A single dose, randomized, four-way cross-over, bioavailability and food interaction study of PedPRM (Pediatric Prolonged Release Melatonin, Neurim Pharmaceuticals Ltd) and Circadin® tablets in healthy male and female volunteers.

Completed

Conditions: Insomnia
sleeping disorder
10040991

Registration Number: NL-OMON44644

Lead Sponsor: eurim Pharmaceuticals Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 24

Inclusion Criteria

1. Signed informed consent prior to any study-mandated procedure.
2. Healthy male or female subjects, 18 to 55 years of age, inclusive at screening.
3. Body mass index (BMI) between 18 and 30 kg/m2, inclusive at screening.
4. All women of child bearing potential must practice effective contraception during the study and be willing and able to continue contraception for at least 90 days after the final administration of study treatment. All males must practice effective contraception and abstain from sperm donation during the study and be willing and able to continue contraception and abstention from sperm donation for at least 90 days after the final administration of study treatment.
5. Has the ability to communicate well with the investigator in the Dutch language and willing to comply with the study restrictions.

Exclusion Criteria

1. A history of gastrointestinal disorder likely to influence drug absorption
2. Evidence of renal, hepatic, cardiovascular or metabolic dysfunction or any active or chronic disease or condition that could interfere with, or for which the treatment of might interfere with, the conduct of the study, or that would pose an unacceptable risk to the subject in the opinion of the investigator (following a detailed medical history, physical examination, vital signs (systolic and diastolic blood pressure, pulse rate, body temperature) and12-lead electrocardiogram (ECG)). Minor deviations from the normal range may be accepted, if judged by the investigator to have no clinical relevance.
3. Clinically significant abnormalities, as judged by the investigator, in laboratory test results (including hepatic and renal panels, complete blood count, chemistry panel and urinalysis). In the case of uncertain or questionable results, tests performed during screening may be repeated before randomization to confirm eligibility or judged to be clinically irrelevant for healthy subjects.
4. Positive Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at screening.
5. Use of melatonin (Circadin®, food supplement, pharmacy preparation) within 4 weeks before first dose administration.
6. Use of any medications (prescription or over-the-counter [OTC]), within 14 days of dose administration, or less than 5 half-lives (whichever is longer). An exception is paracetamol (up to 2 g/day). Other exceptions will only be made if the rationale is clearly documented by the investigator.
7. Use of any vitamin, mineral, herbal, and dietary supplements within 7 days of dose administration, or less than 5 half-lives (whichever is longer). Exceptions will only be made if the rationale is clearly documented by the investigator
8. Current or previous clinically relevant neurological disorders or neurosurgery.
9. Current or previous clinically relevant history of psychiatric disorders or sleep-wake disorders.
10. Current or previous clinically relevant history of drug or alcohol abuse.
11. Current or previous clinically relevant history of chronic headache or migraine.
12. A history of drug or food allergies or other clinically significant allergies (e.g. asthma, hay fever, neurodermatitis).
13. A history of hypersensitivity and/or idiosyncrasy to any of the test compounds or excipients employed in this study.
14. Participation in an investigational drug or device study within 3 months prior to dose administration or more than 4 times a year.
15. Night-shift worker or subjects with a significantly shifted diurnal activity pattern.
16. Subjects who have traveled across 3 different time zones within 1 week prior to screening or baseline.
17. Following a diet, e.g. kosher, halal, vegetarian, vegan or medically prescribed diet.
18. Positive test for drugs of abuse or alcohol at screening or pre-dose.
19. Smoker of more than 5 cigarettes per day within one month prior to screening or who use tobacco products equivalent to more than 5 cigarettes per day.
20. Excessive consumption of xanthine-containing products (more than eight cups of coffee or equivalent per day).
21. Loss or donation of blood over 500 mL within three months prior to screening.
22. If a woman: pregnant, breast-feeding, or planning to become pregnant during the study. <b

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Safety and tolerability endpoints<br /><br>* Adverse events which will be summarized by treatment, and will be categorized<br /><br>in subsets of all treatment-emergent AEs, and of all treatment-related AEs.<br /><br>* Clinical laboratory and vital signs which will be summarized by treatment and<br /><br>change from baseline.<br /><br><br /><br>Pharmacokinetic Endpoints<br /><br>A 24-hour individual baseline profile of plasma and saliva melatonin<br /><br>concentrations will be measured. PK parameters of PedPRM or Circadin® will be<br /><br>calculated after endogenous level subtraction.<br /><br><br /><br>Primary endpoints are the following pharmacokinetic (PK) parameters:<br /><br>* AUC0-* PedPRM.<br /><br>* Cmax PedPRM.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary PK endpoints include:<br /><br>* AUC0-* Circadin® and Cmax Circadin®.<br /><br>* Other pharmacokinetic parameters derived from serum samples<br /><br>including AUC0-t, tmax, kel, t1/2, clearance (CL/F), and Vd/F.<br /><br>* Pharmacokinetic parameters derived from saliva samples (e.g. AUC0-<br /><br>*, AUC0-t, Cmax and tmax).</p><br>