A PET study to determine biodistribution and binding characteristics of [11^C]AZ14132516 in healthy participants

Exclusion Criteria

• 1) Current significant major or unstable respiratory disease, heart disease, cerebrovascular disease, hematological disease, hepatic disease, renal disease, gastrointestinal disease, or other major diseases.
• 2) Participants with unstable hypertension (as judged by the Investigator) or symptomatic hypotension, history of pre-syncope or syncope due to orthostatic hypotension and/or induced by change of posture (orthostatic hypotension defined as 25 mmHg decrease in systolic and/or 15 mmHg).
• 3) Significant abnormalities on the clinical examination, including neurological and physical examination, vital signs, ECG and clinical.
• 4) Chemistry, hematology, or urine analysis results that may interfere with the study or present a safety risk to the participant.
• 5) Abnormal vital signs, after 10 minutes of supine rest as judged by the PET centre physician. As a guide, any readings outside the following should be considered in the evaluation:
• a) systolic blood pressure (BP) ≥ 140 mmHg
• b) diastolic BP ≥ 90 mmHg
• c) heart rate ≤ 35 bpm or ≥ 100 bpm
• The inclusion of participants meeting the above criteria may be decided on a case-by case basis by PET center physician.
• 6) Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG that may interfere with the interpretation of QTc interval changes. This may include participants with any of the following:
• (a) PR (PQ) interval prolongation of clinical significance as judged by the Investigator
• (b) Intermittent second or third degree AV block (AV block II Mobitz type 1, Wenchebach, while asleep or in deep rest is not disqualifying)
• (c) Incomplete, full, or intermittent bundle branch block (QRS ≤ 110 ms with normal QRS and T wave morphology is acceptable if there is no evidence of left ventricular hypertrophy)
• (d) Abnormal T wave morphology, particularly in the protocol-defined primary lead
• (e) Prolonged QTcF ≥ 470 ms or shortened QTcF ≤ 340 ms or a family history of long QT syndrome
• The inclusion of participants meeting the above criteria may be decided on a case-by case basis by PET centre physician.
• 7) Known or suspected systemic infection (eg, hepatitis B virus, hepatitis C virus, human immunodeficiency virus [HIV] and tuberculosis), including previous or ongoing infectious or autoimmune disease.
• 8) Participants must abstain from taking prescription or non-prescription drugs (including vitamins, recreational drugs, and dietary or herbal supplements) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) before the start of study intervention until completion of the follow-up visit, unless, in the opinion of the investigator and sponsor, the medication will not interfere with the study.
• 9) Current drug abuse or dependence or positive screen for drugs of abuse at screening visit.
• 10) Participants on anticoagulant treatment.
• 11) Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
• 12) Suffers from claustrophobia that limits the ability to undergo the scanning procedure.
• 13) Participant has abnormal blood flow confirmed by a negative Allen’s test in both hands at screening.
• 14) Blood donation within 1 month of screening or any blood donation/blood loss greater than 500 mL during the 3 months prior to screening.
• 15) Positive severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) rapid antigen test at screening.
• 16) Any other reason that, in the study PI opinion, prohibits the inclusion of the participants into the study.
• 17) Judgement by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements.