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

Phase 1

Completed

• Conditions: Qt Interval, Variation in
• Interventions: Drug: NPC-15 and/or Placebo

• Registration Number: NCT03475459
• Lead Sponsor: Nobelpharma

Brief Summary

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

Detailed Description

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.

Study Timeline

• Study First Submitted: 2018-02-22
• Study First Submitted QC: 2018-03-16
• Study First Posted: 2018-03-23
• Status Verified: 2018-04
• Study Start: 2018-04-03
• Primary Completion: 2018-04-29
• Study Completion: 2018-04-29
• Last Update Submitted: 2018-06-26
• Last Update Posted: 2018-06-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
study drug	NPC-15 and/or Placebo	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

SOUSEIKAI Hakata Clinic; 🇯🇵 Fukuoka, Japan