Single + multiple ascending dose and food effect study of AZD7986 in healthy volunteers, PK, PD and safety study

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 results or the subject’s ability to participate in the study.
• - History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• - Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
• - Subject has increased risk of infection:
• • History and/or presence of tuberculosis (TB); positive result for interferon gamma release assay (IGRA) (i.e., QuantiFERON TB-Gold), subjects who have resided in regions where tuberculosis and mycosis are endemic during 90 days before screening, or who intend to visit such a region during the duration of the study i.e. deserts areas, Eastern Europe, Central and South America, Africa except Egypt, Russia, Asia, Indonesia
• • Oral body temperature of > 37.7°C on Day -1, or as judged by the Investigator.
• • Blood neutrophil count < 1.7 x109/L (Screening and Day -1 morning sample).
• • Is in high risk-group for HIV infection within the last 6 months (i.e., men who have had unprotected sex with men, women who have had sex without a condom with men who have sex with men, people who have had sex without a condom with a person who has lived or travelled in Africa, people who inject drugs, people who have had sex without a condom with somebody who has injected drugs, people who have caught another sexually transmitted infection, people who have received a blood transfusion while in Africa, eastern Europe, the countries of the former Soviet Union, Asia or central and southern America).
• • Other latent or chronic infections (e.g., recurrent sinusitis, genital or ocular herpes, urinary tract infection) or at risk of infection (surgery, trauma, or significant infection) within 90 days of screening, or history of skin abscesses within 90 days of screening.
• • Clinically significant lower respiratory tract infection not resolved within 4 weeks prior to screening, as determined by the Investigator.
• • Volunteers with active malignancy or neoplastic disease in the previous 5 years other than superficial basal cell carcinoma.
• • Disease history suggesting abnormal immune function.
• • Volunteers who have received live or live-attenuated vaccine in the 4 weeks prior to dosing.
• • High-sensitivity C-reactive protein above upper limit of laboratory reference range at screening and on Day -1.
• - Some subjects lacking functional dipeptidyl peptidase 1 (DPP1) enzyme have been described to have periodontitis and palmoplantar hyperkeratosis:
• • For Part 1a and Part 1b: Subjects with signs of current gingivitis/periodontitis. Gingival evaluation (by inspection) will be performed by a dental hygienist or trained study physician.
• • For Part 2: Subjects with a history of recurring gingivitis/periodontitis or signs of current gingivitis/periodontitis. Gingival evaluation will be performed by a dental hygienist or trained study physician. Evaluation of bleeding propensity due to gingivitis will be performed by using dental hygienist instrumentation. Exact measurement of gum pockets is not needed.
• • Subjects with a history of hyperkeratosis or erythema in palms or soles.