Clinical trial NCT04225078: A Study to Evaluate the Effects of Loperamide (JNJ-289679) 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 Loperamide (JNJ-289679) on Electrocardiogram Intervals in Healthy Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2020-01-13
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: DIAGNOSTIC

Brief summary: The purpose of this study is to assess the effects of loperamide on QT/ QT interval corrected for heart rate (QTc) intervals and electrocardiogram (ECG) morphology at therapeutic and supratherapeutic exposures in healthy participants.


Eligibility criteria: Inclusion Criteria:

* All female participants, except if postmenopausal, must have a negative serum beta-human chorionic gonadotropin (beta hCG) pregnancy test at screening and a negative urine pregnancy test on Day 1 of each treatment period
* 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 (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
* Must have a body mass index (body mass index \[BMI\]; weight kilogram per meter per height per square per meter square \[kg/height\^2 m\^2\]) between 18.0 and 30.0 kg/m\^2 (inclusive) with a body weight not lower than 50 kilogram (kg)
* Must have a blood pressure (after the participant is supine for 5 minutes) between 90 and 140 millimeters 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:

* History of or current renal insufficiency (estimated glomerular filtration rate \[eGFR\] less than (\<) 90 milliliter per minute per meter square (mL/min/1.73m\^2) based on the Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] formula at screening only)
* 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, as deemed appropriate by the investigator. It is expected that laboratory values will generally be within the normal range for the laboratory, though minor deviations, which are not considered to be of clinical significance to the investigator, are acceptable
* 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 Cytochrome (CY) P3A4, CYP3A4, CYP2C8, or P-glycoprotein (P-gp) 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
* Received a known inducer of CYP3A4 or CYP2C8 activity within 28 days before the first dose of the study drug is scheduled

Primary outcomes:
measure: Change from Baseline in QT Interval Corrected for Heart Rate (QTc) Intervals for Loperamide
timeFrame: Baseline up to 9 weeks
measure: Percentage of Participants with Change from Baseline in T-wave Morphology
timeFrame: Up to 9 weeks
measure: Percentage of Participants with Occurrence of Abnormal U-wave Morphology
timeFrame: Up to 9 weeks
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of Loperamide and its M1 Metabolite
timeFrame: Up to 9 weeks
measure: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Loperamide and its M1 Metabolite
timeFrame: Up to 9 weeks
measure: Area Under the Plasma Concentration-Time Curve from the Time of Dosing to the Last Measurable Plasma Concentration AUC (0-last) of Loperamide and its M1 Metabolite
timeFrame: Up to 9 weeks
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC[0-inifinity]) of Loperamide and M1 Metabolite
timeFrame: Up to 9 weeks
measure: Apparent Terminal Elimination Rate Constant Lambda (z) of Loperamide and its M1 Metabolite
timeFrame: Up to 9 weeks
measure: Apparent Elimination Half-Life Associated with the Terminal Slope (t1/2) of Loperamide and M1 Metabolite
timeFrame: Up to 9 weeks
measure: Metabolite to parent ratio (M/P) for (AUC[0-inifinity]) of Loperamide and M1 Metabolite
timeFrame: Up to 9 weeks
measure: Relationship Between Systemic Plasma Concentrations of Loperamide and QT/QTc Changes
timeFrame: Up to 9 weeks
measure: Number of Participants with Adverse Events (AE) as a Measure of Safety and Tolerability
timeFrame: Up to 9 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: