Healthy
Conditions
Keywords
alpha2-adrenoceptor, receptor occupancy, positron emission tomography, [11C]ORM-13070, striatum, brain, noradrenaline, norepinephrine, endogenous, binding, Validation studies
Brief summary
The purpose of this study is to validate \[11C\]ORM-13070 as an alpha2C-adrenoceptor imaging agent for human positron emission tomography (PET) studies of brain alpha2C-adrenoceptor occupancy.
Interventions
DRUGAtipamezole
Administration of a single dose of 5-150 micrograms of atipamezole as an intravenous infusion
DRUGAtomoxetine
A single dose of 1.2 mg/kg of atomoxetine administered orally
DRUGKetamine
A single dose of ketamine (approximately 60 mg) administered as an intravenous infusion
OTHERCold pressor test
30-45 min cold pressor test of the foot
DRUGInsulin
Insulin administered as an intravenous infusion to induce hypoglycemia
DRUGPlacebo
A single dose of placebo (capsules) administered orally
Sponsors
Orion Corporation, Orion Pharma
University of Turku
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
MALE
Age
20 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Written informed consent (IC) obtained. * Good general health ascertained by detailed medical history, laboratory investigations and physical examination. * Males between 20 and 40 years of age (inclusive). * Body mass index (BMI) between 18-28 kg/m2 inclusive (BMI = weight/height2). * Weight 60-100 kg (inclusive).
Exclusion criteria
* Suspected poor compliance with the protocol or inability to communicate well with the study personnel. * Veins unsuitable for repeated venipuncture. * CYP2D6 slow metabolizer or ultrarapid metabolizer genotype. * Evidence of clinically significant cardiovascular, renal, hepatic, haematological, gastrointestinal, pulmonary, metabolic-endocrine, neurological, urogenital or psychiatric disease as judged by the investigator. * Any condition requiring regular concomitant medication including herbal products or likely to need any concomitant medication during the study. * Susceptibility to severe allergic reactions. * Intake of any medication that could affect the outcome of the study, within 2 weeks prior to the tracer administration (2 months for enzyme inducing drugs like rifampicin or carbamazepine), or less than 5 times the half-life of the medication. * Regular consumption of more than 21 units of alcohol per week (1 unit = 4 cl spirits, about 13 g of alcohol). * Current use of nicotine-containing products more than 5 cigarettes or equivalent/day. * Inability to refrain from using nicotine-containing products during the stay at the study centre. * Inability to refrain from consuming caffeine-containing beverages during the stay at the study centre, e.g. propensity for headache when refraining from caffeine-containing beverages. * Blood donation or loss of significant amount of blood within 2 months prior to the screening visit. * Abnormal 12-lead electrocardiogram (ECG) finding of clinical relevance after 10 minutes rest in supine position at the screening visit, for example: * QTc (calculated using Bazett's formula) \> 450 msec, * PR \< 120 msec or \> 210 msec, * QRS \< 70 msec or \> 120 msec. * Heart rate (HR) \< 40 beats/minute or \> 90 beats/minute after 10 minutes rest in supine position at the screening visit. * At the screening visit, systolic blood pressure (BP) \< 90 mmHg or \> 140 mmHg after 10 minutes in supine position, diastolic BP \< 50 mmHg or \> 90 mmHg after 10 minutes in supine position. * Any abnormal laboratory value, vital sign or physical examination result, which may in the opinion of the investigator interfere with the interpretation of the test results or cause a health risk to the subject if he takes part in the study. * History of drug abuse or positive result in drug abuse test. * Positive serology to human immunodeficiency virus antibodies (HIVAb), hepatitis B surface antigen (HBsAg) or hepatitis C virus antibodies (HCVAb). * Anatomical abnormality in brain MRI which may in the opinion of the investigator interfere with the interpretation of the PET results. * Any other condition that in the opinion of the investigator would interfere with the evaluation of the results or constitute a health risk to the subject. * Participation in another clinical drug study within 3 months prior to this study. * Participation in a prior PET study or other medical or occupational exposure to significant doses of ionizing radiation. * Any contraindication to MRI of the brain.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Receptor occupancy | 30 minutes | PET tracer (interventional drug) uptake in the brain is measured for 30 minutes by PET after various pharmacological and physiological pre-treatments. |
Countries
Finland
Outcome results
None listed