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

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

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

Study Overview

• Status: Completed
• Conditions: Qt Interval, Variation in
• Intervention / Treatment: Drug: NPC-15 and/or Placebo

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 Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan, 8120025
    • Souseikai Hakata Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: study drug; 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; 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); Other Names: Melatonin and/or Placebo

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Nobelpharma
• Investigators: Principal Investigator: Masaharu Hayashi, MD, PhD, Shukutoku University

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2018
• Primary Completion (Actual): April 29, 2018
• Study Completion (Actual): April 29, 2018

Study Registration Dates

• First Submitted: February 22, 2018
• First Submitted That Met QC Criteria: March 16, 2018
• First Posted (Actual): March 23, 2018

Study Record Updates

• Last Update Posted (Actual): June 28, 2018
• Last Update Submitted That Met QC Criteria: June 26, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: QTc prolongation effect
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Protective Agents; Antioxidants; Melatonin
• Other Study ID Numbers: NPC-15-7

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No