A Phase I Study to Assess PK of AZD7986 Alone & With Verapamil, Itraconazole or Diltiazem in Healthy Subjects

Inclusion Criteria: 1. Provision of signed and dated, written informed consent prior to any study specific procedures. 2. Healthy male and/or female subjects aged 18 to 55 years (inclusive) with suitable veins for cannulation or repeated venepuncture. 3. Females must have a negative pregnancy test at screening and on admission to the unit, must not be lactating and must be of non-childbearing potential, confirmed at screening by fulfilling 1 of the following criteria: Post-menopausal defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments and follicle-stimulating hormone (FSH) levels in the post menopausal range(\> 40 milli-International unit \[mIU\]/mL). Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy, but not tubal ligation. 4. Have a body mass index (BMI) between 18 and 30 kg/m2, inclusive, and weigh at least 50 kg and no more than 100 kg, inclusive. 5. Provision of signed, written and dated informed consent for optional genetic/biomarker research. 6. Hormone replacement therapy is not allowed for females to exclude any drug drug interaction between the hormone replacement therapy and AZD7986. Exclusion Criteria: 1. 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. 2. History or presence of gastrointestinal (GI), hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs. 3. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of AZD7986. 4. Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results, as judged by the investigator. 5. Any positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody, and human immunodeficiency virus (HIV) antibody. 6. Any clinically significant abnormal findings in vital signs after at least 10 minutes of rest, defined as the following: * Systolic blood pressure \< 100 mmHg or \> 140 mmHg; * Diastolic blood pressure \< 50 mmHg or \> 90 mmHg; or * Pulse rate \< 50 or \> 85 beats per minute. 7. Any clinically important abnormalities in rhythm, conduction or morphology of the resting electrocardiogram (ECG) and any clinically important abnormalities in the 12 Lead ECG as considered by the investigator that may interfere with the interpretation of ECG interval measured from the onset of the QRS complex (electrical activity or ventricular contraction on the ECG where Q represents the downward deflection, R represents upward deflection and S represents a downward one) to the end of the T wave corrected for heart rate (QTc) interval changes, including abnormal ST-T-wave morphology, particularly in the protocol defined primary lead or left ventricular hypertrophy. 8. Prolonged QT interval corrected for heart rate using Fridericia's formula (QTcF) \> 450 ms or shortened QTcF \< 340 ms or family history of long QT syndrome. 9. PR (PQ) interval shortening \< 120 ms (PR \> 110 ms but \< 120 ms is acceptable if there is no evidence of ventricular pre-excitation). 10. PR (PQ) interval prolongation \> 200 ms, intermittent second or third degree atrioventricular (AV) block (Wenckebach block while asleep is not exclusive), or AV dissociation. 11. Persistent or intermittent complete bundle branch block (BBB), incomplete bundle branch block (IBBB), or intraventricular conduction delay (IVCD) with QRS \> 110 ms. Subjects with QRS \> 110 ms but \< 115 ms are acceptable if there is no evidence of e.g., ventricular hypertrophy or pre-excitation. 12. Known or suspected history of drug abuse, as judged by the investigator. 13. Current smokers or those who have smoked or used nicotine products within the 3 months before screening. 14. Known or suspected history of alcohol or drug abuse or excessive intake of alcohol as judged by the investigator. 15. Positive screen for drugs of abuse or cotinine at screening or on each admission to the study centre or positive screen for alcohol on each admission to the study unit. 16. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD7986. 17. Excessive intake of caffeine containing drinks or food (e.g., coffee, tea, chocolate,) as judged by the investigator. 18. Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to the first administration of AZD7986. 19. Use of any prescribed or non-prescribed medication including antacids and other drugs for gastric acid-related disorders, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to the first administration of AZD7986 or longer if the medication has a long half-life. Note: Hormonal replacement therapy is not allowed for females. 20. Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to screening. 21. Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 3 months of the first administration of AZD7986 in this study. The period of exclusion begins 3 months after the final dose or 1 month after the last visit whichever is the longest. Note: Subjects consented and screened, but not dosed in this study or a previous phase I study, are not excluded. 22. Subjects who have previously received AZD7986. 23. Involvement of any AstraZeneca, PAREXEL or study site employee or their close relatives. 24. Judgment by the investigator that the subject should not participate in the study if they have any ongoing or recent (i.e., during the screening period) minor medical complaints that may interfere with the interpretation of study data or are considered unlikely to comply with study procedures, restrictions, and requirements. 25. Subjects who cannot communicate reliably with the investigator. 26. Subjects who are vegans or have medical dietary restrictions. 27. Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order. 28. 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. The test may be repeated if the initial test result is indeterminate. * 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. * Subjects with active malignancy or neoplastic disease in the previous 5 years other than superficial basal cell carcinoma. * Disease history suggesting abnormal immune function. * Subjects 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. 29. Subjects with a history or signs of current gingivitis/periodontitis or a history or current hyperkeratosis of palms and soles will be excluded. (Due to the fact that many subjects lacking functional DPP1 enzyme have been described to have periodontitis and palmoplantar hyperkeratosis.) 30. Subjects with total urinary protein/urine creatinine ratio outside the normal range. 31. Drugs affecting CYP3A4 should be refrained from use for 3 weeks prior to study commencement and thereafter until study completion. In addition, the following is considered a criterion for the exclusion from the optional genetic component of the study: 32. History of bone marrow transplant 33. Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection. 34. Hypersensitivity to the verapamil or to any of the excipients. 35. History of serious cardiac events such as myocardial infarction. 36. History of sino-atrial block; sick sinus syndrome; chronic or uncompensated heart failure (including left ventricular heart failure). 37. History of atrial flutter, atrial fibrillation or Wolff-Parkinson-White syndrome. 38. Known hypersensitivity to diltiazem or to any of the excipients. 39. Known hypersensitivity to itraconazole or to any of the excipients. 40. Elevated or abnormal liver enzymes or active liver disease, or who have experienced liver toxicity with other drugs.