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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04225078
Recruitment Status : Suspended (Trial was put On Hold due to COVID-19. The Site will not start recruiting activities until further notice)
First Posted : January 13, 2020
Last Update Posted : June 22, 2020
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Tracking Information
First Submitted Date  ICMJE January 9, 2020
First Posted Date  ICMJE January 13, 2020
Last Update Posted Date June 22, 2020
Actual Study Start Date  ICMJE January 17, 2020
Estimated Primary Completion Date November 2, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 9, 2020)
  • Change from Baseline in QT Interval Corrected for Heart Rate (QTc) Intervals for Loperamide [ Time Frame: Baseline up to 6 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 [ Time Frame: Up to 6 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 [ Time Frame: Up to 6 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 9, 2020)
  • Maximum Observed Plasma Concentration (Cmax) of Loperamide and its M1 Metabolite [ Time Frame: Up to 6 weeks ]
    Cmax is defined as the maximum observed plasma concentration.
  • Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Loperamide and its M1 Metabolite [ Time Frame: Up to 6 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 [ Time Frame: Up to 6 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 [ Time Frame: Up to 6 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 [ Time Frame: Up to 6 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 [ Time Frame: Up to 6 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.
  • Metabolite to parent ratio (M/P) for (AUC[0-inifinity]) of Loperamide and M1 Metabolite [ Time Frame: Up to 6 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.
  • Relationship Between Systemic Plasma Concentrations of Loperamide and QT/QTc Changes [ Time Frame: Up to 6 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 [ Time Frame: Up to 6 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Effects of Loperamide (JNJ-289679) on Electrocardiogram Intervals in Healthy Adult Participants
Official Title  ICMJE 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
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Diagnostic
Condition  ICMJE Healthy Participants
Intervention  ICMJE
  • Drug: Loperamide
    Loperamide will be administered as a single oral dose at the expected therapeutic or supratherapeutic doses respectively.
  • Other: Placebo
    Matching loperamide placebo capsules will be administered orally.
  • Drug: Moxifloxacin
    Moxifloxacin tablets will be administered orally.
Study Arms  ICMJE
  • Experimental: 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.
    Interventions:
    • Drug: Loperamide
    • Other: Placebo
    • Drug: Moxifloxacin
  • Experimental: 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.
    Interventions:
    • Drug: Loperamide
    • Other: Placebo
    • Drug: Moxifloxacin
  • Experimental: 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.
    Interventions:
    • Drug: Loperamide
    • Other: Placebo
    • Drug: Moxifloxacin
  • Experimental: 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.
    Interventions:
    • Drug: Loperamide
    • Other: Placebo
    • Drug: Moxifloxacin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Suspended
Estimated Enrollment  ICMJE
 (submitted: January 9, 2020)
52
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2, 2020
Estimated Primary Completion Date November 2, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04225078
Other Study ID Numbers  ICMJE CR108643
2019-003776-39 ( EudraCT Number )
R018553NAP1001 ( Other Identifier: Janssen Research & Development, LLC )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

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

URL: https://www.janssen.com/clinical-trials/transparency
Responsible Party Janssen Research & Development, LLC
Study Sponsor  ICMJE Janssen Research & Development, LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
PRS Account Janssen Research & Development, LLC
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP