Healthy Participants
Conditions
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.
Interventions
DRUGLoperamide
Loperamide will be administered as a single oral dose at the expected therapeutic or supratherapeutic doses respectively.
OTHERPlacebo
Matching loperamide placebo capsules will be administered orally.
DRUGMoxifloxacin
Moxifloxacin tablets will be administered orally.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DIAGNOSTIC
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in QT Interval Corrected for Heart Rate (QTc) Intervals for Loperamide | Baseline up to 9 weeks | Change from baseline in QTc intervals for loperamide at therapeutic and supratherapeutic doses will be reported. |
| Percentage of Participants with Change from Baseline in T-wave Morphology | Up to 9 weeks | 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. |
| Percentage of Participants with Occurrence of Abnormal U-wave Morphology | Up to 9 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC[0-inifinity]) of Loperamide and M1 Metabolite | Up to 9 weeks | (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. |
| Apparent Terminal Elimination Rate Constant Lambda (z) of Loperamide and its M1 Metabolite | Up to 9 weeks | 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. |
| Apparent Elimination Half-Life Associated with the Terminal Slope (t1/2) of Loperamide and M1 Metabolite | Up to 9 weeks | t1/2 is defined as the apparent elimination half-life associated with the terminal slope lambda (z) of the semilogarithmic drug concentration-time curve. |
| Maximum Observed Plasma Concentration (Cmax) of Loperamide and its M1 Metabolite | Up to 9 weeks | Cmax is defined as the maximum observed plasma concentration. |
| Relationship Between Systemic Plasma Concentrations of Loperamide and QT/QTc Changes | Up to 9 weeks | The relationship between systemic plasma concentrations of loperamide and change in QT/QTc will be reported. |
| Number of Participants with Adverse Events (AE) as a Measure of Safety and Tolerability | Up to 9 Weeks | 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. |
| Metabolite to parent ratio (M/P) for (AUC[0-inifinity]) of Loperamide and M1 Metabolite | Up to 9 weeks | 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 to Reach the Maximum Observed Plasma Concentration (Tmax) of Loperamide and its M1 Metabolite | Up to 9 weeks | Tmax is defined as the time to reach the maximum observed plasma concentration. |
| 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 | Up to 9 weeks | 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. |
Countries
Belgium
Outcome results
None listed