceptive Agents
- Reproductive Control Agents
- Contraceptives, Oral, Combined
- Contraceptives, Oral
- Contraceptive Agents, Female
- Moxifloxacin
- Norgestimate, ethinyl estradiol drug combination
Other Study ID Numbers
- CR108459
- 2017-004770-33 (EUDRACT_NUMBER)
- 42847922MDD1007 (OTHER: Janssen Research & Development, LLC)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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