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

Qt Interval, Variation in Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03475459
• Other study ID #: NPC-15-7
• Status: Completed
• Phase: Phase 1
• Start date: April 3, 2018
• Est. completion date: April 29, 2018

Study information

• Verified date: April 2018
• Source: Nobelpharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: April 29, 2018
• Est. primary completion date: April 29, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Qt Interval, Variation in

Intervention

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)

Locations

Country	Name	City	State
Japan	SOUSEIKAI Hakata Clinic	Fukuoka

Sponsors (1)

Lead Sponsor	Collaborator
Nobelpharma

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Terminal elimination rate constant (?z) 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)
Secondary	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)
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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