Competition With Striatal [11C]ORM-13070 Binding by Atipamezole and Endogenous Noradrenaline

• Status: Completed
• Trial end date: 2012-01-01
• Target enrollment: 0
• Participant gender: Male

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Turku
• Collaborator: Orion Corporation, Orion Pharma
• Treatments: Atipamezole; Atomoxetine Hydrochloride; Insulin; Insulin, Globin Zinc; Ketamine; Norepinephrine

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.