NCT02432664 - Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Effects of ODM-108: in Healthy Male Volunteers | Crick

Eligibility

Sex: MALEMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

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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).

Outcomes

Primary Outcomes

Number of participants with adverse events in Part I and Part II.

Clinically relevant changes from baseline of safety assessment

Time frame: From screening up to 8 weeks

Secondary Outcomes

Part III (optional) Effect of ODM-108 on the activity of CYP3A4 (cytochrome P450 3A4) isoenzymes

Measurement of biomarkers

Time frame: Day 1 up to Day 11

Part I Peak plasma concentration Cmax of ODM-108

Cmax of ODM-108 after single dosing

Time frame: Pre dose,15, 30, 45 mins, 1 h, 1 h 15, 1 h 30, 2 h, 2 h 30, 3 h, 4 h, 6 h, 8 h, 12h, 24 h, 48 h, 72 h, 96 h post dose at each dose level.

Part I Metabolite screening in plasma and urine

Metabolite screening in plasma and urine after single dosing

Time frame: Pre-dose and 30 min, 1 h, 2 h, 4 h, 6 h, 12 h, 24 h and 48 h post dose at each dose level. Urine samples pre-dose and for 24 hours post dose at each dose level.

Part I Sedation scores on Visual Analogue Scales

Assessment of sedation by subject

Time frame: Pre-dose, 2 h 30 min and 10 h post dose at each dose level

Part I Cognitive function - Digital Symbol Substitution Test

Assessment of cognitive function

Time frame: Pre-dose, 2 h 30 min and 10 h post dose at each dose level

Part I Intensity of spontaneous pain

Intensity of spontaneous pain as assessed by a visual analogue scale

Time frame: Screening and day 1 at 1, 5, 15, 30, 60 and 120 min after capsaicin injection.

Part I Area of hyperalgesia

Area of hyperalgesia quantified by a Von Frey monofilament

Time frame: Screening and day 1 at 15, 30, 60 and 120 min after capsaicin injection.

Part I area of flare response

Area of flare response measured by Doppler blood flow scan

Time frame: Screening and day 1 at baseline and 15, 30, 60 and 120 min after capsaicin injection.

Part II Peak plasma concentration Cmax of ODM-108

Cmax of ODM-108 after multiple dosing

Time frame: Days 1 and 7: Pre-dose and 0.25, 0.5, 0.75,1,1.25,1.5, 2, 2.5, 3,4,6,8,12h post dose. Day 2-6 pre-dose, Day 7: 24, 48, 72 and 96h post dose

Part II Peak plasma concentration Cmax of ODM-108 fed day 5 period 1

Cmax of ODM-108 after multiple dosing

Time frame: Days 1,5 and 7: Pre-dose and 0.25, 0.5, 0.75,1,1.25,1.5, 2, 2.5, 3,4,6,8,12h post dose. Day 2-6 pre-dose, Day 7: 24, 48, 72 and 96h post dose

Part II Time to peak plasma concentration (tmax) of ODM-108

tmax of ODM-108 after multiple dosing

Time frame: Days 1 and 7: Pre-dose and 0.25, 0.5, 0.75,1,1.25,1.5, 2, 2.5, 3,4,6,8,12h post dose. Day 2-6 pre-dose, Day 7: 24, 48, 72 and 96h post dose

Part II Time to peak plasma concentration (tmax) of ODM-108 fed day 5 period 1

tmax of ODM-108 after multiple dosing

Time frame: Days 1,5 and 7: Pre-dose and 0.25, 0.5, 0.75,1,1.25,1.5, 2, 2.5, 3,4,6,8,12h post dose. Day 2-6 pre-dose, Day 7: 24, 48, 72 and 96h post dose

Part II Area under the plasma concentration versus time curve (AUC) of ODM-108.

AUC of ODM-108 after multiple dosing

Time frame: Days 1 and 7: Pre-dose and 0.25, 0.5, 0.75,1,1.25,1.5, 2, 2.5, 3,4,6,8,12h post dose. Day 2-6 pre-dose, Day 7: 24, 48, 72 and 96h post dose

Part II Area under the plasma concentration versus time curve (AUC) of ODM-108 fed day 5 period 1

AUC of ODM-108 after multiple dosing

Time frame: Days 1,5 and 7: Pre-dose and 0.25, 0.5, 0.75,1,1.25,1.5, 2, 2.5, 3,4,6,8,12h post dose. Day 2-6 pre-dose, Day 7: 24, 48, 72 and 96h post dose

Part II Elimination half-life of ODM-108

Elimination half-life of ODM-108 after multiple dosing

Time frame: Days 1 and 7: Pre-dose and 0.25, 0.5, 0.75,1,1.25,1.5, 2, 2.5, 3,4,6,8,12h post dose. Day 2-6 pre-dose, Day 7: 24, 48, 72 and 96h post dose

Part II Elimination half-life of ODM-108- fed day 5 period 1

Elimination half-life of ODM-108 after multiple dosing

Time frame: Days 1,5 and 7: Pre-dose and 0.25, 0.5, 0.75,1,1.25,1.5, 2, 2.5, 3,4,6,8,12h post dose. Day 2-6 pre-dose, Day 7: 24, 48, 72 and 96h post dose

Part II Binding of ODM-108 to proteins in plasma

Assessment of binding of ODM-108 to proteins in plasma

Time frame: Days 1 and 7 -1 h 30 min post dose

Part II Metabolite screening in plasma and urine

Metabolite screening in plasma and urine

Time frame: Day 1 and 7 pre-dose and 30 min, 1 h, 2 h, 4 h, 6 h, 12 h, 24 h and 48 h post dose. Urine samples pre-dose and for 24 hours post dose at each dose level on days 1 and 7.

Part II Sedation scores on Visual Analogue Scales

Assessment of sedation by subject

Time frame: Day 1 and day 6 pre-dose, 2 h 30 min, and 10 h post dose

Part II Computerised psychomotor test battery measuring: attention, concentration, vigilance, memory, visual motor coordination and body sway.

Assessment of psychomotor function

Time frame: Days 1 and 6: pre-dose, approx. 2 h 30 min and 10 h after first daily ODM-108 dose

Part II Intensity of spontaneous pain

Assessed by numerical rating scale

Time frame: Screening and day 5 at 1, 5, 15, 30, 60 and 120 min after capsaicin injection.

Part II Area of hyperalgesia

Area of hyperalgesia quantified by a Von Frey monofilament

Time frame: Screening and day 5 at 5, 15, 30, 60 and 120 min after capsaicin injection.

Part II Cutaneous blood flow and area of flare response

Pain assessments

Time frame: Screening and day 5 pre -dose and 5, 15, 30, 60 and 120 min after capsaicin injection.

Part II Intensity of spontaneous pain

Intensity of spontaneous pain as assessed by a visual analogue scale

Time frame: Screening and day 7 at 1, 5, 15, 30, 60 and 120 min after mustard oil challenge.

Part II Area of hyperalgesia

Area of hyperalgesia quantified by a Von Frey monofilament

Time frame: Screening and day 7 at 5, 15, 30, 60 and 120 min after mustard oil challenge.

Part II Area of flare response

Area of flare response measured by Doppler blood flow scan

Time frame: Screening and day 7 baseline and 5, 15, 30, 60 and 120 min after mustard oil challenge.

Part III (optional) Peak plasma concentration Cmax of midazolam

Cmax of midazolam

Time frame: day 1 and day 10 or 13

Part III (optional) Time to peak plasma concentration (tmax) of midazolam

tmax of midazolam

Time frame: day 1 and day 10 or 13

Part III (optional) Area under the plasma concentration versus time curve (AUC) of midazolam.

AUC of midazolam

Time frame: day 1 and day 10 or 13 (

Part III (optional) ODM-108 levels in cerebrospinal fluid

Assessment of levels of ODM 108 in cerebrospinal fluid

Time frame: day 9

Part I Time to peak plasma concentration (tmax) of ODM-108

tmax of ODM-108 after single dosing

Time frame: Pre dose,15, 30, 45 mins, 1 h, 1 h 15,1 h 30, 2 h, 2 h 30, 3 h, 4 h, 6 h, 8 h, 12h, 24 h, 48 h, 72 h, 96 h post dose at each dose level.

Part I Area under the plasma concentration versus time curve (AUC) of ODM-108.

AUC of ODM-108 after single dosing

Time frame: Pre dose,15, 30, 45 mins, 1 h, 1 h 15,1 h 30, 2 h, 2 h 30, 3 h, 4 h, 6 h, 8 h, 12h, 24 h, 48 h, 72 h, 96 h post dose at each dose level.

Part I Elimination half-life of ODM-108

Elimination half-life of ODM-108 after single dosing

Time frame: Pre dose,15, 30, 45 mins, 1 h, 1 h 15,1 h 30, 2 h, 2 h 30, 3 h, 4 h, 6 h, 8 h, 12h, 24 h, 48 h, 72 h, 96 h post dose at each dose level.

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes