Clinical trial NCT02393950: Safety, Tolerability,Pharmacokinetics and Pharmacodynamics of ODM-106 in Healthy Volunteers
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer Study
Lead sponsor: Orion Corporation, Orion Pharma
Sponsor class: INDUSTRY
First posted: 2015-03-20
Enrollment: 16
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Adverse Events as a Measure of Safety. Number of Participants With Adverse Events Related to Tolerability.
timeFrame: From screening up to 16 weeks
Secondary outcomes:
measure: Peak Plasma Concentration (cMax) of ODM-106
timeFrame: 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.
measure: Area Under the Plasma Concentration Versus Time Curve (AUC) of ODM-106
timeFrame: 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
measure: Time to Peak Plasma Concentration (Tmax) of ODM-106
timeFrame: 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
measure: Elimination Half-life of ODM-106
timeFrame: 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.
measure: Metabolite Screening in Plasma and Urine
timeFrame: 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
measure: Effect of ODM-106 on Growth Hormone Levels
timeFrame: Predose and 1, 2, 3,4, 6 and 8 hours post dose at each dose level.
measure: Sedation Scores on a Visual Analogue Scale (VAS)
timeFrame: Pre-dose and at 1, 6 and 10.5h post dose at each dose level
measure: Dexterity and Reaction Times
timeFrame: Pre-dose and at 1 and 6h post dose at each dose level
measure: Quantitative EEG
timeFrame: Pre-dose and at 1, 6 and 10 h post dose at each dose level
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Parexel International GmbH
Study officials:
affiliation: Parexel International GmbH, Berlin, Germany
name: Rainard Fuhr, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Orion Corporation, Orion Pharma
name: John Whiteside
role: STUDY_DIRECTOR
References: