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

NCT04225078 | Completed Phase 1 FDA Drug

• 3 other identifiers: CR1086432019-003776-39R018553NAP1001
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Participants

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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 Outcomes (9)

• Maximum Observed Plasma Concentration (Cmax) of Loperamide and its M1 Metabolite

  Up to 9 weeks

• Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Loperamide and its M1 Metabolite

  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

  Up to 9 weeks

• Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC[0-inifinity]) of Loperamide and M1 Metabolite

  Up to 9 weeks

• Apparent Terminal Elimination Rate Constant Lambda (z) of Loperamide and its M1 Metabolite

  Up to 9 weeks

Study Arms (4)

Treatment Sequence 1: Treatment ADBC

EXPERIMENTAL

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.

Drug: Loperamide; Other: Placebo; Drug: Moxifloxacin

Treatment Sequence 2: Treatment BACD

EXPERIMENTAL

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.

Drug: Loperamide; Other: Placebo; Drug: Moxifloxacin

Treatment Sequence 3: Treatment CBDA

EXPERIMENTAL

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.

Drug: Loperamide; Other: Placebo; Drug: Moxifloxacin

Treatment Sequence 1: Treatment DCAB

EXPERIMENTAL

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.

Drug: Loperamide; Other: Placebo; Drug: Moxifloxacin

Interventions

Loperamide DRUG

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

Treatment Sequence 1: Treatment ADBC; Treatment Sequence 1: Treatment DCAB; Treatment Sequence 2: Treatment BACD; Treatment Sequence 3: Treatment CBDA

Placebo OTHER

Matching loperamide placebo capsules will be administered orally.

Treatment Sequence 1: Treatment ADBC; Treatment Sequence 1: Treatment DCAB; Treatment Sequence 2: Treatment BACD; Treatment Sequence 3: Treatment CBDA

Moxifloxacin DRUG

Moxifloxacin tablets will be administered orally.

Treatment Sequence 1: Treatment ADBC; Treatment Sequence 1: Treatment DCAB; Treatment Sequence 2: Treatment BACD; Treatment Sequence 3: Treatment CBDA

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (1)

Clinical Pharmacology Unit

Merksem, 2170, Belgium

Location

MeSH Terms

Interventions

Loperamide; Moxifloxacin

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2020
• First Posted: January 13, 2020
• Study Start: January 17, 2020
• Primary Completion: December 21, 2021
• Study Completion: January 12, 2022
• Last Updated: March 30, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share

Locations

BE (1)