Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ODM-104 in Healthy Volunteers

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and tolerability of escalating doses of ODM-104 when given to healthy male volunteers.

Detailed Description
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The study is divided into two parts. Part one is a crossover study where healthy volunteers will receive two doses of ODM-104 and one dose of placebo. Part II of the study is a multiple ascending dose parallel group study where healthy volunteers will receive ODM-104 three times daily for seven days. Healthy volunteers taking part in Part II of the study will also receive levo/carbidopa and entacapone four times daily on day 1 and levo/carbidopa in addition to ODM-104 on day 9. The study will also look at the pharmacokinetic(how the body handles the drug) and pharmacodynamics (how the drug affects the body) of ODM-104.

Official Title
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Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Effects of Single and Repeated Escalating Doses of ODM-104: a Randomised, Double-blind, Placebo- and Entacapone-controlled Single Centre First-in-man Study in Healthy Volunteers.

Conditions
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Healthy

Intervention / Treatment
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* Drug: ODM-104
* Drug: Placebo
* Drug: Entacapone
* Drug: levodopa/carbidopa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male subjects aged between 18 and 45 years BMI 18-30 kg/m2 Weight 55-95kg Written informed consent Good General Health Exclusion Criteria: Vulnerable subjects Veins unsuitable for repeated venipuncture Evidence of clinically significant cardiovascular, renal, hepatic, hematological, Gi, pulmonary, metabolic-endocrine, neurological, urogenital or psychiatric disorder History of or positive test for drug abuse Any condition requiring regular concomitant medication Blood donation or significant loss of blood within 2 months prior to screening Abnormal 12 lead ECG finding of clinical relevance Heart rate (HR) <50bpm or >90bpm after 10 minutes in a supine position Systolic blood pressure <90mmHg or >140mmHg after 10 minutes in a supine position Diastolic blood pressure <50mmHg or >90mmHg after 10 minutes in a supine position Abnormal 24 hour Holter recording of clinical relevance at screening Any abnormal laboratory value, vital signs or physical examination causing a health risk to the volunteer

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

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ODM-104<br>Oral capsules dosage 10-800mg once daily for one day or three times daily for 7 days | Drug: ODM-104<br>* ODM-104<br>|
| Placebo Comparator: Placebo<br>Oral capsules given once daily for one day or three times daily for 7 days | Drug: Placebo<br>* Placebo<br>|
| Active Comparator: entacapone + levodopa/carbidopa<br>entacapone: oral tablet 200mg given four times daily for one day; levodopa/carbidopa: oral tablet 100/25mg given four times daily for one day | Drug: Entacapone<br>* entacapone + levodopa/carbidopa<br>Drug: levodopa/carbidopa<br>* entacapone + levodopa/carbidopa<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Erythrocyte Catechol-O-methyltransferase (COMT) inhibition. | Maximal COMT inhibition and area under the COMT inhibition curve (AUCC) | 0, 0.16, 0.33, 0.5, 0.75,1.0,1.5, 2, 3, 4, 6, 10, 16, 24h post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration curve (AUC) | AUC under the plasma concentration curve | 0, 0.16, 0.33, 0.5, 0.75, 1, 1.5, 2, 2, 4, 6, 10, 16, 24h post dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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First in man study, Volunteer study