Patient case (clinical description): A 30-year-old man who is a computer scientist came to the clinic with the lab result stating azoospermia.  The patient is sexually active with his wife and does not use any contraception methods.  They have been trying to conceive for the past year with no success.  The patient has a past medical history of recurrent pneumonia, shortness of breath, and  persistent cough that produces large amounts of thick sputum. The patient had multiple lung infections during childhood. He does not smoke, use illicit drugs or alcohol.  The patient has no history of other medical conditions including allergies or any kind of surgery.  On physical examination, the digits show clubbing.  An ultrasound shows bilateral absence of the vas deferens, and FEV1 was 75% on the respiratory function test.

Patient's own account: I'm a 30-year-old computer scientist. I did some lab tests that came back quite alarming, stating that I have azoospermia?! I'm sexually active with my wife and we don't use contraception. We've been trying to have a child for the past year. I have a medical history of pneumonia and shortness of breath and regular wet cough. I had several lung infections when I was a kid. That's why I'm very careful and don't smoke, do drugs, or drink. I don't have other medical conditions including allergies or any kind of surgery. The doctor did the clubbing test on my fingers, which was positive. I also did an ultrasound and it showed that I'm missing the tubes that carry sperm around. I also had a 75% for my respiratory function test.

Clinical trial: Single + Multiple Ascending Dose and Food Effect Study of AZD7986 in Healthy Volunteers, PK, PD and Safety Study

Eligibility criteria:
Inclusion Criteria:

          1. Provision of signed and dated written informed consent prior to any study specific
             procedures.

          2. Healthy male or female subjects aged 18 to 50 years (inclusive) at screening with
             suitable veins for cannulation or repeated venepuncture.

          3. Females must be of non-child-bearing potential, confirmed at screening by fulfilling
             one of the following criteria:

               -  Post-menopausal defined as amenorrhoea for at least 12 months or more following
                  cessation of all exogenous hormonal treatments and follicle stimulating hormone
                  (FSH) and luteinising hormone (LH) levels in the post menopausal range.

               -  Documentation of irreversible surgical sterilisation by hysterectomy, bilateral
                  oophorectomy or bilateral salpingectomy but not tubal ligation.

          4. Male subjects must be non fertile, i.e., surgically sterilised with documentation of
             azoospermia or must practice an effective contraceptive method to prevent pregnancies.
             Effective contraceptive methods are:

               -  Sexual abstinence from before the first administration of the IMP until 3 months
                  after final administration of the IMP, only if this is in line with the preferred
                  and usual lifestyle of the subject.

               -  Use of a condom plus spermicide agent in addition to having their partner use
                  another acceptable method (oral or injectable hormonal contraceptives,
                  contraceptive patch, intrauterine devices, vaginal hormonal rings, vaginal
                  diaphragm or cervical caps) from before the first administration of the IMP until
                  3 months after final administration of the IMP.

               -  Subject's sexual partner is of non childbearing potential, i.e., post menopausal
                  or surgically sterilised (e.g., tubal ligation, hysterectomy in medical history).

          5. Have a body mass index (BMI) between 18.0 and 30.0 kg/m2 inclusive and weigh at least
             50 kg and no more than 100 kg inclusive at screening.

        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.
No condition on gender to be admitted to the trial.
Accepts Healthy Volunteers
Subject must be at least 18 Years old.
Subject must be at most 50 Years

Eligibility (NLI label): Contradiction