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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
DIAGNOSTIC
Masking
QUADRUPLE
Enrollment
66
Loperamide will be administered as a single oral dose at the expected therapeutic or supratherapeutic doses respectively.
Matching loperamide placebo capsules will be administered orally.
Moxifloxacin tablets will be administered orally.
Clinical Pharmacology Unit
Merksem, Belgium
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.
Time frame: Baseline up to 9 weeks
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.
Time frame: Up to 9 weeks
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.
Time frame: Up to 9 weeks
Maximum Observed Plasma Concentration (Cmax) of Loperamide and its M1 Metabolite
Cmax is defined as the maximum observed plasma concentration.
Time frame: Up to 9 weeks
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.
Time frame: Up to 9 weeks
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.
Time frame: Up to 9 weeks
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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.
Time frame: Up to 9 weeks
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.
Time frame: Up to 9 weeks
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.
Time frame: Up to 9 weeks
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.
Time frame: Up to 9 weeks
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.
Time frame: Up to 9 weeks
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.
Time frame: Up to 9 Weeks