Healthy Volunteer Study
Conditions
Brief summary
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
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.
Interventions
DRUGODM-106
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.
DRUGPlacebo
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.
Sponsors
Orion Corporation, Orion Pharma
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events as a Measure of Safety. Number of Participants With Adverse Events Related to Tolerability. | From screening up to 16 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration Versus Time Curve (AUC) of ODM-106 | 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 | AUC of ODM-106 after single oral dosing of either Capsule B or Capsule A. |
| Time to Peak Plasma Concentration (Tmax) of ODM-106 | 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 | tmax of ODM-106 after single oral dosing of Capsule B or Capsule A |
| Elimination Half-life of ODM-106 | 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 after single dosing of either Capsule B or Capsule A |
| Metabolite Screening in Plasma and Urine | 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 | Metabolite screening in plasma and urine after single dosing |
| Peak Plasma Concentration (cMax) of ODM-106 | 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. | cMax of ODM-106 after single dosing of either Capsule B or Capsule A |
| Sedation Scores on a Visual Analogue Scale (VAS) | Pre-dose and at 1, 6 and 10.5h post dose at each dose level | Assessment of sedation by subject |
| Dexterity and Reaction Times | Pre-dose and at 1 and 6h post dose at each dose level | Selected battery of psychomotor tests |
| Quantitative EEG | Pre-dose and at 1, 6 and 10 h post dose at each dose level | Quantitative analysis of EEG |
| Effect of ODM-106 on Growth Hormone Levels | Predose and 1, 2, 3,4, 6 and 8 hours post dose at each dose level. | Growth hormone levels (Cmax) in serum after single oral dosing with either ODM-106 Capsule B, ODM-106 Capsule A or placebo. |
Countries
Germany
Participant flow
Recruitment details
Healthy male volunteers were recruited
Pre-assignment details
Screening : Male subjects were screened and following PE, vital signs, EEG, ECG and lab. assessments were randomised into the study. Sixteen subjects were randomised to 2 panels of 8, each subject received 3 single doses of ODM-106 and 1 dose of placebo in a randomised crossover design. Panel 1 was completed before Panel 2 commenced dosing.
Participants by arm
| Arm | Count |
|---|---|
| Panel 1 Single oral doses ODM-106 Capsule B 2, 10, 25, 50mg, placebo | 9 |
| Panel 2 Single oral doses ODM-106 Capsule B 100, 100, 200 mg. ODM-106 Capsule A 100mg, placebo | 9 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Panel 1 | Panel 2 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 9 Participants | 18 Participants |
| Gender Female | 0 Participants | 0 Participants | 0 Participants |
| Gender Male | 9 Participants | 9 Participants | 18 Participants |
| Region of Enrollment Germany | 9 participants | 9 participants | 18 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 6 | 4 / 6 | 5 / 6 | 1 / 6 | 2 / 6 | 1 / 6 | 3 / 6 | 2 / 6 | 3 / 16 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 16 |
Outcome results
Primary
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.
Time frame: From screening up to 16 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ODM-106 Capsule B 2mg | Number of Participants With Adverse Events as a Measure of Safety. Number of Participants With Adverse Events Related to Tolerability. | 0 subjects affected |
| ODM-106 Capsule B 10mg | Number of Participants With Adverse Events as a Measure of Safety. Number of Participants With Adverse Events Related to Tolerability. | 4 subjects affected |
| ODM-106 Capsule B 25mg | Number of Participants With Adverse Events as a Measure of Safety. Number of Participants With Adverse Events Related to Tolerability. | 5 subjects affected |
| ODM-106 Capsule B 50mg | Number of Participants With Adverse Events as a Measure of Safety. Number of Participants With Adverse Events Related to Tolerability. | 1 subjects affected |
| ODM-106 Capsule B 100mg (1 x 100mg) | Number of Participants With Adverse Events as a Measure of Safety. Number of Participants With Adverse Events Related to Tolerability. | 2 subjects affected |
| ODM-106 Capsule B 100mg (10 x 10mg) | Number of Participants With Adverse Events as a Measure of Safety. Number of Participants With Adverse Events Related to Tolerability. | 1 subjects affected |
| ODM-106 Capsule B 200mg | Number of Participants With Adverse Events as a Measure of Safety. Number of Participants With Adverse Events Related to Tolerability. | 3 subjects affected |
| ODM-106 Capsule A 100mg | Number of Participants With Adverse Events as a Measure of Safety. Number of Participants With Adverse Events Related to Tolerability. | 2 subjects affected |
| Placebo | Number of Participants With Adverse Events as a Measure of Safety. Number of Participants With Adverse Events Related to Tolerability. | 3 subjects affected |
Secondary
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.
Time frame: 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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ODM-106 Capsule B 2mg | Area Under the Plasma Concentration Versus Time Curve (AUC) of ODM-106 | 16.9 h*ng/ml | Standard Deviation 8.8 |
| ODM-106 Capsule B 10mg | Area Under the Plasma Concentration Versus Time Curve (AUC) of ODM-106 | 61.3 h*ng/ml | Standard Deviation 44.1 |
| ODM-106 Capsule B 25mg | Area Under the Plasma Concentration Versus Time Curve (AUC) of ODM-106 | 213.8 h*ng/ml | Standard Deviation 78.7 |
| ODM-106 Capsule B 50mg | Area Under the Plasma Concentration Versus Time Curve (AUC) of ODM-106 | 559.4 h*ng/ml | Standard Deviation 310.9 |
| ODM-106 Capsule B 100mg (1 x 100mg) | Area Under the Plasma Concentration Versus Time Curve (AUC) of ODM-106 | 297.4 h*ng/ml | Standard Deviation 346.3 |
| ODM-106 Capsule B 100mg (10 x 10mg) | Area Under the Plasma Concentration Versus Time Curve (AUC) of ODM-106 | 1089.2 h*ng/ml | Standard Deviation 977 |
| ODM-106 Capsule B 200mg | Area Under the Plasma Concentration Versus Time Curve (AUC) of ODM-106 | 2850.8 h*ng/ml | Standard Deviation 2319.8 |
| ODM-106 Capsule A 100mg | Area Under the Plasma Concentration Versus Time Curve (AUC) of ODM-106 | 82.0 h*ng/ml | Standard Deviation 64.7 |
Secondary
Dexterity and Reaction Times
Selected battery of psychomotor tests
Time frame: Pre-dose and at 1 and 6h post dose at each dose level
Secondary
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.
Time frame: Predose and 1, 2, 3,4, 6 and 8 hours post dose at each dose level.
Population: Only timepoints 2 - 6h evaluated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| ODM-106 Capsule B 2mg | Effect of ODM-106 on Growth Hormone Levels | 1.7 ng/ml | Standard Deviation 3.2 |
| ODM-106 Capsule B 10mg | Effect of ODM-106 on Growth Hormone Levels | 0.47 ng/ml | Standard Deviation 1.04 |
| ODM-106 Capsule B 25mg | Effect of ODM-106 on Growth Hormone Levels | 1.05 ng/ml | Standard Deviation 2.88 |
| ODM-106 Capsule B 50mg | Effect of ODM-106 on Growth Hormone Levels | 1.93 ng/ml | Standard Deviation 1.99 |
| ODM-106 Capsule B 100mg (1 x 100mg) | Effect of ODM-106 on Growth Hormone Levels | 0.8 ng/ml | Standard Deviation 1.36 |
| ODM-106 Capsule B 100mg (10 x 10mg) | Effect of ODM-106 on Growth Hormone Levels | 2.23 ng/ml | Standard Deviation 6.12 |
| ODM-106 Capsule B 200mg | Effect of ODM-106 on Growth Hormone Levels | 0.82 ng/ml | Standard Deviation 0.68 |
| ODM-106 Capsule A 100mg | Effect of ODM-106 on Growth Hormone Levels | 4.14 ng/ml | Standard Deviation 4.96 |
| Placebo | Effect of ODM-106 on Growth Hormone Levels | 1.01 ng/ml | Standard Deviation 2.45 |
Secondary
Elimination Half-life of ODM-106
Elimination half-life of ODM-106 after single dosing of either Capsule B or Capsule A
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ODM-106 Capsule B 2mg | Elimination Half-life of ODM-106 | 9.5 h | Standard Deviation 5.5 |
| ODM-106 Capsule B 10mg | Elimination Half-life of ODM-106 | 20.6 h | Standard Deviation 12.7 |
| ODM-106 Capsule B 25mg | Elimination Half-life of ODM-106 | 23.0 h | Standard Deviation 2.1 |
| ODM-106 Capsule B 50mg | Elimination Half-life of ODM-106 | 27.3 h | Standard Deviation 4.7 |
| ODM-106 Capsule B 100mg (1 x 100mg) | Elimination Half-life of ODM-106 | 23.5 h | Standard Deviation 6.3 |
| ODM-106 Capsule B 100mg (10 x 10mg) | Elimination Half-life of ODM-106 | 27.4 h | Standard Deviation 9.2 |
| ODM-106 Capsule B 200mg | Elimination Half-life of ODM-106 | 32.1 h | Standard Deviation 10 |
| ODM-106 Capsule A 100mg | Elimination Half-life of ODM-106 | 21.7 h | Standard Deviation 3.2 |
Secondary
Metabolite Screening in Plasma and Urine
Metabolite screening in plasma and urine after single dosing
Time frame: 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
Secondary
Peak Plasma Concentration (cMax) of ODM-106
cMax of ODM-106 after single dosing of either Capsule B or Capsule A
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ODM-106 Capsule B 2mg | Peak Plasma Concentration (cMax) of ODM-106 | 9.1 ng/ml | Standard Deviation 4.2 |
| ODM-106 Capsule B 10mg | Peak Plasma Concentration (cMax) of ODM-106 | 18.4 ng/ml | Standard Deviation 11.4 |
| ODM-106 Capsule B 25mg | Peak Plasma Concentration (cMax) of ODM-106 | 67.8 ng/ml | Standard Deviation 51.7 |
| ODM-106 Capsule B 50mg | Peak Plasma Concentration (cMax) of ODM-106 | 119.2 ng/ml | Standard Deviation 60.1 |
| ODM-106 Capsule B 100mg (1 x 100mg) | Peak Plasma Concentration (cMax) of ODM-106 | 22.0 ng/ml | Standard Deviation 20.1 |
| ODM-106 Capsule B 100mg (10 x 10mg) | Peak Plasma Concentration (cMax) of ODM-106 | 225.9 ng/ml | Standard Deviation 177.2 |
| ODM-106 Capsule B 200mg | Peak Plasma Concentration (cMax) of ODM-106 | 547.7 ng/ml | Standard Deviation 319.5 |
| ODM-106 Capsule A 100mg | Peak Plasma Concentration (cMax) of ODM-106 | 8.3 ng/ml | Standard Deviation 9.1 |
Secondary
Quantitative EEG
Quantitative analysis of EEG
Time frame: Pre-dose and at 1, 6 and 10 h post dose at each dose level
Secondary
Sedation Scores on a Visual Analogue Scale (VAS)
Assessment of sedation by subject
Time frame: Pre-dose and at 1, 6 and 10.5h post dose at each dose level
Secondary
Time to Peak Plasma Concentration (Tmax) of ODM-106
tmax of ODM-106 after single oral dosing of Capsule B or Capsule A
Time frame: 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
| Arm | Measure | Value (MEAN) |
|---|---|---|
| ODM-106 Capsule B 2mg | Time to Peak Plasma Concentration (Tmax) of ODM-106 | 0.7 h |
| ODM-106 Capsule B 10mg | Time to Peak Plasma Concentration (Tmax) of ODM-106 | 1.9 h |
| ODM-106 Capsule B 25mg | Time to Peak Plasma Concentration (Tmax) of ODM-106 | 1.5 h |
| ODM-106 Capsule B 50mg | Time to Peak Plasma Concentration (Tmax) of ODM-106 | 2.1 h |
| ODM-106 Capsule B 100mg (1 x 100mg) | Time to Peak Plasma Concentration (Tmax) of ODM-106 | 5.8 h |
| ODM-106 Capsule B 100mg (10 x 10mg) | Time to Peak Plasma Concentration (Tmax) of ODM-106 | 1.5 h |
| ODM-106 Capsule B 200mg | Time to Peak Plasma Concentration (Tmax) of ODM-106 | 1.5 h |
| ODM-106 Capsule A 100mg | Time to Peak Plasma Concentration (Tmax) of ODM-106 | 3.0 h |