PET study to determine Muscarinic receptor occupancy in lungs after inhalation of AZD2115 and Tiotropium

Exclusion Criteria

• • History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the study results or the subject’s ability to participate in the study.
• • Any clinical significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of investigational medicinal product (IMP)
• • Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results, as judged by the investigator.
• • Any positive results on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV)
• • Abnormal vital signs, after 10 minutes of supine rest, defined as any of the following:
• - Systolic blood pressure (BP) <90 mmHg or >140 mmHg
• - Diastolic BP <50 mmHg or >90 mmHg
• - Heart rate <45 bpm or > 100 bpm
• • Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG that may interfere with the interpretation of QTc interval changes, as determined by the investigator. This may include subjects with any of the following:
• - PR (PQ) interval prolongation of clinical significance as judged by the Investigator
• - Intermittent second or third degree AV block (AV block II Mobitz type 1 Wenchebach, while asleep or in deep rest is not disqualifying)
• - Incomplete, full, or intermittent bundle branch block (QRS less than 110 ms with normal QRS and T wave morphology is acceptable if there is no evidence of left ventricular hypertrophy)
• - Abnormal T wave morphology, particularly in the protocol-defined primary lead
• - Prolonged QT interval corrected for heart rate using Fridericia’s formula (QTcF) greater than 450 ms or shortened QTcF less than 340 ms or a family history of long QT syndrome.
• • History of alcohol abuse or excessive intake of alcohol, as judged by the investigator.
• • Positive screen for drugs of abuse at visit 1.
• • History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, other than seasonal allergies, as judged by the Investigator, or history of hypersensitivity to drugs with similar chemical structure or class as AZD2115.
• • Use of any prescribed or non-prescribed medication, during the 4 weeks (or longer depending on the medication’s half-life) prior to the administration of IMP.
• • Use of drugs with enzyme inducing properties such as St John’s Wort within 4 weeks prior to the investigational product administration.
• • Current smokers or subjects who have smoked or used nicotine products within 6 months prior to visit 1
• • Plasma donation within 1 month of screening or any blood donation/blood loss equal to or greater than 500 mL during the 3 months prior to screening.
• • Previous enrolment in the present study
• • Involvement in the planning and/or conduct of the study
• • Participation in another clinical study with an investigational product during the last 3 months
• • Negative Allen test in both hands
• • Claustrophobia that would contraindicate PET measurement.