A Study to Evaluate the Effects of Loperamide (JNJ-289679) on Electrocardiogram Intervals in Healthy Adult Participants
Phase 1
Completed
- Conditions
- Healthy Participants
- Interventions
- Registration Number
- NCT04225078
- Lead Sponsor
- Janssen Research & Development, LLC
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 66
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Treatment Sequence 1: Treatment ADBC Placebo Participants will receive treatment A (Loperamide therapeutic dose) on Day 1 on treatment period 1, followed by Treatment D (Moxifloxacin) on Day 1 of treatment period 2 followed by Treatment B (Loperamide supratherapeutic dose) on Day 1 of treatment period 3 followed by Treatment C (placebo) on Day 1 of treatment period 4. Each treatment period will be separated by a minimum of 7-day washout period and no more than 21-day. Treatment Sequence 3: Treatment CBDA Moxifloxacin Participants will receive Treatment C on Day 1 of treatment period 1 followed by Treatment B on Day 1 of treatment period 2 then Treatment D on Day 1 of treatment period 3 and then Treatment A on Day 1 of treatment period 4. Each treatment period will be separated by a minimum of 7-day washout period and no more than 21-day. Treatment Sequence 2: Treatment BACD Placebo Participants will receive Treatment B on Day 1 of treatment period 1 followed by Treatment A on Day 1 of treatment period 2 then Treatment C on Day 1 of treatment period 3 and then Treatment D on Day 1 of treatment period 4. Each treatment period will be separated by a minimum of 7-day washout period and no more than 21-day. Treatment Sequence 3: Treatment CBDA Placebo Participants will receive Treatment C on Day 1 of treatment period 1 followed by Treatment B on Day 1 of treatment period 2 then Treatment D on Day 1 of treatment period 3 and then Treatment A on Day 1 of treatment period 4. Each treatment period will be separated by a minimum of 7-day washout period and no more than 21-day. Treatment Sequence 1: Treatment ADBC Loperamide Participants will receive treatment A (Loperamide therapeutic dose) on Day 1 on treatment period 1, followed by Treatment D (Moxifloxacin) on Day 1 of treatment period 2 followed by Treatment B (Loperamide supratherapeutic dose) on Day 1 of treatment period 3 followed by Treatment C (placebo) on Day 1 of treatment period 4. Each treatment period will be separated by a minimum of 7-day washout period and no more than 21-day. Treatment Sequence 1: Treatment DCAB Placebo Participants will receive Treatment D on Day 1 of treatment period 1 followed by Treatment C on Day 1 of treatment period 2 then Treatment A on Day 1 of treatment period 3 and then Treatment B on Day 1 of treatment period 4. Each treatment period will be separated by a minimum of 7-day washout period and no more than 21-day. Treatment Sequence 2: Treatment BACD Loperamide Participants will receive Treatment B on Day 1 of treatment period 1 followed by Treatment A on Day 1 of treatment period 2 then Treatment C on Day 1 of treatment period 3 and then Treatment D on Day 1 of treatment period 4. Each treatment period will be separated by a minimum of 7-day washout period and no more than 21-day. Treatment Sequence 1: Treatment ADBC Moxifloxacin Participants will receive treatment A (Loperamide therapeutic dose) on Day 1 on treatment period 1, followed by Treatment D (Moxifloxacin) on Day 1 of treatment period 2 followed by Treatment B (Loperamide supratherapeutic dose) on Day 1 of treatment period 3 followed by Treatment C (placebo) on Day 1 of treatment period 4. Each treatment period will be separated by a minimum of 7-day washout period and no more than 21-day. Treatment Sequence 2: Treatment BACD Moxifloxacin Participants will receive Treatment B on Day 1 of treatment period 1 followed by Treatment A on Day 1 of treatment period 2 then Treatment C on Day 1 of treatment period 3 and then Treatment D on Day 1 of treatment period 4. Each treatment period will be separated by a minimum of 7-day washout period and no more than 21-day. Treatment Sequence 3: Treatment CBDA Loperamide Participants will receive Treatment C on Day 1 of treatment period 1 followed by Treatment B on Day 1 of treatment period 2 then Treatment D on Day 1 of treatment period 3 and then Treatment A on Day 1 of treatment period 4. Each treatment period will be separated by a minimum of 7-day washout period and no more than 21-day. Treatment Sequence 1: Treatment DCAB Loperamide Participants will receive Treatment D on Day 1 of treatment period 1 followed by Treatment C on Day 1 of treatment period 2 then Treatment A on Day 1 of treatment period 3 and then Treatment B on Day 1 of treatment period 4. Each treatment period will be separated by a minimum of 7-day washout period and no more than 21-day. Treatment Sequence 1: Treatment DCAB Moxifloxacin Participants will receive Treatment D on Day 1 of treatment period 1 followed by Treatment C on Day 1 of treatment period 2 then Treatment A on Day 1 of treatment period 3 and then Treatment B on Day 1 of treatment period 4. Each treatment period will be separated by a minimum of 7-day washout period and no more than 21-day.
- Primary Outcome Measures
Name Time Method 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.
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.
- Secondary Outcome Measures
Name Time Method 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.
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.
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.
Maximum Observed Plasma Concentration (Cmax) of Loperamide and its M1 Metabolite Up to 9 weeks Cmax is defined as the maximum observed plasma concentration.
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.
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.
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.
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.
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.
Trial Locations
- Locations (1)
Clinical Pharmacology Unit
🇧🇪Merksem, Belgium