A Study to Evaluate the Effects of Therapeutic and Supratherapeutic Doses of KRP-S124 Compared to Placebo With Moxifloxacin on QTc Interval in Healthy Participants
A Randomized, Partially Double-Blind, Five-Period, Five-Treatment, Crossover Study to Assess the Effects of KRP-S124 on QTc Interval Using Therapeutic and Supratherapeutic Doses Compared to Placebo, With Moxifloxacin as a Positive Control, in Healthy Participants: A Thorough QTc Study
This study is being done to see how KRP-S124 affects the electrical activity of the heart (known as the QTc interval [QT interval corrected for heart rate]) in healthy volunteers. This helps researchers check the heart safety of the study drug.
Studieoversigt
Status
Status
Betingelser
Betingelser
Intervention / Behandling
Intervention / Behandling
Undersøgelsestype
Undersøgelsestype
Tilmelding (Anslået)
Tilmelding
Fase
Fase
- Fase 1
Kontakter og lokationer
Studiekontakt
Studiekontakt
- Navn: Clinical Development Center Kyorin Pharmaceutical Co., Ltd.
- Telefonnummer: +81-3-6368-4834
- E-mail: ml-kyorin_clinicaltrials.gov@mb.kyorin-pharm.co.jp
Studiesteder
-
-
Quebec
-
Québec, Quebec, Canada
- Rekruttering
- Syneos Health
-
-
Deltagelseskriterier
Berettigelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion Criteria:
- Male or non-childbearing potential female, non-smoker (no use of tobacco or nicotine products within 3 months prior to screening), greater than or equal to (>=) 18 and less than or equal to (<=) 55 years of age, with body mass index (BMI) greater than (>) 18.5 and less than (<) 30.0 kilograms per square meter (kg/m^2) and body weight >=50.0 kilograms (kg) for males and >=45.0 kg for females.
- Female participants of non-childbearing potential should not donate ova for 90 days after the last dose.
- Male participants (including men who have had a vasectomy) with a pregnant partner must agree to use a condom from the first dose and for 90 days after the last dose.
- Male participants must be willing not to donate sperm for 90 days after the last dose.
- Able to understand the study procedures and provide signed informed consent to participate in the study.
Exclusion Criteria:
- Any clinically significant abnormal finding at physical examination at screening or Baseline (Day -1 of Period 1).
- Clinically significant abnormal laboratory test results or positive serology test results for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antigen and antibody at screening.
- Any of the following laboratory parameters above the upper limit of normal (ULN) values at Screening or Baseline (Day -1 of Period 1): alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl-transpeptidase (GGT), direct bilirubin and total bilirubin. Only abnormal values between 1-1.5 * ULN may be repeated once for confirmation to below ULN.
- Known allergic reactions to KRP-S124 or other related drugs, or to any excipient in the formulation.
- Clinically significant vital signs abnormalities (systolic blood pressure lower than 90 or over 140 millimeters of mercury [mmHg], diastolic blood pressure lower than 50 or over 90 mmHg, or heart rate less than 50 or over 100 beats per minute [bpm]) at screening or Baseline (Day -1 of Period 1).
- History of drug abuse within 1 year prior to screening or recreational use of soft drugs (such as marijuana) within 1 month or hard drugs (such as cocaine, phencyclidine [PCP], crack, opioid derivatives including heroin, and amphetamine derivatives) within 3 months prior to screening.
- History of alcohol abuse within 1 year prior to screening or regular use of alcohol within 6 months prior to screening that exceeds 10 units for women or 15 units for men of alcohol per week (1 unit = 340 mL of beer 5 percent (%), 140 mL of wine 12%, or 45 mL of distilled alcohol 40%).
- Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days prior to the first dosing (or 5 half-lives, whichever is longer), administration of a biological product in the context of a clinical research study within 90 days prior to the first dosing (or 5 half-lives, whichever is longer), or concomitant participation in an investigational study involving no drug or device administration.
- History of sustained and non-sustained cardiac arrhythmias (ECG demonstrated), family history of sudden cardiac death, and history of additional risk factors for Torsade-de-pointes, (e.g. [for example]: heart failure, hypokalemia, unexplained syncope, family history of Long QT Syndrome).
- Any reason which, in the opinion of the Investigator, would prevent the participant from participating in the study.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Crossover opgave
- Maskning: Firedobbelt
Antal våben
Våben og indgreb
Deltagergruppe / ArmDeltagergruppe / Arm |
Intervention / BehandlingIntervention / Behandling |
|---|---|
|
Eksperimentel: Treatment T (Therapeutic Dose)
Participants will receive a single oral dose of Therapeutic dose (T) (KRP-S124 [low dose]) and placebo matched to KRP-S124. |
Orally. Orally. |
|
Eksperimentel: Treatment ST1 (Supratherapeutic Dose 1)
Participants will receive a single oral dose of Supratherapeutic dose 1 (ST1) (KRP-S124 [medium dose]) and placebo matched to KRP-S124. |
Orally. Orally. |
|
Eksperimentel: Treatment ST2 (Supratherapeutic Dose 2)
Participants will receive a single oral dose of Supratherapeutic dose 2 (ST2) (KRP-S124 [high dose]). |
Orally. |
|
Placebo komparator: Treatment P (Placebo)
Participants will receive a single oral dose of placebo matched to KRP-S124. |
Orally. |
|
Aktiv komparator: Treatment M (Moxifloxacin)
Participants will receive a single oral dose of moxifloxacin (M). |
Orally. |
Hvad måler undersøgelsen?
Primære resultatmål
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Placebo-corrected Change From Baseline in Fridericia's Corrected QT interval (delta delta [ΔΔ]QTcF) for KRP-S124
Tidsramme: Baseline (pre-dose at -1.5, -1, -0.5 hours) up to 24 hours post-dose
|
Placebo-corrected change from baseline QTcF will be reported using a linear mixed-effects model analysis. |
Baseline (pre-dose at -1.5, -1, -0.5 hours) up to 24 hours post-dose
|
Sekundære resultatmål
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Placebo-corrected Change From Baseline in Heart Rate (ΔΔHR) for KRP-S124
Tidsramme: Baseline (pre-dose at -1.5, -1, -0.5 hours) up to 24 hours post-dose
|
Placebo-corrected change from baseline HR will be reported using a linear mixed-effects model analysis. |
Baseline (pre-dose at -1.5, -1, -0.5 hours) up to 24 hours post-dose
|
|
Placebo-corrected Change From Baseline in PR interval (ΔΔPR) for KRP-S124
Tidsramme: Baseline (pre-dose at -1.5, -1, -0.5 hours) up to 24 hours post-dose
|
Placebo-corrected change from baseline PR interval will be reported using a linear mixed-effects model analysis. |
Baseline (pre-dose at -1.5, -1, -0.5 hours) up to 24 hours post-dose
|
|
Placebo-corrected Change From Baseline in QRS interval (ΔΔQRS) for KRP-S124
Tidsramme: Baseline (pre-dose at -1.5, -1, -0.5 hours) up to 24 hours post-dose
|
Placebo-corrected change from baseline in QRS interval will be reported using a linear mixed-effects model analysis. |
Baseline (pre-dose at -1.5, -1, -0.5 hours) up to 24 hours post-dose
|
|
Number of Participants With Categorical Outliers for QTcF, HR, PR and QRS
Tidsramme: Baseline (pre-dose at -1.5, -1, -0.5 hours) up to 24 hours post-dose
|
HR, PR, QRS, and QTc will be measured by continuous electrocardiogram (ECG) recordings. Number of participants with categorical outliers for QTcF, HR, PR and QRS will be reported. |
Baseline (pre-dose at -1.5, -1, -0.5 hours) up to 24 hours post-dose
|
|
Number of Participants With Treatment-emergent Changes in ECG Morphology for KRP-S124
Tidsramme: Baseline (pre-dose at -1.5, -1, -0.5 hours) up to 24 hours post-dose
|
Baseline (pre-dose at -1.5, -1, -0.5 hours) up to 24 hours post-dose
|
|
|
Area Under the Plasma Concentration-time Curve From Time Zero Until the Last Observed Concentration (AUC0-t) for KRP-S124 and Moxifloxacin
Tidsramme: Pre-dose up to 12 hours post-dose on Day 1 and 24 hours post-dose on Day 2
|
Pre-dose up to 12 hours post-dose on Day 1 and 24 hours post-dose on Day 2
|
|
|
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) for KRP-S124 and Moxifloxacin
Tidsramme: Pre-dose up to 12 hours post-dose on Day 1 and 24 hours post-dose on Day 2
|
Pre-dose up to 12 hours post-dose on Day 1 and 24 hours post-dose on Day 2
|
|
|
Percentage of AUC0-inf Due to Extrapolation From the Time of the Last Observed Concentration to Infinity (Residual Area) for KRP-S124 and Moxifloxacin
Tidsramme: Pre-dose up to 12 hours post-dose on Day 1 and 24 hours post-dose on Day 2
|
Residual area will be calculated as [1 - (AUC0-t divided by AUC0-inf)] multiplied by 100. |
Pre-dose up to 12 hours post-dose on Day 1 and 24 hours post-dose on Day 2
|
|
Maximum Observed Plasma Concentration (Cmax) for KRP-S124 and Moxifloxacin
Tidsramme: Pre-dose up to 12 hours post-dose on Day 1 and 24 hours post-dose on Day 2
|
Pre-dose up to 12 hours post-dose on Day 1 and 24 hours post-dose on Day 2
|
|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) for KRP-S124 and Moxifloxacin
Tidsramme: Pre-dose up to 12 hours post-dose on Day 1 and 24 hours post-dose on Day 2
|
Pre-dose up to 12 hours post-dose on Day 1 and 24 hours post-dose on Day 2
|
|
|
Terminal Elimination Half-life (T1/2 el) for KRP-S124 and Moxifloxacin
Tidsramme: Pre-dose up to 12 hours post-dose on Day 1 and 24 hours post-dose on Day 2
|
Pre-dose up to 12 hours post-dose on Day 1 and 24 hours post-dose on Day 2
|
|
|
Terminal Elimination Rate Constant (Kel) for KRP-S124 and Moxifloxacin
Tidsramme: Pre-dose up to 12 hours post-dose on Day 1 and 24 hours post-dose on Day 2
|
Pre-dose up to 12 hours post-dose on Day 1 and 24 hours post-dose on Day 2
|
|
|
Apparent Clearance (Cl/F) for KRP-S124 and Moxifloxacin
Tidsramme: Pre-dose up to 12 hours post-dose on Day 1 and 24 hours post-dose on Day 2
|
Pre-dose up to 12 hours post-dose on Day 1 and 24 hours post-dose on Day 2
|
|
|
Apparent Volume of Distribution (Vz/F) for KRP-S124 and Moxifloxacin
Tidsramme: Pre-dose up to 12 hours post-dose on Day 1 and 24 hours post-dose on Day 2
|
Pre-dose up to 12 hours post-dose on Day 1 and 24 hours post-dose on Day 2
|
|
|
Number of Participants With Adverse Events
Tidsramme: Up to approximately 10 weeks
|
Up to approximately 10 weeks
|
|
|
Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Values
Tidsramme: Up to approximately 10 weeks
|
Up to approximately 10 weeks
|
|
|
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs Measurements
Tidsramme: Up to approximately 10 weeks
|
Up to approximately 10 weeks
|
|
|
Number of Participants With Clinically Significant Changes From Baseline in 12-lead Safety ECG Measurements
Tidsramme: Up to approximately 10 weeks
|
Up to approximately 10 weeks
|
|
|
Number of Participants With Clinically Significant Changes From Baseline in Physical Examination Findings
Tidsramme: Up to approximately 10 weeks
|
Up to approximately 10 weeks
|
Samarbejdspartnere og efterforskere
Sponsor
Sponsor
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Studiestart
Primær færdiggørelse (Anslået)
Primær færdiggørelse
Studieafslutning (Anslået)
Studieafslutning
Datoer for studieregistrering
Først indsendt
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Først opslået
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering sendt
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
Andre undersøgelses-id-numre
- KRPS124-T101
Plan for individuelle deltagerdata (IPD)
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