Investigation of Arrhythmogenic Effect of NPC-15 (NPC-15-7)

Study Overview
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Brief Summary
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A study to assess the QTc prolongation effect of NPC-15 (melatonin 8mg or 16mg)

Detailed Description
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This study is a single center, open label, dose escalation trial to evaluate prolongation effect on QT interval of NPC-15 (melatonin 8mg or 16mg). The trial compose of 3 periods; During the each period, eligible volunteers wll be administered placebo, NPC-15 4g (melatonin 8mg) and NPC-15 8g(melatonin 16mg) as a sequential manner.

Official Title
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A Clinical Pharmacology Study of NPC-15 to Evaluate Arrhythmogenic Effect in Healthy Adults

Conditions
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Qt Interval, Variation in

Intervention / Treatment
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* Drug: NPC-15 and/or Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject with BMI ≥ 17.6 kg/m2 and < 30.0 kg/m2. Subject who falls asleep at between 21:00 and 25:00 and wakes up at between 5:00 and 9:00 during 1 week prior to the first study drug administration. Subject who is able to comply with the study requirements during the study period. Exclusion Criteria: Subject with QTcF interval greater than 450 ms in male or greater than 470 ms in female on the 12-lead electrocardiogram (ECG), or with clinically significant ECG abnormalities in other findings. Subject who has a family history of Torsades de Pointes (TdP) or long QT syndrome. Subject who has a history of hypersensitivity or allergies to melatonin or ramelteon. Subject who has a current or a history of disease which is considered inappropriate to be involved in the study, or who has any current disease to require treatments. Subject who received any non-prescription or prescription drug within 2 weeks prior to the first study drug administration. Subject who received any product containing St Jones Wart or any supplement containing melatonin within 4 weeks prior to the first study drug administration. Subject who has a history of smoking habit or was possibly exposed to passive smoking on a daily basis within 24 weeks prior to the first study drug administration. Subject who, in the opinion of the investigator or sub-investigator, is unsuitable to be involved in the study.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: study drug<br>Study drug (NPC-15 and/or Placebo ) will be orally administered once with 200 ml of water at 20:00 on the first days of Period I, Period II and Period III. | Drug: NPC-15 and/or Placebo<br>* The dosage and regimen of the study drug in each period is the following. Period I : NPC-15 placebo granules 8 g Period II : NPC-15 placebo granules 4 g + NPC-15 granules 0.2% 4 g (melatonin 8 mg) Period III : NPC-15 granules 0.2% 8 g (melatonin 16 mg)<br>* Other names: Melatonin and/or Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time matched, baseline-adjusted change in Fridericia-corrected QTc (QTcF) intervals | QTcF interval is a common endpoints to evaluate arrhythmogenic effect of test drug | Day1 and Day2 of each periods (3 periods) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum melatonin concentration | NPC-15 is a preparation containing melatonin , therefore the change in blood concentration of melatonin is useful to evaluate the QTc prolongation effect of NPC-15. | Up to 12 hours post dose in each period (3 periods) | 
| Maximum drug concentration (Cmax) of melatonin | NPC-15 is a preparation containing melatonin , therefore pharmacokinetic parameter is useful to evaluate the QTc prolongation effect of NPC-15. | Up to 12 hours post dose in each period (3 periods) | 
| Maximum drug concentration time (Tmax) of melatonin | NPC-15 is a preparation containing melatonin , therefore pharmacokinetic parameter is useful to evaluate the QTc prolongation effect of NPC-15. | Up to 12 hours post dose in each period (3 periods) | 
| Area under the blood concentration time curve (AUC) of melatonin | NPC-15 is a preparation containing melatonin , therefore pharmacokinetic parameter is useful to evaluate the QTc prolongation effect of NPC-15. | Up to 12 hours postdose in each period (3 periods) | 
| Terminal elimination rate constant (λz) of melatonin | NPC-15 is a preparation containing melatonin , therefore pharmacokinetic parameter is useful to evaluate the QTc prolongation effect of NPC-15. | Up to 12 hours post dose in each period (3 periods) | 
| Mean residence time (MRT) of melatonin | NPC-15 is a preparation containing melatonin , therefore pharmacokinetic parameter is useful to evaluate the QTc prolongation effect of NPC-15. | Up to 12 hours postdose in each period (3 periods) | 
| Elimination half-life (t1/2) of melatonin | NPC-15 is a preparation containing melatonin , therefore pharmacokinetic parameter is useful to evaluate the QTc prolongation effect of NPC-15. | Up to 12 hours post dose in each period | 
| Clearance (CL) of melatonin | NPC-15 is a preparation containing melatonin , therefore pharmacokinetic parameter is useful to evaluate the QTc prolongation effect of NPC-15. | Up to 12 hours post dose in each period (3 periods) | 
| Volume of distribution (Vd) of melatonin | NPC-15 is a preparation containing melatonin , therefore pharmacokinetic parameter is useful to evaluate the QTc prolongation effect of NPC-15. | Up to 12 hours postdose in each period (3 periods) | 
| Adverse Events | All events that emerge during treatment, having been absent pretreatment, or worsens relative to the pretreatment state | Up to 36 hours post dose of Period III | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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QTc prolongation effect