Early Phase I Microdosing Study of ORM-14540 and ORM-12741

Pharmacokinetic Properties of ORM-14540 and ORM-12741 After Administration of a Microdose of 14C-labelled Drug; An Open, Non-randomised, Single Dose, Single Centre Study in Healthy Male Subjects

The purpose of this study is to determine pharmacokinetic parameters of ORM-12741 and ORM-14540 in healthy volunteers.

Inclusion Criteria:

• Written informed consent (IC) obtained.
• Good general health ascertained by detailed medical history and physical examinations.
• Males between 18 and 45 years (inclusive).
• Body Mass Index (BMI) between 18-30 kg/m2 (inclusive, BMI = weight/height2).
• Weight 55-100 kg (inclusive).

Exclusion Criteria:

• A predictable poor compliance or inability to communicate well with the investigator or study centre personnel.
• Veins unsuitable for repeated venipuncture
• Evidence of clinically significant cardiovascular, renal, hepatic, haematological, gastrointestinal, pulmonary, metabolic-endocrine, neurological, urogenital or psychiatric diseases as judged by the investigator.
• Any condition requiring regular concomitant medication including herbal products or likely to need any concomitant treatment during the study.
• Susceptibility to severe allergic reactions.
• Intake of any medication that could affect the outcome of the study, within 2 weeks prior to the first study treatment or less than 5 times a half-life of the medication. Possible enzyme inducing drugs will be discussed case-by-case with the sponsor.
• Regular consumption of more than 21 units of alcohol per week (1 unit = 4 cl spirits, about 13 g of alcohol).
• Current use of nicotine-containing products more than 5 cigarettes or equivalent/day.
• Inability to refrain from using nicotine-containing products during the stay at the study centre.
• Inability to refrain from consuming caffeine-containing beverages during the stay in the study centre, e.g. propensity in getting headache when refraining from caffeine-containing beverages.
• Blood donation or loss of significant amount of blood within 2 months prior to the screening visit.
• Abnormal 12-lead electrocardiogram (ECG) finding of clinical relevance in supine position after resting for 10 minutes at the screening visit, for example:- QTc (calculated through the Bazett's formula) > 450msec,- PR < 120 msec or > 210 msec,- QRS < 70 msec or > 120 msec.
• Heart rate (HR) < 45 beats/minute or > 100 beats/minute in supine position after resting for 10 minutes at the screening visit.
• At the screening visit, systolic blood pressure (BP) < 90 mmHg or > 140 mmHg in supine position after resting for 10 minutes, diastolic BP < 50 mmHg or > 90 mmHg in supine position after resting for 10 minutes.
• Any abnormal value of laboratory, vital signs, or physical examination, which may in the opinion of the investigator interfere with the interpretation of the test results or cause a health risk for the subject if he takes part into the study.
• History of drug abuse or positive result in drug abuse test.
• Positive serology to human immunodeficiency virus antigen/antibodies (HIVAgAb), hepatitis C virus antibodies (HCVAb) or hepatitis B surface antigen (HBsAg).
• Any other condition that in the opinion of the investigator would interfere with the evaluation of the results or constitute a health risk for the subject.
• Participation in a clinical drug study within 3 months prior to the screening visit in this study, or earlier participation in a clinical study with ORM-12741.
• Exposure to 14C-labelled drugs or diagnostics within 12 months prior to the screening visit.
• Men who are not practising clinically accepted method of contraception during the study and next 3 months after the study treatment administration.