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

26. april 2022 opdateret af: Janssen Research & Development, LLC

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

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.

Studieoversigt

Status

Afsluttet

Betingelser

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

66

Fase

  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

      • Merksem, Belgien, 2170
        • Clinical Pharmacology Unit

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år til 55 år (Voksen)

Tager imod sunde frivillige

Ja

Køn, der er berettiget til at studere

Alle

Beskrivelse

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

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Diagnostisk
  • Tildeling: Randomiseret
  • Interventionel model: Crossover opgave
  • Maskning: Firedobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Treatment Sequence 1: Treatment ADBC
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.
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.
Eksperimentel: Treatment Sequence 2: Treatment BACD
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.
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.
Eksperimentel: Treatment Sequence 3: Treatment CBDA
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.
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.
Eksperimentel: Treatment Sequence 1: Treatment DCAB
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.
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.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Change from Baseline in QT Interval Corrected for Heart Rate (QTc) Intervals for Loperamide
Tidsramme: Baseline up to 9 weeks
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
Tidsramme: 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.
Up to 9 weeks
Percentage of Participants with Occurrence of Abnormal U-wave Morphology
Tidsramme: 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.
Up to 9 weeks

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Maximum Observed Plasma Concentration (Cmax) of Loperamide and its M1 Metabolite
Tidsramme: Up to 9 weeks
Cmax is defined as the maximum observed plasma concentration.
Up to 9 weeks
Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Loperamide and its M1 Metabolite
Tidsramme: Up to 9 weeks
Tmax is defined as the time to reach the maximum observed plasma concentration.
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
Tidsramme: 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.
Up to 9 weeks
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC[0-inifinity]) of Loperamide and M1 Metabolite
Tidsramme: 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.
Up to 9 weeks
Apparent Terminal Elimination Rate Constant Lambda (z) of Loperamide and its M1 Metabolite
Tidsramme: 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.
Up to 9 weeks
Apparent Elimination Half-Life Associated with the Terminal Slope (t1/2) of Loperamide and M1 Metabolite
Tidsramme: 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.
Up to 9 weeks
Metabolite to parent ratio (M/P) for (AUC[0-inifinity]) of Loperamide and M1 Metabolite
Tidsramme: 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.
Up to 9 weeks
Relationship Between Systemic Plasma Concentrations of Loperamide and QT/QTc Changes
Tidsramme: Up to 9 weeks
The relationship between systemic plasma concentrations of loperamide and change in QT/QTc will be reported.
Up to 9 weeks
Number of Participants with Adverse Events (AE) as a Measure of Safety and Tolerability
Tidsramme: 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.
Up to 9 Weeks

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

17. januar 2020

Primær færdiggørelse (Faktiske)

21. december 2021

Studieafslutning (Faktiske)

12. januar 2022

Datoer for studieregistrering

Først indsendt

9. januar 2020

Først indsendt, der opfyldte QC-kriterier

9. januar 2020

Først opslået (Faktiske)

13. januar 2020

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

27. april 2022

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

26. april 2022

Sidst verificeret

1. april 2022

Mere information

Begreber relateret til denne undersøgelse

Andre undersøgelses-id-numre

  • CR108643
  • 2019-003776-39 (EudraCT nummer)
  • R018553NAP1001 (Anden identifikator: Janssen Research & Development, LLC)

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

JA

IPD-planbeskrivelse

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency.

As noted on this site, requests for access to the study data can be submitted through Yale open Data Access (YODA) Project site at yoda.yale.edu

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ja

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

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Kliniske forsøg med Loperamide

3
Abonner