Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Effects of ODM-108: in Healthy Male Volunteers

Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Effects of Single and Multiple Escalating Doses of ODM-108: A Single Centre Study in Healthy Male Volunteers

The purpose of the study is to investigate to what extent this new study drug is tolerated in humans.

The study is divided into 3 parts (Part III is optional and may go ahead depending on the results of Parts I and II). The volunteers will only be enrolled to one part of the study. In parts I and II the volunteer will receive active study drug or placebo. In part I the volunteers will receive a single dose of one of the eight planned escalating dose levels.

In part II volunteers will receive 4 planned dose levels based on the results obtained in Part 1 of the study, with the option to include an additional dosing group.

In optional part III the volunteer will receive ODM-108 and an already registered drug so that interactions with other drugs can be studied.

It will be investigated how quickly and to what extent the study drug is absorbed and eliminated from the body (this is called pharmacokinetics). In addition, in parts I and II the effect of the compound on the sensation of pain and on cognition (activities of thinking, understanding, learning, and remembering) will be investigated (this is called pharmacodynamics).

This is the first time that this compound is being given to humans.

The study will only take place after it has been approved by the Independent Ethics Committee.

Inclusion Criteria applicable to Parts I - III:

• Written informed consent.
• Good general health
• Males between 18 and 55 years (inclusive).
• Body mass index (BMI) between 18-30 kg/m2 inclusive
• Weight 55-95 kg (inclusive).
• Participants with female partners of child-bearing potential must adhere to a proper form of contraception.
• Subjects with light coloured skin.

Exclusion Criteria:

• A predictable poor compliance or inability to understand and comply with the protocol , instructions and protocol restrictions or communicate well with the investigator.
• Vulnerable subjects.
• Veins unsuitable for repeated venipuncture.
• Evidence of clinically relevant cardiovascular, renal, hepatic, haematological, gastrointestinal, pulmonary, metabolic-endocrine, neurological, urogenital or psychiatric disease as judged by the investigator.
• Medical history of relevant psychiatric disorders or evidence of clinically relevant neuropsychiatric disease.
• Suicidal ideation in the 6 months before screening or current risk of suicide based on the investigators judgement.
• History of hypersensitivity to drugs or excipients.
• Any condition requiring regular concomitant medication.
• Intake of any medication that could affect the outcome of the study.
• History of Alcoholism.
• Inability to refrain from using nicotine-containing products for 48 h before and during the stay in the study centre.
• History of drug abuse or positive drug screen.
• Blood donation or loss of a clinically relevant amount of blood within 2 months before the screening visit.
• Abnormal 12-lead ECG
• Heart rate < 40 bpm or > 100 bpm at screening.
• Systolic BP < 90 mmHg or > 140 mmHg, diastolic BP< 45 mmHg or > 90 mmHg, orthostatic hypotension - decrease of more than or equal to 20 mmHg for systolic BP, decrease of more than or equal to 10 mmHg for diastolic BP at screening.
• Abnormal 24-h Holter of clinical relevance at screening.
• Positive serology for HIV antibodies (HIVAb), hepatitis B surface antigen (HBsAg) or hepatitis C virus antibodies (HCVAb).
• Thrombocytes and neutrophils count is < the lower limit of normal range.
• alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and total bilirubin > upper limit of normal (ULN).
• 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.
• Participation in an investigational drug study within 2 months before entry into this study.
• An employee or direct relative of the employee of the CRO or sponsor.
• 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.

Additional exclusion criteria for Part I and II:

• An abnormal screening EEG.
• A history of skin conditions or bad reactions after exposure to capsaicin or mustard oil.
• Following intradermal injection of capsaicin (100 μg) at screening visit, the area of hyperalgesia was < 10 cm2, or if the area of flare < 10 cm2 at 15 min.

Additional exclusion criterion for Part II:

• Use of nicotine-containing products within the previous 3 months.

The following additional exclusion criterion will be checked in Part I and II:

• Inability to complete either Digital Symbol Substitution Test (DSST) (for Part I) or psychomotor test battery (for Part II).