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

University of Turku

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Placebo; Drug: Ketamine; Drug: Atipamezole; Drug: Insulin; Other: Cold pressor test; Drug: Atomoxetine

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01435213

3099002

Details and patient eligibility

About

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.

Enrollment: 10 patients

Sex: Male

Ages: 20 to 40 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Single Blind

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10 participants in 6 patient groups

Atipamezole

Experimental group

Treatment:

Drug: Atipamezole

Atomoxetine

Experimental group

Treatment:

Drug: Atomoxetine

Ketamine

Experimental group

Treatment:

Drug: Ketamine

Insulin-induced hypoglycemia

Experimental group

Treatment:

Drug: Insulin

Cold pressor test

Experimental group

Treatment:

Other: Cold pressor test

Placebo

Experimental group

Treatment:

Drug: Placebo