A Study to Evaluate the Effects of Loperamide (JNJ-289679) on Electrocardiogram Intervals in Healthy Adult Participants

Healthy Participants Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04225078
• Other study ID #: CR108643
• Secondary ID: 2019-003776-39R0
• Status: Completed
• Phase: Phase 1
• Start date: January 17, 2020
• Est. completion date: January 12, 2022

Study information

• Verified date: April 2022
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: January 12, 2022
• Est. primary completion date: December 21, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Participants

Intervention

Drug:
• Loperamide
Loperamide will be administered as a single oral dose at the expected therapeutic or supratherapeutic doses respectively.

Other:
• Placebo
Matching loperamide placebo capsules will be administered orally.

Drug:
• Moxifloxacin
Moxifloxacin tablets will be administered orally.

Locations

Country	Name	City	State
Belgium	Clinical Pharmacology Unit	Merksem

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline in QT Interval Corrected for Heart Rate (QTc) Intervals for Loperamide	Change from baseline in QTc intervals for loperamide at therapeutic and supratherapeutic doses will be reported.	Baseline up to 9 weeks
Primary	Percentage of Participants with Change from Baseline in T-wave Morphology	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.	Up to 9 weeks
Primary	Percentage of Participants with Occurrence of Abnormal U-wave Morphology	The percentage of participants with the occurrence of abnormal U-waves morphology that represent the appearance or worsening of the morphological abnormality will be reported.	Up to 9 weeks
Secondary	Maximum Observed Plasma Concentration (Cmax) of Loperamide and its M1 Metabolite	Cmax is defined as the maximum observed plasma concentration.	Up to 9 weeks
Secondary	Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Loperamide and its M1 Metabolite	Tmax is defined as the time to reach the maximum observed plasma concentration.	Up to 9 weeks
Secondary	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	AUC (0-last) is defined as the area under the plasma concentration-time curve from the time of dosing to the last measurable plasma concentration.	Up to 9 weeks
Secondary	Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC[0-inifinity]) of Loperamide and M1 Metabolite	(AUC[0-inifinity]) is defined as the area under the plasma concentration-time curve from time zero to infinity, calculated as AUClast+Clast/lambda (z), where Clast is the last observed measurable concentration.	Up to 9 weeks
Secondary	Apparent Terminal Elimination Rate Constant Lambda (z) of Loperamide and its M1 Metabolite	Lambda (z) is defined as the apparent terminal elimination rate constant, estimated by linear regression using the terminal log-linear phase of the log-transformed concentration versus time curve.	Up to 9 weeks
Secondary	Apparent Elimination Half-Life Associated with the Terminal Slope (t1/2) of Loperamide and M1 Metabolite	t1/2 is defined as the apparent elimination half-life associated with the terminal slope lambda (z) of the semilogarithmic drug concentration-time curve.	Up to 9 weeks
Secondary	Metabolite to parent ratio (M/P) for (AUC[0-inifinity]) of Loperamide and M1 Metabolite	M/p ratio is defined as metabolite to parent ratio (M/P) for (AUC[0-inifinity]) corrected for molecular weight using the following molecular weights: loperamide 477.045 gram per mol (g/mol), M1 463.018 g/mol.	Up to 9 weeks
Secondary	Relationship Between Systemic Plasma Concentrations of Loperamide and QT/QTc Changes	The relationship between systemic plasma concentrations of loperamide and change in QT/QTc will be reported.	Up to 9 weeks
Secondary	Number of Participants with Adverse Events (AE) as a Measure of Safety and Tolerability	An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	Up to 9 Weeks