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

Phase 1
Completed
Conditions
Healthy
Interventions
Registration Number
NCT01435213
Lead Sponsor
University of Turku
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
10
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
KetamineKetamine-
Insulin-induced hypoglycemiaInsulin-
Cold pressor testCold pressor test-
PlaceboPlacebo-
AtipamezoleAtipamezole-
AtomoxetineAtomoxetine-
Primary Outcome Measures
NameTimeMethod
Receptor occupancy30 minutes

PET tracer (interventional drug) uptake in the brain is measured for 30 minutes by PET after various pharmacological and physiological pre-treatments.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (2)

University of Turku, Clinical Research Services Turku CRST

🇫🇮

Turku, Finland

University of Turku, Turku PET Centre

🇫🇮

Turku, Finland

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