Clinical trial NCT01435213: Competition With Striatal [11C]ORM-13070 Binding by Atipamezole and Endogenous Noradrenaline
Official title: Competition With Striatal [11C]ORM-13070 Binding by Atipamezole and Endogenous Noradrenaline - a PET Study in Healthy Human Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: alpha2-adrenoceptor
receptor occupancy
positron emission tomography
[11C]ORM-13070
striatum
brain
noradrenaline
norepinephrine
endogenous
binding
Validation studies
Lead sponsor: University of Turku
Sponsor class: OTHER
Collaborators: name: Orion Corporation, Orion Pharma
First posted: 2011-09-16
Enrollment: 10
Sex: MALE
Minimum age (years): 20
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Receptor occupancy
timeFrame: 30 minutes
Secondary outcomes:
Other outcomes:
Locations:
city: Turku
country: Finland
facility: University of Turku, Clinical Research Services Turku CRST
city: Turku
country: Finland
facility: University of Turku, Turku PET Centre
Study officials:
affiliation: University of Turku
name: Juha Rinne, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: