Safety, Tolerability,Pharmacokinetics and Pharmacodynamics of ODM-106 in Healthy Volunteers

Study Overview
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Brief Summary
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The study is a dose escalation study with 8 planned dose levels. The study is a 4-period crossover design where each healthy volunteer will be randomised to receive three dose levels of ODM-106 (single doses) and one dose of placebo. The study will look at the pharmacokinetics (how the body handles the drug) and pharmacodynamics (how the drug affects the body) of ODM-106.

Detailed Description
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Eight planned dose levels of ODM-106 will be compared with placebo.There will be 2 panels of subjects with 4 dose levels in each panel. Subjects will be randomised to receive 3 dose levels of active treatment (single doses) and 1 dose of placebo. The dose levels will be escalated from the smallest dose upwards within the study and within the study subject. A third panel of 8 subjects may be included to investigate further dose levels of ODM-106, investigate the effect of taking ODM-106 with food or to compare two different formulations of ODM-106. For an individual subject, the study will consist of a screening period (maximum 4 weeks), 4 study treatment periods with a wash-out period between each study treatment administration and a post-treatment period of about 2 weeks. The study duration for an individual will be approximately 12-16 weeks. Blood samples will be collected for the assessment of the concentration of ODM-106 and its metabolite.Plasma samples and cumulative urinary samples will be collected for metabolite screening. Safety will be assessed by a 12-lead electrocardiogram (ECG), continuous ECG monitoring, Holter ECG, supine and orthostatic blood pressure and heart rate, body temperature, physical examination, electroencephalogram (EEG), laboratory safety assessments and adverse events. Sedation and psychomotor tests and a quantitative EEG will also be performed.

Official Title
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Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Effects of Single Escalating Doses of ODM-106: A Randomised, Double-blind, Placebo-controlled Single Centre Study in Healthy Males

Conditions
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Healthy Volunteer Study

Intervention / Treatment
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* Drug: ODM-106
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent obtained. Participants must be able to speak, read and understand German. Good general health ascertained by detailed medical history and physical examinations. Males 18-45 years (inclusive). Body mass index (BMI) 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 from first study treatment administration until 3 months after the end-of-study visit. Exclusion Criteria: A predictable poor compliance or inability to understand and comply with protocol requirements, instructions and protocol-stated restrictions or communicate well with the investigator. Vulnerable subjects. Veins unsuitable for repeated venipuncture. Evidence of clinically relevant cardiovascular, renal, hepatic, haematological, gastro-intestinal, pulmonary, metabolic-endocrine, neurological, urogenital or psychiatric disease as judged by the investigator. The participants should be healthy subjects. Subjects with a medical history of relevant psychiatric disorders or evidence of significant neuropsychiatric disease Any condition requiring regular concomitant medication including herbal products or likely to need any concomitant medication during the study. Definite or suspected personal history of hypersensitivity to drugs or excipients. Intake of any medication that could affect the outcome of the study, as judged by the investigator, within 2 weeks before first study treatment administration (2 months for enzyme inducing drugs like rifampicin or carbamazepin), or less than 5 times the half-life of the medication. A history of alcoholism or excess alcohol intake (including regular consumption of more than 21 units of alcohol per week) . Use of nicotine-containing products within 6 months of admission and inability to refrain from using nicotine-containing products during the study. History of drug abuse or positive drug screen for amphetamine, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates, methamphetamine or methadone. Propensity to get headache when refraining from caffeine-containing beverages. Blood donation or loss of clinically relevant amount of blood within 2 months before the screening visit. Abnormal 12-lead ECG finding of clinical relevance at the screening visit Heart rate (HR) < 50 bpm or > 90 bpm after 10 min in rest (supine) at the screening visit At the screening visit: systolic BP < 90 mmHg or > 140 mmHg, diastolic BP < 50 mmHg or > 90 mmHg, orthostatic hypotension decrease of greater than or equal to 20 mmHg for systolic BP, decrease of greater than or equal to 10 mmHg for diastolic BP. Abnormal 24-h Holter of clinical relevance at the screening visit, Positive serology to human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies. 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 in the study. Participation in an investigational drug study within 2 months before entry into this study. An employee, a direct or indirect relative of the employee of the contract research organisation or the 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. Subject with abnormal standard EEG judged as clinically relevant by the investigator at screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug: ODM-106<br>Oral capsules dosage 2-800mg once daily for one day | Drug: ODM-106<br>* Single oral escalating doses of ODM-106 will be administered. Each subject will participate in 4 study periods and will therefore receive 3 single doses of ODM-106 and one single dose of placebo.<br>|
| Placebo Comparator: Drug: Placebo<br>Oral capsules given once daily for one day | Drug: Placebo<br>* Single oral escalating doses of ODM-106 will be administered. Each subject will participate in 4 study periods and will therefore receive 3 single doses of ODM-106 and one single dose of placebo.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events as a Measure of Safety. Number of Participants With Adverse Events Related to Tolerability. | Clinically relevant changes from baseline in safety laboratory assessments (haematology, clinical chemistry, urinalysis), vital signs (pulse and heart rate), 12 lead electrocardiograms, Holter electrocardiograms, telemetry, physical examination. | From screening up to 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Plasma Concentration (cMax) of ODM-106 | cMax of ODM-106 after single dosing of either Capsule B or Capsule A | Pre-dose and 15, 30 and 45 min, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 48, 72 and 96 hours post dose at each dose level. | 
| Area Under the Plasma Concentration Versus Time Curve (AUC) of ODM-106 | AUC of ODM-106 after single oral dosing of either Capsule B or Capsule A. | Pre-dose and 15, 30 and 45 min, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 48, 72 and 96 hours post dose at each dose level. Urine sampling, pre-dose and for 24 hours post dose at each dose level | 
| Time to Peak Plasma Concentration (Tmax) of ODM-106 | tmax of ODM-106 after single oral dosing of Capsule B or Capsule A | Pre-dose and 15, 30 and 45 min, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 48, 72 and 96 hours post dose at each dose level | 
| Elimination Half-life of ODM-106 | Elimination half-life of ODM-106 after single dosing of either Capsule B or Capsule A | Pre-dose and 15, 30 and 45 min, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 48, 72 and 96 hours post dose at each dose level. | 
| Metabolite Screening in Plasma and Urine | Metabolite screening in plasma and urine after single dosing | Plasma samples at pre-dose and 15, 30 and 45 min, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 48, 72 and 96 hours post dose at each dose level. Urine samples, pre-dose and for 24 hours post dose at each dose level | 
| Effect of ODM-106 on Growth Hormone Levels | Growth hormone levels (Cmax) in serum after single oral dosing with either ODM-106 Capsule B, ODM-106 Capsule A or placebo. | Predose and 1, 2, 3,4, 6 and 8 hours post dose at each dose level. | 
| Sedation Scores on a Visual Analogue Scale (VAS) | Assessment of sedation by subject | Pre-dose and at 1, 6 and 10.5h post dose at each dose level | 
| Dexterity and Reaction Times | Selected battery of psychomotor tests | Pre-dose and at 1 and 6h post dose at each dose level | 
| Quantitative EEG | Quantitative analysis of EEG | Pre-dose and at 1, 6 and 10 h post dose at each dose level |