Changes in Striatal [11C]ORM-13070 Binding Elicited by Changing Levels of Endogenous Noradrenaline

• Status: Completed
• Trial end date: 2012-12-01
• Target enrollment: 0
• Participant gender: Male

Summary

The primary objective of the study is to further investigate whether striatal [11C]ORM-13070 uptake can be reduced by physiological and pharmacological challenges that increase the synaptic concentrations of noradrenaline in the human brain. Each subject will undergo 3 PET scans, a baseline PET scan and two scans with noradrenaline challenges: intravenous administration of ketamine and oral administration of atomoxetine combined with a cold pressor test where the subject's foot is placed in an 8 °C water basin. Eight healthy male subjects will be included in the study.

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

Details

• Lead Sponsor: University of Turku
• Collaborators: Orion Corporation, Orion Pharma; Turku University Hospital
• Treatments: Atomoxetine Hydrochloride; Ketamine; Norepinephrine

Criteria

Inclusion Criteria:

1. Written informed consent (IC) obtained.

2. Good general health ascertained by detailed medical history, laboratory investigations and physical examination.

3. Males between 20 and 40 years of age (inclusive).

4. Body mass index (BMI) between 18-28 kg/m2 (inclusive).

5. Weight 60-100 kg (inclusive).

Exclusion Criteria:

1. Suspected poor compliance with the protocol or inability to communicate well with the study personnel.

2. Veins unsuitable for repeated venipuncture.

3. CYP2D6 slow metabolizer or ultrarapid metabolizer genotype.

4. Evidence of clinically significant cardiovascular, renal, hepatic, haematological, gastrointestinal, pulmonary, metabolic-endocrine, neurological, urogenital or psychiatric disease as judged by the investigator.

5. Any condition requiring regular concomitant medication including herbal products or likely to need any concomitant medication during the study.

6. Susceptibility to severe allergic reactions.

7. 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.

8. Regular consumption of more than 21 units of alcohol per week (1 unit = 4 cl spirits, about 13 g of alcohol).

9. Current use of nicotine-containing products more than 5 cigarettes or equivalent/day.

10. Inability to refrain from using nicotine-containing products during the stay at the study centre.

11. 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.

12. Blood donation or loss of significant amount of blood within 2 months prior to the screening visit.

13. Abnormal 12-lead electrocardiogram (ECG) finding of clinical relevance after 10 minutes rest in supine position at the screening visit

14. Heart rate (HR) < 40 beats/minute or > 90 beats/minute after 10 minutes rest in supine position at the screening visit.

15. 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.

16. 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.

17. History of drug abuse or positive result in drug abuse test.

18. Positive serology to human immunodeficiency virus antibodies (HIVAb), hepatitis B surface antigen (HBsAg) or hepatitis C virus antibodies (HCVAb).

19. Anatomical abnormality in brain MRI which may in the opinion of the investigator interfere with the interpretation of the PET results.

20. 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.

21. Participation in another clinical drug study within 3 months prior to this study.

22. Participation in a prior PET study or other medical or occupational exposure to significant doses of ionizing radiation.

23. Any contraindication to MRI of the brain.