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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer Study
• Intervention / Treatment: Drug: ODM-106; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany
    • Parexel International GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Drug: ODM-106; Oral capsules dosage 2-800mg once daily for one day	Drug: ODM-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.
Placebo Comparator: Drug: Placebo; Oral capsules given once daily for one day	Drug: Placebo; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Orion Corporation, Orion Pharma
• Investigators: Principal Investigator: Rainard Fuhr, MD, Parexel International GmbH, Berlin, Germany; Study Director: John Whiteside, Orion Corporation, Orion Pharma

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: March 6, 2015
• First Submitted That Met QC Criteria: March 13, 2015
• First Posted (Estimate): March 20, 2015

Study Record Updates

• Last Update Posted (Estimate): December 23, 2016
• Last Update Submitted That Met QC Criteria: October 28, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Other Study ID Numbers: 3117001; 2014-001317-33 (EudraCT Number)