Clinical trial NCT04342273: A Through QT/QTc Study of KW-6356
Official title: A Through QT/QTc Study of KW-6356 in Japanese Healthy Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Parkinson's Disease
Lead sponsor: Kyowa Kirin Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-04-13
Enrollment: 128
Sex: ALL
Minimum age (years): 20
Maximum age (years): 54
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the effects of multiple therapeutic and supratherapeutic doses of KW-6356 on the QT interval corrected for heart rate in Japanese healthy adults.


Eligibility criteria: Inclusion Criteria:

* Subjects having issued written consent to this study at their own discretion
* Men or women aged 20 to 54 years at the time of informed consent
* Subjects with BMI ≥18.5 and \<25.0 at screening
* In case of women of childbearing potential,\* subjects who have agreed to use highly effective and appropriate contraceptive methods from the time of informed consent to 4 weeks after the last dose of the investigational product or the index drug. Women of childbearing potential must have a negative serum pregnancy test at screening
* At screening and Day -2, subjects with resting pulse rate of ≥45 and \<100 bpm, systolic blood pressure of ≥90 and \<140 mmHg, and diastolic blood pressure of ≥40 and \<90 mmHg when measured in the supine position
* Subjects whose standard 12-lead ECG data obtained at screening and Day -2 meet the following criteria and show no clinically significant abnormalities as confirmed by the investigator or subinvestigator Normal sinus rhythm: HR of ≥45 and ≤100 bpm QTc interval (QTcF): ≤450 msec QRS interval: ≤120 msec (must be re-measured manually if exceeding 120 msec) PR interval: ≤220 msec
* Subjects whose potassium, sodium, calcium, and magnesium levels at screening are within institutional normal limits

Exclusion Criteria:

* Subjects with any current disease requiring treatment
* Subjects having drug allergy or its history
* Subjects having psychiatric disease or its history
* Positive results for any of the following infection-related items examined at screening: hepatitis B surface (HBs) antigen, HBs antibody, hepatitis B core (HBc) antibody, hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antigen/antibody, human T-lymphotropic virus (HTLV)-1 antibody, rapid plasma reagin (RPR) test, or Treponema pallidum (TP) antibody
* Subjects being alcohol- or drug-dependent or having a positive result for any of the drug abuse test items
* Subjects previously or concurrently having any of the following diseases or subjects with a family history of any of the following diseases:

Hypokalemia, hypocalcemia, and/or long QT syndrome Risk factors for torsade de pointes such as cardiac failure, cardiomyopathy, and a family history of long QT syndrome Sick sinus syndrome, second- or third-degree atrioventricular block, myocardial infarction, pulmonary congestion, cardiac arrhythmia, QT interval prolongation, or atrioventricular conduction disturbance Repeated or frequent syncope or vasovagal attack Hypertension, angina pectoris, bradycardia, or severe peripheral arterial circulatory disorder

* Subjects categorized as patients listed in the warnings or contraindications section of the package insert of moxifloxacin hydrochloride
* Subjects unable to be compliant with Specified "Concomitant Medication and Concomitant Therapy" and "Instruction for Subjects"
* Subjects having participated in a clinical study of a pharmaceutical product or a medical device or any equivalent study and used the investigational product or the unapproved medical device within 4 months prior to administration of the investigational product
* Subjects having used any drug within 2 weeks prior to administration of the investigational product
* Subjects having consumed grapefruit or any food or beverage containing St John's wort within 1 week prior to administration of the investigational product
* Subjects having smoked or used smoking cessation agents within 4 weeks prior to administration of the investigational product
* Subjects categorized as "yes" to "active suicidal ideation with some intent to act, without specific plan" or "active suicidal ideation with specific plan and intent" on the Columbia-Suicide Severity Rating Scale assessed on Day -2 or subjects with a history of or currently observed suicidal behavior
* Subjects having undergone ≥400 mL of blood collection within 12 weeks prior to administration of the investigational product or ≥200 mL of blood collection within 4 weeks prior to administration of the investigational product for blood donation or in a clinical trial, etc. or subjects having undergone blood collection for pheresis donation within 2 weeks prior to administration of the investigational product
* Subjects having issued no consent to adoption of any appropriate contraceptive method during the period from day of informed consent to 4 weeks after the final administration of the investigational product or the index drug for women of childbearing potential and during the period from start day of study treatment to 12 weeks after the final administration of the investigational product or the index drug for men of reproductive potential. The appropriate contraceptive method

Primary outcomes:
measure: Change from baseline in QTc interval [QTcF] (ΔQTcF)
timeFrame: Day 1 through Day 7
Secondary outcomes:
measure: Changes from baseline in the HR
timeFrame: Day 1 through Day 7
measure: Changes from baseline in the QTc interval [QTcF]
timeFrame: Day 1 through Day 7
measure: Changes from baseline in the PR interval
timeFrame: Day 1 through Day 7
measure: Changes from baseline in the QRS interval
timeFrame: Day 1 through Day 7
measure: Placebo-corrected ΔQTcF
timeFrame: Day 1 through Day 7
measure: Placebo-corrected ΔHR
timeFrame: Day 1 through Day 7
measure: Placebo-corrected ΔPR interval
timeFrame: Day 1 through Day 7
measure: Placebo-corrected ΔQRS interval
timeFrame: Day 1 through Day 7
measure: Outliers in terms of category for HR
timeFrame: Day 1 through Day 7
measure: Outliers in terms of category for QTc interval (QTcF)
timeFrame: Day 1 through Day 7
measure: Outliers in terms of category for PR interval
timeFrame: Day 1 through Day 7
measure: Outliers in terms of category for QRS interval
timeFrame: Day 1 through Day 7
measure: Frequency of morphological changes in T wave after administration of the investigational product
timeFrame: Day 1 through Day 7
measure: Frequency of morphological changes in U wave after administration of the investigational product
timeFrame: Day 1 through Day 7
measure: Incidence of treatment-emergent adverse events
timeFrame: Day 1 through Day 20
measure: Plasma concentrations of KW-6356
timeFrame: Day 1 through Day 8, and Day 12
Other outcomes:
Locations:
city: Sumida-ku
country: Japan
facility: Medical Co. LTA Sumida Hospital
state: Tokyo
city: Fukuoka
country: Japan
facility: Medical Co. LTA Fukuoka Mirai Hospital Clinical Research Center
Study officials:
References: