Clinical trial NCT03475459: Investigation of Arrhythmogenic Effect of NPC-15 (NPC-15-7)
Official title: A Clinical Pharmacology Study of NPC-15 to Evaluate Arrhythmogenic Effect in Healthy Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Qt Interval, Variation in
Keywords: QTc prolongation effect
Lead sponsor: Nobelpharma
Sponsor class: INDUSTRY
First posted: 2018-03-23
Enrollment: 12
Sex: ALL
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Time matched, baseline-adjusted change in Fridericia-corrected QTc (QTcF) intervals
timeFrame: Day1 and Day2 of each periods (3 periods)
Secondary outcomes:
measure: Serum melatonin concentration
timeFrame: Up to 12 hours post dose in each period (3 periods)
measure: Maximum drug concentration (Cmax) of melatonin
timeFrame: Up to 12 hours post dose in each period (3 periods)
measure: Maximum drug concentration time (Tmax) of melatonin
timeFrame: Up to 12 hours post dose in each period (3 periods)
measure: Area under the blood concentration time curve (AUC) of melatonin
timeFrame: Up to 12 hours postdose in each period (3 periods)
measure: Terminal elimination rate constant (λz) of melatonin
timeFrame: Up to 12 hours post dose in each period (3 periods)
measure: Mean residence time (MRT) of melatonin
timeFrame: Up to 12 hours postdose in each period (3 periods)
measure: Elimination half-life (t1/2) of melatonin
timeFrame: Up to 12 hours post dose in each period
measure: Clearance (CL) of melatonin
timeFrame: Up to 12 hours post dose in each period (3 periods)
measure: Volume of distribution (Vd) of melatonin
timeFrame: Up to 12 hours postdose in each period (3 periods)
measure: Adverse Events
timeFrame: Up to 36 hours post dose of Period III
Other outcomes:
Locations:
city: Fukuoka
country: Japan
facility: SOUSEIKAI Hakata Clinic
Study officials:
affiliation: Shukutoku University
name: Masaharu Hayashi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: