Qt Interval, Variation in
Conditions
Keywords
QTc prolongation effect
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.
Interventions
DRUGNPC-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)
Sponsors
Nobelpharma
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
This study is a single-arm, open label, dose escalation study. QT interval will be evaluated by blinding outcome assessor in this study.
Eligibility
Sex/Gender
ALL
Age
20 Years to 45 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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 |
| 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. |
Countries
Japan
Outcome results
None listed